Pocket Guide ENDO-DIAB-NET® 2024

"Medicine is a science of uncertainty and an art of probability" William Osler

Table of Contents

1. Goals & Manual on how to use it 16. Bone & Calcium Metabolism
2. Art. Hypertension & adrenal Incidentaloma 17. Female Gonads
3. Hyperaldosteronism 18. Male Gonads
4. Pheochromocytoma & Paraganglioma (PPGL) 19. Hypothyroidism & Radioiodine
5. Cushing Syndrome & Hypercorticism 20. Hyperthyroidism & TSH-Suppression
6. Addison Syndrome & Therapy with Steroids 21. Goiter & Thyroid “Cancer”
7. Diabetes mellitus (Dm) – General Aspects 22. Polyglandular Endocrinology
8. Dm Type 1 23. The Pituitary
9. Dm Type 2 & Metabolic Syndrome 24. Water & Salt
10. Hyper- & Hypoglycemic Derailings 25. Rare Diseases & Inborn Errors of Metabolism
11. Dm in Medicine, Surgergy & Dialysis 26. Gender Incongruence & -Dysphoria
12. Pregnancy 27. Hormones in Poly-Morbidity
13. Diabetes Counselling & Insulin therapy 28. This & That
14. Clinical Nutrition & Counselling 29. Laboratory Reference Values
15. Dyslipidemia & Obesity 30. EndoDiabNET

Emergencies Addison's (p6), Hypertensive crisis (2, 4); Hyper- & Hypoglycemia (10).
Calcium (16), Thyrotoxicosis (20), Myxedema Coma (19); Visual acuity (20, 23, 24)

1. Goals & Manual on how to use it

• Practical & as best as possible evidence-based, weighted guidelines (%Sensitivity / %Specificity), ie.
Essential, Important, Good-to-know, Helpful, "my Prof told me" a/o controversial, Passed eye test! You never give up, do you? Forget it, there are more important things in life

• Guidelines  structured "standard of care"  Optimization of patient care

• Stepwise (1→2→ 3→4→5) & standardized assessment (evtlibly by specialist; better by specialist)
• Can be adapted individually, if well-founded. Several mosaic pieces are needed to get a medical picture.
• Should cover about 75% of the daily clinical routine. Remaining 25%  "Meet-the-Professor" & "gut feeling" & PubMed
• State of error  will be adjusted "on a daily basis"  constructive input most welcomed
• Knowledge, learned by and then soon expected of the endo/diab/metabolic ward doctor
• Additional information become visible when clicking on text passages highlighted in yellow
• Consensus EndoDiabNet™ Aarau - Basel - Lucerne - Winterthur & associated clinics, under patronage of SGEDSSED
• Weblinks [Link] ; Lecture archive
SWISS ENDO GRAND ROUNDS PW for videos: !endograndRounds24*
• Any changes to the Pocket Guide & suggestions for the seminar can be submitted to office@[Link]
Abbreviations: 1°=primary; 2°=secondary; 3°=tertiary; =Delta, change; ABI=Ankle-Brachial Index; acc=according to; CEI=angiotensin
converting enzyme inhibitor; AI=adrenal insufficiency; Aldo=aldosterone; AKF=acute kidney failure; ARR=aldosterone renin ratio;
AUI=autoimmune sy; BP=2xdaily; BMD=bone mineral density (Dexa), BP =blood pressure; BR=bed rest; BT=blood test; bw=body weight;
Ca=carcinoma, calcium; Carb=Carbohydrate CDE=[Link] educator, C2=OH=alcohol; cf=see; CI=contraindication; CIR=Carbohydrate-to-
Insulin-Ration = Resistenzfaktor (RF); cvR=cardiovascular risk (factors); CHF=congestive heart failure; CKD=chronic kidney disease;
CL=clearance; COC=combined oral contraceptives; d=day; dly=daily; DC=diabetes counselling; DD=differential-dg; Dg=diagnosis;
Dm=diabetes mellitus; E=Epinephrine; ED=erectile dysfunction; ER=emergency room; esp=especially; evtl=eventually FD=first dg; F=female;
FA=fatty acids; FamH=family history; fct=functional; GW=Gestation Week; FAQ=frequently asked questions; F/U=follow up; fMN=free
metanephrine; fNMN=free normetanephrine; Fx=fracture; FNA=fine needle aspiration; GD=Graves' disease; GP=general practitioner;
gw=gestational week; Has=hashimoto; HC=hydrocortisone; HCL=Hybrid Closed Loop; HRT=hormonal replacement therapy; IHT=insulin
hypoglycemia test; HF=heart failure; HR= heart rate HRT=Hormonal Replacement Therapy; Hx=history (anamneses) IBD=irritable bowel
syndrome; ICM=ionated contrast media; IR=insulin resistance; HI=health insurance; LADA=Late-onset/Latent Autoimmune Dm of Adulthood;
LF=liver failure; LSI=last sexual intercourse; LY=lifeyear M=male; M=mol/L; M=meal; MD=physician; MDI=Multiple Daily Injections;
Meta=metastasis; met Sy=metabolic Syndrome MRA=Mineralocorticoid-Antagonist; NB=nota bene!; NE=norepinephrine; NC=nutrition
counseling, n=normal/normally; NAD=no abnormality detected; NC=nutritional counselling; NTI=non thyroidal illness; fast=fasting; OAD=oral
antidiabetic drugs; OC=oral contraceptive; OSAS=obstructive sleep apnea sy; P=plasma; PG=pregnancy; pHpt=prim. Hyperparathyroidism;
PerH=personal history, PG=pregnancy POI=premature ovarian insufficiency; PoHI=permission of health insurance (“PoHI”) pop=population;
pp=postprandial; PPFT= posterior pituitary function test (PPFT); psb=please see below PRL=prolactin; qid=4x/d; qd=1x/d; q6h=6 hourly;
sa=see above; sb=see below; S=serum; SE=side effect, SGA: Small for Gestational Age; SOP=standard operating procedure;
Subst=substitution; Susp of=suspicion of, Stx=strumectomy; Sx=surgery Sy=syndrome, symptom, TC=total cholesterol, TG=triglycerides;
Tg=thyroglobulin; Thy=thyroid; tid=3x/d; TIR= Time In Range TMNG=Toxic multinodular goiter; TPN=total parenteral nutrition; Tu=tumor;
Tx=therapy, TMNG=toxic adenoma; U=urine; US=ultrasonography; VF=visual field; VP=venipuncture; wt=weight; WHR =waist (aBPominal ø)-
Hip (Troch. major)-ratio; wkly=weekly, AbküFi KSA
Disclaimer: Half of what we teach you is wrong, but we don’t know which half…support research to find out !
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Thanks to countless colleagues and patients; Legal Notice: Be careful about reading health books. You may die of a misprint! Marc Twain
Impressum ©☺ Editorial board [Link]@[Link] Reprints & copies with permission only!
Version 4/23/2025 250101 Pocket-Guide ©[Link]@[Link]
 2. Art. Hypertension & adrenal Incidentaloma
„When you hear hoof clapper in the central park, first think of horses, then look for zebras“

Arterial Hypertension ”Office BP” > 140 / 90mmHg (“automated BP” >130 / 80 mmHg), ≈20-30% of adults
>90% „essential“, cost/benefit of further diagnostics is debated -> selection based on cvR; verify increased BP with 24h-BP
(mean 24h-BP <120 / 80 mmHg, nocturnal BP-drop <10%  risk for end organ damage, OSAS, neuropathy) or patient self-
measurement (automatic machine measurements (3x))
When to think of 2° hypertension?
- Suggestive history & findings: sudden onset, <25-40Yrs, BP>160/100mmHg, "Spills", pos FamHx
- Resistance to tx: BP>140/90 despite quadrupple-therapy for several wks (incl diuretics), BP under Tx (Compliance?)
- End organ damage: left ventricular hypertrophy (Echo, BNP & EKG (insensitiv)), atherosklerosis (Makroangiopathy (CHD, CVI<50Yrs,
aortic aneurysm, CKD, Microalbuminuria (Alb/Crea iU), macular edema cvR: met. Sy, smoking, age, pos FamHx, no nocturnal dipping

Stepwise diagnosis of 2° hypertonsion

1) "Stress/life-style", 30%. „white-coat“( 24h-BP), intracranial pressure, NaCl-diet >9g/d? (Na >180mmol/24hUrin)
2) Met Sy? (p7ff), OSAS Score D, F: snoring, day-time sleepiness, headache pulsoxymetry
3) Vascular: Renal (>70% renal artery stenosis, often atheroscl.): flow murmurs, >30% Crea  after ACEI
 duplex-US (90%/80%) & active plasma renin (aPR) recumbent  (p3) urine sediment, MRI-angio (97%/93%)
Aortic insufficiency or stenosis (atheroscl./coarctatio)? Radial-Femoral Pulse Delay or BP BPs: righ>left arm or BP right Arm>Bein  angiography
4) Drugs compliance? NSAID, steroids, anabolics, cyclosporin, antidepressiants, COC (e2), alkocol(-withdrawal), cokain, licorice
5) Pregnancy (EPH-gestosis, p12: LMP? (HCG-test), polyglobulia, porphyria
6) "Dessert" Endocrine cause (10-20%) Screening-Test (clinical pretest-probability → laboratory test → Imaging!)
Hyperaldosteronism (2-10%, p3)  S-K<4mM? (on diuretiks <3.5mM? OSAS?) →aldosterone/renin-ratio (ARR)
Cushing syndrome (p5)  Signs & Symptoms? → free urine cortisol (FUC)
Pheochromocytoma /Paraganglioma (p4)  Trias? → plasma metanephrines & normetanephrines
Dysthyroidism (Hyper→BPsyst; Hypo→BP ) (p19f) diastole.  TSH
pHpt, acromegaly (signs & symptoms?) (p16, 23)  Ca2+, IgF1
Deoxycortisol (DOC)-excess  K & Aldo & Renin low → HPLC steroid profile i 24h-urine Inselspital Bern
Monogenetic variants (e.g. mutations of mineralocorticoid-receptors)  pos. FamHx, evtl. K, Mg low, Aldo & Renin “normal”, worseninf in pregnancy or cyklus, → genetics A. Lauber, Fribourg

Tx:  Lifestyle! Nicotine, Excercise (>5x30’/wk), wt (5kg≈10mmHg, vegetable & fruits, saturated fattyacids), NaCl (2g/d
ideally <5g/d, 24h-urine Na<80mM/d, avoid premanufactured food, use Na-depleted salt (e.g. magdi sol), fresh herbs). Drug choice & BP-target depend
of cvR: ACEI & diuretics, Ca-Antag (P-Ca), Blocker (KHK), AT-II Antagon. (ATA), evtl. with Neprilysin-inhib. (Entresto ® in CHF), Renin-
inhib. aliskiren (Rasilez Tbl. 150, 300mg qd) MRA (KI: K): spironolactone (Aldactrone ® Tbl. 25-100mg) / eplerenone (Inspra ® Tbl. 25mg BP; Ind: CHF) / finerenone
(Kerendia ® Tbl. 10-20mg qd, Ind: Dm2 to delay CKD, PoHI); -Blocker monoxidine Physiotens Tbl. 0.4mg qd; aldosterone synthase inh baxdrostat, lorundostat
Tx-resistant hypertension: „drug rotation“, orthostasis? Compliance? evtl. before bedtime (nächtl. Dipping!), individualised Tx
(rel) CI: thiazide: CKD, gout, pHpt; B: Asthma; Cyp3A4 (verapamil / diltiazem, Plendil): grapefruit; NSAID  antihypertensive-effect, pregnancy: p12
Hypertensive urgency BP > 180/110mmHg & headache, epistaxis, psychomot. agitation & NO acute end organ damage; Tx: po & ambulatory,
nifedipine (adalat ret 20mgCR 60po, CI: SS, aortic stenosis), captopril (Lopirin® 12.5-25mg po tid (-100mg/d), CI: SS, bilat NAS, CKD), labetalol
(Trandate 200-400mg po tid, CI: asthma, AV-block, acute CHF, low T1/2 3-6h), clonidine (Catapresan®, OH-delirium, 0.15mg po, CI: CHD, AV-block)
Hypertensive emergency DG: BP +/- > 200/120mmHg & acute end organ damage (Neurol Sy (enzephalopathy, bleeding), acute pulm.
edema, ACS, eye sy (papillary edema, bleeings, exsudates)), TH: iv & inpatient (ICU), immediate BP, labetalol (Trandate, CHD, 10-20-80mg iv q15’,
CI: sa), urapidil (Ebrantil® 10mg weise iv; phentolamin (Regitin, pheochromocytoma, 5-10mg iv q10’); ICU: Nitroprussid (CHD w CHF, 0.25-10ug/kg/’);
nitroglycerin (Perlinganit, CHD w acute HF, 5-100 ug/‘ iv); esmolol (Brevibloc®, CHD, 200-500 x 4min50-300 mg/kg/’ kont. iv), furosemide (Lasix, acute
HF, 40-250mg iv)

Adrenal incidentaloma DEF: Incidentally detected adrenal mass >1cm; ENS@T-biobank

Prevalence: 2% (20y) -7% (70y, Tu-Pat), 10% bilateral 2 questions: hormonally active? (typ. <2cm & <10-20HU, 25% hormonally active
(cortisol>catechol.), 30% of these asymptomatic); malignancy
(ACC)? (4%, 99% metastases, size (<4cm 5%, >6cm 25%), course in F/U, peak 1-10 & 50-60y)
SY: Hypertension? S-K<4mM? signs of Cushing (p5, incl. met. Sy, osteopenia/porosis)? Pheo-Triad? Virilisation?
DD „bilat. big adrenals": CAH/AGS (p17), Conn, Cushing (incl. BMAH p. 5); MEN, metastasis, infection (tbc), assess adrenal insuff.
DG: Na, K, Crea, Urea, ARR (p3), FUC (p5), ACTH, fMN, fNMN (CHUV, if >10HU i CT), DHEA-S; Testosteron, 17OH-Prog n 250ug ACTH (p 17)
- & metabol. Sy a/o osteopenia/porosis → autonomous cortisol-secretion (20-50%)? 1mg DST <50nM no, >50nM mild
autonomous cortisol secretion (MACS); individually based on RF (f>m, genetics (fam. history, 25% pos in bilat. MACS, RMC-5, KDM-1a); 1mg
DST>100nM, low-normal ACTH <10-15pg/ml, P-DHEA-S <3M (wg part. suppr. ACTH-suppr.) 6-12mtl. F/U vs. Sx after AVS (adrenal vein sampling) if
bilat. tu on CT, evtl. 3x salivary cortisol a/o 24h-urine (20ml 6M HCl): K, Aldost, Cortisol, MN, NMN
suspected ACC  steroidprofile 24h-urine to measure precursors with mineralocorticoid action, e.g., 11-DOC
Imaging: Benign: noncontrast CT < 10HU and homogenous (myelolipoma: heterogenous, <-40HU in lipid rich areas), cysts (>10HU homogenous, no
enhancement) →No F/U ( > 40 yrs) CT w contrast: relative washout: > 58% (> 40%?), (absolute > 60%?), MRI: loss of signal in/out phase; FDG PET-CT:
Absence of FDG uptake or uptake less than liver;. Indeterminate noncontrast CT HU > 10 (> 20) and / or heterogenous and / or size > 4cm (illustration), MRI:
no loss of signal, PET-CT: high uptake, CT with contrast: washout slow; further action dependent on est. malignancy risk → tumor board; immediate
additional imaging, interval imaging 6-12 months or surgery (with prior tumor staging: CT Thorax;PET-CT). Earlier surgery in pat < 40 yrs
F/U no F/U if <10HU in CT & homogenous; else 6-12 mthly, if no surgery, if no change in size in non-contrast CT /MRI:no further F/U; if significant growth with
largest diameter > 20% a/o >2.68mm/y) a/o hormonally active → Sx. if growth < 20%: evtl. additional F/U imaging 6-12 months. Adrenal biopsy: limited indication,
[Link]-adrenal malignancy if change of management. Lesion must be hormonally inactive and indeterminate. NOT in suspected ACC or parasitiy cysts
NNR-Ca “ACC” resectable: individualized (depending on ENSAT staging, degree of resection, Ki67 index): Surgery, mitotane (Lysodren tab 0.5-1g QID, blood level
14-20mg/L, side effects: adrenal insufficiency, GIT, neuro), chemotherapy, local radiotherapy; unresectable: mitotane (s.a.), chemotherapy, local therapies (RT, SIRT, RFA).

*Validation Crea i 24h-U: 100 (Twiggy) - 250 (A. Schwarzenegger) umol Crea/kg/d; M 11.7 – 17.6 mmol/d; F 7.0 – 9.5 mmol/d
GFR: ClCrea (ml/’) = UCrea x UVol / (SCrea x 1440')  (140-Age) x kg x 1.23 / SCrea [uM]; F x 0.85; reference range: M 97-140; F 75 -125ml/’
Version 4/23/2025 250101 Pocket-Guide ©[Link]@[Link]
 3. Hyperaldosteronism
"Conn-Syndrome has generated a number of publications that equals the number of patients in whom it is the cause of hypertension"

Physiology: angiotensinogen (renin)  angiotensin I (ACE)  angiotensin II  aldosterone  renal K+/H+-excretion ;

metabolic alkalosis (VBGA: HCO3-, Cl-), S-Na(),P-Ca, P-Mg; Hyperaldo = cvR (CVI <50J (OR 2.5), CHD & CHF (OR 2), AFib, OSAS)
Na-deficiency→ P-aldosterone ; K-deficiency→ P-aldosterone, typ. salt in CH wholefood NaCl/d  12.5g (=5g Na+) 
215mmol (1g Na = 43mmol); K/d  50-140mmol; K-losses: urine  40-120mmol > stool, sweat  0-10mmol each
1) Screening (debated! Cut-offs depend on context „functional vs hyperplasia vs adenoma“-continuum)
- art. Hypertension, especially if P-Potassium (spontaneous < 4 or <3.5 mM with „low-dose diuretics“),
a/o incidentaloma, OSAS, pos FamH, tx-resistant hypertension

2) Initial Dx intraindividual variation, algorithms, stop aldactone/eplerenone & aliskiren for 4 wks. -Blocker, ACE-H/ATA (+/-Thiazid) ok, if aPR.
"AaRR" (P-Aldo / aktive P-Renin (aPR)-Ratio) n <30 (Sens. 98%, Spez. 82%) bzw. >35 (90%/ 86%) pM/mU/L, cave:
a) BT 08h, fasting, seated for 10’, analytics (KSA): EDTA-plasma, aktive tenin LIAISON direct renin assay, aldosterone LIAISON
b) AaRR validated for euvolemia & K>3.5mM & S-aldosterone >420pM, evtl. repeat (hypo-Na a/o hypovol. -> Renin & Aldo)
 K-enriched diet a/o KCl Hausmann 2 drg tid (745.5mg=10mmol K/Drg) evtl w ACEI/ATA ( aPR only () → demasks hyperaldo & art. hypertension
c) AaRR Blocker, NSAID, methyldopa, clonidine, drospirenon / luteal phase & OC, CKD, Age; 8am, aliskiren (<2Wo (PRA →ARR)
AaRR aldactone & licorice (4wks); aliskiren (2 wks (aPR), P-K, amilorid(aldo/aPR)/thiazide/saluretic., ACEI & ARB (2wks), amlodipin, diltiazem, Dm, coffee, 11am
3) Confirmation Dx ideally with “normal” NaCl-diet) (dh, mMol/d 120 Na, 60 K), evtl. K-enriched diet, women 1. half of mens. cycle
I) AaRR adapted BP-Tx doxazosin (Cardura CR ® 4-8mg qd), amlodipin (Norvasc ® 5-10mg qd), verapamil (Isoptin RR ® 240 qd-BP), minoxidil (Loniten ® 10-20mg bid)
& orienting spot urine K-U/P >10
II) 24h-urine stop KCl-Tbl. 2d pre-collection! Aldosterone (n<33nmol/d; >42), K (>30 (40) mmol/d,), Na >100 (200) mmol/d
III) Aldosterone-suppression tests S-aldo <140 pM (”exclusion”) >280 pM (”diagnostic”), evtl. Suppression >50% if basal value  & aPR <5mU/L
a) oral NaCl-load NaCl 1-2Tbl 1g=17mmol (UNa>200mM/d) & KCl 1-3 Tbl 745 mg (10mmol) or KCitrat effevescents (30mmol) tid or amilorid (due to S-K)
b) NaCl stress test D F outpatient: 2l 0.9% NaCl x 4h, supine, VP 0&2h m Na, K, crea, urea, aldosterone, cortisol f. a/c ratio (sens >90% (seated pat.))
c) Florinef-test inpatient; Tbl 0.2mg BP x3d & 1-3 KCl Drg tid/iv  VP 09h n. 60’ upright ( K-Kontrolle 2x/d; rel. CI: CHF, BP)
d)Captopril-test 2h n 25mg lopirin ® po, (normal: renin; Aldo 30%, ARR 20%, spec f APA, diagnostic performance limited if low salt intake

4) Localisation & Classification

MRI or CT-Abd (adrenal morphology & anatomy of adrenal veins), cave: Incidentaloma.
In patients who seek surgical intervention adrenal venous sampling (AVS) (taking into account: age, potassium, Aldo
following SIT, adrenal morphology). AVS in specialized centers (including intra-procedural cortisol measurement, e.g. USB):
selectivity index and lateralization index depending on the usage of ACTH stimulation (e.g. Sl: >2 and LI > 4 without ACTH). Upon
AVS interpretation -> laparoscopic unilateral ADX or medical treatment with MRA.
Additional tests, if still ambiguous DD adenoma to hyperplasia
- Dex-ACTH-test: 1mg dexamethason (Milicorten®) 11pm; 250ug ACTH test 08h, BE n 0, 30, 60, 90 min, Conn-Sy: S-aldo >1050nM or >4x-increase 90 min / 0 min
- Orthostasistest: adenoma: 8am supine S-aldo>700pM (>400) (60%/100%),  2h upright (40%/100%); if S-aldo 400-700  aldactone-trial (100→300mg/d spironolactonex 4/52  if BP   evtl adrenalectomy
- 1.25l NaCl 0.9% iv x 2h  aldosterone (“A”, pM); cortisol (“C”, nM); Adenom: A/Cafter NaCl>2(>A/C before NaCl )
- > 131-Iodine-cholesterol-szintigraphy under prednisone (ACTH; Ind: side-localisation of bilaterally enlarged adrenals

A) 1° Hyperaldosteronism: aldo (typ. >450pM) & renin (typ. <1mU/L)  ARR

Mostly caused by multiple microscopic aldosterone- producing foci with somatic driver mutations, formally divided into:
a) Conn-Sy (“dominant unilateral nodule or adenoma (APA/APN) present”): 50-70%, typ. 0.5-2.5cm, P-Aldo >550pM (90%/90%), Ca <2%
TH: lapr. adenomectomy → aldactone 1wk preop prevents postop aldo (K, BP) Tx: NaCl po; Florinef Tbl. 0.05-0.1mg qd, if not possible/rejected → MRA & NaCL 5g/d
50% persist. hypertension (RF: >2 antihypertensive drugs; BMI >25mg/kg2; >6yrs hypertension; male), nevertheless cvR
b) Bilateral hyperplasia (“multiple aldosterone producing micronodules or diffuse hyperplasia”): 30-50%, DD: CAH (psb)
Tx: MRA (Mineralocorticoid-Receptor Antagonist): aldactone (Spironolactone 50-200mg/d, high dose is needed for effective tx, monitor compliance and adjust ds based
on potassium and renin levels), SE: gynecomastia→eplerenone (Inspra® 25-100mg/d), less potent, PoHI (Ind f CHF); firenerone; aldosterone synthase inh (baxdrostat,
lorundostat, dexfadrostat) Alternative BP-Tx: Norvasc ® 10mg/d, Reniten ® 20mg/d, Midamor ® (Amilorid) 5-30mg/d b K; PAMO-criteria to assess tx outcome
c) Familiar Glucocorticoid-remediable aldosteronism (GRA, <5%)
aut.-dom, pos FamH, promotor 11--hydroxyl. on aldo-synthaseACTH-dependt, often only mild Sy K  (50%, thiazids), and BP (CVI)
DG Dex-suppressions-test 0.5mg po 6h x 3d  S-aldo <55pM (2ng/dl), 24h-U-aldo<5.4nmol/d (2ug/d)  PCR f mutation; 250ug ACTH-Test  aldo 30’&60’,
TH: Amilorid (Midamor® 5-30mg/d; Dex 0.5mg/d (adrenal-suppr, stressprophyl.), aldactone (Antiandrogen, irregularities of mens. cycle), nifedipin
D) Urinary 18-oxy-cortisol  (steroidprofiling of 24h-urine @ Inselspital Bern)

B) 2° Hyperaldosteronism: typical: S-K, alkalosis, but S-Na () & aldo & renin  ARR
a) BP n/: cirrhosis, CHF, hypovol., GIT (vomitus, diarrhoa, Laxativa), hereditary or acquired (diuretics!) nephropathys
- Thiazids  Gitelman-Sy (Mut. Na/Cl transporter in distal tubule  Na-reabsorption, K, Mg; Tx: amilorid (Midamor ®), E’lyt Subst.
- Loop-diuretics (furosemide, torasemide, "Pseudo-Bartter"-Sy),  Bartter-Sy (Mut. Na/K/Cl2 trsp in Henle-loop, K, Mg, Ca) Tx: NSAID,
substitution of electrolytes, K-sparing diuretics
b) BP: renovascular hypertension (renal artery stenois > renal insufficiency >> renin-prod Tu  crea, US/Duplex)
C) Aldosterone-independent mineralocorticoid-exzess: Aldo() & Renin()  ARR()
a) Familial (<2%, renal 11-HSD2 : pos FamH, DD: licorice, chew tabac; DG: S-aldo urin: cortisol (mineralcort. activity) / cortisone (>10, n <1), Tx: amilorid,
eplerenone (evtl aldactone), if no effect or SE: cortisone 10mg/d
b) CAH/AGS (p17): 11- (virilisation) >> 17-hydroxylase (androgen), corticosterone (DOC) & compound S, urine steroid profile (Inselspital)
c) abnormal steroid production (e.g., DOC) b incidentaloma (p 2), Cushing Sy (ectopic ACTH)
d) Liddle-Sy: aut-dom mutation of tubular Na-canal  Na-reabs & K-excr  TH: amilorid (Midamor), typical improvement to Bactrim ® (UTI)
e) K (fct. hypoaldosteronism) DD: interstitial nephritis; renal-tubular acidosis, hypovolemia, CHF, Dm, drugs: ACEH / ATR-blocker; spironolactone, NSAID; pos.
FamH: Gordon-Sy K&BP, renin , aldo →; “pseudohypoaldo type 2”, mut. KLHL3-gene thiazide-sens NaCl channel Tx: thiazide & NaCOH 1.2g
f) Monogenetic variants (e.g.,. mut. mineralocorticoid-receptors)  pos. FamH, evtl. K, Mg low, aldo & renin “normal”, exacerabtion pregnancy, mens. cycle, → for genetics A.. Lauber (Fribourg)

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 4. Pheochromocytoma & Paraganglioma (PPGL)
"The “great mimic”: often sought, rarely found (prevalence 5/Mio)…yet, mostly discovered when it is too late… in autopsies
Endocrine Reviews 2021, Clin Endo 2022

10%(-40%!) rule children, extraadr. (symp od parasymp [=Glomustu]), bilat., multiple, maligne, recurrent., 40% genetic (35% germline- mut (va <20J), 35% somat. mut.)
1) SY Pressure elevation (BP, only 50% paroxysmal, typ. palpation/biopsy puncture BP, less psych. stress, ≈10% normoton)
& Paroxysmal trias (“spells”) a) Pain (headache), b) Perspiration / Pallor (trunk) c) Palpitationen (90%“or”/94%“and”)
Plethora other Sy: dizziness, constipation, wt, PG, BP (shock), orthostasis (Dopamin?), micturition-dependent crises
(bladder tu), flush („menopause“), T, „psychosis“, „spells“ after metoclopramid, 50% „incidentaloma“!
Polyendo Sy? MTC (MEN-2; 50% symptomatic, 30% BP); cerebral/retinal angioma or stroke (VHL) neck tu (glomustu), neurofibromas
2) DD sweating & flushing, panic attacks (>3/13 Sy; acute & max. within 10': palpitations, angina, dyspnoea, paresthesia,
trembling, chills/flushing, sweating, nausea, drowsiness, fear of suffocation, derealisation/depersonalisation, feeling loss of control / going crazy,
fear of death), carcinoid (red head, BP↓), drugs / toxins (cannabis, cocaine, ephedrine, ”fashion drugs & pills” )

3) „Before you start“ assure specificity (avoid false positives)

Drugs? carbidopa – u levodopa (Madopar®)  Dopa (→ Methoxytyramin)
Stop >2wk antidepressants (, tricyclics >SSRI (Venlafaxin)), clonidine (), >48h Extasy ®, paracetamole (peak NMN in old assays without [Link]),
 &  blocker (labetalol & dibenzyrane ), C2; BP-Th w Norvasc ®, Co-Reniten ®, Loniten ®
Stress, exercise, hypoglycemia, OSAS, acute illness, renal insuff. (15-50%, renal clearance of free “conjugeated” sulfated (nor)metanephrines)
Diet? Effects on catecholamine & tyrosine (va false pos): avoid coffee (inkl. decaf), tea, cocaine & coke, nicotine, banana, chocolate
4) Screening; „reference values“ dependent, if „healthy“ („incidental.“) or DD of arterial hypertension („hypert.“), cave: CKD & HD
- Plasma Pat. Info D, F, morning, fasting, 30’ supine, "no stress" wait 30’ after insertion of canula, centrifuge within 30’, transport on ice
Metanephrine (MN) (95%/93%, adrenal, typ. intermittently secreted, MEN2), Free: “incidental.” >0.56nM; “hypert.” >0.85nM, Total:
“incidental.” >7.5nM; “hypert.” >11nM
Normetanephrine (NMN) (extra-adrenal, typ. continuously secreted, VHL) free: “incidental.” >0.7nM, total: “incidental.” >13nM; “hypert.”
>30nM; “Hypert.” >1.3nM
Dopamin → 3-Methoxytyramin if >0.2nM -> paraganglioma? neck → SDHB mut. & metastasia, false pos b CKD & nutrition (“total”, sa),
if unclear: A (n 0.02-1.23nM, “adrenal”), NA (n 0.64-6.55nM, “extraadrenal”) “Pheo” A+NA>12nM (2000ng/l); "Vd. a" >5nM (70%/86% wg “Stress”, Sport)

- 24h-Urin (ohne(!) HCl-Säure, auf Sammelzeit & Lagerung (4°C) achten→ Pat. instruction for correct sampling ; evtl „postictale“ urine (event  discard unirne  collect next spoturine)
MN „Incidental.“ > 653nM/25h; „Hypertensiv“ >1490nM/24h), NMN „Incidental.“ >1759nM/24h; „hypertensiv“ >3800nM/24h)
only rarely needed: A (n<15nmol/mmol Crea; <110nmol/d); NA (<75/<472) (90%/90%), VanillinMandelSäure (VMS) (<5/<33) (42%/ 95%) → obsolet!, maligne:Dopamin u. HVMS
Chromogranin A? (<5% nonsecretinng, cave PPI)

5) Further testing (if basal MN & NMN (>4x))

Clonidin-suppression (80%/98%) drugs to stop sa (spec); 08-09h, fasting, recumbend  300 ug Catapresan po 60-80 kg bw (4.2ug/kg bw).
 BT -5’, 0, 2h, 3h (+BP +HR)  Minimum NMN >0.6nM & Abnahme v initial erhöhten NMN um <40%

6) Local. typ. >3cm, cystic-vaskular/hemorrhagic, 95% intraaabdominal, >10cm u/o suspicion of (fam.) paraganglioma screen skull
base to pelvis (“full body”) CT (skull base to pélvis, typ. density >10HU nativ or MRI (cystic, signal T2), 18F-DOPA-PET-CT (adrenal Pheo)
68Ga-DOTATATE-PET-CT (extraadrenal paraganglioma)>18F-FDG-PET-CT (93%/89%) >123J-metaiodbenzylguanidin (MIBG)-scintigraphy (60%(cave: B, Ca-
Antag., extraadr od NA prod pheo)/64%) > Octreotid-Scintigraphy
10% paraganglioma (PGL) along back trunk (head, neck (parasympathic) bzw. thorcic-abdomen (sympathetic), typ NA>A & 3-
methoxytyramin; 30% malign, & GIST (Carney-diad → genet w. FamH (SHD-B/C/D Mut)); & GIST & pulm. chordoma (Carney-triad → genet. but neg. FamH
(spontaneous mut 1q loss)), Tx: Sx vs radioth a/o metastasis (10% pheo, 40% araganglioma)  US/CT/MRI-neck/skull base (MTC,
Paraganglioma / Glomustu); ophthalm. consult (retinal angioma  VHL?)
7) Genetics (p22, esp. PGL, CH gene experts, PoHI, 2x5ml EDTA plasma & informed consent) PPGL 30% germline mut., 40% somatic driver mut.
consult pro/con to patient (incl. screen of family (family tree template)), nudge <60y, pos FamH, NMN>MN, paraganglioma/glomustu (SDHD/B, Krebs
cycle-enzymes) / bilat / extraadren. / malign Pheo / MTC / Angioma / CVI (VHL) / GIST / RCC , RET/MEN II (p22; MTC, pHpt, 50% pheo, adrenal-bilat, typ
MN>NMN), VHL (50% Pheo=Typ2, typ NMN>MN, (retinal) Hemangio-blastoma, visc. Tu), SDH-(AF2)/B/C/D (paraganglioma (psb, p-succinate as biomarker?), “3PA-Sy”
(pheo, paragangl., Pit. Tu, GIST, RCC), Carney-Dyade/triad/complex?, NF 1 (neurofibromatosis typ e 1, 2% pheo., typ. A>NA), FH (leiomyomatosis & renal cancer), EPAS 1
(polycythemiea somatostatinoma);TMEM-127, MAX (30% malign), 3PA’s (comb. pheo & paragangliome & pituitary Tu), evtl. complex genetics (Incomplete penetrance, “maternal imprinting” SDHD, i.e., mut only
manif. a father -> paternal inheritence)

7) Tx
Hypertens. crisis (p2) Tx: uradipil (Ebrantil® 10→25→50mg iv Every 15-30', evtl. Inf 2mg/min -> 9mg/h)
cardial arrhythmias Tx: esmolole (Brevibloc® 50-200ug/kg/’ iv), lidocain (50-100mg iv)
preop. preparation debatable 7 14d outpatient (esp. secreting paraganglioma with tachyarrhytmia, no need for orthostasis, intraop initial venoligation →
complications ) Phenoxybenzamine (Dibenzyrane ®, irrevers. -block, cave: postop hypotension) Cps: 10→30mg BID/TID), doxazosine (Cardura ®, revers. -Block.) Tbl
2→16mg QD) gradual dosing, increase 2-3daily, cumulation! SE: orthostasis  check euvolomia  >5-6g NaCl po (1L /d Bouillon or Isostar ® ),
cave:, no “unopposed” -blocker! ( vaskovonstr. BP); tachykardia  &  blocker needed in 30% (metoprolole (Beloc Zok ® 100-200mg QD-BP, Inderal ® 10-20mg QID)
consider: nifedipine (Adalat ret ® Tbl 20mg QID→CR60), Duramipress (D) 2-5mg TID; Hytrin BPH ® (starter pack→ 20mg);<1L NaCl 0.9% iv
Sx: laparoscopic vs open (>6cm, susp. of invasive) SE: intraop. BP peak  nitroprusside 0.5-10mg/kg/‘ / phentolamine
Postop.: enough fluid e.g., 4-7l/24h Glc 5% until BP stable and cessation of polyuria
look out for hypoglycemia with rebound-hyperinsulinemia, postop. hypotension: adrenaline, evtl. Vasopressin iv)
F/U: 25% essential / fixed Hypertension
Follow-up: recurrence 10% (rare <5cm), min 10yrs to live-long for high-risk patients, (6-mthly SDHB mut.; Yearly: young., germeline mutationen,
tu-size, paraganglioma; → biomarker (MN & 3 methoxythyramine, chromogranin A if low-metanenephrine neg. tu, cave: PPI u CKD) resp. imaging (Dopa-PET,
Sandostatin PET)
Malignant (rare) dg by follow-up not histology (infiltration in capsule a/o vessels not dg!), alpha-blockade if hypersecretion, Sunitinib (onco. consult), evtl.
chemoebolisation, ablation w radiofrequency, radioth, polychemoth (cyclophsophamid?, Vincristin?, dacarbacin?) → inclusion in clinical studies

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 5. Cushing Syndrome & Hypercorticism
"If you think Cushing is easy, you have not seen enough cases to do it yourself." Besserism
NEJM 17; 376:1451-1459, Lancet Diab Endo 2021;12:847-87
Exogenous (tx with steroids incl topical (e.g., fluticasone, if combined with CYP3A4-inhibotor (e.g., ritonavir ® (Norvir ®, Kaletra ®)), “pseudo”) >
ACTH-dependent (2 pat./mio/yr, f>m, M Cushing, ectopic) >> ACTH-independent (adrenal-adenoma >> Ca)
1) SY Photo history! rapid weight gain w typ. fat distribution (>3kg, trunk, full-moon face, buffalo hump, filled fossae
supraclaviculares, evtl. edema), muscle weakness (squads, ”signe du tabouret”), metabolix sy, osteopenia/-porosis, skin (parchment
thin, >3 ekchymosis >1cm, stria rubrae, plethora, acne), amenorrhoa & hirsutism (virilisation  Ca?), psych. Sy (depression, manic, anxiety
disorders, psychosus), thromboembolism, infections, Lc, Eos, Ly Tc, P-Na, P-K, HGH, TSH cave: signs can be masked, e.g.
ectopic Cushing Sy with cachectic tu od young patients, drug history!

2) Outpatient Screening repeat 2-3x (DD cyclical Cushing-Sy), evtl follow-up after 3-6 mo
- 24h-FUC (free urine cortisol) no<500 nmol/24h (Cu>700; assay-dependent, 95% (false low ClCrea<30ml/’) / 98% (false high m HPLC: carbamazepine (cross
PCO, stress, >4l urine volume, pregnancy 2. &. 3. trim., fibrates, digoxine, HAART (hepat. degratation); if >10x Upper Norm → ectopic → CT-Th/Abd
reaction), pseudo-Cu,
FUC/Crea <70 nM/mM (24h urine), <21 nM/mM (overnight = 22-8h; 87% (CKD) / 95%)
- 1mg DST (dexamethasone suppression test) Ind: Susp of subklin. Cushing-Sy (“autonomous cortisol secretion”)? dexamethasone Tbl. 1mg
24h po  cortisol 08h no<50 (<140) nM; Cu>280) (90%(CKD, LF, M. Cu) / 75% (pseudo-Cu, HAART)), “Pitfalls”: CBG(SS, E2), dex-metabol(CYT
P450phenytoine, carbamazepine, rifampicine, phenobarbital, pioglitazone), compliance?P-dex 8h 5-17nM, evtl. 2mg DST;
- LNSC 23:30h (late night salivary cortisol), repeatedly, no< 1 - 2.5 nM (HPLC, 95%/80%): NB: 4h prior NO teeth brushing, false high “jet-lag” & “life-lag” (be
relaxed …no sex, drugs, rock’n’roll, thriller...), soak the tampon well (1-2 min f 1-2ml)

3) DD «Pseudo-Cushing» = increased cortisol levels depression, stress, C2, anorexia, obesity (PCO, WHR)
- Cortisol-day-profile: VP 8h,16h (>50% v.8h) u. 24h (>47% v.8h od absol. n<150nM, venflon 10pm, hosp, "sleeping", VP within 2': no<50 (>70)nM)
- Desmopressine-test: M. Cu: basal cortisol >331nM nM AND Δ-ACTH 0-30’ >18ng/L (>4 pM) n 10ug desmopressine iv (Minirin ®), PPV 95% DD: Pseudo-Cu
- Dex-CRH-test: 0.5mg Dex 6hx2d (8x; D112h - D36h), D38h 1ug/kg CRH iv  ACTH & cortisol 0’ & 15’
DD: Cortisol Cu>38 (>70)nM (0’: 80/90%; 15’: 90/90%) & ACTH 15’ >15 (>27)ng/L (n<10ng/L, cave: literature w ovine CRH = stronger stimulus than hrCRH)
- Liddle test: Sens/Spez. only 70-80%) 0.5mg dex 6+12+18+24h on day 2&3; day 1&3 FUC each (n <27 (>50)nmol/d; Tag1/3 n >2; 79%/74%),
day 1 & 3 S-Cortisol (day 3< 50 (138) nM) u. P-ACTH 08am (no suppr>50%)

4) DD ACTH–dependent
- 2x P-ACTH 08h on ice: <5ng/Ladr; 5-15CRH-Test >15central or ectopic (typ >80)
- hrCRH-Test (ideal b IPSS (psb), 1ug/kg iv, VP: 0’, 15’, 30’ (peak) M Cu: P-ACTH >20ng/L bzw >35% (90%/95%) od S-Cort. >20% (90%/95%)
- Grenzwert  8mg high DST? (8mg@24Uhr po/ivS-Cort+P-ACTH v & n. Dex@8h; [Link]: Cort. n. Dex <32% of basal (<140), P-ACTH>50%; ektop: [Link] >140, P-ACTH<50% (80%/95%)

5) Localisation
a) M Cushing MRI-Sella (1.5-3T, with & without contrast i coronary u sagittal fine layering; resolution 3mm)
cave: falsch neg da 95% d. Adenome<1cm  b neg MRI od Befund <5mm  18F-FET-PET-CT (O-(2-[18F] fluoroethyl)-l-tyrosine) or Methionin-PET-CT
(PoHI (or hospitalization in consult. with dept. of nuclear medicine!) & IPSS; 10% false pos (incidentaloma!)
"IPSS" (Inferior Petrosal Sinus Sampling; in consultation with dept. of neuroradiology, 4 assistants, check catheter positioning regularly!)
VP -10‘, -5‘, 0, 3, 6, 10, 15‘ SP left & right, peripheral (+ 30’, 60’); ACTH, TSH; PRL, 100ug CRH or 10ug Desmopressin i.v. (PPV >95% in peripheral blood)
Dg: I) M. Cushing? ACTH central/peripheral >2 (1.6)  post-CRH >3 & early peak  peripheral ACTH >35%, Cortisol>20% (sa)
II) ectopic? <2 resp. <3  ad b); III) side localisation? ratio ACTH right/left >1.4, pre- & post-CRH (relative to PRL resp. TSH)
b) Ectopic «whole body»-CT/MRI (neck>thorax>abdomen), if neg. 68Ga-SSA-PET-CT, mammography, “whole body-catheter”
DD: NET (p22); Ca (lungs, MTC, thymoma, pancreatic, other)  rapid progress, ACTH & FUC, S-K
c) Adrenal MRI adrenal / CT-abdomen  adenoma > Ca (>10HU & inhomogenous; Pregnenolone u. Compound S) > BMAH (Bilateral Macronodular
Adrenal Hyperplasia (prev. „AIMAH“, but in part ACTH-dependent. resp. other aberrant receptoren on hyperplast. adrenal cortex !-> comb. stimulations-test, e.g.): sporadic hypercort &
hyperandrog (17-OH-progesteron after ACTH ()), > ACTH-dependent McCune Albright, MEN 1, Carney Complex (p22)

6) Therapy
5yr mortality untreated 50% or 4x>norm (cvR & infections), diet under steroids, thromboembolic prophylaxis from Dg to 6Wk postop
a) M Cushing: Transsphenoidal resection remission 80%, preop metopirone/ketoconazole (psb) &HC); postop. T+1, +2, +3 +5d: S-
Cortisol 08h <50 (50-200) nM  „cure“; 20% recurrence in 5yrs (LNSC yrly) → pasireotide (Signifor® 0.6 – 1.8mg bd sc; Signifor LAR® 10 – 30mg mg/Mon im.,
50% response, PoHI with evidence of FUC-decrease needed, SE: hyperglycemia (75%), Pat. info D, F) u/o carbegoline (Dostinex®) Tbl. 0.5 – 6mg/Wo titration w FUC, 30%
response; a/o Osilodrostat (Isturisa®,Tbl. 2-30mg bid 50% response) a/o other adrenostatics (sb)
F/U & exclude recurrence?  LNSC( > 24h-FUC, DST, DDAVP-test postop) 3-6mthly; → Re-Sx od bilat. adrenalectomy (30% Nelson-Sy (dark
→ preop. -knife or adrenostatics; postop HC +50-100ug florinef/d. Inform patients for possible GCWS (glucocorticoid withdrawal
skin, pituitary adenoma)
sy) after surgical cure and stay alert for new autoimmune disease (esp. w pos FamHx).
- MRI follow-up → Tu visible → -knife 50% remission in 6-60Mon, SE hypopit., adrenostatics until effect occurs
Normalization of HPA-function within 1 – 2.5 yrs (adrenale > M. Cushing), offer psychological support and consultation screening of psychologic Veränderung
anbieten. Dose control? signs & symptoms, 24h-FUC (target 250-500nM), Cortisol fasting (n), Cortisol 12.30-17.30 >100nmol/ol, stop 2 wks pre-op
b) ectopic Cushing-Sy: 50% pulmonary (NET & SCLC)>MTC>thymoma>Pheo, MRI or Ga-SSTR-PET/CT, rapid Op a/o adrenostatics (monitor P-K+)
c) Adrenal Cushing-Sy: Adrenalectomy, life-long follow-up 1x/yr: cvRF / psycholog. sy /vaccination, evtl. DXA, DST/SC 23:30 if HU >
10, MRI/CT follow-up, HC 15-30mg/d (initial -60mg/d) & stressprophylaxis (sa)
Adrenostatics (e.g., inoperable/ectopic Cushing, recurrence or drugs preop, adrenal-Ca p2), PoHI, «block & replace w stressprophylaxis»
- ketoconazole (Cps 200mg, 1-2tbl bd-tid (magistralrp hospital-pharmacy, PPI stop), SE: LFT, hypogonad. & gynecom., QT, Cyt3A4 drug-interaction
Ind: 4wk preop. od palliative a/o metyrapone (Metopiron Tbl. 250-1000mg tid-qid, initial tx, fast response, titration m 24h-FUC & SC 23:30? not
teratogenic SE: GI-Sy & vertigo, hypertension & K-loss due to 11-DOC (→ FUC by massspec Lab KiSpi USZ), acne, hirsutism, osilodrostat (Isturisa, start 2mg
bd, max. 20mg bd, 80% remission within 3mo long-term tx, SE: arthralgias, nausea, diarrhea, cortisol-withdrawal, Cyp3A4 interaction & QT-prolongation etomidate
infusion (IPS, init. 5mg bolus + 0.02mg/kg/h, qd. cortisol), mitotane (Lysodren ® 3-5g/24h, more side-effects than effects?; derivate of DDT); Ca: Doxorubizin (Onkolgie, delayed effect, SE: GIT & neuroogical,
hypercholest., hypogonadismus, hypothyroidism; trilostane; Mifepristone (Rez-blockade, va b [Link]ör 10-30mg/kg/d SE: Nausea, Fatigue, Kopf u Gelensz, Oedem),
→ Stress prophylaxis! Withdrawal! (p6) → cortisone base tx. e.g., HC initial 20-10-5mg  15-5-0 od Plenadren ® bedtime, thromboprophylaxis

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 6. Addison Syndrome & Therapy with Steroids
"Addison’s disease represents, as Syphillis, the Cameleon of Medicine"
Lancet 14; 383: 2152-67, [Link]/de
Prod: DHEA(S) 25mg/d > Cortisol: 5 (-15) mg/d, “Stress” max 6x100mg/d > Corticosterone 4mg/d > Aldosterone 0.1mg/d
DX: Typically an atypical clinical presentation (sensitivity/specificity <50%  coin flip is superior),
- e.g. fatigue, sleep disturbances, driveless, weakness, muscle/joint pain, nausea, vomiting, aBPominal pain, loss of appetite, weight loss:
≥3kg, orthostasis, reduced stress resistance, salt cravings, neuropsychiatric symptoms (“hypo”), hypoglycemia
- U-Na+/K+ <30 (Renin in primary Adrenal Insufficiency (AI), after Hyponatremia stimulus due to “SAAD”), BG <3.3mM (or "new" hypos under Insulin),
HCO3−; urea, Ca, Eosinophilia >3%, Leucopenia, lymphocytosis
-Blood cortisol (fasting, 8am): <100 (<80) nM (& ACTH)  Dx; >500 (415) nM  Exclusion, 100-500nM  ACTH test !
- Salivary Cortisol 8 a.m. (≈free Cortisol) <5nM (& ACTH)  Dx; >16nM  Exclusion, 5-16nM  Synacthen test !
1° DD Addison’s disease autoimmune polyglandular sy (APS; 75% p.22) > Mets (lung)/ Hemorr./HIV&TB/Hemochrom.>drugs
Immune-checkpoint-Inhibitors (ICI, evtl. Assess 8am Cortisol monthly with every cycle of ICI-th up to one 1yr after discontinuation, cut-off <140nm?, 141-274nm? Refer to endocrinologist), Metopirone, Ketokonazole, Opiate, Etomidate,
Rifampicin, Phenytoin, Imipramine, Chlorpromazine) >Congenital adrenal hyperplasia (CAH)> Adrenoleukodystrophy (X-chrom Sx: can be oligosy, hypogonadism, dementia, spasticity, blindness, Dx: screening of male patients if
autoantibodies neg & no other causes,; genetics ABCD1-mutation very long fatty acids  (> C24; C26:0, C26:C22; C24:C22) KisSpi ZH, Tx: Bone marrow transplantation, gene tx?)

Sx: Pigmentation (mucous membranes, areolae, hand lines, pressure points), "salt craving" orthostasis, ♀:  Libido, dry itchy skin
- 250ug iv ACTH (Synacthen®) test D F iv cortisol p̄ 60’>550 (>415-600) nM; lying Renin30’  (esp. w/ RF e.g. pos. 21OH-Ab)
- Synacthen depot test (1mg/d im over 1d or 3d:  iv Cortisol p̄ 8h or 80h. >1000nM in secondary AI or healthy subjects. <1000nM in primary AI.
- P-ACTH 08 a.m. >50 (>100) pg/ml), 21OH-Ab (80%/95%), DHEA
2° DD: S/P Steroid-Tx (±independent from duration [5-30d] & dose [30-250mg]) > Hypophysitis / Pituitary tumors (other axes? p23)
- Basal cortisol 24h after last dose >300nM ok to stop glucocorticoid replacement, 150-300nM instruct stress prophylaxis, repeat in 1-
4wks, consider ACTH test, <150nM continue glucocorticoid replacement and stress prophylaxis, repeat in 1-4mo
- Short ACTH (Synacthen®) test 1ug (250ug) ACTH iv Cortisol 25’ >500 nM (>550nM w/ HRT&Pregnancy, >700 w/ Extreme Stress e.g. shock)
Salivary cortisol 30’ post ACTH >40nM (free cortisol, i.e. indep. HRT/Pregancy); cave: in acute pituitary insult: Synacthen test falsely negative 2-4 wk!
- waking salivary cortisone? (<251ng/dl (7nmol/l)) or cortisol <80ng/dl (500ml of saliva)
- Standard (250ug) ACTH (Synacthen ®) test: cortisol >550 nM (>600 HRT&Pregnancy) 30’ (pituitary), 60’ (adrenal)
- Insulin hypoglycemia test (IHT) 0.05-0.15U/kg Insulin iv (evtl. 2x); Goal: BG <2mM & Hypoglycemia Sx nadir gen. p̄ 15’-45’
CI: CHD/Arrhythmia (ECG), Epilepsy, > 65y.o. Info: last hydrocortisone dose to be taken at midday the day before;
VP -30’, 0’, 20’, 30’, 45’, 60’, 90’; cortisol norm. peak >550nM; ACTH norm. peak >150ng/L, BG: 3-5x; GH norm. peak >5 ng/ml; if <2.66 ng/ml Tx (p23)
can be combined w/ GnRH-Test (no mens. p̄ 3 months HRT-stop, p18) or TRH-Test (200ug iv): 30’ TSH norm. 2-25mU/L; PRL norm. >2x (Info: 2months stop T4, 10-days stop T3)
- Metyrapone test Ind: when IHT not evtl. Proc: 8 caps. of 250mg at 12 a.m. p̄ late snack (S/E GI)  VP 7:30 a.m. Cortisol (<140nM (<276)) & ACTH (>150ng/L) or
Compound S (CS) +Cortisol (>450nM, 71%/69%) or CS alone (>260nM, 67%/68%, unstimulated CS<12)
- CRH-Test: DD sec./ter., Proc: 100ug iv; VP 0’, 30’, 60’; ACTH p̄ 30’ norm. >6,6-8,8 pM (30-40pg/ml) / 2-4x, Cortisol norm. peak>500nM (CRH weaker stimulus)

Tx “Crisis” (Asthenia, Hypotension, GI-Sx) w/ “Stress” (INF, Trauma, SX)  VP cortisol & ACTH  Solucortef 100mg iv
Bolus & 2L [5% Glucose] or [0.9% NaCl] over 1h  50mg q6h → q1d; if need be Rectodelt ® (D) Notfallset (KSA Ambi Med
Daily (LT) Replacement Cortisol 10-15mg mornings, 5-10mg afternoons, (HC Galepharm 500 caps 10mg, cost  50.-/mo) 
10mg/m2/d, w/ more symptomatic or infection-prone patients -> HC-dual-release-retard Plenadren® caps. 5&20mg 1-0-0 (CHF 700.-
/mo., mimics circadian rhythm, weight benefit!), Efmody ®, Chronocort® (EU) or Prednison MR (Lodotra® cap. 1, 2, 5mg at 22p.m.), both w/ insurance’s cost
approv., (p̄ 6 mo. of HC Tx w/o response)) cave: Stress prophylaxis w/ „norm.“ HC or Pred !
Increased requirement: Pregnancy: +50% in 3rd trimester, „Stress“ (subj, physical >> psychological), 1°>2°, CYP450 Induction, T4,
Stress prophylaxis “Minor” (common cold): 2-3x[dos]x 2-3d; “Major” (Trauma, SX, «Men’s cold») 100-200mg/d HC (Solucortef®), e.g.
uncomplicated Sx: (T0) 50mg i.v. q8h; T1 50mg i.v. q12H, T2 50mg iv morning, T3 HC po 30-10-0; T4 HC po 20-5-0; Patient training KSA
Emergency sheet & set, Emergency-Sheet «mild», Pat Brochure (KSA D F I E SGED D / F / I); Self Help Groups (also for relatives) / / / ;

1°: Florinef Tab 0.1mg ¼- ½ Tab/d in 80% of cases (Orthostasis? K+, Renin?  dosage in pregnancy,  dosage in Hypertension & HF); Hypertonie: Prednisom instead

♀: DHEA: 25-100mg/d, Pilger Apotheke, BS

of HC?

Tx-Control: clinical (ask suggestive signs for under- (see above) and over-substitution (p5, Tips on Nutrition w/ Steroid tx.)
„Corticotroph Insufficiency Related to Critical Illness» („CIRCI“) HPA-Axis “Exhaustion” after several weeks of ICU stay w/ initially normal
HPA function : DD: steroids, etomidate, opiate, etc. Dx: persistent vasoactive requirement, delirium, basal cortisol or 30’ p̄ 250ug ACTH <550nM ACTH (slight)
increase  Tx: 60mg Hydrocortison p.o. Solucortef iv (tid?)

Pharmacology „Steroids, misused, enable a patient to walk to his autopsy room“

Substance Trade Name® Biol. T1/2 Glucocort. & Mineralocort. Cushing
e.g. [Plasma T1/2] [Link] Potency Dose (mg)
Hydrocortison Hydrocortisone 8-12h 1 1  20
= Cortisol Solu-Cortef [2-4h]

Prednison Prednison, (Lodotra) 12-36h  3.5  0.6 5

 Prednisolon Spiricort [4-6h] 4

Methylprednisolon Solu-Medrol 12-36h 5 4

[2-4h]
Dexamethason Fortecortin 36-72h  30-150 0  0.1-1
 Triamcinolon Kenacort [3-5h; no crossreaction with cortisolassay]
Betamethason Celestone 36-72h  30-150  0.1-1
Betnesol [5-8h]
Fludrocortison Florinef Tbl 18-36h  10  125 ( 2-3)
Aldosterone [3-4h]  700

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 7. Diabetes mellitus (Dm) – General Aspects
“There is no disease that requires of its sufferer such discipline and decision-making each day.”

DEF (ADA): venous Plasma-Glucose (PG) 2x >7 (fasting =8h no food) or >11.1 mM (random) or HbA1c >6.5%
„Prediabetes“= Impaired Fasting Glucose (IFG: PG 5.6-6.9mM, random 7.8-11mM or HbA1C 5.7-6.4%  risk f death, cvR, Dm (5x) → control i 6-12Mt, incl
cvR, prevention, (75g oGTT (old & lean): Dm = PG fast 2h >11mM; 7.8-11mM =impaired Glc Tolerance IGT)
Evaluation PG: Diabass Pro, cont. PG-measurement (p13); HbA1c-pitfalls: falsely: black pts (avg. +0.5%); falsely: in uremia (ca -0.5%); asians with
HbE (->Immunoassay) → Fructosamin estimated HbA1c: HbA1c = 0.017 * Fructosamin (uM) + 1.61
DD: Type 1 (10%, p8), Type 2 (80%, p9, unofficially “Dm Typ 1.5“; overweight. Dm 1 / initial Dm 2 with secondary failure), Gestational diabetes (p12),
«Type 3» (3a) Monogenetic Dm (alt "MODY", S. 8 genetically defective β-cell function; [Link]) 3b) insulin effect , 3c) pancreatoprive/hemochromatosis (p8),3d)
impaired hormone product.; 3e) Drug-induced (Steroids (p9), Immunosuppressants (CNI, mTORi) Neuroleptics), 3f) Viral; 3g) Autoimmune; 3h) genet. Syndrome, e.g.
Lipodystrophy Syndromes (umbilical protrusion, very high insulin doses); others: Stress/SIRS/Sepsis (p11 & 27), Posttransplant Dm, Endocrinopathies (p 22)

PG-screening (every 3y after ADA): BMI>25kg/m2, >45y, FA/GDM/PCO/Ethnia, >2 Sy metabol Sy, Atheroscl.,
Dm most common reason for Blindness worldwide resp. dialysis & amputation in CH
DG-scheme (discharge report/diagnosis list)
Diabetes mellitus Typ 1, 2 (insulin-dependent mon/year) or „DD“ (steroid, type 3c pancreas, haemochrome, etc) (ED mon/year)
- currently out of target range (= >3xdaily. gluc measured & daily correction or Gluc fluctuations >5mM or 3x>15mM or 1x<3mM or HbA1c>9%)
- cvR (cardiovasc. riskfactors): Nicotine, metabol. syndr. (BMI, BP, lipids), FA?, GDM?, OSAS?, hyperuricemia?
- followup complications: Angiopathy (macro: CHD, PAVK, CVI; micro: retino-& nephropathy); polyneuropathy (PNP); feet (see below)
- HbA1c good (6-7%), satisfactory (7-8%), unsatisfactory (8-9%), poor (>9%); false low: transfusion., hemolysis, Hb-pathies, anemia  Fructosamin
- Hypoglycemia: none / rarely / frequently; mild / severe (Perception threshold?)
- current therapy: dietary, orale antidiabetics, insulin (basal/“Bedtime“, Basis-Bolus, FIT)
Insulin prescription PG Documentation KISIM-KSA (Quickguide, Carb-to-Insulin-Ratio (CIR) & Carb. Amount), Pat. Info, indiv. Diabetes diet
Staging (Flow-sheet, usually annually., b overt complications 3-6mthly, see. Pat. Info, Tax deduction leaflet)
- Not disabling! With DM generally normal «working & living» is possible. Basic-health-ins., SUVA, IV without restrictions; everything else (extra-
mandatory insurance & daily allowance ins.) with reservations  change of job difficult, self-employment difficult. Tips for allegedly „challening Dm“,
Empowerment, e.g. „Diabetes Pass“ or „Evivo“, DIAfit, "yellow card" for "no shows" to appointments
- Travel & Driving (esp. with Th. hypoglycemia-risk: Sulfonylharnstoffe, Glinide, Insulin), «Clarke Score» to estimate risk for hypoglycemia
Target: PG 5-10mM & > 6 Mth no sympt. Hypo Pat. Info SGEDSSED bzw. Leaflet ((sign & document in patient chart)
 before EVERY car-ride measure PG! <7mM  10g CH; <520g CH & PG n 20'; <3.5 45’ n CH PG; if nec. check fitness to drive acc.
guidelines SGEDSSED; Reporting (right to report to GP / Mandatory report to medical consultant insurance, policies (BGU 1C_391/2019), form AG, BS.
Dm on Insulin a/o tx with hyporisk: impossible to pilot airplane, tram, train („commercial“ transport. of passeng., Kat. D), Taxi/Uber ok with «good compliance»
- Nutritional counselling (USB, KSA): Carbs (g & distribution), calories, „24-h recall“, Alcohol, beware of nutritional dogmas
- Diabetes counselling (p13), hypoglycemia symptomes, PG-measuring, insulin inj. (p13f), Th-refractory? → in-hospital PG adjustment
- cvR: FamH (F<65y, M<55y) & PerH (PAVK/ CVI/MI), >65y, nicotine, met Sy (p9), Alb/Crea iU, susp. KHK: MPS/Ergometry
- Status: Weight (kg/m2), aBPominal circ., HR, BP (Orthostasis), „ankle-brachial-index“ PAVK <0.9, severe <0.4; Mediacalcinosis>1.3), vessels
(murmurs, Aa. carot., renalis, aBP., ing), Injection sites; Potency; Hands (Cheiropathy, Dupuyten); dental status, feet (Pulse, ASR, Vibration
x/8, 10g Monofilament, Arch, Hyperkeratosis, Skinlesion, funghi, nails, Charcot) , Shoes (Sole > Foot!)
follow-complic.: „Legacy“ (initial) good HbA1c! Labor Crea (Clearance), Lipids, Liverenzymes (NAFLD / NASH, p9), uric acid
- Microangiop.: Retinop.: Ophtalmology (priv., consult) after 20y 90% Dm1 (prolif) & 70% Dm2 (exsudative) Makulaedema -> Lucentis (VGEF)
Nephropathy Alb/Crea iU 2. morning urine, falls 2x   ACEH, GFRcalc<40ml/’ad Nephro (treat cvR incl. BP, Dietary protein
<0.8g/kg/d, Hkt 34-36%, uric acid <300uM; no NSAID), Ctrl: Dm 2 6mthly, Dm 1 after 5y disease;
Alb/krea without Dm (in adip. M >50y, smoker  independent of cvR; DD: UTI, Orthostasis, work, amyloidosis)
- Macroangiopathy (esp. in Dm2): Atherosclerosis with clin sy PAVK (Pulse?) / CHD  Angio / cardio consultation
Polyneuropathy (PNP): sensory: symm. "socks&gloves" ;Tinel’s sign pos -> ad [Link] for Nerve decompress.; autonom: cv (Orthostasis, fixed RR,
tachycardia at rest, silent CHD), GIT, UGT; mot: III, IV, VI, VII, Amyotrophy TH: euglycemia! (Hosp. w. Insulin/Thioctazid iv?); Vit B12? (evtl. Meformin stop) Pain:
Panadol  (&) Saroten(10→75mg/d)/Tolvon  (&) Pregabalin (Lyrica Cps 75, 150, 300mg, Duloxetin (Cymbalta pill 30-60(-120)mg qd), evtl. SSRI 
(&)Tramal („start low, go slow“)  Lidocain (Neurodol) dermal plaster or Capsaicin Magistral-Rp Creme0.075% tid-qid x8/52; Orthostasis & P-K with
Vasodysregulation & hyporeninäm. Hypoaldosteron TH: Fludrocortison Florinef pill. 0.05 – 0.1mg mornings;Midodrin (Gutron pill. 2.5-10mg qid) Gastroparesis:
Th-trial dep. on Sy w. Metoclopramid (Paspertin), Domperidon (Motilium), Erythromycin; Immodium, Transipeg
Sexual dysfct: (couples) therapy F: address it! -> [Link] M: Erect. dysfct (ED) / Impotence DD: cvR (-> exerc-EKG?) Urology
/ Angio? Hypogonadism? -Blocker? TH: success in 40-50% w. DM , not subj. to insurance! Viagra (25-100mg po/sl), Cialis (5mg qd po ED&BPH), Levitra KI: Nitrate
Paradontosis  dental state, sleep-apnea Syndrome ? (Screening Epworth Score), fatty liver (ASH, NASH) ?
CHF? Screening Resting Tachycardia, NT-ProBNP (?) >500 –1000ng/L → Echo, if nec. Optimize Th (ACE-I, diuretics, Blocker, Aldo-Antagon.)
Diabetic Foot Risk groups, review, pat. info KO: Exam, Sens.  (Vibr. <4/8, Finger, Monofilament) PNP 3 mthl  interdiscipl.
consultation, Podology (PoHI, Verordnung) no barefoot walking, PNP: no hot water bottle, dly. Selfinspect., evtl. w. mirror incl. between toes (→
Onychomykosis? swab?,TH: Loceryl/Lamisil pill 250mg x 3 (-6) Mon Interdigital: Imazol-Paste/Lamisil-crème), Hyperceratosis Th. (Allpresan foam Nr. 3 (in
DFB available) or 20% Urea Footcreme (Eubos BP)), Perfusion / Footpulse? →Angio-consult, Deformities? TH: Podology ([Link], only
subj. to ins. w. Diploma) & Orthoped. shoemaker [Link] (e.g., Härdi Schöftland, Malgaroli Aarau&Baden, Villiger Niederlenz): local pressure relief with
Orthosis / bandage shoe /. Recipe for 2 Pairs „[Link] shoe w diabetesadapt. footbedding” / orthoped. Customized shoe (cave: PoHI <65y (IV)
better than >65y (AHV) → Orthopedics: Gait analysis → OPED“/Vacu-Diaped shoe → immobilization & “Total Contact Cast”, Charcot-foot: pressure
release! NSAID (as Sudeck?, p16), anti-TNF? Malum perforans? Wound therapy SOP; Edema tx (compression socks, cave ischemia, angio-consult),
Debridement (scalpel, Derma), Creams (e.g. Regranex, Apligraf if Tx-resistant), Infection? DG: Pus or inf. Sy (>2 local [in PAVK underestimated Rubor,
Calor, Tumor, Dolor] or systemic) Lc, Cellulitis, Plantar fasciitis (Sy: blisters, plantar pressure point emergeny SX!; Biopsy (most. Mixed Inf.. acute: S. aur.,
Strept. Grp BACG / Anerobians (ischemia&gangrene) / Gram-neg (AB-pretreated); Osteomyelitis? DG: "Probe to bone” (50%/85%, scratch w metal object),
Rx, MRI; MOAB SPECT CT TH: Orthop. cleanout / Debridement & antibiotics, e.g. Clindamycin (Dalacin) pill 2x300mg tid (alt. Rifampicin (Rimactan) pill. 600mg) & Augmentin
pill. 625mg tid (alt. Tavanic Tbl. 500mg BP); x 2/52 (tissue infection) up to 6-12/52 (Osteomyelitis); if recurrent a/or pretreated & Ciproxin pill 2x750mg (Gram neg), GCSF/sytem.
hyperbaric O2 (anaerobians)

Vaccinations: see [Link]: yearly: Influenza, > 65y: pneumococci (1x Prevenar13 Konjugat, CHF 90.-, not ins. obligat); 10-yrly: DiTePer, if nec. HBV, HPV, HZV

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 8. Dm Type 1
„Tell me and I'll forget. Show me, and I may not remember. Involve me, and I'll understand.”

typical: young, slim, acute, ketonemia (Freestyle -ketone-strips!), wt, HDL-C no, inheritance risk 4%( father>mother), Twin<50%;
Prg f honey moon: GAD-II Ab (90% Sens, evtl. IA-2, ZnT8-Ab), random C-peptid e<200pM b PG>6mM (glucagon-stimul. <600pM),
LADA (Late Autoimmune Dm in Adults): >35yrs, pos GAD-II and other-Ab; check for polyglandular autoimmune syndrome (p22)

DD: a) Hemochromatosis: transferrin saturation >45%, Ferritin >1000  (gene-analysis  consult gastroentorology)
b) pankreatopriv / C2, CF (typ. ASAT/ALAT>1). Arginin stimulation test Proc: 0.5g/kg Arginin x30’; VP 0’, 15’, 30’, 45’, 60’ m PG,
Glucagon, Insulin, C-Peptid. Dg: Glucagon n100%, Dm 1  200% (i. Ggs zu flachem Insulin), pankreatopriv/C2<50%
c) Monogenetic (old "MODY"): most common: HNF1A, HNF4A, and GCK etiologies RF: aut.-dom! → Pedigree [Link]
probability-calculator -> risk >25%: PoHI EDM gene experts in CH (USZ, HUG, Munic), Tx: OAD,; mitochondrial Dm: w sensorineural hearing loss; CI f metformin; Tx:
OAD, rarely need for insulin; Lipodystrophy Syndromes (umbilical protrusion, very high insulin doses)

d) „ketose-prone“ Dm type: (typ. in coloreds): severe insular glucose toxicity and ketoacidosis

Screening for late complications (p7): dep. of cvR & initial dg <10y after 1-5yrs, diabetes-pass to set common goals
TH: to be supervise by specialist, care concept for newly dg Dm type 1, concept for inpatient PG adjustment
Experimental / immunosuppressive: Teplizumab preventative in patients with genetic risk a/o increase of lag-time of C-peptide decline → screening prg ?
Nutrition & diabetes counselling: yrly, esp recurrent Hypo., wt >5kg, problems CH-estimation (“Nutri-Lernbuffet”)
Initial base-bolus insulin regimen: during honeymoon  reduce or pause insulin, verapamil ? (p9), multiple daily injections (“MDI”)
- Base: rule of thumb: units (U) = kg / 4; Lantus / Levemir / Insulatard
- Bolus: Fiasp/Humalog/NovoRapid/Apidra, Actrapid; regimen to meals dep. on carbohydrates (30-100g)
e.g., before meals f 40gKH: 2U (PG<5mM), 3U (5-7) 4U (7-9), 5U (9-12), 6U (12-15), 8U (>15), 10U (>20)
- Insulin pump (p13) Ind: unstable PG (e.g., comfort, pregnancy, sports, hypglycemia, -perception, dawn-phenomon) & good compliance
Checklist PG target missed: change catheter?, adapt injection site? (incl. abdomen, leg, buttocks), estimation error? ( weigh food !),
protein a/o fat-rich meal ( set pumpt to mulitwave bolus mode, i.e., 50% rapid, 50% over 5h)
- Dm & terminal CKD: systematic evaluation of a combined kidney-pankreas- or kidney-islet cell-transplantation
- address issues of disease acceptance, evtl. psychosomatic a/o psychiatric consult, , military service ? pregnancy ? (p12)
- Obese Dm1: empower diet & exercise, GLP-1 Agon. (semaglutide (p9) HbA1c 0.2%, insulin need 5-10%), metformin (weight -1%), SGLT-2 Inh. (HbA1c 0.5%, less hypoglycemias, ,cave: DKA 5%,

Basic rules (of thumb) of functional insulin tx ("FIT") manual, to be learned in a course, control booklet
- Total requirement: bw x (0.5 - 0.7)  U Insulin/d; insulin action time p13; insulin degradation: ca 2/3 hepatic, 1/3 renal
- Carbohydrate to Insulin Ratio (CIR) = Resistance Factor (RF): 1 U insulin for 10g CH or for lowering PG 2mM
Insulin requirement min around 2am (0.5U/h), max around 06am (1.5U/h dawn phenomenon); during menses & luteal phase
A) Basic depot insulin (dose finding fasting day or skip meal tests), evtl CGM, 40-50% of daily requirement;
.e.g., Tresiba ® (qd), Lantus ® (BP) - qd, Levemir ® BP – qd, Insulatard ® BP - tid, reduce dosing starting pump 10-20%
PG>8mM1U NovoRapid ® / Humalog ® sc; <4mM10 g dextrose po (e.g., 3 Dextro-Energen ®),
measure PG 2hrly (at night 22, 02, 06h):if PG>8 bzw <4mM check 1hrly
B) Fast acting meal insulin Fiasp ®, NovoRapid ®, Humalog ®, Apidra ®, Actrapid ® (inject 15-30min before meals)
Correct estimation of CH essential  meals test, “Nutri-Lernbuffet”, evtl nutr. counsil refresher cours, individualized diabetes diet KISIM
45-55% of daily requirement, usually 0.5-2E/10g KH (dep. on bw & RF = CIR, simplified CH bolus insulin scheme),
F/U 2h pp PG (ideally pp = fasting PG); nutritional table
e.g., 200g CH & 20U Tag = 1U/10g CH; typ breakfast 20-60g; lunch 60-90g; diner: 60-90g. snacks not necessary;
>10g CH  insulin required, fat- (or protein od extremely rich on CH (>100g)) → delays gastric emptying & CH resorption
evtl. improved pp PG & less hypo with CH w lower glycemic index (high fiber like apple, oranges, pears, artichocks, broccoli; vs low fiber like bananas, fruit juices, tomatoes)

C) Correction insulin 1U lowers PG ca 2 (1.5-6)mM (fasting day), usually to be added to meals bolus
Goal preprandial 5-7 mM; cave: lower insulin dosing for corrections at night (23-05h), F/U 2hrly
D) Exercise & sport (g CH/h; e.g., 70kg): 20hiking (5km/h), cleaning; 50 running (10km/h), soccer; 100 racing (15km/h), cross-country
skiing  plan ahead, leave time between meals & exercise, reduce insulin (90’ before exercise reduce bolus 25% a/o exercise mode in pump;
post-exercise: basal insulin afterward 10-50%), typically Hypo evening/bedtime after extensive & prolonged (>4h) excercise in the
afternoon (max. n 8-16h, can be reduced by 10sec „final sprint“), drizzle-in CH (10-20g amounts (& caffeine)). Individual differences! leaflet Diamon,
DIAfit.

E) Illness Depot-Insulin (10-50%), PG 2-4h  correction-Ds, if PG not, Ketodiabur ® test if PG>15mM

F) Travel E→W (USA): "long day "; correct with fast acting or depot (1/10 d Ds x Std. ZZ); W→E (Asien): "shortened Tag"; Basal or skip
Driving (p7) Risk for accident: Dm1: , esp. if poorly controlled, Dm2: not increased (also not if on (basal) insulin)
G) Hypoglycemia also seep 10 & 22; in a „well controlled“ diabetic patient one hypoglycemia grade II – III pa is expected
- Grading: I (PG <3.5mM w/o sy, manageable by patient), II (PG<2.5mM, extermal help required), III (PG<1.8mM, unconscious, seizure)
- Signs & symptoms: multiple, e.g., „stressed“, hunger, neuroglycopenia (confusion, behavioral abnormalities, visual disturbances)
- Tx: Glucose in pocket PG < 4mM10g CH, < 3mM  20g CH, check PG after 1h
a) Acute PG increase: 10g CH = 3 sugar cubes, Dextro Energy ®, Insta Glucose ® Gel, 1dl Cola or fruit (orange) juice
b) PG stabilization: 10g CH = 3 Darvida ®, ½ slice of Swiss whole wheat bread, 1 apple, 1 yogurt light, 2dl milk,
c) Unconscious: Glc iv: 10g CH = 100ml 10% = 50ml 20% = 25ml 40% = 20ml 50% Glc, glucagon (Baqsimi  nasal PoHI; GlucaGe ® Hypokit
(1mg sc) & 20g CH), if desperate CH in cheek pouch
- search for causes, check PG goals  Pat.-education, evaluate CGMS (with alarm, cave: analytic variability at low glucose levels->
check with capillary measurement if PG<2.5mM) or CSII, try coffee (awareness?), adapt PG targets? (e.g., elderly patients)
- Unnoticed a/o severe hypoglycemias? «Clarke-Score» for hypoglycemia unawareness
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 9. Dm Type 2 & Metabolic Syndrome
"An ounce of prevention is worth a pound of cure"

„typical“: pos FamH a/o GDM, hyperuricemia, metabolic Sy = cluster of metabolic cvR
DEF (>2): PG fasting >5.6mM, BP>130/85mmHg, waist circumference (belly button equator) M>102, F>88 cm (M>94, F>80 cm)
TG >1.7mM; HDL-C M<1, F<1.3mM (ATP III) DD: LADA (p8): no metabol. Sy, hypoglycemia under Tx, "slim" dm type 2  low C-
peptide, GAD II-Ab; if neg  MODY, mitochondr. Dm, hemochromatosis?, pancreatoprive (p8), steroids (drugs, Cushing-Sy, “stress”), other diabetogeic durg: atyp.
neuroleptic, cyclosporin A, tacrolimus, thiazides, HAART, dopamine

TH Empower the patient to treat all cv-risk factors (AGLA guidelines) (i.e. pat can support tx & reach goals independently)
1) Nutritional counselling PoHI, (USB, KSA) to instruct calory-reduced diet, Goal: wt >10% resp. not. Special diets Obesity, Dm
(KSA), CH-adapted aso, p14 &15, low carb? (p23), «Villger's Oat days»), Snacks if tendency for hypoglycemia (10gKH) → bariatric surgery ?
2) Exercise 1-2h/d „walking“ (dog a/o pedometer), >30Min/d «sweaty» exercise, stairs 5-10min, home cycling, swimming, DiaFit, Fitness-Myths, Pat. info
3) Diabetes counselling: baseline & follow-up; wt u/o HbA1c, switch to/from Insulin resp. OAD
4) Nicotine Nikotinell TTS / chewing gum, [Link], varenicline (Champix), Zyban, Cymbalta, Smoking counselling (Pulmology, OSAS ?)
5) Polypharmacy! SGED-SSED Guidelines, compliance? cost / benefit? Metabolic Surgery ? (p15)
- Statins independent of LDL-C level, >40Y a/o ApoB >65-100mg/dl.; 2° prophylaxis,«polypill» (statins, HTZ, atenolole, ramipril, ASS) already for 1° prophylaxis ?
6) Target-PG: fasting 5-7, pp <10 mM (2h n Essensbeginn), no hypoglycemia (CHD w Insulintx), Th-resistance?--> inpatient PG control
HbA1c individually 6 - <8% (HbA1c x 2)-4  mean PG past 6-8wks. analysis of PG control, e.g. with DIABASS.
Antidiabetics: Comb. metformin & SGLT-2 Inh → ≈ 20 E Insulin → HbA1c ≈ 1-2%  initially). PoHI for «high cvR» w comb SGLT-2 & GLP-1 Agon
- Metformin (Glucophage, Metfin) 1g 0-0-½1-0-1, SE: GIT, Vit B12-Mangel-> check yarly Tx: Vitarubin oral po qd or Vit.B12 Amino®1000ug [Link],
malabsorption CI: ClCrea<30ml/’ dose red GFR 30-50ml/’, OH, >80j, hypoxemic acidosis  48h preop & v ICM stop
- Gliflozins SGLT2-Inh., Pat. Info Ind: (obese) Dm2 w SU a/o meformin, comb w GLP-1-Agon. w CHF a/o albuminiuria f PoHI; wt & BP 2-5%, fasting & pp
PG, SE: genital myocosis, ketoazidosis w acute co-morbidity, statin levels (Invokana ® & Crestor ®), osteoporosis?, limb-ischemias? Fournier gangrene ?? CI: GFR<30ml/‘)
Dapagliflozin e(Forxiga Tbl. 10mg qd; Xigduo XR (+ metformin 1000mg) qd; Qtern (+saxagliptine 5mg) qd), empagliflozine (Jardiance Tbl. 10/25mg qd JardianceMet (5/12.5mg+metformin
500/850/1000mg) BP; Gyxambi ® (10mg +linaglitptine 5mg) qd)), canagliflozin (Invokana Tbl. 100, 300mg qd, for CKD (ClCrea >30ml/’, Vokanamet Tbl. 50/850 – 150/1000mg qd), saxagliflozine
(Onglyza Tbl. 2.5, 5mg qd, ertugliflozine (Steglatro Tbl. 5mg qd; Segluromet (Tbl. 2.5mg + metformin 1000mg) qd; Steglujan (+sitagliptine 100mg)
- GLP-1 Analogues (wt 2-5%, pp PG, Ind: lowering of (basal) insulin needs: semaglutide (Rybelsus® p.o. Tbl. 3, 7 u 14mg qd Ozempic® Pen 0.25 - 2mg sc 1x/wk
PoHI,); liraglutide (Victoza 0.6→1.2→1.8 mg qd), Degludec (Xultophy & insulin degludec 0.36mg & 10E→increase to 1.8mg & 50E qd, PoHI f comb w SGLT-2 a/o insulin, BMI>28m/kg2),
lixisenatide (Lixumia 10g →20g qd) & insulin glargine (Suliqua «100/33»: 3g & 9E→ up to 20g & 60E qd od «100/50»: 5g & 10E→up to 20g & 40E qd ), dulaglutide (Trulicity® Pen
0.75→4.5mg sc 1x/Wo, PoHI), exenatide (Bydureon 2mg sc 1x/Wo; Byetta 5ug sc BP x1-2 Mon 10ug sc BP), comb GIP/GLP-1 Analogs: tirzepatide (Mounjaro ® 2.5, 5, 7.5, 10m, 12.5,15mg s.c.
1x/Wo; SE: nausea, gradual dosing (increase 1-2wkly), «Ozempic-Face»; orforglipron p.o. (HbA1c -2%, Phase 3), Retatrutide (p 15)
- „Gliptine“ Ind: combined or mono-Th, hypglycemia, weight neutral: Linagliptin (TRAIenta®) Tbl. 5mg qd (no Ds adaptation in CKD), Sitagliptin (Januvia, Xelevia®) Tbl.
100mg qd (crea-Cl<50ml/‘: 50mg; <30ml/‘ / dialysis: 25mg), Vildagliptin (Galvus) 50mg qd (CI: GFR <60ml/’), Saxagliptin (Onglyza®) Tbl. 5mg qd CKD (Cl <50ml/‘→halbe Ds; CKD (!)
together with metformin without CKD. Jentadueto® 2.5/ 500, 2.5 850, 2.5/1000mg BP , Janumet XR® 100/1000 qd od 50/1000 BP, less GI-SE), Velmetia®, Galvumet®, Combiglyze ®)
- Sulfonureas (SU): SE: Hypoglycemia, wt↑, secondary failure
Gliclazid e(Diamicron 1-4Tbl MR 30 1-0-0, no need to check PG before car driving) , glimepiride (Amaryl) Tbl 1-4mg 1-0-0, glibornuride (Glutril ®) Tbl 25mg 2-1-0, glyburide = glibenclamide (Daonil® SE:
prolonged hypoglycemias (metabolites!), metformin/glibenclamid (Glucovance), CKD Glinide to meals: repaglinide (NovoNorm® Tbl. 0.5, 1, 2mg tid
- Glitazone delayed effect on PG after 4-8Wo; pioglitazone (Actos) Tbl 1545mg qd, Competact® Tbl. 15mg pioglitazone & 850mg Metformin) BP;
SE: wt, CHF., osteoporosis?, cvR? bladder cancer ?; CI: HF NYHA >I, pregnancy, LFT, tx duration max 2yrs
- Orlistat (Xenical) Tbl 120mg pre-meals; Ind: BMI>28m2 & Dm 2 (+1 OAD); proof of success (6mo wt 5kg a/o HbA1c 0.5%; max tx duration 2yrs, Acarbose (Glucobay Tbl 50100mg tid), SE: flatulence

Insulin? never too early often too late Ind: poor metabolic control (HbA1c>8% w OAD, PG fasting>10mM, Sy, ketonuria); e.g.,
Glucophage & Insulin w self-adaptation Levemir / Lantus / Tresiba (8-16E evening (0.2E/kgKG PG fasting>6mM x 3d 2-4E; PG<4mM 2-4E, 
0.5-1E/kgKG) od NovoMix 30 2/3-0-1/3; Humalog 50 Mix 3xtgl to meals, evtl.& glp-1 agon., nutritional counselling (CH-, fat- & kcal amounts)
(transient) switch to (basal-bolus) insulin (p7): Pregnancy & breastfeeding (p12), anabolism (cystische fibrosis), painful
polyneurophathy; severe co-morbidity (CKD (pause OAD!), HF, LF, sepsis / AMI / ICU / perioperatively (p11)
Steroid-tx: insulin resistance & hepat gluconeogensis, -cell-Fct (->OAD inefficient)  pp PG >11.1mM (prednisone morning (), (after-
)noon, evening) TH: dose- & T1/2-dependent! HumalogMix 50 0.1E /kg bw / 10mg prednisone, max. starter dose 50E) 2/3 morning & 1/3 noon, full
dose in the morning only if meals are secured; inpatients-> Steroid favorite KISIM-KSA. PG 12-15mM: Metformin (CKD?) & GLP1-Agon?

7) BP >120/90mmHg  ACEH / AT II-Blocker (esp.w stroke a/o microalbuminuria, if 24h-BP; BPsyst Nacht/Tag>0.9 -> evening dosing; Target: alb/crea50%
u/o<1g/d, crea 30%, K<6;  & diuretics (GFR>30/’: thiazide (“Co-“); <30/’: torasemide (-200mg morning))  a/o blocker  a/o Ca-antag., a/o
mineralocorticoid-antagonist (MRA →S.2, finerenone (Kerendia ®) f CKD with Dm2, PoHI); cave: orthostasis / syncopes mainly in elderly pat,
indivualised Tx; screen for HFpEF (Heart failure with preserved Ejection Fraction) ? (SGLT-2Inh & GLP-1Agon. effective Tx)
8) Dyslipidemia (p15) in 2° prophylaxis, evtl. Statins & ezetimibe or PCSK-9-Inh., OSAS (p2)
9) Fatty liver (Metabolic, non-alcoholic Fatty Liver Diseases (MAFLD) / Steatohepatitis (MASH), FIB-4-Index  (Fibroscan / US / liver biopsy) → LFTs  
F/U 3mo, >1.5x Hbs-Ag, HCV-Ab, transferrin-satur. >45%, Tx: wt! C2! hepatotox. drugs! (statins?), Resmetirome (Rezdiffra ®), Efinopegdutide, survodutide
10) Gout: production (90%, Tu, Psoriasis, hemolysis), renal clearance (10%, CKD, thiazides, ASS, ua), RF: uric acid (>400uM 0.5% pa,
>600 30% pa), pH, temp DG: typ. inflamm. sy, joint puncture (cristals), nephrolithiasis (Uric acid i.U > 600mg/d) Tx-acute: Indozid 200-
400mg/d, colchicine (D: Colchicum-Dispert Tbl, Colchysat Sol 1mg hrly max 1mg(CKD)-8mg (GI-SE, CYP3A4) initally, then 1mg/d), prednisone po
(0.5mg/bw x 2-3d/ lokal; chron:: mediterrean diet, weight, beer, coffee, VitC, allopurinol (Zyloric Tbl 50(CKD)-300mg qd (-BP) 4Wo after
podagra-attack; b Cl-Crea>50ml/‘ urikos-urics: probenecide (Santuril Tbl. 500mg 1-2Tbl. BP – qid, CI: urate stones), if hypertensive losartan, if dyslipidemic statin
11) Vaccination: Ind Co-Morb. ([Link]); influenza (1x/J) pneumococci (1x Prevenar CHF 90.-, no oblig. reimbursement)
12) Gastroparesis: frequent small meals, low fat, avoid bloating dietary fibers, mashed, chew well, if pp hypoglycemias fruit juices / lemonade
to meal, avoid C2; Tx: domperidone trial (Motilium ® ling. Tbl. 10mg before meals) or metoclopramide (Paspertin ® Tbl/Gttes 5mg to meals) Insulintx
adapt Inj.-Meal-Intevall, Actrapid ® as pp bolus; DD: celiac disease in pat w Dm type 1
Proposal for GP if HbA1c>8%, unsatisfactory control / compliance, final visit a treatment center
“Bei Dm werden empfehlen wir Kontrollen wie folgt: bei jede Visite PG, BP & wt, 3 mtl HbA1c & Inspektion d diab. Füsse & Schuhe, 6-12 mtl Lipidprofil &
Microalbuminurie, jährl. Ophthalmologie“; auch Empfehlungen d ERB & DFB weiterleiten. Die beiliegenden Richtlinien vom MedNET Bern sind zielführend. Der
Patient kann auch zur vorübergehenden Optimierung d Blutzucker i d diab. Sprechstunde überwiesen werden. Bei therapieresistentem u/o rezidivierendem
Uebergewicht und Adipositas sollte der Patient an ein Metabolisches Zentrum überwiesen werden.»

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 10. Hyper- & Hypoglycemic Derailings
"Sweet dreams may have bitter endings"

DD: Insulin deficiency ("forgotten", expired, ampoule leakin, needl clogged), infection, other stress, steroids, initial present
SY: Polyuria/-dypsia, nocturia, weight loss 10%/2Wo, visual problems, Tachypnea, infection? (History, focus?)
DG-NF: Blood gas analysis (BGA), Chemogram, lactate, SOsm. ECG (initial S-K, after Insulin K “no pot, no T, but U”)
- Ketone bodies (acetoacetate> -OH-butyrate>acetone (n <0.5mM) i urine or (better) in Blut with PG-device Freestyle -Ketone-strips!
- Patients on insulin pumps: if PG remains elevated despite correction by pump  change to pen & basal-bolus injection
DD metabol. acidosis: anion gap (AG) =Na - (HCO3- + Cl-) = 8-12mM, expected PCO2 (mmHg) = [HCO3-] + 15
- Not diabetic w normal AG: uremia (SO4, PO4, urea), rhabdomyolysis
- Not diabetic with AG>12: ketone bodies a) alcohol (PG<10mm, -OH-butyrate >2mM (n <0.5mM) > >acetoacetate, cave: urine-keto-Stix ® or
® -ketone-strips measure also -OH-buturate), b) fasting
nitroprussid evtl neg, because only purple due to acetoacetate & acetone → Freestyle
ketosis (AG typ 5-10, ketonuria +++, HCO3- >18 mM -), salicylates, metanol, (m)ethylenglycol (Tx: alcohol!), lactate (>4-5mM; lack of O2l [shock,
CHF, anemia, met-Hb, intox. with CO, CN, NO], hepatic, biguanids, typ Kussmaul-breathing patter & low pH-value despite only moderately elevated ketones)
Diabetic with hyperglycemic derailing
A) Diabetic Ketoacidosis („DKA“): mostly Dm 1 (initial dg or “forgotten” Insulin → leaflet for patients) SGLT-2-Inh. !
Dg: PG>14mM, pH<7.3, HCO3<15mM, AG>12mM, U-ketone >+++ (va Acetoacetat, Freestyle ® -ketone-strips)
evtl. pH>7.3 if DKA & vomiting (evtl. acute abdomen = "Pseudoperitonitis/Gastritis diabetica")  HCO3 & aniongap? (sa)
B) hyperosmolar derailing usually Dm 2 (often infections, sa)
Dg: PG>33mM, pH>7.3, HCO3>15mM, AG<12mM; U-ketones +, S-Osmeff >320mOsm
S-Osmeff = S-Osmmeasured – urea = 2xNa + PG (mM) + OH; Dm-derailing explains coma if S-Osmeff >320 mOsm/l
TH: generally for both DKA und hyperosmolar, mortality DKA <5%, hyperosmolar <15%
→ instable/polymorb./DKA Pat need intensive surveillance (IPC/IMC/SIC) for insulin-perfusor, K-F/U
1) Fluids! Requirements: past wt – current wt (correct within 24h, but max 10% of bw within first 12h), hyperosmolar (8-10L) > DKA (6-8L),
if GCS 14-15 free drinking, cave: brain edema (even with aequate tx, RF children & Sosm>3mmol/h)
- 1. hr: 1L (20ml/kg/h) 0.9%NaCl iv, thereafter dep. on CVP & S-Nakorr = Nagem + 0.3x(PG-5),
- 2-7 hr: 3L/6h 0.9% NaCl, 0.45% NaCl if Nakorr>135mM (if Na>155  only 0.5mM/h)
- Hypotension / CHF 1L/h (CVP <3cm), 0.75L/h (3-8), 0.5L/h (8-12), 0.25L/h (>12)
2) Insulin 0.1-0.15E/kg Humalog ® / NovoRapid ® / Apidra ® iv Bolus; sc if pH>7.25, PG<20mM; GCS>12
 Perfusor (50E insulin / 50ml NaCl 0.9%, initially 0.1E/kg/h od NovoRapid ® / Humalog ® sc 0.2E/kg/2h → to be adapted during course !
 Goal-PG: 6-10mM; 1-2h PG-F/U; PG <2.5 od>4mM/h  insulin x2 od /2,
PG<15mM 1L Glc 5% i 5h iv, don’t stop insulin (0.5E/h bis pH>7.3); pause insulin if K<3.3mM
3) KCl 30-40mmol/h (K<3mM pause insulin); 20 (K=3-4); 15 (K=4-5); 10 (K=5-5.5); pH>7.1 K-requirement  next lower step
mild cases: 20-30mmol K/ L NaCl (cave: hyperosm. & acidosis  K falsely  (K 0.5mM pro pH 0.1 od 10mOsm)
4) Phosphat (PO43-): esp. in DKA, substitute if <0,3 mM or symptomatic (weakness, paresthesia, persist. coma)  p14
5) Other thromboprophylaxis, evtl gastric tube if atony or vomitus
- NaHCO3 (1.4%=167mM,) if pH<6.9, Ds: BE(mval) x bw(kg) x 0.1) = mmol over 2h, Ca & Mg if arrhythmic
6) F/U 1hrly (1-6h)  2hrly (6-24h): PG, K, Na 4stdl: VBGA, SOsm, Urea, Crea, Cl
30% amylase (Pseudopancreatitis diabetica), CK, Hematemesis; pulmonary edema, Crea by Jaffe methods falsely  if ketones
if switching to insulin sc, overlap insulinperfusor for 2h, basal-bolus insulin correction, diab. consult
Cave: «TIND» (treatment-induced neuropathy of diabetes): Non-length-dependent neuropathic pain and dysautonomia if (too) rapid lowering
PG → HbA1c-lowering <3% / 3 mo if intial HbA1c >9%

Hypoglycemia (b Dm p8, insulinoma p22)

DEF adult: Whipple Trias PG<2.8mM & Sy (<2.2mM ohne Sy) & responsive to carbs  DD:
Lab (ideally during hypoglycemia!): PG, insulin, C-peptide, lactate, ketone bodies, free fatty acids, cortisol, HGH, IGF-1, crea
1) „Factitia“:
- Insulin (PG (mM) / Insulin (mU/L) <0.11; C-peptide <35pM), Drugs (asserve urine): OAD (protracted! →24h-surveillance), insulin & C-peptide), Venlafaxin ® ao
SSRI, MAOI, Tramadol ®, Tavanic ®, sulfonamides, INH, NSAIDs, Poentamidine, chinine, ACEI, ARB; non-selective -blockers, antihistamins
2) typically „fasting“ (i.e. = >6h pp)
- Insulinoma (p22), sulfonylureas (asserve blood), NNR-Insuff. (p6, P-Insulin), HGH-deficiency,
- C2, Liver- (lactate?), kidney- (crea?), heart (BNP)-failure., tu (insulin, IGF-1/2, SST), malaria, glykogenosis, MCADD-Mangel (p 25, hypoglycemia & CK & FFS↑),
3) typically “postprandial” (pp „dumping“): → ”mixed meal test”
- Post-bariatric (p 15,): ca 0.2%, OR 2-7, F>M, pp upright > pp supine) Tx: lay down pp; carb-restriction, GLP-1-analogues / SGLT-2 inh ? PoHI (Art 71, template
LUKS), “gverstich” (endoscopic tightening of anasthomosis / transoral gastric outlet restriction, MECCO-Study (LUKS)?, ultima ratio: reversion of surgery?
- Autonomous dysregulation, nesidioblastosis, Insulin-Ab (IAA, C-peptide<Insulin, RF: lymphoman/ myeloma, other autoimmune / rheumatic disorders)
- early phase of Dm2, Tx: nutritional counselling (low carb meals, lower glycemic index, Maizena ®), Acarbose ®, diazoxide?, DD: Hered. Fructoseintol. ("fruit intolerance”)
4) Insulin independent (fasting a/o pp): ”NICTH” non-islet-cell tumor-induced hypoglycemia (e.g., IGF-1, IGF-2, somatostatin, (GLP-1?)), tu/liver metast.
TH: 10-20g CH (→ p8!), PG F/U 15‘, 1h, 2h, 4h), evtl. glucagon (Baqsimi  nasal PoHI), evtl. somatostatin 0.1mg sc 8h & search for causes!
- if Hyperinsulinemic (insulinoma): Surgical Resection, evtl. endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA; inoperable, high surgical risk,
sporadic, tu size <2cm & >1mm distance from main pancreatic duct),
preop Sx: Maizena® bedtime, Diazoxid (Proglicem® cps. 25mg, 100-600mg qid; SE BP, Nausea, HF, Edema (evtl.
Torem®), hirsutism) + hydrochlorothiazide (Esidrex® 25-50mg BP), Dex 0.5mg before bedtime, nightly snacks; Phenytoin, Everolimus, glucocorticoids (e.g., Solucortef 100mg iv/d, DD Addison-Sy!), in
refractory hypoglycemia a/o malignant insulinoma, SSA: octreotide (Sandostatin 0.05 – 0.5mg sc 8h) / pasireotide (Signifor® 0.3-0.9mg sc BP); PPRT with 177Lu-DOTATATE:
consider for advanced insulinomas with hypoglycemia refrator to SSA; RZ358=Anti-Insulin Ab: reportedly successful (closing gap)
Prg: poor if prolonged hypoglycemia, pathological imaging (MRI), polymorbid or handicapped before event.
Cave: repetitive hypoglycemias → frontal brain syndrome

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 11. Dm in Medicine, Surgergy & Dialysis
"A seriously ill patient is grateful to see a diabetologist rather sooner than later”

Medicine: TARGET-PG: fasting (5) 7 – 10 mM, NO HYPOs, (measurement 2-3x/d w OAD, 4-6x/d w insulin, 2-4h w perfusor)
In hospitalized Pat: switch from OAD to insulin advisable (esp. metformin contraindicate in CKD & ischemias, better control of PG in acute phase w
functional insulintx)  PG-curve KISIM-KSA w RF = CIR & CH counts, pat. info, indivualized diabetes diet KISM
Blutzucker (BZ) Novorapid® oder Humalog ® subcutan (sc) in Bauch DEPOT
Messungen: 1. Korrektur 2. Essen je nach Kohlehydrat 3. Resistenzfaktor (durch Arzt festzulegen) Total o Levemir® o Lantus®

Zwischensumme
o bei Frühstück Zielbereich 5.5-7 mmol/l Menge (g KH) evtl. nach Startkriterien (x2 bei >1Kriterium) Nach sc i Oberschenkel um 22Uhr
o bei Mittagessen "TP" = Tagesprofil (bei Frühstück, Mittag- u Abendessen) Mahlzeit spritzen o CRP >100mg/L o Prednison >10 mg/d 23Uhr
o bei Abendessen o Sepsis, PCT>0.5ug/L o >60 E Insulin/Tag nur 50% 25% d Gesamtinsulindosis bei
o vor Bettruhe (22Uhr) Kontrollen Isst nichts (<10g) 0 E o BMI > 30 kg/m2 der Eintritt um 22Uhr als Depot
o Nachts (02Uhr) "TP" 4-stdl 2 -stdl Isst wenig (20g) 1 E Im Verlauf Dosis Im Verlauf 50% der Gesamt-
<4.0 4.1- 7.1- 9,1- 13.1- 16.1- 19.1- Isst Hälfte (30g) 2 E x: BZ-Abfall <3 mM oder Anstieg auf >7mM insulindosis des Vortages
> 21
Datum Zeit BZ 7.0 9.0 13.0 16.0 19.0 21.0 Isst alles (60g) 4 E x: BZ<4mM oder Abfall ≥50% E E Zeit Visum Pflege
Beispiele
Start 18:20 13.6 isst wenig 3E 1E 4E x2 (PCT 1ug/L, zu Hause 64E Insulin) 8E 18:25 V. Wyss
Verlauf 21:30 12.5 Patient isst alles 2E 4E 6E x3 18 E 16 E 21:40 V. Wyss
Start 0E 1E 2E 3E 4E 5E 6E 0E 1E 2E 4E x1 x2
Verlauf …..:…..
s
n
I

0E 1E 2E 3E 4E 5E 6E 0E 1E 2E 4E x1 x2 x3 x4 x5
…..:….. 0E 1E 2E 3E 4E 5E 6E 0E 1E 2E 4E x1 x2 x3 x4 x5

Surgery: TARGET-PG: 7 - 9 mM (peripartum / sectio 4.5-7mM), HbA1c: 7-8% (to be adapted individually!)
Basically for hospitalized pat. MDI w basis-bolus-regimen subcutanously (sc) quick-guide Insuline sc (p.13); Basals Insulin = Depotinsulin:
Levemir (evtl. Lantus), Bolusinsulin: Humalog/NovoRapid/Apidra (Actrapid s.c. for prolonged action for 4-6h)
Inulin dose calculated automatically in KISIM. Daily insulin prescription by arrangement: Dm 2 surgical intern after diab. consult; Dm1 & derailed Dm2 diab consult
Evtl. delay surgery if despite MDI PG>12mM in view of increased periop morbidity & mortality
„Staging“-late complication (p7), nutritional and diabetes consult on admissiont (≈25-35 kcal/kg/d, nutrintional parameters & check lab values (p14))
Perioperative Therapy (SOP KSA, periop use of insulin pump, Insulintx same day surger (SDS), training lecture, FAQ).
- daily profile = PG morning (7h), noon (11h), evening (17h), before bedtime (22h), if risk for nocturnal hypoglycemia 02h, if PG <7 od >12mM 2 hrly
- Insulin-injection scheme adapted to carbohydrate count with NovoRapid ® / Humalog ® / Apidra ® sc if PG > 7mM even in undiagnosed DM
Variable insulin requirement dep. of resistance to insulin. RF=CIR 1-5x in exceptional cases up to 1000U/d dep. on type of Dm / patient / stress level / morbidity.
Start with low insulin doses, thereafter increase 1-2U gradually to PG-goal  dose to be adapted individually, uncertainties / fluctuating PG → diab consult
cave: Increased risk of hypoglycemia at night  22 - 07 Uhr inject only ½ insulin dose! Tresiba ®, Ryzodec ®, Xultophy ® up to 72h duration of action
GLP-1 Agon. → delayed gastric emptying, esp. w high Hb1Ac, RF for periop aspirations, treat as non-fasted “full” stomach, consider gastric US, liquid diet a/o bridging with insulin if RF
PRE-OP DAY pause OAD from the evening before. At 22h apply 25% of previous daily insulin dose ( basal and boli a/o mixed insulin) as Levemir ® sc. If
mixed insulin has already been injected for dinner, inject Levemir ® only if PG >10mM. Skip 1 GLP1-agonist dose before surgery (residual gastric content)?
DAY OF SURGERY (OP-DAY, SX-DAY)
a) Non-derailed Dm (PG<12) & whs food intake at noon & small interventions i regional anesthesia/LA standby
- Pause (oral) antidiabetics (OAD) (and short-acting GLP-1 agon.?) on Sx (pre)day. Clear fluids without sugar until 2h preop; no G10% humalog infusion
- With basal bolus setting, usually inject basal unchanged + post-injection regimen sc (psb)
- For mixed insulin, give 25% of the previous daily dose as "basic" insulin sc (Levemir) + post-injection regimen sc (psb)
b) General anesthesia or longer procedures under regional anesthesia
- Dm without insulin: pause OAD for 24h (caution: ketoacidosis m SGLT-2). OP-day fasting, daily profile, no insulin-glucose infusion
- Dm with insulin treatment: "Normal" insulin distribution basal / boli 50%/50%. In the morning of the surgery: Pat. need glucose & insulin periop.
(reduces ketosis, catabolism) Þ from 7h 10E NovoRapid Inf in 1L G10%: 100ml/h (b cardiac and renal insufficiency w volume problem 50ml/h), additionally
apply 25% of the previous daily insulin dose ( basal + boli) as Levemir sc in the morning & post-injection regimen (e.g., NovoRapid ® sc).
For pump patients, run basal rate + post-injection regimen (psb). If persistent PG>12mM consider insulin perfusor iv (psb).

INTRAOP SIMPLIFIED: Insulin sc as Multiple Daily Injections (MDI) INTENSIVE: Insulin Perfusor iv
SCHEME IND: all DM patients, incl. sectio (target PG 4.5-7mM), IND: DM-Pat postoperatively on ICU, evtl. pat with
except indication for scheme INTENSIVE PG>12mM despite MD sc
• G10% insulin-Infusion ongoing (50-)100ml/h • G20% 20ml/h without supplements
• PG-control (strip device)& insulin dosing sc: 2 (4-6) stdl • PG controls (strip device / lab value): 1-hrly
• Insulin: NovoRapid ® /Humalog ® / Apidra ® (NOT Actrapid ®) • Insulin: NovoRapid ® / Humalog ® / Apidra ® / Actrapid ®
• Dosierung dependent von PG • Perfusor solution: 50 E NovoRapid ® / 50ml NaCl 0.9%
PG < 4 mM  100ml G20% iv immediately (stat!) • Dosing dependen on PG
PG 4-6.9  check PG 2hrly PG < 4 mM  100ml G20% iv, stop perfusor
PG 7-8.9  1-2U Insulin s/c (Belly, upper arm, thigh) PG 4-6.9  1ml/h (=1E/h)
PG 9-11.9  2-4U Insulin s/c (Belly, upper arm, thigh) PG 7-8.9  2ml/h
PG 12-15  4-6U Insulin s/c (Belly, upper arm, thigh) PG 9-11.9  3ml/h
PG >15  6-8U Insulin s/c (sa, cave: cumulation) PG 12-15  4ml/h
Check after 2h: if PG > 12mM despite injections PG >15  dependent on clinical signs & symptoms
 consider scheme INTENSIVE w Humalog ® Perfusor iv • Potassium/Kalium: <4mM: max 20mval/h KCl short infusion
POSTOP: ICU: → ICU/IMC-scheme, recovery room / ward: PG-daily profile → Bolus-insulin-MDI sc (2hrly control only if PG <7 or >12mM),
Prehosp. therapy (OAD, Iinsulin) re-start after lunch if uncomplicated course & well controlled PG, else follow guidelines / SOPs:
- nü: 10 E NovoRapid in 1L G10% 100ml/h m Nachspritzschema & allfälliges Basisinsulin, parenteral  2/3 d Tagedosis i TPN (p14) & NSS
- Ward Insulin continued as basal ( ½ of daily total insulin dose) & bolus-insulin-MDI to correct PG & cover carbohydrates (insulin 1-4U/10g CH!),
- if recurring PG > 12 mmol/l→ diab consult

Dialysis: Dose adjustments a) with progression of kidney failure & b) at start of dialysis
Hämodialysis (HD) Glucose-Goal: PG <11mM at the start of the HD session; check capillary glucose before leaving the dialysis unit (>5mM if driving)
Insulin: At the start of dialysis an increase of total insulin dosage of up to 30% may be required; thereafter a) Basal: Reduction of up to 25% on HD days b)
Preprandial bolus: reduction by 10-15% before a HD-session
In patients with altered cognition and a shortened life expectancy, consider administration of long-acting degludec 2x/wk at the end of the HD-sessions

Peritoneal-Dialysis (PD): Day: 2L Glc-Lsg 30’ before meals tid, Nacht: non-resorbable Isodextran-Solution (=Glc polymere) at 10pm
Nutrition: protein enriched (1.2 g Kg bw), CH-adapted, include Glc in bag (3x1.36%&1x3.86%150gGlc  Resorption 60-70% b. CAPD, 30-50%)
A) Basal insulin: 50% of previous daily dose (alternativ Cycler m nächtlicher Glc Lsg peritoneal  PG morgens, evtl. Levemir v BR)
B) Insulin f CH in meals & PD-bag:+2/4/6E Humalog sc f ≈1.5/2.5/4% Glc-Beutel (≈12.5/25/35g Glc/L),
e.g., daily dose 40E; Day 20E (= 50% v. 40)  distributed to 3 bag: 7 – 7 – 6E (b 3.86% Glc-bag: 13 – 13 – 12E); night 13E (30%x40), bzw. 19E b. 3.86% bag
C) Correction Insulin: Adapt to PG nü / pp (mM): - / <2.5 -12E; <2.5 / 4.4mM  -8E; <4 / 6.4 -4E; <8 / 11 0E; <13 / 22 +4E; <22 / >22 +8E; - / >22  +12E

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 12. Pregnancy
"Love is a boogie-woogie of hormones“
Notification of maternity (no franchise & deductible in pregnancy)
Dm: Target-PG: fasting 4.5-7mM; pp <8mM. optim. PG before start pregnancy (Decgludec ®, Levemir ®, Insulatard ®)
Dm1 discuss CGM a/o pump (-10% more TIR, % large f gest. age & neonatal hypoglycemia ), Guideline Dm1 & pregnancy (G) F
Insulin requirement: 1. trimester (), 2.& (3.) trimester  (up to 300%, if suddenly  placentar insuff.); postpartum  (psb)
Ophthalmol F/U before pregnancy & each trimester (Retinopathy risk  if HbA1c ?), Fructosamin (no<285uM,  PG letzte 3Wo  HbA1c 6.5%), consider
psychosocial Aspects
PCOS: metformin (Glucophage ®) stop at Dg pregnancy; might continue if risk for preterm delivery; MODY in pregnancy

Gestational diabetes (GDM) Pat. Info, guidelines F&K KSA, USB DD: preceeding Dm2
Risk factors (RF): St n makrosomia (>4kg) / abortion, pos history f GDM / PCO, > 25yrs, BMI >25 kg/m2, Ethnicity
(Africa, Asia, Balkan, Hispanics). RF explain (only) 50% → general screening, Risk = continuum dep. on PG! Enforce lifestyle changes if RF
DG: PG >4.8mM fasting (6h fast, nocturnal hunger attacks?) without RF 24-28GW with RF on Dg Pregnancy (<10-16 GW)
PG self measurement, evtl. CGM (Time in Range “TIR” 3.5-7.7mM >70%), evtl. 75g oGTT 8h fast >5.1; 1h>10; 2h>8.5 mM (1 value pos  GDM; if fast >5.1mM no
oGTT needed!) TH: benefits: less peripartal compl. (infant deaths, dystocias, Fx, paralyses, neonatal IPU or ikterus), prescription template
Nutritional (25-30kcal/kg/d) & diabetes counselling (PG measurement, morning ketonuria >++  late CH-snack), BP-Tx (psb),
PG fast a/o before bedtime <5.3mM  Levemir ® od. Insulatard ® od. Huminsulin ® Basal (0.15U/bw),
PGpp: 1h <8; 2h <7.0mM  NovoRapid ® / Humalog ® initial 2-8E z MZ Insulin dosage table (low risk for hypoglycemia due to insulin resistance)
F/U: wkly until PG ok, then if on diet falls → F/U in Gyn, if on insulin EDM 1-4wkly, CGM?, Dm 1 pump?
- higher prevalence for Gestosis EPH/HELLP-Sy (headache, [Link], Edema, BP, Proteinuria)?  evtl Ketodiabur, BB, Chemogr
→ Aspirin 100mg/d if gestosis risk after 12GW and Dm Typ 1 & 2.
Dm-Risk 30%/5J (Pat. Info!) postpartal weight reduction (counselling, lifestyle, Sport) & >3mt. breastfeeding
→ F/U at 3 mo: PG fast >7mM / HbA1c >6.0% Dm 2; >5.6mM / >5.7%  Lifestyle & counselling; <5.6mM / <5%  idem & 1-3j PG at GP
Long-term maternal complications: T2DM, CV diseases, MASLD, depression. Insist on weight control & lifestyle changes.
Lung maturation: Betamethasone (Celestone®, T1/2 36-54h), 12mg x 2d  GDM risk & insulin requirement : a) on diet: Insulatard ® 10-0-0-
10E x 3-5d; b) insulin-dependent: basal +10U – 0 – 0- +10U, bolus x1.5-2 f 3-5d; risk f ketoazidosis on steroid & -agonists 
Peripartal Insulintherapy Guidelines F&K KSA D & F, USB
- "preventive" hosp. (initiation of labor >12h) Th unchanged, ideal 38GW. Colostrum collection (≈5ml/d) after 36GW?
- Evening prior to birth / sectio: basal insulin as usual, complete form G F for Dm1 & 2, GDM w insulin
- During labour / birth Target-PG 4.5-7mM (assess 1-2hrly)
- On admission: morning of the section or birth „in sight“: (pat fasting): no Insulin sc; stop pump
- Insulin-perfusor Ind: Dm2/GDM m fasting PG >7mM resp.. Dm1
Infusomat® 50E Actrapid / 500ml 0.9%NaCl /24h (0.1E/ml) initially: 1/48 der previous daily dose per h;
if in previous 12-24h depot insulin injected  ds 50%; if addtl. Glc Inf (evtl.) add insulin to prefusor dose
(1-) 2h PG-F/U: <4-4.5mMInsulin 50%; >6.5-7mMInsulin 50% (Steroidth b >10E/h)
- Peripartal Glc-inf. Ind: GDM w basal insulin without oral CH feed, PG <4mM, ongoing labour / stress
Glc 10% 1L/10h ( 10g Glc/h); PG F/U 1-2h PG<4-4.5 insulin stop or Glc 50% (Glc is venotoxic!)
- After removal of placenta: Target-PG 5-8mM preprandial
- Dm1: cave hypoglycemia → Insulin  to 1/4 previous daily dose, sc Insulin if CH po; adj. PG target, CIR & wt.
- Dm2 & GDM: stop insulin stop, PG-TP → diab. consult if preprandial PG >8mM
- 1-3d postpartal w Dm1 insulin dose 50(25)% of dose before pregancy, meals: 0.25E/10gKH, 10-20g CH after breast meals
x

Hormones in Pregnancy
Thy: HCG (hyperemis gravid., twins) → fT4 (2-10%). TSH-suppr (10-50% 1. Trim), TBG 2x, TT4, TT3, T4 & Jod-need  (250ug/d, Natalben
Plus ® (200ug) oder Burgerstein Schwangerschaft ® 150ug) instead of Elevit ® (contains no iodine); Th-target: TSH: 0.3 - 3mU/l, fT4 upper Norm, evtl. fT4-
IndexF/U: 4, 8, 12, 16, 20GW & postpartal TSH-Screening? all vs. risk (i.e., >30Yrs, infertility/ abortions, typ. clin. Sy (Score!), pos history,
goiter a/o iodine deficiency areas, TSH a/o pos TPO-Ab (risk for abortions 2-5x, preeclampsias 2x, IQ offspring of SCH, postpart. thyroiditis,
progressive hypothyreoidism), Dm1, St. n. ICM, RAI or STx. Guidelines: 1) pregnancy 2) postpartal / pediatric Placental passage: TRAb (fetal surveillance
(sonographic goiter?), iodine, -blocker, CBZ>PTU, T4 20-50%, T3 not al all
- Hypothyroidism: ab SS T4 Ds 30-50%, Beginn T4-Subst: TSH>(Trimester)Norm u/o pos TPO-Ak va b Risiko-SS diskutieren
- Graves D.: Dg. in pregnancy: TSH, fT4, TRAb (neg & 12 Mon Th -> stop th ?),  18 GW, TSH, fT4 (goal: upper Norm), TRAb (falls ) → US Gyn (fetal HR,
goiter, SGA, amniotic fluid)  4-6wkly Tx: PTU (1. choice, RR-teratogenicity 16%), CBZ (RR-teratogenicity 32%), evtl -Blocker if symptomatic (vomitus)
- Postpartum = silent thyroiditis (5%, Dm1 25%); hyper (2mon)→ hypo (TPO-Ab, 4-12 mthly) → 80% euthyr.; F/U 4-8 wkly
- Breast feeding: PTU up to 300mg or CBZ up to 30mg, probalbly without relevant side effect on baby
Adrenal: CBG 3x, HC- & Florinef ® needs 50%?, stressprophylaxis (incl. supp. !), birth 50mg HC q8h, DD: Cushing-Sy: red striae, hirsutism
- aPR & Aldo -10x,pProgesterone -1000x (antialdost.), if K od BP → Conn-Sy?: Renin, ARR, (evtl prog/aldo<20); Tx: 2. Trim. Eplerenon? amiloride?
Pituitary: size 100% (-1.2cm), PRL ≈10x; IGF1, "GH" (from placenta (non-TRH responsive), hypophyseal GH), S-Osmol & P-Vol 40% (Oxytocin 10% ADH-effect)
- Prolaktinoma: symptomatic tumour growth in 3% (micro-) up to 30% (maroadenoma)
- no injection of milk +/- failure of other axes  DD lymph. hypophysitis; Metopiron ® i Cushing’s disease; hemorrhagic birth  Sheehan-Sy?
- adapt dosing of thyroid medication (+30-50% gem. fT4), evtl. also HC-Ds; Subtly prepare women for possible inability to breastfeed
- Vasopressinase activity of placenta, mainly in late pregnancy  mimics polyuria-/dypsis-sy; Tx: adapt fluid addition , evtl nocturnal Minirin ®
- Spontaneous births also possible with (pan)hypopituitarism & multiple axis failures, oxyocin i.v. or nasal postpartal for breastfeeding currently not yet possible
Bones: Ca 1.5g/d, 4% BMD w breastfeeding  Osteoporosis; placental PTHrp: transient Ca  (if addtl. Vit D -> 1.25 hydroxylase ) → preeclampsia
BP-Tx (>160/110mmHg) Methyldopa (Aldomet®) Tbl 250-1000mg tid, SE: hepatitis; Metoprolol (Beloc®) 50-200mg qd, nifedipine (Adalat ret®) 20-90mg BP, amlodipine
(Norvasc) 5-10mg qd, labetalole (Trandate®) 200-400mg po tid, 20-80 mg iv/30‘ (max 300mg), 1-2mg/’, SE: growth retard., evtl. nitroprusside (Nipruss®) 0.5-10mg/kg/‘ =20-
600ug/‘, Hydralazin (Apresolin® aus D), evtl. eplerenone in 2./3. Trim. if prim. Hyperaldo (Dg: suppr. Renin) NEVER: ACEIH, ARBs, renin antagonisten
(Malformations of the kidney and urinary tract)
Postbariatric Overview, KSA D Increased risk of premature birth, SGA, lower risk for GDM & maternal morbidity. GDM-screening: PG, HbA1c, not OGTT

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 13. Diabetes Counselling & Insulin Therapy
The 3 important things in diabetes: education, education, education. The diabetic who knows the most, lives the longest. P. Joslin
Diabetes counselling (DC) provides basic infos, secondary complications, therapy options, hypoglycemias (unawareness p8)
- Care concept for newly discovered Dm 1, Guideline for inpatient care of poorly controlled diabetics KSA
- Check-ups (leaflet for pat.): In principle, annual contact with DFB for long-term patients, especially with HbA1C above target value, PG
perception disorders, late complications (foot care advice PoHI podology), patch problems with sensors & pumps
Insulins (5x3mlPenfill Amp or Fertipen5x3ml), cave: cloudy NPH-(e.g., Insulatard) & „Mix“-insulins: tilt 20x before drawing up
- Application: Injektion-quantiy if >40E divide into 2 injektion sites, Injektionssite: Bolus & mixed insulin: abdomen; Depot: tigh. pay
attention to changing injection sites (lipodystrophy, hematomas), «Insulin accelerators»: temperature (sauna!), exercise, massage.
- «if you don’t know what to do?»: ask the patient, adapt (reduce) insulin dose, eat less, check injection site
- Humalog®, Humalog Mix® 25 / Mix® 50, Abasaglar: Humapen Savvio 1-60E, LuxuraHD ½-30E, Kwikpen1-60E, Efsitora wkly
- NovoRapid®, Levemir, Insulatard, Tresiba® (100 & 200E/ml), Ryzodeg® (30% NovoRapid, 70% Tresiba), Novopen5 1-60E, NovopenEcho Plus ½-30E,
InPen, Flexpen1-60E, FlexTouch 1-80E (nur NovoRapid, Tresiba & Ryzodeg), FlexTouch 2-160E (Tresiba 200E/ml), Xultophy® (1 Ds=1E Tresiba + 0.036mg
Victoza; max 50 U/day, only T2D)
- Apidra®, Lantus® (100E/ml, HWZ ≈ 22h), Toujeo® (300E/ml, HWZ ≈ 28h): Click-Star 1-80E, Solostar1-80E
- Spritz-Ess-Abstand: NovoRapid / Humalog / Apidra. Inject immediately before (or after) meal; PG <5mM inject after meals
”Closed-loop” & AIDs (Automated Insulin Delivery Systems)
Checklists: at start: KSA PG target missed: DiaMon
Order forms: Medtronic 740G, 780G, Roche Accu-Chek Insight, Solo, Insulet Omnipod,
Hybrid Closed Loop Systeme (u.a. Medtronic 780G & Guardian 4; Minimed 740G, Dexcom G6,Tandem t:slim X2, Ypsompump CAM APS)
Insulins: Humalog ®/ NovoRapid ®/ Apidra ® sting amp à 10ml od 3ml pen amp, Insumane ® Infusat U 100 5x 3.15 ml Amp
Leaflets Calculation of Basalrate & Bolus Insulin (based on RF = CIR), blood sugar diary, hypoglycemia & ketoazidosis
Important: if pump fails a/o stops start immediately with basal insulin, boli similar dosing to pump therapy
CGM (continuous glucose measurement, 72-144h. Analysis: short, extensive, nutrition. cave: PG falsely with paracetamol, Vit C), Rx by specialist EDM Ind: Dm w
(nocturnal) Hypo II a/o ER-cons./Hosp w hypo a/o difficult to control „brittle Dm“, , HbA1c>8%, Dm1 plus (planned) pregnancy w HbA1c >7% or to reach target glucose valusee (fasting <5.3, pp <7mM). Unexplained
PG-fluctuations w good compliance, traffic assessment, Dawn phenomenon, discrepancy PG to HbA1c,
- Freestyle Libre Ind: «Dm w FIT», Dg PG over 2wks (KSA-ID Libreview 05321468 no pumpconnect, Libre 2 (with hypo-alert), Libre 3, Guardian 4 & InPen
- Dexcom G7 Ind: PG-control over 1wk (no connection to pump yet, no PoHI needed), (G6 w PoHI); Roche Eversense (Ind: longterm 3-6mo)
- Medtronic (PoHI only needed if connected w pump)
Measurement devices (how-to upload data, Diabass SecureSend, Medtronic Smartpen); all compatible with CAPD, plasmareferenced, Roche: Accu-
chek (Aviva,Nano,Mobile), Ascensia: Contour (next one / AC Guide / Instant), Abbott: Freestyle (Lite, Freedom Lite, Precision Freestyle Ketone-strips
(messen -Hydroxybuturat!), Insulinx (HbA1c)), Ypsomed: mylife Pura / Unio, nicht CAPD tauglich:Life scan: One touch (VerioFlex / IQ)
Lancets f pricking aid: Ascensia: Microlet Lancets(25G),Klinion soft fine color(28G), Lifescan: One touch Comfort (22G) / Delica, Roche: Accuchek
Fastclix(30G) Abbott: ThinLancetten(28G)
Pen-needles: for all pens: Mylife Click fine(4/5/6/8mm), BP Micro-Fine ultra(4/5/8mm), BP Autoshield Duo(5/8mm). Flexpen, Flextouch,
Novopen 5: NovoFine (6/8mm), NovoTwist (5/8mm). In case of extreme injection phobia evtl. «iPorts» (no listing at health insurances)
Needles 4mm, even in obese patients. Divide injections if Depot >40E, rasche Insuline>20E
Ev alcohol wipes, Baqsimi ® i.n. Ind: history of severy hypo grade III, evtl. GlucaGenHypokit → shelf life → Free exchange after expiry in pharmacy
Measurement of ketone bodies ? evtl. in capillary blood Freestyle -Ketone-Streifen Dm1, pump therapy, SGLT-2. Ketodiabur urine ketone strip (out)dated

Duration of action of insulins sc schematic → Insulin dosing regimen KSA outpatient (old PG in mM or mg/dl),
inpatients, Pat. Info on inpatient glucose mgmt with insulin KSA , *specific action profile of degludec (Tresiba®)
Zeit der s.c. Injektion
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 h

Korrektur Basis
Liumjev > Fiasp >
6E

Essen
NovoRapid / Humalog / Apidra 24E

Actrapid 6E
24E
Insulatard 12E
36E
Levemir 36E
Lantus, Abasaglar, Toujeo 36E
Tresiba (*„Steady state“ nach 2-3 Tagen) *
>42h
Misch

Humalog Mix 25 36E

Humalog Mix 50 36E
Ryzodeg (*„Steady state“ nach 2-3 Tagen) 36E *
>42h
1.5 E/h
Insulinbasalbedarf 1.0 E/h
Pumpenrate
0.5 E/h
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 h
Uhrzeit

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 14. Clinical Nutrition & Counselling
„Man ist, wie man isst“… gilt für ALLE Menschen !
[Link], [Link], [Link]; others
Energy requirements total basic metabolic rate 20-
20-25kcal/d*kg current weight (for target-weight add or substract % kcal) =
25kcal/kg/d (10% lower for elderly & obese pat) & stress/morbidity 10-50% (1°T10%, T4 / ICU -30%) & activity 10-50% (in bed +10%,
mobile+20-40%, heavy labour +100%; e.g. (kcal/h f 70kg, outpatient): supine 80; seated 100; standing 150; walking (5km/h) & bicycle (15km/h) 250; swimming
(0.4km/h) & golf 300; eerobic 490; tennis 420; jogging (10km/h) 500; squash 600.  24h hiking to ”burn” 1kg fat
Protein: 0.8-1.2g/kg/d: urine-urea (mM/24h) / 6 = g prot. turnover/d (n 1g/kg / d; more precise: U-Urea x 0.028  70gN/d x 6.25 = gProt/d + 3g Prot-losses/d)
Fluid: 20-35ml/kg/d (dep. on underlying diseae / balance / age) Electrolytes (mmol//kg/d): Na 1-2; K 1-3; Ca&Mg 0.3-0.4 each; Cl 5-6, P043- 0.3-0.8
Malnutrition 20% of inpatients (Pat-Info malnutrition despite abundance (D), dietary recommendations for lack of appetite (D))
DG: Screening with Nutritional Risk Score (NRS), BN KSA →Personalized nutritional tx EFFORT (D E F I) (psb)
Lab (DD acute phase response): 1. Basal: diff blood count, e’lytes, erea, urea, Quick, protein, lipids, PG, LFTs, amylase 2. Visceral
proteins: Albumin<28g/dl (only without acute disease!), prealbumin (transthyretin) <120mg/L (shorter T1/2, follow-up), 3. Immunity: Lymph<1200/mm3,
4. Muscle masse: crea iU (p 2) <80% (mild) <40% (sevdre); 5. Lipids: -Caroten (<1.5uM), Retinolbinding protein <20mg/L, Cholesterol <3mM, 6.
Trace elements & Vitamins: Iron: Transferrin<1,5g/L (hepat. protein synthesis marker), ferritin<20ug/L, Vit. B12 < 176 pM (≈230 pg/ml),
Erythrozcyte-Folsäure <300nM, zink <10uM; selenium <0.8uMM; 25OH-Vit D<25-50nM
Anorexia nervosa tx concept (D), DD eating disorders (D); DD «IBD»: celiac disease, IBS, FODMAP, >50J.-> Colo; Mastozytose, Endometriose, Porphyrie
Refeeding-Syndrome RF: too rapid food build-up after wt loss (>5%/mo, >7.5%/3mo, >10%/6mo) e.g., after malnutrition, C2 abuse, anorexia Sy:
within 1-3wk Na-retention w edema, P-PO4 (<0.32mM idR w CNS-Sy, coma, rhabdomyolysis, hyperparathyr., insulin resistance), K, Mg, Ca, Zn, Vit B1
TH: oral > enteral > parenteral; initally only 50% of calory requirements (10 → 20 → 30 kcal/kg/d or liquids in ml/kg /d over 1-2wk, evtl add-on w liquid food /
Sondenkost/parenteral); elektrolyte gem Labor (Bedarf sa): PO4 Phosphat Sirup KSA 500ml 10mmol=15ml tid, Phoscap Bichsel® 5 Cps à 100mg=3mmol qid, K-
PO4 amp 1mmol/ml 100ml ad inf (no mix w Ca2+), K KCl Hausmann 2 drg tid (745.5mg=10mmol K/Drg), K-Hausmann 1 effervesc. tbl =30mmol K tid;iv: KCl 15%
amp à 10ml (20mmol K) Mg Mg-Card granulate (5mmol) or effervesce. tbl (7.5mmol) or lozenges (2.5mmol) tid, iv: MgCl amp 50% à 2ml (4mmol=1g Mg) Ca/Vit
D Calcimagon® BP (p16), Vit B1 Benerva® 300mg po / iv qd, Multivit. Supradyn®, double ds x 7d, iv Soluvit® & Vitalipid® each 1 Amp tgl, Zink Zn-Glukonat Burgerstein® tbl. à
30mg qd, iv ZnCl Amp à 10ml (5mmol Zn), Selenium (CH: Selenase ® 500ug/Trinkamp=CHF 8.-; D: Cefasel® 300ug/Tbl = 80Rp), Fe- (Ferrinject® 100-250mg iv) subst ab d7, KO:
vitalsy, fluid balance (max +1L /d), edema, wt / BMI, e‘lyte d1-7 daily, dependent on severity & course

Stages of nutritional therapy early nutritional counselling (NC) (list of indications during hospitalization, PoHI)
Ind: present or foreseeable malnutrition (>3d <500kcal /d or NRS-screening), pat. info , EFFORT-study NNT mortality 36, complications 25!
MD-Consult: Malnutr. w refeeding risk, parent. nutrition, short bowel-sy (p27), Goal: ENTERAL asap & as much as necessary!
1) Elective food "if the gut works, use it or loose it"; dep. on energy requirement, pat. info
Nutritional value (1kcal = 4.2J, food pyramid) Prot: 4kcal=17kJ/g Fat: 9kcal=37kJ/g CH*: 4kcal =17kJ/g OH 7kcal=28kJ/g
„Standard“ 2000kcal i g/d (% enery content) ≈95g (20% d kcal/d) ≈80g (30%, 2.5% ess FA) ≈180g (50%) F<20g/d; M<40g/d
*Diabetes diet (KSA) fixed CH (main meals / late snack or dessert) 2400kcal: each  60 / 20g; 2000: 50 / 20g; 1600: 40 / 10g; 1200: 30 / 10g

2) Food forms comparison different products No unnecessary restrictions in disease

Special cases (evtl consult EDM): medicine Ind f. NC, Dm (p7), obesity (p15), dyslipidemia (p15), hemodialysis (1-1.2g Prot/kg, <1g PO4,
<4-6g NaCl, <3g K, H20: urine+500ml), steroid tx (1.2g prot, fat, 1200-2000kcal, KH, no grapefruit), NaCl (5-6g), energy- & protein enriched, gout
(wenig Fleisch, C2), ICU, Surgery: Ind f. NC, bariatric bypass, pre-op fasting, postop feeding, chylothorax

3) Drinking foods (Sortiment KSA, USB, Vit K  adapt AC) normal calory & protein content (a) increased (b) fat-free preparations (c)
Preparations (Indications, serve cold, supplementary food, div. flavours), per 100ml, Energy Prot Fat CH trace-e./Vit
a) Fresubine Protein Energy (1-2x/d, low in lactose, portion 200ml) 150kcal 10g, 7g, 13g, 1/8
a) Resource Protein (low in fibre- & lactose, portion 200ml) 125kcal 10g, 4g, 14g, 1/8
b) Resource Compact (low in fibre- & lactose, portion 125ml) 250kcal 10g 10g, 30g, ¼
b) Ensure Plus (low in fibre- & lactose, portion 200mml) 150kcal 7g, 5g, 20g, 1/6
c) Enlive Plus Drink (2h preop “carboloading“, fat-free, low in fruit acids; portion 200ml) 150kcal 6g, 0g, 36g, 1/3
4) Tube diets (overview, Sortiment KSA, USB, Bedarf>4 (-8)Wo  PEG (insert, removal) tube feeding regimens: (initially contiunuous w pump (w
jenunal tube, 6h night break to reduce aspirations debated), increase 20-40ml-wise, portion admin. asap; SE: Diarrhoe, Elektrolytstörungen, Hyperglykämie, Tx:
Paspertin 10mg tid, Oberkörperhochlagerung, Trend RV  Insulin-dependent Dm: meal within a) 1-2h  Humalog®; b) 4-6h  Actrapid® c) over 24h 
Actrapid®-Perf, Levemir® (w night break), Lantus
Preparations (Indications all products free of purine-, laktose-, gluten & low on sodium), per 500ml Energy Prot Fat CH trace-e./Vit
Peptamen HN (digestive disorders: malabsorption, short bowel / post-GIT-Sx, IBD (Crohn/Colits) 665kcal 33g, 25g, 78g, 1/3
Peptamen AF (ICU) 750kcal 45g, 32g, 67g, 1/3
Nepro HP (renal failure w ClCrea<30 without dialysis, 1.8kcal/ml)) 900kcal 41g, 49g, 74g, 1/2
Isosource Protein Fibre (protein demand IPU, postop., radioth, dekubitus, dialysis w K & Po43-) 665kcal 33g, 22g, 80g, 1/2,5
Isosource Energy Fibre (normal needs with fibr, high caloric, long-term) 800kcal 30g, 31g, 96g, 1/2,5
Isosource „Standard“ (normal needs, free of fibres) 525kcal 20g, 18g, 71g, 1/3
Novasource GI control (USB, normal need w fibre) 550kcal 20g, 17g, 72g, 1/3
Novasource GI forte (KSA, normal need w fibre, high caloric, long-term) 750kcal 30g, 30g, 92g, 1/3
Fresubin 2kcal HP (fibre) (standard, high claoric, w fibres) 1000kcal 50g 50g 84g 1/2
Impact Glutamin (KSA, n-3, Arg, RNA: elective visceral surgery, trauma) 550kcal 32g, 15g, 73g, 1/3
5) Parenteral nutrition Ind: >3-8d expected >50% enteraler malnutr. (dep. nutritional status) Additives (add to mixed solution; stable for
24h) 1. Soluvit N® (water soluble Vit) & Vitalipid® (fat-soluble Vit) 1amp. each, 2. Addaven N® trace-el. 1-1.5 amp or Peditrace ® (if iron-overload)
3. evtl. Actrapid® b DM1E/10gKH i bag, Perfusor; 4. evtl. Dipeptiven® L-Ala & L-Glu b hyperkatabolism & BMT f opt. N-balance; 0.3g/kg/d (=1.5ml/kg/d) i PE-
bgd, CI Crea-Cl. < 25ml/min, severe hepat. failure, pH < 7,2 F/U: Tgl. wt & balance (Goal: Na i.U. >20mM, Na/K i.U >1, n U-Vol (>15ml/kg bw/d), d1 - d3 tgl Na,
K, PG, P04, Tg (>4.6mM bzw. >10mM → red. or stop lipid solution); wkly. Ca, PO4, Cl, Mg, Zn; TG, INR, PTT, Bili, alk. phosph., GOT, lipase, alb, crea, urea
(falls isolated  -> reduce aminoacid solutions-Lsg), CRP, blood count, iron status. Insulintx & parenteral nutritition: USZ-scheme
Preparations Na+ K+ Ca2+ Mg2+ Cl- PO43- mOsm/L ml, Energy, Prot. Fat, CH trace-e./Vit.
SMOFkabiven (1, 1.5, 2L) 80 60 5 10 70 25 mmol 1500 1970ml, 2200kcal 100g, 75g, 250g, add (sa)
SMOF peripher (1.2L, [Link].) 30 23 2 4 27 10 mmol 850 1206ml, 800kcal 38g, 34g, 85g, add (sa)
SMOF EF (1.5L, free of electrolytes) 4 mmol 1300 1477ml, 1600kcal 75g, 90g, 187g, add (sa)

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 15. Dyslipidemia & Obesity
A successful diet is the triumph of mind over platter

Dyslipidemia primary/familial forms often aggravated by secondary causes

A) PRIMARY (genetic; „DD-rule“: TCDD: polygenetic, FH, FDB; TC&TG DD: FCH, remnant disease, sec.; ”rarinomas”), TH: immer
Dyslipoproteinemia Prevalence, genetics Clinical signs & symptoms CHD-risk Lipids
I. HYPERCHOLESTERINEMIA (FH) PoHI f genet Test nötig! Risiko für FH
A) "common" polygenetic (IIa) ≈1/10,10% fam.,rez? Unspezifisch + TC&LDL-C  , TG n
B) mono-/[Link] (IIa, b) 1/500, aut-dom, compound heteroc. Xanthelasmen, Tendinöse Xanthome, ++++ LDL-C & TC   DG FH
- FH: LDL-Rez Defekt - >700 Mut Arcus cornealis va b Lp(a) altersabh<20 20-29 30-39 >40
- FDB: Fam Defct Apo-B100 - 1 Mut [Link] 1°pos FA 5.7 6.2 7.0 7.5
II. COMBINED HYPERLIPIDEMIA 1/200, ++ TG & Apo-B >1.2g/L & LDL-C
A) FCH (Fam. comb. H., IIb, IV) Aut-dom ApoB-overproduction A) Xanthelasm, Arcus cornealis
B) Remnant Disease 1/10’000, Aut-rez ApoE2/E2 (KK-pfl) B) Xant. striata palmarum +++ VLDL-Remnants (IDL)
(=FDL=fam. Dys-Lipoprotein, III) Genotyp v 1% d pop. only 5% of gene carriers are symptomatic TG/TC>1 & fluctuating
III. HYPERTRIGLYCERIDEMIA General: Eruptive xanthomas, - TC n-;
A) Fam. (IV, V: VLDL, V: Apo-CII) 1/500; GPIHBP1-defect? pankreatitis (esp. if TG>10 → many a)TG (CH mainly VLDL)
B) Chylomikron syndrome 2-4/Mio,? Chylomikrons) b)TG(Fat mainly Chylo)
(I, V: LPL or Apo-CII-defect) sec. causes & Tx psb frame (“aufrahmen”) at 4°C
IV. HYPO-LIPOPROTEINEMIA (autosomal-recessive) DD: Tangier, Fish eye, LCAT +++ / - HDL-C b n TG

B) SECONDARY (acquired); VP for DD: PG, TSH, LFT & Crea, urine status
- Metabolic Sy (p9), PG: IRLPLlipolysis circlating FFS hepat VLDL-prod/catabol.TG & ApoB & HDL, LDLTot→ ; HL small dense LDL, LDL
- C2/OH: TG in prim. hyperlipoprot, HDL () in healthy, Dx & Tx: abstinence (min. 2wk), drugs: TG: steroids, HAART (p27), unsel. -blocker,
diuretics, Tamoxifen ®, IFN, TG & TC: Immunsuppr. (CyA), olanzapin, Roacuttan ®, HDL : anabolic steroids, B-blocker
- Estrogens (high doses, pregnancy); TG & HDL-C; hypothyroidism (LDL-C, TC up to ~10 mM), cholestasis (TC 7-15 (-40) mM, LpX Tx: Quantalan, Colestipol;
nephropathy (TC 6-12 mM, TG n-5mM, LDL-C, w severe nephr. Sy TG), dialysis: TG, SIRS (Chol. (HDL), TG), HIV, anorexia LDL-C, parenteral
nutrition TG, myeloma: TC&TG , myeloprolif. Sy:TC, TG, Bexaroten (Targretin, revers., dsabh. RXR-Fct  i Hepatocyten) HGH-deficiency: TG ,Glycogenose 1 TG
DD Xanthoma with normal TC: -Sitosterolemia DG: sterols from plants , TH: Quantalan ®, Colestipol ®
Tx: Mediterranean diet olive oil, nuts, wine, fish, moderate amounts (red) meat & salt, <30% cal/d as Fett, <5% tot calories/d, saturated / trans-fatty acids; „non-fried“, fibres), u&o
«Functional Food»; coffee & chocolate; 2cvR  lipid screening  Tx-Ind & Target (mM) risk adapte 10J cvRisik (QRISK, AGLA, U-Prevent)
LDL-C: Statins: 5mg Crestor ® (FH)  10mg Sortis ® (Dm) 20mg Zocor ® (Dm; rel. CI: coradrone, verapamil, dilitazem, amlodipin)  40mg Selipran® (CKD)  80mg
Lescol ®), 10% cvRisik/mM LDL-C, LDL(ApoB)-target: <3 / 2.6 / 1.8 (<0.8g/l) / 1.4mM (<0.65g/l) (low / moderate / high /very high risk & sek. prophylaxis) SE: dose
dependent, 10% myalgias, 1% CK <10x, <1%o hepatopathies a/o rhabdomyolisis w crea (20% fatal; RF CYP3A4-inh. (e.g., cordarone, amlodipin, fluoxetine, fluconazol, Ritonavir
®, grapefruit), gemfibrozil, cyclosporin A, age >70yrs, CKD, LF); F/U: 0→3→6mthly,myalgias >3dCK <10x; LFT <3x; evtl & ezetimibe (Ezetrol & Atorvastatin (Atozet),
Ezetrol & Simvastin (Inegy), Statin-SE or failure to reach target values: retry after drug abstinence (1-3 Mon); Tx of other cvR!, bempedoic acid (Nilemdo®Tbl 180mg qd od Nustendi®
180/10mg qd), PCSK9-Inh. CH ≈5'000.-pa, Evolocumab (Repatha®, 140mg sc 2-wchtl. KK-Ind.) Alirocumab (Praluent®, 75-150mg sc 2-wchtl. KK-Ind.), siRNA Inclisiran (Leqvio 284mg 6mtl sc Ind: add-on/instead of v
Statin b LDL-C >1.8 sec. prevention >2.6 fam. hypercholest (prim & sec. prevention), Colestryramin (Quantalan ® 1-2Sachet in 2dl. BP)
TG >1.7mM - >10mM (Chylomicron Sy) PG: Dm derailment, C2, prim. hyper-TG, sacharose (softdrinks, also fructose i light beverages); pregnancy (E2), drugs sa,
SY: acute pancreatitis (amylase ev. falsely ), Microcirculatory dysfct (paresthesias, neuropsychiatric sy), eruptive xanthomas; (pseudo)-hyponatremia
Tx: Acute: Fasting! (NPO, nourishment/energy-, fat & C2-abstinence), LPL: Inf 40E Actrapid ad 1L Glc 20%/d & Fragmin 5000 sc qd, olezarsen?, plasmapheresis
Chronic: Weight & C2, nutr. fat (<30% fat (<25% of calories, 50% of which MCT )e.g., Ceres®, essent. FS, 1 Tbsp sunfloweroil), low-fat protein-suppliers), fast-acting CHO (if PG
initially insulin-therapy), Sport nutrition counselling!, Icosapent-ethyl (Vazkepa® Cps 2g BP Ind: PoHI Art. 71b required, TG>1.7mM under statins for patients after MI or very high cvR;),
Fenofibrates Lipanthyl Tbl 200M bzw. 267M qd, Orlistat (psb), TG>10mM: [Link]<15%, plozasiran (25 mg sc 3/12), olezarsen (80mg sc mthly), zodasiran (100mg 100mg sc)

Obesity ”Myths & Facts”, DEF: Overweight BMI > 25; obesity grade I >30; II >35; III>40 kg/m 2
Medical history Status: wt. course (Kind, 20j, SS, max., min., diets, target-wt), cvR (p7, waist circumference (F>88cm, M>102cm)), drugs
(antidepressives, neuroleptics, anticonvulsive), personality (Binge-Eating, EDNOS (eating disorders not otherwise specified), affective disorder, social stigmatization &
discrimination), meal-structure (food diary, or simpoler (follow-up) checklists what, how often?, eating- and exercise behavior) Perception
disorders:  kcal intake – demand (p14), low-fat protein sources; age >70yrs, chronic disease → consider sarcopenic obesity → SARC-F score
Complications: Dm &CVI 3x, CHD 2x (<65yrs), HFpEF, psycho-social challenges (incl. sexual dysfct), periop. risk, arthritis, carcinomas
Tx: only combination of behavioral changes, calory & excercise are successful long-term ! (leaflet)
NUTRITIONAL COUNSELLING (NC)! (tx concept (D), KEEA KSA & SZ, single- vs. group-tx. e.g., „BASEL“, Weight Watchers®), set realistic goals
300kcal/d  1kg/Mon; ab 3-5% wt → seconary complications) & no fashion diets „high protein low carb“ prob. long-term slightly more effective than „low fat“
1200-1600kcal fibres, fat-adapted, complex>simple CH, non-caloric „sweet“ drinks (KH kcal > need  fat burning = 0 für 3-4h & change from CH→Fett (0.5L Cola  10g Fett), <1200kcal diet only
exceptionally (e.g., preop); not long-term (deficiencies of Vit. & Ca2+, among others)
Psychiatr./psychosom. Tx of eating disorder & self-esteem (KEEA KSA & SZ, evtl. Fluoxetine (Fluctine®) Tbl. 20-60mg qd, Lurasidon (Latuda Tbl. 40, 80, 120mg, qd)
Semaglutide (Obesity: Wegovy ® 0.25-2.4mg PoHI dokumentiert Motivation Pat (500kcal/Diat, begeitende ERB, Aktivität) & % [Link] n 4 Mon (7% b BMI 35 bzw. 5% b BMI >30 /
>27 m Dm kg/m2 & 10 Mon (zusätzl. 5%), Dm 2: Ozempic 0.25-1mg s.c. wchtl. (0.4mg/d = 2.8mg/Wo s.c., po Rybelsus 3mg p.o; -15% kg, ; evtl f PoHI OGTT PG>11.2mM?
Liraglutide (Saxenda 0.5-3mg s.c.-> change to Wegowy ® use 50% of current Saxenda ® dosage), Retatrudie (Triple Glucagon-GIP-GLP-1 Agonist): up to 25% reduction of body weight
Orlistat (Xenical Tbl. 120mg bid-tid nach PoHI;, BMI>35 od >28kg/m2 b Dm2 & OAD, n 6Mt bw>10% , 5kg b Dm, HbA1c >0.5%↓; max. 2J. SE:Steatorrhoe,
Operation (Gastric Sleeve bei BMI >50-55 →) prox. laparascop. Roux-Y-Bypass), guidelines for interdiscpl. centers [Link]; careful pat.-
selection! (co-morbiditoes, rel CI TVT/LE, OSAS), Flyer bariatric surgery KEEA KSA
- Ind: KK-reimbursed BMI>35 (50)kg/m2 resp. 30-35 w Dm2 a 2 (1)yr failed cons. Tx & will f min 5yr follow-up (compliance-contract signed!)
- Präop. checklist pat-info & informed consentp,SMOB-consent
- Peri-/Postop.: prescriptions surgery KSA, dietary build-up p14; 10% acute compl. (postop. bleeding, obstruction, anastomotic insufficiency, arrhythmia, PE)
F/U: Nachsorge Bariatrie / Kurzdarm-Sy, Ernährung, GP recommendation, abd pain -> susp. of leakage (early postop) / Stenosis (2-3wk postop) / internal
hernia (months postop (pp)) / → surg. consult w ind for Esoph-GIT-passage w ICM resp. CT-abd a/o gastroscopy a 12-24mo Exercise (catabolism → muscle
loss), adjust / reduce Insulin/OAD, diuretika, antihypertensivs; Vit. & trace-elements. overview drugs Supradyn® Energy QD (overdos. Vit B6 → Migros Actilief all-
in-one®; underdos. Fe, Zn, Vit B12 → WLS forte® from G, Tardyferon® QD (evtl Ferinject® 200mg iv 6-12 mtl), Calcium 1.5g/d, K-citrate Tbl if hyperoxaluric; if deficient: Vit.B12
Amino®1000ug 3-1mothly sc / Vitarubin oral or Vit B12 Ankermann po qd, Vit.D® 0.3ME [Link], Folvite® 1mg QD, Zink Burgerstein® 30mg QD-qid, copper; Vit.A (-caroten Carotaben® Tbl. 25mg
qd – BP in pregnancy (not teratogenic); evtl. Burgerstein (CH) or Jenapharm (D) 20 do 100 Cps à 30’000E; Vit. A Amp i.m (D), contraception!)
Challenges: patient satisfaction → surg. re-evaluation if EWL<50%, evtl. GLP-1 analogues (Saxenda 3mg/d, CHF ≈ 500.-/kg pa, PoHI (Art 71, template GLP-1 LUKS);
Ind: wt. gain & high surg. risk, (late) dumping → Tx: NC, SGLT-2 Inh (p9), other Hypo-Tx (p10), MECCO-Study (LUKS)? diarrhoea: Loperamid, Tinctura opii 2% Trpf,
rarely Octreotid s.c. (>3L Fl/d loss), Amitryptillin; fatty stools Creon® Cps tid, gall-stone risk ursodesoxycholic acid (Ursofalk®, Ursochol® 1-2 Tbl. 500mg qd),
nephrolithiasis (hyperoxaluria, esp. dist. Bypass u biliodigest. anastomosis; Tx. nutrional-oxalate u Ca, Urocit® 1-2 Tbl. z. Mz), bacterial overgrowth w (foul)
flatulence → Perenterol®, Metronidazol (Flagyl® Tbl. 500mg tid x 10d), Rifaximin (Xifaxan Tbl. 550mg x 2/52, PoHI) postop. osteoporosis: Ca, Vit D, protein requirement,
reflux (20% n sleeve): PPI; «abd. pain» DD demasierte Porphyrie: PPI; OAC: Marcoumar accord. Q > NOAC (apixaban Eliquis® Tbl.5mg BP?) ; dermatochalasis & lipedema w pain →
plast. surgery.!, Vit.B6-intox (Norm: 35-110nM; Sy: parästhesia, neurol. sy), addiction shifts, avoid postop pregnancy 1-2yrs due to catabolic state, oral
contraception unreliable (esp. after biliopancr. diversion)

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 16. Bone & Calcium Metabolism
Aging is inevitable...maturity is optional.
Calcium calculator, [Link]
Ca-requirement/d: 0.8-1.2g; Ca/L; milk  1g, mineral water: Valser/Eptinger  500mg, „H2O“  50-100mg, Ca-questionnaire MD & Pat
Osteoporosis Lifetime risk f osteop.-fracture (Fx): F 40%>M 15%  2% healthcosts, doubling of overall mortality risk after osteoporotic fracture
DG: pathol. Fx (inadeq. trauma, Grö>3cm, back pain)Rx thoracic/lumbar spine ap/lat (Rx w/o trauma F>65yr & T-score<-1; F (&M) >70J T-score <-
2.5; F/U only lat.), szintigraphy (Susp. tu), whole-bodey CT/ MRI (myeloma?)
Risk factors (RF) F>80% prim (5-10j postmenop); M>50% sec; Fx-Risiko>2): I) History: steroids/T4 (BMD -1SD=10%/J),
hypogonad.(<40yr, >6mo 1-2%/J), age (1%/J, F>50J, M>70J), FHx (peak bone mass (20-40j) = 70% genetic), immobilty, malnutrition (bariatric Sx, veganism),
CKD, BMI<18, OH, Vit. D, Hcy, pHpt, smoking, antiepileptics, glitazones, acidosis, rheum. arthritis, hepatopathy, IBD, mastozytosis, cystic fibrosis
II) Densitometry (DXA femur, lumbar 1-4; Ind: Dg, stop Tx, Fx, <-2SD → look for sec. cause; F/U. after 2 (high risk) – 15yrs (low-risk)
Z-score (age-adapted) f premenop. F u M<50J, else T-score -1SD  Fx-risk 2x (Hip) - 1.5x (WS); -3.7SD  37% bone-mass↓, trab. bone score w steroid
T-score <-2.5: ”osteoporosis”-> Tx if Fx-risk (psb), BMD-F/U 2yr; <-1: "osteopenia" BMD-F/U. 2-5yr, Ca&VitD; Fx-riskTh; >-1: ”normal”
PoHI Steroide >3Mon, chron malnutrition, hypogonad.(F nur <40j), pHpt f Sx-Ind, Fx b inadeqate trauma („fall from standing“) trauma, Th-Verlauf n 2J, T-score <-2.5;
no PoHI: postmenop, pos FHx, organ-Tx, clin a/o radiol susp. of osteoporosis (sa)
III) Turnover(esp. trabec. bone, for Tx-F/U, fast., [Link] urine, low protein diet) formation: (bone-specific.) [Link] (>50%Osteocalcin) ,P1NP (N-terminal
Typ I procollagen degradation: C-terminal crosslinks (CTx) i P or U (fast., 2h morning urine), no meat prior meal; IV) bone biopsy if susp. of renal a/o metabol. bone disease
- VP diff. blood count, BSR (b CRP<5mg/l), chemogr (Crea, SGOT, Prot, Ca, PO4, [Link] ), TSH, testo/E2, 25-OH-Vit D, evtl Mg, iPTH,
U-Ca/Crea, U-PO4/Crea, 24h-FUC, S & U-protein-immunelectrophoresis, Tryptase v Vd a Mastocytose
TH: Fall prophylaxis! (sedatives, BP-Tx, orthostasis, visus, tripping hazards (carpets, cabels, nightlight), hip-protector, training, Fracture Liaison Service (FLS)
- Nutrition (1g Ca2+/d)  Calcium (if diet <800mg/d (Ca-questionnaire) med. Diet a/o dairy (soy) products, K-Citrat Eff. 30mval BP, Vit D (Ind: winter?, 25OH-Vit
D<75-125nM?, Ds: 800-1500E/d (ViDe3 8-15Trpf/d, Vit D3 Streuli® 0.3ME ½ Amp 3-6mtl po/im); GFR <30ml/’  Rocalctrol Cps 0.25-0.5ug 1-2x/d, b art. Hypertonie: Thiazide)
- Fx-risk „Frax-Score“ a) T-score (-1SDFx-risk x2), b) RF (sex, age, steroid-tx>1-3mo ([Link], DXA >40yrs & RF, earlier Fx, low
BMI, bone-turnover (Fx-risk x2) → medication dependent of Fx-risik (SVGO 2021)
a) Antiresorptive Tx Ind: from moderate Fx-risk 10% (F> 50J., M >70J) to severe risk 50% (100J.)
- Bisphosphonate BMD <2.5%/J ≈ CHF 400.- pa, Tx-pause a 3-7yrs? (BMD T-score >-2.5, Rx lumbar - no Fx?) CI: Reflux (PPI or iv), GFR<30ml/’, cave
dentist (1/10’000Kiefer-Osteonekrose RF: iv, Dm, steroids), inflam. eye disease, AFib?: alendronate (Fosamax®) Tbl 70mg/wk, isredronate (Actonel®) Tbl 35mg/wk ibandronate
(Bonviva®) Tbl 150mg/Mon, 3mg iv, zoledronat (Aclasta) 5mg short inf.. every 18 (12-24) mo. if GFR >50ml/’;
- Denosumab (Prolia® 60mg sc 6mothl. x 5-10yrs, ≈ CHF 600.- pa) Ind: postmenop. T<-2.5; mamma-Ca w aromataseinh. resp. prostate-Ca w hormoneablation &
Frax, SE: hypocalcemie; infections (HWI, LRTI), limb paints, atyp. Femur-Fx, longterm?? After stop: bisphosphonatse f 1-2yrs due to osteoclast rebound!
- HRT/Testo DXA 1-2%/yr; SERM Ind: Menop. >2-5yrs a/o mamma-Ca kisk raloxifen (Evista® Tbl 60mg qd, bazdoxifen (Conbriza Tbl. 20mg qd) Ind: prophyl.
if RF+T-score <-1.5); only spine-Fx → evtl comb. w Fosamax); Tibolon (Livial Tbl 2.5mg qd, ab 1J postmenop., p17), SE: postemenop.. sy., TVT, CVI?

b) Bone-anabolic Tx Ind: very high / imminent Fx-risk (e.g., first 2yrs a osteoporot. Fx) w PoHI also as first-line Tx
- Teriparatid (Teriparatid Mepha®, Terrosa®, Movymia®, (Forsteo® 50% more expensive) amp 750ug/3ml; 20ug/400U sc/d x24mo, sequential antiresorpt. Tx; Ca-F/U, Dexa
7%/yr Ind: Fx during Tx w bisphosphonates (PoHI)
- Romosozumab (Evenity®, sclerostin-inh.) 2x105mg sc motly. x 12mo → denosumab 12Mo. → bisphosphonate x 2-5yrs Ind: ”major osteoporotic Fx” (MOF; spine,
hip, pelvis, humerus) + T-score <3.5 (lumbar spine or hip) or 2xMOF or SVGO 2000 very high risk. SE: Hypo-Ca; CI: KHK, CVI, cvRisk?

Hypercalcemia (Prvalence 2%, usually asymptomatic, evtl depr., ment. sy, polyuria, nephrolith., CKD); "Crisis" Ca>3.5 (psychiatr.→coma)
DD: pHpt (outpatients) > Tu (inpatients, mamma & lung (PTHrP), plasmocyt.) > CKD & Thiazides, ”Renni” >1,25Vit D &A, Li (p28) > immob., rhabdomyolysis,
sarcoidosis (granulomatöse Infl., also extrapulmonal) > FHH (Familial Hypocalciuric Hypercalcemie: pos FHx (loss of function mut. calcium-sens.-rec. (CASR)-Gen), young, U-Ca
[Ca/Crea clearance ratio = Fractional Excretion (FE) Ca <1% = <0.01: fast. 2nd Spot- U-Ca × P-Crea / P-Ca × U-Crea, UCrea >10mM, else FE-Ca falsely low; DD: CKD, Vit D deficiency], no Tx) > T4, M. Addison
TH: NaCl 0.9% 500ml/h iv (& furosemide Lasix 40mg iv 6h in CHF or CKD), bisphosphonate (e.g., Zometa® 4mg iv over 30min if Cl-Crea >30ml/’,
else Xgeva 120mg sc), CT (Miacalcic 10E/kg bw sc od iv x48h (tachphylaxia), Ketokonazol (250mg tid - qd), Prednisone (0.5mg/kg), dialysis
prim. Hyperparathyreoidism 1 adenoma 75% > 2-5 adenomas 15% > hyperplasia 10% (RF: CKD u. MEN, p22) > Li DD: FHH (sa)
DG: >2x P-Ca(evtl. upper norm); P-PO4, Mg (), U-Ca/Crea (RF:CKD!) , U-PO4/Crea; PTH n- (>25pg/ml); Crea, 25-Vit. D
- DXA (radius & spine & hip); Ca ()  Ca-challenge 1g Ca po (effervescent tbl.) PTH basal & 2h (norm: >50%)
- Local.: US (80/90%, round/oval, hypoechogenic, posterior / at pole ofThy, sharp edge w vessels) → Sestamibi Szinti (70% (Cinacalcet)/90%) → 18F-Cholin
PET/CT → NSD-Punktion
TH: drugs bisphosphonate, (thiazides?), cinacalcet (Cinacalcet Devatis® / Mimpara Tbl. 30→60mg po BP→qid) SE: nausea, Ca2+  Ca & Vit D subst.)
Phosphate sirup KSA 500ml 10mmol=15ml tid od Phoscap Bichsel® 5 Cps à 100mg=3mmol qid, NO Thiazides F/U: P-Ca2 & PO4, Crea, DXA, vs Sx typ.
adenoma, <50yrs, P- Ca>2.9mM; T-score <-2.5 (any site), GFR<60ml/’ od 30%, local. w intraop. PTH? Evtl. “Cinacalcet Trial” to test effect on
symptoms Cave: preop Ca & alk. phosp  postop hungry bone: postop severe tetanic cramps w P-Ca, Mg & PO4)

Hypocalcemia
DD: PTH (postop PTH<10pg/mL, Thy/pHpt, AUI), Vit D, Mg, alkalosis >hypercalciuric Hypocaleämia (n U-Ca/U-Cr!) > genet. (AUI, Pseudo-Hypo-PTH, Barakt Sy (PTH, deafnes, CKD)
SY: acute: paresthesias (perioral, akres)  tetanus (Chvostek, Trousseau)  laryngospasm, cv compl., epilepsie; chron: cktod. dystrophy (skin, cataract, hair, nails)
TH: Calcium 20ml (=1880mg) calciumgluconat or Ca-Glubionat (4.4mmol = 180mg Ca2+) x 10' iv bolus followed by 0.5-1.5mg Ca2+/kg/h i Glc 5% iv or 1-2g po tid to meals, Ca-citrate if PPI a/o
nephrolithiasis, P-Ca target 2.1-2.3mM; Mg-Oxid sachets, <0.5mM2ml 50% (=1g) iv, Ca a/o Mg NEVER i PO4-solution, Calcitriol (1,25-OH2-Vit D = Rocaltrol 0.25-1,5ug BP x 2/12), paricalcitol
(Zemplar® Tbl. 1-2ug s.c.)  Vit D ViDe3 (50000 x 1wk → 1000E qd po) or Dihydrotachysterol = Alphacalcidol (1-Hydroxy-Vit-D Analogon, hepat. 25-hydroxil. needed, A.T.-10® 10Trpf  0.25ug – 3ug/d
Rocaltrol, longer T1/2), Yorvipath (18ug qd sc, Ind: renal insufficiency, P-PO4 a/o U-Ca, PoHI m KV71 HMG), nutritional counselling, evtl. thiazid trial w K-monitoring

Osteomalacia / sec. Hpt: often asympt., bone pains, osteoporosis, sy of malabsorption., PO4 (b CKD), alk. phosph
DD: VitD (25-VitD ab <75nM, outdoor <1x/d), GIT, LF, CKD, Medi (PO4: antiepilept;antacids, Ferinject®) > FGF-23 (P-PO4, FE-PO4; DD: genet.
(FA?), mesenchym. tu Dg: PET (FDG -> octreotide) Tx: Phosphat p.o., Rocaltrol, evtl. burosomab (FGF23-Ak)) > NaCl rich diet (U-NaCa-CotrspU-Ca Ca-loss) > Vit
D dependent rickets (VDDR I, II, x-linked) > Fanconi Sy
TH: Ca, PO4 & Vit D (evtl. Rocaltrol®), Dialysis: CaCO3 Tbl à 0.5g 1-4 to meals & Rocaltrol 0.125-0.5mg qd, S-PTH>500-1000Sx (Paracalcitol, Cinacalcet),

Heterotopic Ossification: NSAID, Radiotx, evtl zoledronate (Aclasta) 5mg short infusion., F/U: Ca, PO4, crea BP -2d; evtl Ca iv
M Paget: 50% bone pain/deform (pelvisfFemur>tibial>skull>spine), alk. phosszintiRx; Sz-Tx: bisphosphonates x 2-6/12 (CT 100E nas BP)
”CRPS” M Sudeck/Charcot Dg: si&sy! Rx/MRI Tx: Ergo/Physio-Tx, zoledronate (Aclasta) 5mg Kurzinf. Vit C prophyl. 500mg BP x3/12, Pred 0.5mg/kg x 6/52, taper

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 17. Female Gonads
„Ich weiss es nicht!“ Sigmund Freud replied to the question „Wie versteht Mann die Frau?“
Update AKB, SMF 17; 17: 284-90
DEF: Metrorrhagia: bleeding outside menses OGYN., Hypermenorrhea: heavy menstrual bleeding (Hb); Polymenorrhea: cycle <21d;
Oligomenorrhea: rare, irregular. menses, cycle >35d; prevalence cycle disorders 2-3%

Amenorrhea
1°: no menarche 15LY (norm 12.5LY, FHx?, to be diagnosed from 13LY, telarche/pubarche <14LJ, (norm10.5LY)) DD: gonadal dysgenesis/Turner-Sy (Checkliste D; I; F); --> karyotype;
2°: no menses >3 (if before regular mens. cycle) – 6mo (if before irregular mens. cycles)
DD: Exclude pregnancy/lactation, Hyperandrogenemia (PCO; CAH; NCCAH (psb); TU (NNR: DHEAS, Ovar: Testo>5nM, AFP, US),
Cushing-Sy; hyperthekosis; genital causes (Curettage (Asherman-Sy), Tbc, Müller-Duct-abnormalities), Hypogonadism DD
1° ovarial: E2, FSH DD ”POI“ (primary ovarian insufficiency) = Menop <40j, DDD: AUI (p22), Turner/fragile X-chromosome, post-radiatio/chemotx
2° pituitary: E2, FSH DD „post-pill“, PRL; TSH /, Hypopituitarism (→ p23); genet. Sy (Mutation GnRH (w. anosmia →Kallmann-Sy), Pit1, Prop1 → genetic)
3° Hypothalamic: E2, LH, FSH, LH/FSH<1 DD female athletes triad (sport / stress / anorexia) / co-morbidity (liver / CKD / derailed Dm)
DG: Hx (FHx, BMI, sports, ”stress”, co-morb., drugs), galactorrhea, Tanner stage, androgenization (psb) → -HCG i.U.
 VP d3 (-d5, follicular phase) if cyclic resp. after gestagens): E2, FSH, (LH), SHBG, testosterone, PRL, TSH, fT4, chemogram; densitometry
evtl. gestagentest: Duphaston® Tbl 10mg BP x10d  bleeding after 2-10d = pos.: → functional endometrium, enough E2, intact anatom. structures (in F <40LY often false pos) DD: FSH:
POF (Ovarialreserve?--> AMH); XO/XX (Turner-Mosaik), 46 XY (Swyer-Sy); FSH→: PCO, pituitary, neg.: postmenopausal (>45LY FSH,>1J. A.), ovarial dysplasia; oestrogen-Gestagentest: pos: --> functioinal endometrium → DD: pituitary, fct.
Regulation disorder; neg: endometrium (sa), Androgen-Insensitivity-Sy

Tx: causal (Lifestyle!, consult OBGYN, principles) a) premenopause< 45-50LY → Goal: regular bleeding + estrogensubst.; oral
contraceptive (OC) e.g., Minulet (30ug Ethinyl (E)-E2, 75ug Gestogen), Mercilon (20ug E-E2, 0.15 Deogestrel), Yasmin (E-E2 30ug, Drospirenon 3mg),
Diane 35/Ellacnelle/Cypresta 35/Cyprelle 35/Holygerne (E-E2 35ug, CPA 2mg); HRT Cyclacur, Trisequens N, CyloPremella …Tbl, Estragest Pfl x21d, Progynova Tbl 0.625 (-
desire for children & sec. hypogon: GnRH-pump resp.. gonadotropines, desire to have children & anov.
1.25)mg/d & Duphaston 10mg x 10d/(-3)Mon,
cycles: clomifen, metformin (off Label): reversible, evtl. Kisspeptin? b) Menopausal hormone tx «MHT». <60LY or <10Y since onset
menopause Pat. Info! Benefit: flush↓, osteoporosis↓, colon-CA↓ vs Risk: mamma-CA (5Y-Risk<1.67%: ok; >5%: no) , TVT, cv-10J.-Risiko (<5% ok;
>10% n); Migräne ”early” cykl./HRT (sa); late: “Continuous-combined” Femoston conti  (Dydrogesteron + Estradiol); Estradot Pfl & Duphaston
(dydrogesteron) /Utrogestan (mikron. progesteron), Estalis Pfl (norethisteron + estrogen) E2-subst. Tibolon (Livial Tbl 2.5mg, from 1Y pmp w climact. sy, advantages:
vag. bleeding, libido, coagulation not affected; CI: endometrium-Ca, HDL-C); raloxifene (Evista Tbl 60mg qd, >55LY or menop. >2-5y w flushes, osteoporosis
p16); „Flushes“ E2 (sa), SSRI e.g., Citalopram Tbl. 10-20mg qd or Efexor ret Tbl. 75 – 150mg qd x4/52, ≈50% [Link]; SE: nausea, constip.), megestrol
(Megetstat Tbl 40mg qd, SE: endometrium-Ca, TVT, spotting, clonidine 0.1mg/d, increase (SE: dry mouth, consitpation); gabapentin 300mg tid, 30% Sy. red.,
SE: fatigue Post-hysterektomy only E2: Estradot Pfl. 50-100ug 2-3x/wk; Progynova (Tbl 2mg E2-valerat qd TG&HDL)

Hyperandrogenism Androgenes = Testo+ Androstendion + DHEA(S); 98% bound to SHBG & albumin
DEF Hyperandrogenemia: Androgenes↑; Hyperandrogenism: Androgenes↑ & symptoms (acne, hirsutism, alopecia); Hirsutism: 5% d. ♀, androgen-dep.
areas; Hypertrichosis: hair growth↑ w/o male distribution pattern Virilisization: marked masculinization (hirsutism, alopecia, low voice, clitoris↑)
Hirsutism: Hirsutometry > 7 Pts (subjective suffering!); DD: PCO (+/- obesity); idiopathic (hirsutometry < 15pts, menses ok, n androgens); drugs
(Partner w transderm. Testo, anabolics, steroids),
Hypertrichosis: DD: hereditary, drugs (cyclosporin, phenytoin, minoxidil), reactive / local after Lastertx or elektrolysis
Hyperandrogenism: DD Ovary (PCO (75%), TU (testo > 5 nM, <0.2%), HAIRAN; SS; pmp. algorithm); adrenal cortex ((NC)CAH (<5%), TU (DHEA-S↑, cortisol↑)
DG (d3): Testo, SHBG, 17-OHP, androstendione & DHEA-S (if (↑): LDDST, n androgenes 50%), 250ug ACTH-Test (17-OHP & cortisol)
TH OC w antiandr. gestagens (30-35ug ethinylestradiol (E2) + cyproteronacetate or drospirenon); after 40LY max. 20ug E2), e.g., Diane 35/Elleacnelle,
Cypestra35, Cyprelle35, Yasmin; evtl. + antiandrogens all CI in pregnancy; always conception! Tx success only after 6-12 mo (≈ 30%↓ hair growth).
cyproteron = Androcur® 10-50mg (d1-15) SE: libido↓; wt↑, thrombembolism; OFF-Label: spironolactone (Aldactone® 50-200mg/d) SE thrombembolism!,
Finasterid (Proscar® 2.5--> 5mg, PoHI!) Cosmetic: Epilation, Laser/electrolysis (sclerotherapy of the hair follicles; SE: burning, depigmentation), eflornithin
cream 11.5% bid (Vaniqa®, not reimbursed, CHF 150/2Mt).

Polycystic Ovary Syndrome (PCOS) = «Metabolic Reproductive Sy» Checklist D; F rule-out dg →DD
DG 1) Irregular cycles & 2) Hyperandrogenism (hirsutism, acne, alopecia, androgenes); if only 1) or 2) present → 3) US: Polycystic Ovaries (Hyperstimulation: min
1 ovary w >12 follicles 2-9 mm diameter, min 1 ovary > 10 ml) or AMH (su). PG: disturbed steroid synth. in ovary & adrenal, insulinresist.
Co-morbidities: (Obesity (30% MAFLD (GOT/GPT/yGT), HbA1c 3-yrly (10% Type 2 Dm), BP, Lipid, OSAS, Depression, Anxiety disorders →GP), RF f. endometrium-CA
B LH> FSH, SHBG↓, testo(↑); PRL, TSH, β-HCG; AMH( Anti-Müllerian Hormone, dependent on age (peak 20-25LY), BMI (lower if BMI higher), OC (stop for 3mo), cycle day (population specific cut-off) ); IGF-1
DD NCCAH (17OHP basal > 6nM, stim. >30nM), adrenal-/ovarial-TU (US; Testo>6nM, DHEA-S> 16M)
TH wt↓; drugs all off label. Hirsutism +/- irregular cycles: 1st line: OC with lowest effective estrogen dose, laser & light therapies; 2nd line
(after 6mt): Anti-Androgens with effective contraception (sa, IUP (Mirena ®)); 2nd line: Metformin alone in BMI > 25 kg/m2 for metabol. indication (combination
OC + Metf. with little additional clinical benefit), GLP-1, bariatric surgery, Inositol? Infertility treatment: (metformin&) ovulation induction Letrozole 2.5mg qd, Clomiphene citrate
(Serophene); Gonadotropins, in vitro fertilization; Folvite 1mg qd FertIL-Studie

Congenitale Adrenal Hyperplasia (CAH) = Adrenogenital Sy (AGS) (Pat. Info)

PG 90% heterologus recombination CYP21A2→A1Pseudo 21-Hydroxylase  cortisol (u aldosterone)ACTHadrenal-hyperplasia a androgens
Prevalence 1/100, aut-rec carrier 1/25, „NCCAH” = non-classical CAH (“late onset AGS”) M: „Pubertas präcox“, F:“juveniles PCO“ & growth or asympt.
DG 17OH-Prog basal d3 (FP & “Pille”>LP), 08h (ACTH) > 20h), n<6nm, AGS >30nM; 6-30nM  60’ a 250ug ACTH-Test heterozygous: > 30-50;
homozygous non-classical: < 300 / 500; class.: >300 / 500nM, cortisol „subnormal increase“ → Gene test (PoHI, DNA asserv. b VP) Genotype does not speak
phenotype; Compound Heterozygous: Phenotype correlates better w mild mutations; Heterozygous: increased 17 OHP levels after stimulation, can be
asympt., (Pediatry: 21-Hydroxyl.: 1/14‘000→ 2/3 classical (F-Baby: Virilis.+Salt-waste+Addison n 1-2Wo) od 1/3 „simple virilizing“(less pronounced enzyme defect), Dg: 17-OH-Progest 2-3d at brith >300nM (n<3,
preterm Babies ) Tx: Dex 0.5mg/d i SS; 11-Hydroxyl.: 1/100‘000 ; virilizing+“mineralocorticoid excess“ (DOC), Dg: DOC (& comp.S)  >435 nM 30‘ n. 250ug ACTH iv; PRA  upright)
TH interdisciplinary w Pediatrics / OBGYN! CAH: Stressprophylaxis! Florinef® 0.05-0.2mg (Goal aPR, Elyte, RR n) Children: Cortisol 5-10mg tid,
Florinef 0.1mg ½-2/d), Adults: Prednison/Prednisolon 0.5-2mg bedtime, evtl. HC daytime; OC w antiandr. gestagens NCCAH: adults: OC mit
antiandr. Gestagens, evtl. dexamethasone 0.25mg every 2.d (only short-term! cave bone), Efmody (Chronocort ®, EU, with inscurance’s cost approv., Ds: 1/3 – 0 – 2/3, Crinecerfont to reduce GC-dose to
8-10mg/d
Pränatal/pregnancy: Genetic! if pos SS-Test Dex 20ug/kg v BR (if ♀Foetus!) Goal: 17OHP & Testo n placental passage; if both parents aut rec carriers → only
1/8 fetuses at risk (♀), 7/8 no risk; Monitoring: cave: androgen excess vs. Cushing-SE of steroid-tx! BMI, RR / pulse, hypercortisolism) ♂: TART
(palpation/US)? ♀ Hyperandrogenism? (17OHP) androstendion no → overtreatment; DHEAS↑→ undertreatment; androstendione: Testo (AD/T-Ratio):
AD/T > 4 if ♀or AD/T >1 if ♂ + LH, FSH ↓↓ → adrenal Hyperandrogenemia; progesterone if ♀ with desire for children < 2 mmol/l; normal spermiogram--> good
tx control (stays impaired yrs after poor control)
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 18. Male Gonads
With testosterone, every human being understands, acts, and looks like a man

Production/d (% testicular/adrenal): 4 (old) - 8 (young) mg testosteron (95/5%) > 10ug estradiol (15/85%) > 2ug estron (5/95%)

Hypogonadism Total testosteron  (TT, age-dependent <6-12nM) u/o spermiogenesis (psb)

DG: Libido u/o erection (morning, LSI, IIEF15), energy, sports / power / endurance, work, size, depression, sleepiness
- Sec. sexual hair, shaving<1x/d, testicular vol., muscle, gynoid fat, infertility, gynecomastia, osteoporosis
- prepubertal: eunuchoid., tall stature, high voice, no beard growth, female pubescence, infantile genitalia & small prostate
- BT 08h: tot. testosterone (evtl. 2x, shift worker), SHBG, LH, FSH, E2, PRL, red BC (Hk), iron status, PG, Alk. Phos., Pyr/Crea iU, Dexa
TT 8-12nM & SHBG → calc FT? [Link]/[Link] age, antiepileptics /steroids, dysthyroidism; cirrhosis (SHBG: obesity, androgen., acromegaly)

A) primary LH bzw FSH >10mU/l, LH or FSH peak n. GnRH >30mU/L

Testes orchidometer, < 12-15ml (4.5x2.5cm) DD: Klinefelter Sy (80% XXY, evtl mosaic, XX-males (translocation Y on X) eunuchoid [i.e., testes
size 10ml, long legs, „arm span“ 5cm > size, gynoid]. Pubertas tarda, infertil, gynecomastia, low social class, tendency for thrombosis, psych. disorder, epiliepsy,
metabol sy, [Link]); cryptorchidism, orchitis, chemotherapy, trauma, radiotherapy, idiop.
DG: karyotypising, US-testes (if conspicuous palpation) & evtl biopsy (ad urology), spermiogramm (psb)
evtl HCG-Test (5000E Choriomon® x d1-3 imTT d1&4, E2 d1&2 in the morning;, TT 1.5-2.5x, E2: 2.3-2.9x) Ind: „testikular reserve“, e.g. bonderline low testosteron and DD prim / sec

B) secondary/tertiary FSH & LH→ (typ. <5 (<10) mU/l), LHpeak a GnRH <15mU/L (or FSHpeak n GnRH <10mU/L)
DD: PRL, hypopituitarism (p23), obesity (BMI>40m/kg2 (>35: tot testo & SHBG, (calc) fTesto n), co-morbidites, stress, morphine, male
athlete triad» (excessive training, malnutrition, eating disorder); idiop., CAH (p17), isolated GnRH deficiency (Kallmann-Sy 60% (Anosmie HNO [Link]) normoosmic variant 40%), genet.
Testing., substiutionsth, 1x therapy breakt as reversible in 10-15%)), Prader-Willy-Sy, Bardet-Biedel-Sy, Laurence Moon Biedel Sy

DG: MRI sella (with and without contrast i coronary a sagittal fine layering; resolution b 3mm)
GnRH-test (100ug GnRH iv 09Uhr: LH & FSH 0', 30', 60’) DD: PADAM (see below): peak LH >15mU/L (100%/70%)
C) combined
DD: Co-morbidity (metabol. sy, critical illness/HIV, CKD, LF, Dm, hemochromastosis), noxae (C2, opiates), medication
(steroids, aldactone, anabolic steroids → psychosom. care [Link]@[Link]), „PADAM“ (“partial androgen deficiency of the aging male” =
climacterium virile=”LOH” late onset hypogonadism) PG: inactive GnRH(?), SHBGfT, > 3 sy & tot. testo < age-adapted reference value (p30) &
symptoms
Tx: PoHI, evtl. 3-6 mo trial if symptomatic & T 8-11nM, cave prolonged post-trial hypogonadism, met. Sy -> first, try loosing wt, wait 6mo after CV event,
rel. KI: TVT & PE, T-undecanoat Nebido® 4ml à 1000mg, ½-1 amp slowly i.m. 0, 6, 12 Wo 10-14wkly), T-enantat (Testoviron depot®125-250mg 2-4wkly im),
unesterified T (Tostran®, Testavan®, 25-100mg 4-8 strokes KK-Ind OAK m Xarelto n HMG-71; KK-Probleme: T-propionat (magistralrep) 2(-5)g ad
100g Nivea cream or Excipial mfu (= misce fiat unguentum), 25-50 mg qd = 1.25 - 2.5 g ointment w measuring spoon, cave exposure to partner & child!; SE & CI:
OSAS/HF, Hk>52, desire to have children (→Kryodepot), libido & aggression, BPH no absol. contraindication (DRU, micturition, incontinence) & Ca? (PSA>4ng/mL),
HDL-C (cvR & ergometry?), Hyperestrogenemia? -> VTE/LE-risk -> aromatase inhibitor (Aromasin®)
F/U (0  3  6-12 mthly): prostate (sa), gynecomastia, BT: BC, liver/lipd value, PSA (<4ng/ml >60j od <2.6; bzw.< 0.4/J)
Erect. dysfct: Viagra, Levitra, Spedra (about 50% effective), „active“ vacuum pump, intrapen. inj. (caverject ®), urolog. a. angiol. Abkl. w cvR , “Post-Finasterid-Syndrom”?

DD: org (T, Dm, co-morb), medi (BP, noxae, beer before LSI!), urogenital sy/trauma, psychosocial (marriage (miss vs mistress), stress)

Gynecomastia DEF: „Tanner“ >2, i.e., gland.>2cm or > than areola, often asymmetric, mild forms frequent!
(„Tanner“ 1: gland<areola; 2: gland>areola; 3: gland>>areola; 4: areola on gland; 5: flat areola)
DG: - palpation, US breast (consult OBGYN) & testes (consult urology), evtl mammography
- BT (per DD): tot. testosteron, SHBG, estradiol, estron, LH, FSH, HCG, AFP, TSH, PRL, chemogramm
DD: adipomastia (pseudogynecoomastia): fat, small gland, e2/testo-ratio(often bilat.) puberty & senium
(prävlence 30-50%), obesity (aromatasee2) > HIV, cachexia / refeeding; testo: hypogonadismus (sa, higher ca-risk in Klinefelter), renal
insuff.; cirrhosis e2: Tu (testicular HCG or E2 (Leydig (E2FSH/T ), Sertoli cells (AFP & HCG), hyperthyreoidism (Aromatoase & SHBG) Drugs:
aldactone (10-25%; 100% >100mg/d), antiandrogen (Casodex 50% >Zoladex 25%>orchiectomy10% ), HAART, anabolics (DHEA), lithium (clearance of
androgen precursors Aromatase E2), ketokonazol, tricyclics, benzo, neuroleptics (except leponex), digoxin, phenytoin, INH, amiodaron, ACEI, Ca-
antag (Nifedipin>Diltiazem), cytostatics, D-penicillamin, H2/HCL-blocker, hair water with e2, aso, noxae (OH, opiates, Cannabis); idiopathic (25%, increased
conversion testo to E2 in fat?, affinity to SHBG Testo>E2)
TH: reassure pat. (40-80% spontaneous regression., bilat no precancer, unilatmammogr.& FNA w. XXY), evtl stop drugs/noxae (sa)
- <1-2Y ( „acute“, reversible), w pain/stress: Tamoxifen(10mg BP x3-6/12 transient effect), anastrozol (Arimidex Tbl 1mg qd)
- >1-2Y („chronic", fibrosing) or Tanner stage >3, usually irreversible, watchful waiting vs surgery (liposuction vs exzision)
Prophylaxis: prostate-Ca Th up to 50% (sa) → low dose bilat. radiatio (12-15 Gy one fraction vs over 3d)

Infertility (i.e. no pregnancy despite 12mo of unprotected & regular LSI; 10-20% of couples; DD: M 20%, F 38%, idiop.
DG: testo, SHBG, LH, FSH, HIV, chlamydia, hepatitis C & B, VDRL&TPHA, consult urology (varikozele?), Spermiogramm (USB) Proc:
abstinence >48h & < 7dvial to EndoMasturb. (@home) within 1h UFK, min. 2x zw. 7Wo-3 Mon. No: vol 1.5-5ml, >15Mio/ml >39Mio spermia per ejaculate
(<5Mio/ejaculate → genet. testng, >15% morphology, >58% vital; >50% motil, ; % IVF-fertility w % motility 83% at >14%; 63% at 4-14%; 8% b <4%
Femal Infertility → consult OBGYN reproductive division
TH: Gondotropin: a) human: hCG (Choriomon 1500U 3x/wk sc; Pregnyl ® 1500U 3x/wk sc: Merional 150U 3x/wk sc) x4-8wk, followed by combination w b) rFSH
(Puregon®, Gonal-f ®, Ovaleap ®, LH (Luveris 75, cheaper); after pretx w hCG, in combination w hCG, mostly 3x150U/wk sc, rarely GnRH-w insulinpump (Zyklomat Pulse Set ®

sc 2stdl 20ug w 3° hypogonadism  a 3-12mo Re-spermiogram  „via naturalis“; evtl ICSI, before all Tx need to get PoHI!

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 19. Hypothyroidism & Radioiodine
In subclinical hypothyroidism, absence of evidence does not mean evidence of absence…rather absence of funding

Jodid (J-)-requirement:100 (children), 150 (adult), -250 (pregnancy & lactation) ug/d; to plummer: >500ug/d acutely inhibit Thy; Nutrition
content: table salt (red or green) 20ug/g, 1 egg 25ug; sea fish 100ug/100g, KJ-Tbl 65mg; ug*7,7=nmol; Drugs: 200mg amiodarone75mgJ
(T1/2≈50d); Rx-contrast 100mg-10g J, e.g., iopromid (Ultravist®) 150 -370 mg/ml (e.g., IVP / CT 1–2 ml/kg bw, phlebography 50–80 ml, cardiac catheter 40–60
ml); natriumioponat (Colegraf®) 330 mg/Cps 500 mg (tx thyreotox. crisis, block dejodase), povidonjod (Betadine®), Pat Info «thyroid guide»

Thy-Tests “trials & tribulations” TSH -50% daily variation, winter > summer, M > F, pulsatile
TSH (fT4)-Screening not useful in sick hospitalized pat.! F>40J (suggest. sy), Goiter/Thy-disease, menses, AFib, LDL-C, Dm1, M Addison,
Tx w amiodarone or Li+ (3-6mthly), pregnancy w pos TPO-Ab, Turner-Sy,
General screening in risk situations (e.g., pregancy & sick hospitalized pat.) debated. 3 challenges:
1. Pregnancy: TBGT4, T3, TSH (4-10), fT4 ([Link]., HCG-induced) Guidelines: pregnancy 2) postpartal / pediatrics (p12)
2. Drugs: TSH: e.g., amiodaron, dopamin-antag, [Link]; “Makro-TSH” (→ PEG precipitation), TSH: steroids (>100mg/d), statins, salizylatse,
dopamin (>1ug/kg/’) bexaroten, metformin; fT4: fragmin, amiodarone, -blocker, fursodemide, valproate, FFA↑, TBG↑., fT4: antiepileptics, salicylates, albumin↑, T3:
dejodase (amiodarone, iopanic acid, PTU, -blocker, steroids, euthyr .sick), All (Hormon) ELISA: Biotin (supplements, tx hair loss), Streptavidin-Biotin-Ab
3. Euthyroid sick Sy: Phys. “hibernation” triggered by fasting/disease T3, fT4n, TSHn(>0.1-<10), fT4/T3>20, rT3 (DD: 2° Hypothyr)

Hypothyroidism Prevalence: subclinical (SCH) 7%; overt 2%, F:M=9:1; >40-60LY (>70LY norm >6mU/l?)
DD: 1°: AUI*(Has > silent/postpart./GD, pos Ab  evtl look for APS (p 22)) > St n Stx/RAI/Rx > Drugs (J (amiod, Rx), Li , alemtuzumab i MS, - +

checkpoint-inh., interferon , ethionamid; AKF)>

de Quervain (5-26%), iodine deficiency (in endemic areas main cause) > thyroid dysgenesis > T4 or T3 resistance-sy
2°: Hypopituitarism (p23, TSH n (max<15mU/l); bexaroten (Targretin, reversible, dosedep. RXR-dep. Inhibition of TSH expression in thyrotrope cells)
SY: can be oligosy. (“depression of old age”, Fibromyalgia) → objectivation Zulewski-Score (<2: n; >5: hypothyr):
hoarseness; hearing; paresthesia; skin: a) cold, b) thick resp. dry, c) sweating (each 1pt),
Periorb. edema, constipation, wt, slowliness, achilles tendon reflex relaxation time , age <55LY
BT: TSH, fT4, T3, TPO-Ak; CK, LDH, LDL-C, Hb & Na (renal Na-Trsp & SIADH, cf p24); crea & uric acid
TH: L-Thyroxin (Tirosint soft-Cps inkl. 12.5ug Ind: PPI), Euthyrox all dosages uni-prize breaking groove, Eltroxin 50&100ug) Ds after tot Stx ≈1.6ug/kg ≈ kg – age
+ 125; 5075100 125150200ug, evtl add 12.5ug, resorption 10-30% w low gastric pH → fasting 30’ before breakfast or at bedtime, max. two sips of water to swallow tbl.
Th Indikation in sublincial hypothyroidism (SCH, isolated TSH w n fT4 & T3): imminent pregnancy, endokrine orbitopathy, Goiter, Sy (Tx-trial 6/12),
TSH>10mU/l & TPO-Ak (→ progression to overt hypothyr. >80%), age <70LY, smoking , LDL-C (ca 10%  in euthyroidsm)
F/U: TSH13612motly, ad GP Persist sy? DD: “therapy-refractory», Zulewski-Score, ACTH-testing (DD: AUI p22)
Increased T4-requirements: pos pregnancy test → T4-Ds 50% (p12); CHF (resorption), nephrotic syndrome (TBG u T4 loss i urine)
T4-Resorption: CHF, gastritis / H-blocker / PPI, calcium, iron (Multivit.), cholestyramin, Al3- (sucralfate), soy, coffee, fibres (intake >60‘ postprandial, e.g. bedtime). After change of
drug check after 4-6wk. Biol. T1/2 T4  8d  190h; T3  19h
Susp. of malcompliance Resorption test if evtl. wkly dosing (under supervision), admin. intake ad bedtime, e.g. with tooth brushing,
evtl trial T4&T3 (T3 SE, Novothyral bid, T4 (reduce dose by 20%) & Cynomel (F, tid, dose L-T4/L-T3=1/3; short T1/2 of T3) DD: Polymorph. deiodinase type 2

Myxedema „Crisis“
SY: pronounced hypothyroidism, T, P, AF, serosa transudates, evtl GCS RF: Co-morbidity (infections), drugs (immune tx, amiodarone)
BT: TSH, fT4, T3 (taken before Tx-start!), cortisol (sic!), typ. anemia, respirat. acidosis; Lc & Na & PG, CK
TH: L-Thyroxin L-Thyroxin Henning (D, 300ug iv, followed by 100µg/24h iv qd),
If cortisol „basal“ <550nM  adrenal insufficiency  HC 100mg i.v. stat -> 12h,
Supportive measures (fluids, vasopressors, ventilation, passive warming, iv. Glucose, evtl empiric antibiotics.
Peroral Tx after clinical stabilization & normalization of fT4.250ug ACTH-Test in F/U

Radioiodine (RAI)- Scintigraphy & Therapy (1Ci = 37GBq; 1mCi = 37MBq)

DG: Na99mTcO4 (123I dosismetry for Tx-plannung) 5% false neg in pap. Thy-Ca
7MBq=0.2mCi; Fct-study only if RAI-Tx planned: RAI-uptake n 2h -10% , 4h 5-15%, after 24h &48h 20-40%
 GD (typ. uptake >60-80% after 24h & diffuse (“butterfly”), Toxic adenoma (1 nodule “shining”, rest suppressed, typ. uptake 40-60%),
multifocal autonomy (multiple nodules, uptake 10-30%, often lower in less pronounced cases (e.g. only TSH-suppression)
 Thyreoiditis (DQV, Has, postpartal / silent, tx w interferons, checkpoint inh.), factitial & T4-Tx (Tg), Goiter ovarii
iodine-exposition (maritime food, amiodarone, desinfective drugs & contrast media containing iodine
(check Iodine in 24hU <100mg/d, elevated after CT/Koro 3-6mo, n ERCP/Lymphographie 1-10yrs)

TH: 131I T1/2 8d; limit for tx in outpatient setting: USA 100mCi; CH 5mCi…
a) Hyperthyrodism: Exacerbation (fT4 & Tg) unter RAI! Thyrostatic pretx reduces risk for “thyroid storm” periinterventionally & post-RAI
hypothyrodisim, but leads to a higher recurrence rate of hyperthyroidism. Proc: young at. w/o cvR stop thyreostatics 3d before RAI-tx high-risk
Pat (q cvR) pause thyreostatics 3d before to 4d after RAI → carbimazole (NeoMercazole ® Tbl. 5mg 1-2 tid x 4-12/12 w TSH F/U), evtl. ropranolol (40mg
BP – tid)
- GD 370-555MBq = 10-30mCi, 50-95% late hypothyreoidism or re-RAI needed if recurrence,
progression of EOP in 25% → protection using steroids (p 20)
- Toxic adenoma: 10-30mCi, 80% euthyreoidism, evtl Goiter (nodular, low TSH) 50mCi (fraktionated 3x)
F/U n RAI w Hyperthyreoidism: 2-4wkly (evtl only BT, post-RAI thyroid storm), if fT4, T3 no  3612mtl. GP
b) Ca: F/U acc. Endo/NUK guideline 30 – 100 mCi (very high risk), pretx measurement of uptake?; max. dose cumul. 1500mCi?
TSH>30mU/l: T4 6Wo od T3 2wk stop or rhTSH (Thyrogen®) 0.9mg im d1&d2d3 150mBq 131Id5 scan, Tg d1&5, Premed Li-CO 300mg tidx7d 3

SE: dosedependent, “Sicca-Sy”, Sialoadenitis  prophyl. Lemon / chewing gum after (!) RAI, 2° Tu (Leukämie?)
Pregnancy: 12-18mo after RAI-Th possible (USA 6mo), contraception mandatory, per 5 mCi  1wk no close social contacts
Overview NUK-«Theragnostics»

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 20. Hyperthyroidism & TSH-Suppression
“Hormone” (greek): impelling, exciting, setting in motion…
[Link]
Hyperthyroidism Prevalence 2.5%, F>M, Pat Info «Schilddrüsen-Ratgeber»
DD: Graves' disease (GD; young F, EOP (60%), TRAb) > Autonomy (TMNG) >45j, palp. nodules, iodine deficiency) > Thyroiditis
RAI uptake : DQV (Pain, BSR, (f)T3/fT4>0.3pM/nM Th. no CBZ/PTU! NSAID → Prednison (15mg/dx1/52 -> tapering), Colchicine), Silent (RF: Interferon-Th, postpartal,
no pain, transient T4, TPO-Ab → risk of hypothyrodism), Amiodarone (psb), > HCG (hyperemesis grav) / Pregnancy (max 12 GW) > Factitia (Tg),
secondary (TSH -subunit, (f)T3/fT4>0.3 pM/nM, SHBG) or pituitary T4-resistance, Goiter ovarii;
SY: may be atypical („senile dementia“, hypopkaliemic thyrotox. period. paralysis ”HTPP”), quantification & F/U→ Zulewski II Score
typical: nervousness; sweating (DD); palpitations; stool frequency ; wt (despite appetite ); sleep disturbances
Hyperkinetic movements; warm and moist skin; pulse>90, hand tremor; goiter ≥ I ("palpable thyroid"), stare in EOP (sb),
DG: TSH , fT4 only ([Link]., amiodarone, NTI, steroids, B-blockers), T3 only (early phase); if pill/PG→ measure fT3
-TRAb (Sens in GD 90%); TPO-Ab; SHBG, Transglutaminase-Ab (celiac dis. i 5%); consider Ca &PO4, PTH&Hb, Glc, Thymus hyperplasia.
2+

-Thyroid-US, scinti DD: Infl or suspect adenoma (Na99m TcO4; cave: Rx contrast), consider densitometry (esp postmenop), ECG
Tx a) GD: Carbimazole NeoMercazole 2-3Tbl 5mg tid x 4wkF/U fT4 & 15mg (qd) (-30)mg x 8wk3(-6)mthly Ds n TSH x tot. 18 (6 to >24,
lifelong?) Mon, evtl. low dose continuous therapy. 2.5-5mg qd ?; SE: 10% allergies (pruritus, exanthema), hepatitis, leukopenia→ if infection (T>38.5°C,
"sore throat") ad Az; PTU 20/100 tbl. propycil 2-4 tbl 50mg tid if PG/breastfeeding, SE: hepatotox. Immunetherapies (e.g. Rituximab) in studies
- Propranolol Inderal Tbl 40mg qid qd; Retard "LA" 80 or 160mg/d Target: pulse 60-80/', Vit D+Ca Calcimagon® BP until 3mon euthyroid, if RF or
postmenop.; Pretibial myxedema Betnovate tid, conception protection until euthyroid, in paralysis K-Subst & low carb diet as long as hyperthyroid.
- Recurrence (30-50%, RF: GREAT-Score)  repeat 18mo CBZ (<40y) vs RAI (>40y, CI: PG; CAVE: EOP) vs Stx (goiter II-III).
Endocrine Orbitopathy (EOP) mild: -40%, severe: 10% (RF: TRAb, Dm, smokking) Ophthalmolog. Cons.& VF in susp. EOP
Sy: "Nomen est omen": Graefe (eyelid stays back in downward gaze), Dalrymple (upper eyelid retraction), Stellwag (rare blinking), Moebius (convergence
weakness), periorb. Oedema, conjunctivitis->exophthalmos (Hertel>20mm; no<18) double vision /motility (upward gaze ) ->visus
Tx: euthyroidism, stop smoking; Lacrovisc tid (cool), eye bandage, head end of the bed, Torem 10mg/d, selenium (100ug BP x 6/12; CH:
severe & active EOP: prednisone 1x wk 0.5-0.75g iv & mycophenolate 0.72g bd x 6 wks
Selenase 100ug/amp=CHF 1.10; D: Cefasel 100ug/Tbl = 70Rp).
→ 6 wks 1x wk 250mg Solumedrol iv (4.5g cumulative Ds!) & 0.25g mycophenolate, evtl. & cyclosporine ; RAI-Th: from T0 0.5mg Pred/kg po x1/12, tapering x
2/12; evtl. 50ug/d T4-Th from 6. Week aft RAI, aft depending on TSH), RAI (Ind: double vision, motility ), Stx (Ind: visual acuity , chronic EOP),
Teprotumumab 10/kg bw i.v. -> 20mg/kg bw i.v. 3-weekly 7x, Rituximab 500 mg iv once, cave: optic neuropathy), tocilizumab; atorvastatin?; Prg: 60% improved, 30%
idem, 10% worse despite Tx

b) TXA/MFA RAI (Dose dependent on uptake, GD: 300Gy) Ind: Sx-Morb, 3d Hosp NUK (patient must be continent & self-sufficient),
10% radiation thyroiditis ( fT4 ), --> F/U: Endo aft 6 mos, NUK aft 3 & 12 mos, then ad GP f annual TSH checks.
Evtl. enucleation/Stx (preop. euthyrosis w/ CBZ/PTU, evtl. “plummering” (CBZ+Iopanic acid 500mg 2x/d (psb)), RFA (LUKS, esp if node vol. <12ml)
F/U: TSH 3mo-2 yrs (GP, b/c late hypothyroidism, esp aft RAI-Tx in GD), mb Dexa aft 6mo, aFib→CHA DS -VASc score, evtl. NOAK 2 2

TSH Suppression Syndrome (TSS)

DD: see above ("subclin. hyperthyroidism"); euthyroid sick in hospitalized pat (f/u after 1/52) depression (metoclopramide test for DD?), bexarotene.
Course: 25-50% spontaneous normalization, 5% progression to overt hyperthyroidism, aFib, osteoporosis, mortality? F/U: 6-12monthly
Contrast media (ICM): Overt ICM-induced hyperthyroidism very rare (0.1%, masked hyperthyroidism w TSH in lower norm in iodine deficient areas (GER, Nordic).
Iodine exposure prophylaxis: emergency TSH only if patients at risk, i.e., iodine deficiency, pos. thyroid history, old age a/o cv risk
TSH <0.01mU/L: antithyroid Tx; TSH 0.01-0.3mU/L: dep. on RF (aFib, osteoporosis, age, Sy), Leaflets KSA D F, LUKS, USB D F
F/U: only if TSH <0.01mU/L a/o at risk: day 3-28?; "formally" until urinary iodine excretion normal (-12/52), Elective definitive Tx depending on etiology.

Amiodarone-Induced Thyrotoxicosis (AIT) F/U TSH q3mo, if borderline on Amiodarone q1mo.

Type I: Iodine-induced if "latent" hyperthyroidism (US: TXA (vol >30ml; nodules >1cm), GD (hyperemia, TRAK, EOP), scinti (>5% uptake/24h).
Type II (more common): Toxic thyroiditis (prev. euthyroid, US NAD (vol <20ml, nodules <1cm) scinti (<5%-uptake aft 24h), Doppler vasc.)
IL-6 500fM (150-1100), CRP (?),

Often mixed type I & II !

DG: TSH, fT4(-index), T3, T4, TRAB, TPO-Ab, Thyroid-US w/ Doppler (increased Vasc indicative for type I).
TH: stop amiodarone? (consult cardiologist, no influence on course of hyperthyroidism, T1/2 100d).
Consider Stx early (!) esp in type II & mixed forms, fT4>60pM, EF<40%, goiter >20ml, >1mo persist. Hyperthyroidism (w/ prednisone poor prgn).
Prednisone (0.5mg/kg qd) & βB (Inderal 40mg qid); & CBZ (15mg tid; no CBZ in absence of nodules (US) or only mild hyperthyr.)
if aft 2 weeks a) fT4>30% ( type II): CBZ stop, Pred. til T4 no, evtl. Iopansre (Colegraf 500mg BP); b) fT4 (→ type I): Prednisone stop;
CBZ (20mg tid-qid); Perchlorate, Irenate 21drps tid, longer duration of Tx, cautious tapering; β-blocker

Thyreotoxic Crisis Mortality 10-20%, clinical Dg!, periph. thyroid values sometimes only moderately elevated
Dg: T>38.5°C, P>110/', CNS-Sy (agitation, nausea, delirium, psychosis, lethargy, convulsion, coma) , HF, GIT/Hep-Sy.
RF: only in 30% pre-existing thyroid dysfct, I-exposition in latent autonomy (TSS); co-morbidity (e.g. infections), post-Sx
Tx: ICU, Inderal (1mg iv/5' to pulse<100/' 40-120mg po q8h to pulse 80/', mb Esmolol 0.25-0.5mg/kg iv 0.05-0.1mg/kg/'); carbimazole (20(
30)mg poq 8h, mb thiamazole (Favistan , D) 40mg iv 8h (p 28); PTU 600-1000mg po/rectal 200mg q4h); "Plummer" before Stx with iodine:
Lugol Sol (13drp. 5%-sol tid = 3 x 81.25mg iodine or "AKW-Army" K-iodide Tbl. (Tbl. 65mg 1-1-1 x 10d) 1st Ds. Iodine only 1h AFTER carbimazole, in
case of iodine allergy: perchlorate, Irenate (21drps tid, from D→ emergency dose in hosp. pharmacy, Na-ClO4 initially 1g = 45drps (ideally 4h before ICM exposure) 15drps
tid (after eating b/c GI-SE) x7d; SE: ICM tox;) or Li-carbonate; dexamethasone (1mg BP)→ Stx aft 2wk, DVT prophylaxis (Liquemin?), Panadol
1g QID (no NSAID & heparin: displaces T4 of TBG), active cooling if therapy resistant -> Stx "à chaud", evtl. plasmapheresis.

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 21. Goiter & Thyroid “Cancer”
"The diagnosis and treatment of thyroid cancer is not an exact science"

Goiter (Pravalence 5-10%, F>M), Pat info «Schilddrüsen-Ratgeber»

Normal Thyroid <20-25ml or size lobe ≈ thumb end phalanx
DD: Bland (80%) > dysthyreosis > Ca > Iodine-deficiency (dietary <25ug/g Crea, main cause for endemic goiter (prevalence - 30%),
drugs (Lithium, thyreostatics), toxins (thiocyanate SCN-, cabbage, manioc-cassava, smoking)
Grad I: palpable; II: visible; III: visible from a distance, retrosternal; a: adenoma; d: diffuse, «normal» aging
DG: a) Palpation from dorsal (w H2O-gulp): Node (60-80% in 60yrs; sonography >>Palpation); Lymphnodes, neck circumference (cm)
- palpabel, growing >1-2cm pa (US conspicuous (TIRADS)? PET-pos?)  FNA; similar Ca-risk uni- vs. multinodular goiter
- multinodular: FNA dominant nodule (dep. on TIRADS >1-2cm); >4cm: esp. if growing  hemi-Stx w histology
b) US-Thyroid & Ln Ellipsoid-Vol (ml) = length x with x depth (cm) * 0.53; objectivizing growth template KISIM, Pat. Info FNA
NO Dg of malignancy by US alone! Risk categories: EU-TIRADS (→ calculator)
Ln: missing fatty hilus, rounded (short axis >0.5cm), hypoechogenic, cystical, microcalcifications, peripheral blood flow (Doppler)
 FNA; CT-Tx: if Susp of intrathoracical goiter ([Link]’s sign (i.e. arms up -> zyanotic head), evtl b Ca, cave: ICM b Autonomie
c) TSH, fT4, T3, TPO-Ak ( Thy-Ca 2x, Thy-Lymphom 75x), evtl. Calcitonin (CT) & ProCT (p 22, ) . Calzium-Stimulationtest likely obsolete

- TSH >4mU/lT4-Tx; <0.3mU/l  scintigraphy, wenn kalter Knoten → evtl FNA

TH: active surveillance F/U je n FNA / US & RF f Ca / Phobie 0.5-2jährl. m. US, evtl. ”nur” klin F/U b GP, Stop Nikotin
- vs strumectomy (Stx, subtotal 7-10ml remnant (→euthyr) or „near total“ 1- 3ml remnant (→hypothyr.))
Ind: large goiter, >4cm, node (US (TIRADS), cytologie (Bethesda) +/- mutation analysis, radiation in childhood),
preop BT: BB, Na, K, Ca, crea, INR TSH, postop. hypocalcemia RF & Tx: psb
- vs suppressive T4-Tx: if basal TSH >4mU/l, target TSH (0.1) 0.3-0.5mU/l, cave: hyperthyroidism SE
- vs RAI: 30% Vol (> T4-Th), radiation SE, Thermoablation? (ca 50% [Link].--> ad LUKS), EtOH-Injektion: rez. non-solidd (ie liquid) benign (FNA!) cysts

Differentiated Thyroid Cancer (Thy-Ca) „SOP“ USB, i.e., papillar & follicular (medullary (MTC) → p22)
Prevalence F>M, autopsy 5-10%, mortality <1%,  the true art is to identify those, that are truly malign! cave Screening!
DG: FNA (3x w purple/(blue) needle a 10ml syringe, US-guided; puncture dominant nodule in multinodular goiter, NSD-Punktion)
Bethesda-Classification (% prevalence, % „malign“ acc. pathology (cave: pathology overestimates biologic malignancy!)
- I Nondiagnostic (20%, <5%; insuff. N of follicels)  Re-FNA in 6-12mth? (thicker 20-22G needle, US-guided FNA (3x)), evtl US/Szinti
- II Benign (50%, <3%; macrofoll., low cell count, colloid rich)  reasure pat  clin. F/U (GP) in 1 (-2) yr (as 5% FNA false neg)
- III AUS (atypia of undeterminded origin,1%, 10%; microfoll,  galectin-3TPO?)  re-FNA 6mo, earlier if growth, Afirma Gene Expr. Classifier (PoHI)
- IV Follicular neoplasia (10%; 25%; onkocytic?)scinti"cold"Hemi-StxHisto (fast cut?: invasion into capsule & vessels.?)
- V & VI «Malign» ((5%, >60%); 5%, >95%; differentiated (papillar/follicular, psb) >anapl > others (lymphoma, sarkoma)  Hemi (<4cm) or total Stx
TH: SOP follow up KSA, depending on risk factors for malignancy, size & expansion
Staging: TNM? ATA 2015? → Tumorboard (KSA; USB, LUKS)
Very low risk T1 ≤1cm, unifocal? multifocal??, N0 (<5 micrometastases <0.1cm),M0
→ active surveillance (>40J., 80% pap. adenoma, growth 10%, Ln-metastasis 1-2% in 15yrs) vs RFA vs hemi-Stx, no RAI, TSH-goal 0.5-2mU/L
low risk T1b, T2 (> 1 cm, < 4 cm) od T1a multifocal (m), N0-N1 (>5 x >0.2-3cm), M0, histol. well differentiated, papillary Ca w vascular invasion
→ individ Tx w total / Hemit-Stx & RAI based on risk/benefit
high risk T3 (≥ 4 cm, extracaps. invasion), T4, N1 >3cm, all M, histol. unfavorable differentiation
→ total Stx, central modif. neck dissection & RAI & T4-Tx w TSH-suppression 0.05 - 0.1mU/l.
Histo  80%papillary typ cellular signs: Grooves, bright Kerne m nucleoles (”Annies eyes”), cytopl Inclusion, Psammombodies, Papillas)
10% follicular [benign specials: noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Encapsuled neoplastic follicles.
Follow-up only US 1x/yr; † >75%onkozytic, insular], 5% medullary (p22, 20% MEN) <1% anaplastic (low to no iodine-uptake (”re-differentiation“ w Roaccutan 1.5mg/kg po x 5/25 v
RAI?), T4-substitution, palliative. ext. Radio-Tx after R1-resection, chemoth (oncology consult, radiosens. m Doxorubicin, sequental w paclitaxel od mitoxantron 7mg/m2 1h iv d 1, 7, 14, 21)

Sx: Hemi- (very low risk) or total strumectomy (Stx) w modif. (preservation of m sternocleidomast.) neck-Ln-dissection
- Tumorinvasion in soft tissues of the neck  tot. neck-dissection (morbidity, radioiodine-assisted surgery?),
- „incidental-Ca“ histology after Goiter-Stx  completion-Stx within 1wk
- cave: if RAI-Tx: postop initially NO T4/T3-Tx (target TSH>30mU/l)
- Postop. hypocalcemia: 5% transient, 0.5% persist. RF: Postop d1 PTH <10pg/ml, PO4 postop >1.4mmM, Prophyl. Vit D 0.3M E po preop
Tx: Ca po 1g tid – qid w meals, evtl. iv (p16), Mg (p16), Rocaltrol ® initially 0.5ug po bd, [Link], evtl. Forsteo 20ug s.c BP (PoHI KK?!)
Ziel: P-Ca²+ korr. 2.1-2.2 mM, 24-U-Calcium <7.5mM/d wg Nephrocalcinose, Normophosphatemia (Ca²+xPO4 < 55mg²/m² , if PO4-rise →CaCO2 w meals, alfacalcidol),
Long-term complications: calcification of basal ganglia & cataract
RAI: high risk patients; 4wk postop & TSH>30mU/L 131I-Th (30mCi) to ablate residual thyroid tissue, if no foci outside Thy  T4-
Tx (1.6ug/kg) po  at 3mths Tg w TSH suppression, if Tg >0.9ng/ml 2. 131I-Tx (100mCi) n rhTSH i.m. (Thyrogen 0.9mg im d1, d2, n 24h
(d3) RAI-Th & Tg, exclude pregnancy before RAI!,
Iodine-refractory Thy-Ca: a) ”Re-Differentiation” dep. on mutation-analysis) → RAI uptake : trametinib (MEK) dabrafenib (BRAF) selpercatinib (RET pos MTC),
selumetimib (NRAS), apatinib od lenvatinib (Anti-VEGF Lenvima, Survival 4 → 18Mte, SE (40%) hypertension, nausea, diarrhea, PoHI!), b) independent of RAI: sorafenib
(Nexavar 2 Tbl.200mg BP; median-survival 6->12 Mon, SE: skin (HFS), alopecia, diarrhea (each 70%, evtl. dose reduction.); PoHI! (CH 100k pa!)
Suppressive T4-Th 100 - 200 (250) ug/d risk-dep. → Target-TSH (mU/L) very low 0.3 - 2, low <0.1 - 0.3, high <0.01- 0.1; ”max.” <0.01
F/U: alternating NUK / Endo, recurrences usually within 5(-10)yrs, status, TSH, fT4, Tg & Tg-Ab, Tg-Sens if TSH>30mU/L
- Tg >2 ng/ml → US, >10 a/o increasing Tg(-Ab)  RAI-scintigraphy (if I- <150g 24h-urine)  (probatory) RAI 50-100mCi, neg Szinti evtl FDG-PET-CT
- after 5-10yrs follow-up without recurrence → adapt risk-assessment & target TSH (high-risk  low-risk  Subst. T4 m TSH 0.5-2mU/L)
- postmenopausal osteoporosis prophylaxis & evtl. Tx if osteopenic (p16).

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 22. Polyglandular Endocrinology
"You only find what you look for, and you only look for what you know”
gene tests: [Link]; [Link]
Autoimmune Polyglandular Sy (APS) DEF: >2 typ. organs affected, F 75%
APS I: Pg: Mut AIRE-Gen Autoimmune PolyEndocrinopathy Candidiasis Ectodermal Dystrophy - typ. Sy (CMC, HypoPTH, M. Addison); non-typ. Sy: endorine (DM1, dysthyr.,
POI / Hypogonadism, GH-deficiency, hypopit.) & non endocrine (urticaria, pneumonitis, perniziosa, hepatitis, interstit. nephritis) & ektodermal Sy (Vitiligo, alopecia, amelogenesis imperfecta). Screening w 1 typ & > 1 non-typ. Sy.
APS II: 20-30Yrs (f>m, pos. family-Hx, aut-dom, HLA-DR3) HAS (GD) >M Add > Dm1 > POF / hypogonadism > perniziosa, celiac disease / “Laktose intolerance”
/ microscop. lymphocytic colitis, vitiligo/alopecia; myasthenia gravis, Sjögren Syndrome, TTP, antiphospholipid Syndrome, Ab against Cyt P450
APS III = APS II w/o M Addison, IPEX-Sy (Immunodysregulation, Polyendorinopathy & Enteropathy, X-linked mutation FOXP3 gene)
POEMS: Plasmocytom Polyneurop (senso-motoric), Organomegaly (liver/spleen), Endocrinopathy (hypogonadism, M. Addison, pHpt, Hashimoto, Dm), M-gradient (Ab
pathogenetic?), Skin changes (incl. oedema); SE immune-checkpoint inhibitors (PD-1; CTLA-4, -> thyroiditis (p 19/20), hypophysitis (p23), Dm “1” (p8), M. Addison (p6))
DG: APS II-screening: Thy & pos FHx or 2 manifestations or initial Dg M. Add / Dm1 (prevalence APS in Dm1 -15%)
- TPO-Ab & TSH; 21OH-Ab & 250ug ACTH-test (evtl aPRliegend); GAD-Ab (evtl IA2- & islet cell Ab), PG fasting, vitiligo
- Intrinsic Factor-Ak  pos  gastroscopy 5yrly, esp. if VitB12 a/o Holo-Tc ([Link]-malonic-acid, makrocytic anemia = late sign), FSH/LH, P-Ca2+
- Transglutaminase-IgA-Ak (with gluten-diet!, often w/o typ. GIT-Sy, Fe/Vit-D deficiency  duodenal villus biopsy; high suspicion & neg Ab → tot IgA Ab u HLA-typing
TH: evtl. T4, HC (stress prophylaxis ), Vit B12 (Amino ® 1mg 1x/d f 1 wk, 1x/wkly f 1mo  3mthly Vitarubin ® oral or Vit B12 Ankermann ® po qd), 5-yrly APS-screen (esp. if
increased hospitalizations, prescription / dose increases of antidepressants, antiemetics, antibiotics), alopecia: Baricitinib ® Tbl. 4mg qd x 36 Wo?, minoxidil??

Multiple Endocrine Neoplasias (MEN) DEF: >2 typ. organs affected, template for pedigree
Genotype-Screening Pheo (p4), MTC (psb & p 21), Tu-manif <30 (-50)Yrs; 2 MEN-typ./multifocal Tu, pos FHx
Guidelines SGED, PoHI, informed consent & 4.5ml EDTA blood  e.g. Clinical Exome ® (TruSight One Expanded ®, ca 6'900 genes, CHF 4000.-, KSA Fr. Dr. Cecilia Bracco
 if pos  family screening / psychol. a/o genetic advice; screening of children in affected families esp. in MEN II for prophyl. Stx;
CoVisum f PoHI w AL-Nr.
634/804-mutation yrly starting at birth; 1x<5yrly in MEN I., mutation-negative pat. («phenocopies») with milder courses & better prognosis; EDM-gene-experts CH
MEN 1 (Wermer-Sy, [Link], chrom. 11q13, >1000 mut., Menin) pHPT (95%, in adolescence, hyperplasia); Entero-Pancreat. NET (40%, often
duodenal: gastrinoma > insulinoma (<40 yrs) > other NETs, often malignant, psb); Pituitary Tu (30%; PRL> inactive >GH or ACTH)
Facial angiofibroma (88%), skin-collagenomas (72%), carcinoids (10%), thymus, children screening debated
DG: Sy (Ca, ulcer, hypoglycemia, PRL)  genotyping & BT: Ca (PTH), PRL; <40y PG, >40y gastrin, IGF1, FUC → 6-12mtl. Tx: Leflunomide ?? →Lumen-1 study
MEN 2 (Sipple-Sy, [Link], chrom. 10cen-10q11.2, RET-proto-oncogene/tyrosinkinase): peak incidence ca 30Yrs (Typ IIB: med. Thy-Ca in children)
good genotype-phenotype correlation (i.e., similar tumor pattern within families); screening of children recommended
medullary Thy-Ca 99%, initial hyperplasie DG: US-neck & FNA, calcitonin (CT) >100ng/L(>20ng/L→Calcium stimulation-test), procalcitonin (PCT) >0.1ng/L (w/o
infection!), PCT / CT-ratio >2 resp. >5 prg unfavorable, Staging: DOPA- PET-CT
TH: Sx, vandetanib (Caprelsa® Tbl. 300mg qd Ind: PoHI „sympt., rapid-progressive“ MTC, SE: diarrhoe, rush, hypertension, QT), selpercatinib (RET-Mut) a/o DOTA-TOC-Th
KO: US, DOPA-PET/CT in consult w oncologist; Pheo (50%, often bilateral / multiple); pHPT (20%) > cutaneous, itching „Lichen amyloides“
Familial Medullary Thyroid Cancer (FMTC): aggressive C-cell tu → family-screening! Evtl. w megacolon (M. Hirschsprung) or “Lichen amyloides”; DG: CT on ice, n<2.8pM; ProCT n<0.15ug/L
MEN 3 (M. Gorlin; <5%): no pHPT, aggr. med. Thy-Ca, mucosal neurinomas (e.g., tongue (100%), full lips), marfanoid habitus (65%),
MEN 4 ([Link], chrom 12p13, CDKN1B,-p27,KIP1): pHPT, pituitary (anterior), adrenal, renal, gonadal tu
Others Mc Cune Albright: gonadal Tu ( pubertas precox), acromegaly, fibrous dysplasia, café-au-lait spots;
Neurofibromatosis (NF) type 1: café-au-lait spots, neurofibromas, 2% pheo, duod. somatostatinomas, Lisch-knots i iris, opticus gliomas, ossous & vasc. dysplasias;
Von Hippel Lindau (VHL): islet cell-Tu, bilat. Pheo, pancreatic cyts, renal cell ca, CNS/retina-angioma  CVI, endolymph. Tu.
Succinyldehydrogenase SDH-B/C/D (familial paraganglioma (Glomustu, 20% Pheo), & GIST (Carney-Dyade), & pulm. chordoma (Carney-Trias); Carney-Complex <30j,
“endocrinomas” (steroid-Tu i adrenal cortex (Cu-Sy, mikronod bilat. NNR-Hyperplasie) + pituitatry (20% HGH-Tu), Thy, gonads (Sertoli-Zell Tu) & (atrial-)myxoma, pigmented skin spots (Lentigines,
Schwannoma, genital, eyes, lips), Pg: inact. [Link]. subunit type 1A of protein kinase A (PRKAR1A)

Neuroendocrine Tumors (NET) (“carcinoids”, “APUDOMAs”) patient info D, F, I

Sy w liver metastasis: “dry Flush” (DD!), diarrhoa or „irritable bowel sy“, "asthma", venous telangiectasias, paraneoplastic endocrine Sy,
«Hedinger Sy»: fibrosis of tricuspidal valve w right heart insuff. ( → TTE, 6-mthly), intest. obstruction, pellagra, muscle atrophy, 70% hormonally inactive
DG: Biomarkers: plasma 5-hydroxy-indolacetic (5-HIA; sens 95% [Ileum!] / spec 80% false: tryptophan in pineapple, avocado, banana, nuts, chocolate, reserpin,
SSRI, celiac disease) Chromogranin A (prognostic, 65% / 90% [CKD, CHF, gastrin, PPI, hyperthyroidism, prostate-ca, diarrhea…)
Biopsy → Grading: histol. diff. / CI-67/ mitosis index: G1: high / <2% / <2; G2: high / 3 - 20% / 2-20%; G3: low / >20% / >20%, synaptophysin (neuro).
Local: US/CT/MRI abdomen (≈70% / ≈85%), octreotid-scintigraphy (≈80% / ≈90%), Ga68-PET-CT (≈ 85% → better prg), FDG-PET-CT (50%, if pos. → worse prg)
TH: NET-Tu boards (Aarau-BS), Sx, radiofrequency ablation (EUS-RFA, p 10), lanreotide (Somatuline Autogel® 60/90/120mg wkly deep sc, self inj.) or octreotide
(Sandostatin-LAR ® 30mg q7-30d, sc 0.1-0.5mg tid), DOTATOC (NUK-USB), sunitinib, everolimus, xeloda & temozolamid, cabozantinib qd: consult w oncologist, nutritional
counselling if flushes, INF; , undiff NET: cisplatin & etoposide PRG: 5yr: G1: >90%, Meta & G3: <30%
Lung NET (Carcinoid): ESMO Guidelines (MEN1, DIPNECH), CaSy (serotonin) > Cushing Sy (ACTH) > acromegaly (IGF-1, GHRH), PTH (Ca),
Dx: Chromogranin A, 5-HIAA, ev. NT-proBNP > cortisol/ACTH > IGF-1 > Ca, CT/MRI, Ga68-dotatate PET/CT, ev. FDG-PET/CT, [Link], Histological Grading,
Tx: Control of functional syndrome (e.g., SSA, steroidogenesis inhibitors), comorbidities and therapeutic interventions (e.g., spriconolactone, potassium, etc.),
local: tumor resection, advanced: tumor resection, systemic therapies (SSA, everolimus, etc.)
Insulinoma (15%) (benign in 90%, small TU): Sy: fasting hypoglycemias (very rarely (only) postprandial (pp)), varied neurol. Sy (93%), wt(<50%), DD: p10
- Fasting test outpatient 16h (after lunch fasting), BT 08h: PG >3.8mM NAD, else inpatient 72h* fasting, 2-3l CH-free fluids (tea, mineralwater, bouillon), PG &
BT (PG, 5.5ml Serum & EDTA-P) 6h, 2h <3.3, 1h<2.8  stopping rules: PG <2.2mM (PG M 3.4mM, F 2.9mM) & Neuroglycop-Sy (p8, "serial-7" 100-7= -
7=…) BT  20g CH po Dg: Insulin(pM)/PG (mM) (>30,“increasing”), Insulin >11pM bzw >3uE/l, C-peptide n>200pM; urin ketones neg; -OH-butyrate <2.7mM
(measure 24, 48 &72h or after stop w Medisens Precision ®), ∆PG >1.4mM 10’- 30’ a glucagon 1mg iv. Evtl. ”mixed meal test”. Localisation tricky!
Conventional imaging (US (endoduodenal/ intraop), MRI, CT (early arterial phase), if neg → 68Ga-Exendin4-PET/CT (NUK USB, detection rate 74%), if susp. of malignant
insulinoma: 68Ga-DOTA-SSA PET/CT, angiography (A. pancreatica w Ca2+-Insulin-Stimulation (2-4x) in V. hepatica (Prof. Th. Pfamatter, USZ)→ intraop. palpation by routined surgeon Tx p10

Gastrinoma (10%): (va MEN I, 80% malignant), SY: zT multiple Ulzera, sekret. Diarrhoe (gr Vol, persistent in fasting state, OsmStuhl = 2x [Na+K]), pulm.
carcinoid DG: gastrin fasting >500pg/ml (n<100, antacids & vagotomy (Dm, Billroth II),<400, atrophy. gastritis (pH>2) & short bowel sy <700), evtl. sekretin-
stimulation test: 2U/kg secretin iv (-10', 0', 10', 15', 30',:  nadir-peak >200pg/ml  Tu TH: Sx a/o PPI

Others (<5%): Glucagonoma (big TU, 50% metastasized at Dg) Erythema necrolyt. migrans, 75% Dm2, wt; P-amino acids, anemia, ESR DG: glucagon
fasting n<20 (>50pM), Somatostatinoma (big Tu, 80% metastasized at Dg), steatorrhoe, gallstones, Dm2, wt; DG: basal somatostatin
VIPoma ("WDHA" (watery diarrhea (persistent 3l -10L despite fasting (DD osmotic diarrhea)), K & HCL, „pancreatic cholera"), VIP-Proteinuria, CT/MRI-Abd, 68Ga-Dotatate-CT-PET
TH: preop Sandostatin 50 - 200(-400)ug BP s.c.-> LAR 30-60mg mthly., NaCl 0.9%/d iv m K (bis 300mval/d); Imodium 2-12Cps/d→Sx,→ evtl. PPRT w 117-Luthetium-Dotatate

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 23. The Pituitary
Die Hypophyse ist der Dirigent des endokrinen Orchesters…und die wahre Perle unseres Körpers
Guidelines SGED-AWMF; Lancet Diab Endo 22; 10: 804-23; SwissPit Registry
Adenoma micro<1cm<macro; 50% PRL > 20% „inactive“ > 15% HGH > 10%ACTH (small Tu!) >> TSH, LH, FSH, [Link]
SY: evtl, menses, headache (apoplexy?) visual field (VF) at dg & 1-2wk a Tx (Sx, drugs), 3mthly (macro) or 6mthly (1yrs micro, 2yrs macro), then yrly
DG: PRL, T/E2, IgF1, fT4,”random cortisol”, if <300-500nM (1ug) ACTH-Test, P-Na
MRI Sella (dynamic w & w/o ICM, coronary & sagittal fine layering; resolution 3mm) DD: «Incidentaloma» 10% of pop, adenoma (w sy),
craniopharyngeoma (CT calcifications, cysts), Rathke cyst, dysgerminoma (germ-cell Tu), Meta (Lung, Mamma), „Granuloma“, Hypophysitis
F/U hormonally inactive: Sx (>1.4cm3, MRI T1-hypo & T2 hyperintense cysts, hypopit., visual field defects)
vs cons. (MRI&VF-F/U (1), 3 & 6yrs, micro a 6yrs  evtl. stop (10% growth, 90% stable), FIPA (AIP-Screening <18J., GH or macro <30J)
Prg: : Shape >3 & ki67>3%, >2 mitoses/10H, p53+, Progred. Tu/Ca: re-Sx a/o radiotx, carbegoline → Temozolomide (Temodal®, Kons. Onkol

Prolactinoma
SY: Hypogonad., F 20% cause of sec. amenorrhoa/infertitlity/osteoporosis; galactorrhea F 50% (up to 25% galactorrhea w n PRL), M 30%,
DG: S-Prolactin (PRL) DD: functional (PIF, stress,usually <1U/L / <50ug/L), pregnancy / breastfeeding (<10U/L; regred to norm. 4-6Mon
postpart.), drugs (<4U/L, E2, progesterone, paspertin, neuroleptics (except Leponex ®, Abilify ®), Tricycl, opiats…), Big-PRL (<40% PRL-recovery), Thy,
CKD&LF, protein-enriched meals, Tu usually >4-fold UNR (<1cm<4U/L ; >2cm >20U/L cave: hook-effect); MRI-pituitary if PRL >2000 or >400 mU/L
w Sy & and no obvious cause, follow-up MRI only if PRL, visual field (octopus)
TH: Sy? Cabergoline (CAB, Cabaser® Tbl. 1, 2mg; Dostinex® Tbl. 0.5mg; 0.5- 4mg ½-2x/wk); bromocriptin (BRC, Parlodel® po 2.5mg evening – 25mg BP) SE: impulse control disorder (M:
non-ergot-derivatives: quinagolide Norprolac® tbl 25ugx3d 50ugx3d75ug evtl. pramipexol (Sifrol® Tbl. 0.125mg → 1.5mg/d), ropinirol (Requip® Tbl. 0.25mg →
hypersex.; F: shopping spree), valvulopathy
rotigotin (Neupro® Pflaster), F/U: 3mtl, haemorrhage? liquorrhoe? (→-Trace), Goal: Menses, PRL i d (lower) ref. range, 10% resistance to dopaminagonists → Sx? Radioth?
4mg/d),

Attempt to wean after 2yrs (mikro, 50% recurrence) – 5yrs (macro, 70% recurrence), postmenop ir PRL n, no Tu i MRI or volume >50% & >5mm to chiasm 6-12mthl F/U
Asympt. Pat: PRL-F/U 6-12mtl w/o tx; Sx: benefit (SE of drugs, cysts, VF) vs risk? Neuroleptics: evtl aripiprazole (Abilify®)
PG: sympt. growth: micro low (3%), macro higher, esp. if untreated (5/21%) Tx: CAB (>BRC), stop after pos. pregnancy-test, continue if suprasellar macro; F/U no
blood tests, clin micro 3mthly, macro 1mthly, vf 3mthly, if vf  MRI → sympt. growth: 1. CAB, 2. Sx (2nd trim. or postpartal); breastfeeding ok

Acromegaly Leaflet for patients D, F, I ; consensus paper

SY: foto history (ID, permis) shoes, rings, dentition, tongue, hidrosis, carpal tunnel sy (CTS), arthralgias, metab. Sy, art. hypertension &
hypertensive heart disease, OSAS, colon Ca-risk 2x
DG: IGF-1 (: age, SIRS, LF, C2, obesitas, anorexia, HRT po; : renal insufficiency (IGFBp, fIGF1), pregnancy, sports, adolescence, fT4) → HGH
suppression test w 75g Glc (HGH after 60', 120' n<0.4ug/L, 2.6mU/I; cave Dm: false neg with chronic hyperglycemia); NET? (no pit lesion in MRI, GHRH
secretion from pancreas, GIT) -> CT-chest-abdomen-pelvis -> 68Ga-DOTATATE PET-CT scan or 111|n-OctreoScan → petrosal sinus sampling
TH: Transsph. adenomectomy (60% cure), random GH 1 day postop. (< 1ug/L), IGF-1 after 3 mths, evtl preop tu-reduction w dopamine agon. in
selected cases No remission postop: First line: somatostatin analogues good response expected if remaining adenoma is hypodense in T2-MRI
compared to temporal lobe; typ. SE: pain after inj., diarrhea, nausea, flatulence & abd.-pain (Tx: Creon®), gallstones. Cabergoline (2-7mg/week; response<25-
30%); Octreotide LAR (® 10mg/20mg/30mg/mth), Lanreotide (®, 60mg/90mg/120mg/mth response (60-70%) Second line Pasireotide (Signifor LAR®, 20->40-
>60mg/mth im, SE + hyperglycemia ) or Pegvisomant (Somavert®, 5mg<10<20 mg sc/d; response 80-90%); evtl. combination-tx Third line: RxT F/U ACRODATE or
SAGIT, MRI if changes in symptoms or IGF-1. Assess co-morbidities (colonoscopy, US heart & thyroid).
F/U: 3/6/12mtl, standardized: IGF1 n, HGH post Glc <1mU/L (<2.6mU/L; random (0'/30'/60'/120/240' <6.5mU/I), hypopit., VF, MRI, Met-PET?, US-ABP, Colonoscopy (5y)
Hypopituitarism IGF1& LH  TSH/FSH  ACTH  ADH ( pinealoma, hypothalamic lesion?), often sec. PRL
DD: Tu > St n Sx/Rx (rate of hypopit.: conventional 60% (+memory loss), sterotactic 40%, radio-sx 20% (+ rarely vision loss)) > Empty sella / post lymphocyt.
hypophysitis (typ obese F w headache, visual field, 1/3 w hypopit (ACTH>TSH>DI) > apoplexy (sudden headache, visual field, fever) / cerebral trauma / Sheehan-Sy
(postpartum, no lactation) > hemochromatosis > ”granuloma” > genetical
SY: dep. on hormonal defect HGH&PRL (p23)  LH/FSH (p17, 18)  TSH (p19)  ACTH (p6)  ADH (p24); evtl headache, visual
field (VF)↓ a/o visual acuity (VA)↓, hair (axilla, pubes, lateral eye brows), pigmentation (areolae), CSF rhinorrhea (postop, -Trace)
BT: IGF1 & HGH, PRL, Testo/E2 (postmenop FSH/LH), fT4, 1ug ACTH-test (latency 2wk, evtl IHT), P-Na, evtl. genetic testing
Size / Staging: MRI, VF testing, neurosx consult. Apoplexy (Sx: headache, visual acuity, hypopit, fever), RF relapse: craniopharyngeomas
Tx: Cortisone (p6), T4 (p19), E2/Progest. (p17); Testo (p18); HGH (evtl.), ADH (p24); pregnancy (p12)

Growth Hormone Deficiency (GHD)

SY: non-specific (fatigue, total/visc. fat mass , lean body mass + BMD, cognitive function, QoL, cvR )
DG: Sy & suggestive Hx & intention to Tx → IgF1 (age-adjusted); if hypopituitarism w <3 deficient axes → dynamic testing after
optimized Tx of other pituitary hormone deficiencies IHT (p6, n>11.5ug/L), GRF & L-Arg stimul. test, glucagon-stimul. test
TH: HGH sc qd (Norditropin® 5/10/15mg, Genotropin ® 5/12mg,, Saizen® 8mg, Omintrope® 5/10mg, Humatrope ® 6/12/24mg) or wkly (Somatrogon, start
0.1mg (old obese male) to 0.3mg (young slim female) qd. Titrate up (clinic, SE, age adjusted IGF-1), adjust 4wkly. F/U QoL,, LDL+HbA1c FU in stable GHD every
6-12m. Reduce dose with age. SE: joint pain, fluid retention, IGT, CTS…acromegaly. Consider costs (2.5-10k/y)

Pituitary Patients on Neurosurgery daily Endo-Consult ! S-Na → posterior pituitary function test (PPFT) p24
- preop. BT: PRL, fT4, Synacthen-test, evtl. HGH&IGF1, Testo or E2 (postmenop FSH/LH), VF, post. pituitary function (p24)
instruct patient (in writing): pause preop. Marcoumar & Plavix 7 days, ASS 100mg 5 Tage, Xarelto 3 Tage
- periop every pat. Fortecortin T-Sx 4mg iv BEFORE anesthesia (except M. Cushing, p5) T4 Subst if fT4<8pM
- postop: T+1: 2mg iv ; T+2&3 (08h): 1mg iv; T+3: S-Cortisol 07h  >450nM: stop; 250-450: HC if stressed!; 100-200: HC 10-20mg
morning; <100: 15-30mg HC/d, before discharge emergency sheet & set (p6), support groups f pat & relatives
- Polyuria (1-3d, 17%, transient) SIADH (2-7d, <2L supply H2O/d)  D.i. (permanent 3%, p24): 3-6h fluid balance & USG (urine >300ml/h for 3h
consecutive & urine specific gravity (USG) <1005) & at least one of the following: excessive thirst (numeric rating scale (NRS) >6 out of 10 → encourage pat to
drink & monitor P-Na, if >145mM & P-Osm >300mosmol/kg & pat. uncomfortable w polyuria)  Minirin 1ug sc, single dose, monitor, as often temporary)
- F/U: n 1, 3, 6 mo postop (basal hormone levels,1ug ACTH-Test); VF/MRI a 3-6mo, wt. (esp. post craniopharyngoma-Sx)

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 24. Water & Salt
Ce qui est important en medicine, c'est de comprendre avant d'apprendre.
[Link] ,
1) Osmolality P & U? (mmol/kg H2OFreezing point): POsm or SOsm: 280-300 mmol/kg = 2x(Na+K)+PG +Urea (+OH +NH3)
- Renal extraction fraction: Pre-renal Indices (Bock) e.g. Na: (UNa x PCrea)/(PNa x UCrea) x100 n 1-2%, prerenal <1%
- Range UOsm young: 50 - 1200mOsm/d  18 – 0.75L/d vs. old: 100 – 700mOsm/d  6 – 0.85L/d & Thiazide/NSAID 300-700 mOsm/d  0.85 – 2L/d
Maximum renal water clearance in middle age: 10L/d healthy; 5L/d renal injury; 1-2L/d NSAID, Thiazides (therefore Hypo-Na with normal drinking volume!)
- „Posterior pituitary evaluation“: Sodium, potassium, creatinine, urea and osmolarity in plasma AND spot urine. In addition, copeptin in plasma
2) Hydratation? Edema, weight trend, volume balance, Orthostasis, neck veins (0°/45°, HJR), HR, Mucosa, Urea, uric acid, Hk, Alb
- H2O-loss 1,7-20 L/d (1-10L skin&lung (sweat 100mM), Faeces 0.1-5L/d ; Urine 0.8-20L/d
3) Dynamics? Acute -Na  acute Sy  acute Th vs chron. (>48h)  oligosy  slow Th, volume balance?
- Acute Hypo-Na & Sy: NaCl 3% Bolus (100ml iv over 10min -> P-Na 2mM), Na-F/U 1h
- Chron.: aim: PNa <10mM/d (Pont. Myelinolysis!, RF: C2, K); if apl. Urea 100ml = 30g Inf 30’ 4-8h, 30-60g tid with orangejuice, Lasix 20mg iv 8h (H2O reabsorption)
- Infusions %→mM Na: 0.45% → 77; 0.9% → 154; 3% (=0.925L 0.9%+75mL 29%) → 513; 5.9% → 1009; 29% → 4959; Aequifusine →40 (K 20);
Ringer→131 (K 5.4); Mixed (Glc/NaCl 2/1)→51; Glc 5%→0;  PNa n 1L Inf: InfNa – SNa / (0.5xkg +1)

Hypo-Na DD: “Pseudo” (P-Osm): PG (S-Na 1.5mM pro 5.5mM PG), Hyper-Tg; ContrastAgents, Mannitol; Hyperprot./Myelom → (a)BGA; Pit-Adren-Insuff/ Hypothyr
I) UOsm <100mM/kg & POsm<280mM: ”habitual Polydypsia” ((Beer-) Potomania, Tea&Toast-Diet) Pg: <1000mOsm/d Narenal ClH20
TH: H20 & NaCl  (“Water”: Na <0.5mM, Bouillon: Na 120mM, NaCl 0.9%: 150mM, Seawater: Na 170mM)
II) & Uosm >100mM/kg (UNa>30mM; cave false high under diuretics!) → Pre-renal Indices (Bock) (P & U: Na, Creatinine, Urea, Uric acid)
a) FEUrea <35% & FEUric-acid <20% (or FEUrea >35% & FEUric-acid <12%)
→ Vol Diuretics (→stop!), Aldost, CSW (Polyuria & UNa>50 DD: SAB (S-BNP) CisPlatin) TH: NaCl 0.9% (-3%) & Florinef Tbl 0.1mg qd
UNa<20mM/kg: Diarrhea, Vomitus (P-Cl), Loss to “third space” (Pancreatitis; Burning, Trauma), Marathon; TH: 2-3L NaCl 0.9% iv/d
→ Vol (Na-Ret., UNa<20mM/kg): Heart failure, cirrhosis TH: H20<0.5L/d, Loopdiuretics, Aldactone
Nephrot. Sy, NSAID, pregnancy (Reset Osmostat & Oxytocin),TH: NSAID stop, Furosemid, if appl. Dialyse
b) FEUrea >35% & FEUric-acid >12% → Renal failure (Crea); S(I)AAD (Syndrom (In)Adäquater Anti-Diurese), TH: H20<0.5L/d
SIAD (P-ADH or renal ADH Sensitivity ; Stress/Disease (“SAAD” Syndrome of stress-adapted antidiuresis)
DG: Uosm >100 (> SOsm), PNa<135mM Posm >280mOsm & UNa >30 mM, P-ADH/Copeptin not helpful for Dg)
H2O-Excess (L): (1-P Na /130)x0.5xkg), Rule of thumb: each 4mM difference from 140mmM Na   1L H2O 

DD: Medi (ACEI, SSRI & tricycl. AD, Mo, NSAID (Prostagland.), Carbamazepin, Cyclophosphamid, Antra, Ecstasy, Ciprofloxacin, Cisplatin), Tu (SCLC ua),
Stress/Pain/Nausea, Lungs (Pneumonia, Tbc), CNS-Tu / Apoplexy / Withdrawal / Sx (5-7d postop, Glc 5% Inf!), HPA-Insuff, TSH,
Porphyrie, HIV, SIAD-like but no SIAD: Thiazide associated hyponatremia (hypo- or euvolemic), Cerebral Salt Wasting (hypovolemic)
TH: Treat underlying disease + correct concomitant Hypo-K (K 0.5mM  pro 10mOsm od pH 0.1; Correct Hypo-Mg+
1) Fluid restriction (Uosm <500mOsm, UNa+UK/PNa <1) (0.5-1L/d broth, fluid intake)
2) Free water clearance (Uosm >500mOsm, UNa+UK/PNa ≥1, “th-refractory”) 1) → a) «Osmoles» substitution: Urea 30 (15-60)g (0.25-0.5 g/kg/day)
in O-juice (30g = 500 mOsm), monitor BUN (Stop/Pause if >53mmol/L, cave: increasing dynamics especially if GFR <60mml/L), CI: crea >176umol/L, baseline BUN
>28,6 mmol/L, bilirubin >34umol/L, hepatic encephalopathy, digestive hemorrhage, gastric ulcer), protein enriched diet, NaCl Tablets (2-3g/Tag), SGLT2i
(off-label) / dietary Protein, NaCl 3% if severe Sy (Vomiting, reduced vigilance) iv: 150ml 3% iv over 20’ boli -> 1-3x -> check Na (Goal: Na 4-6 mM in the first 2h,
then 0.5mM/h; po: Tbl. 1g tid) cave: „isotonic“ NaCl 0.9% (300mOsm/L) leads to P-Na decrease because of AVP-fixed high Hyper-U-Osm (>300mOsm/L), despite an initial possible increase.
b) Uosm↓ if >500mOsm Tolvaptan n PoHI (Samsca® CHF100/d, Jinarc® CHF70/d, Tbl. 7.5 - 30mg, prefer for chron Hypo-Na e.g. every 2-3 Tag (costs), LFT! Interaction CYP3A4-inhibitor: Klacid ®, Grapefruitsaft),
Loop diuretics

Hyper-Na: “Pseudo” Hypoproteinaemia/Alb. →corr. sodium from (a)BGA

I) Na>H2O-Intake: iatrogenic, disrupt. thirst sensetion (UNa<5mM; neurosurgery (A [Link]), Tu, >65j);
II) Na<H2O-Loss: UNa<20mM D.i., Kidney (CI), UNa>20mM GIT (Lactulose), Skin (Sweat100mM; Fever:T1°C1L)
Polyuria-Polydypsia Syndrome (aka Diabetes insipidus (D.i.) OxyTUTION-Study if symptoms of psychological distress
DG: Polydipsia&Polyuria (Urin>50ml/kg/d (>2d &bw) SOsm>295, PNa >145mM  UOsm<300 (part 300-600 (800)) → DD:
I) AVP-resistance (nephrog. D.i.) DG: Copeptin (a) >21.4pM → DD: CKD, Urin-Solute (PG, Urea, Ca), K, SS, Li+, Cetafovir, Aminoglycoside, Cisplatin
II) AVP-deficiency (central D.i.): neurosurg. (1-5d postop, classic dg criteria p23, Copeptin 1d postop <2.5pM) > Idiop. > Tu/Granuloma/ischemia > Infect>
AUI, Pregnancy.> hereditary
III) Primary Polydipsia (“PP“, habitual Polydypsia): initial Na-n, less drinking at night & less Nycturia
DD II) vs III) (if appl. re-estab. of tub. osmo-gradient w. Bouillon/Isostar / fluid restriction (Fluid intake < Urine volume, evtl. Minirin1ug sc x 7d night )
a) Overnight-Water deprivation from 8 p.m. fluid restriction 2. Morning-Urine  Exclusion D.i.: UOsm >600-800mosm or UOsm/SOsm >2,5  sonst b)
(In the past: Controlled water-deprivation test in outpatient setting : Urine 06a.m., Breakfast without flid, no Nicotine, during test only solid food
8h of fluid deprivation v 8-16h; Aim/Termination.: Na >147mM; UOsm>600 (800) od UVol <90ml/3h, Weight>3-5%, BP, HF>100/', fever if after 6h fluid deprivation PNa<145mM (od SOsm <300 mosm) → b) )

b) 3% NaCl-Inf-Test 3% NaCl i.v. 250ml Bolus → 0.15ml/kg/min until Na>147-149mM (vBGA)

 Primary Polydipsia: Copeptin >4.9 pM ; AVP-Deficiency (central D.i.): Copeptin (a) <2.6 pM = complete, (b) <4.9 pM = partial
c) Arginine-Stimulation test : if b) not possible, L-Arg-HCl 21% Braun 0·5 g/kg bw (max 40g) in 500 ml NaCl 0·9% infused over 30’
→Copeptin 60’ n >5.2pM; <=3pM → AVP-Deficiency;3.1-5.2 pM → 3% NaCl-Inf-Test
TH(DI):Flpo/Glc 5% iv/NaCl 0.9%;Aim: S-Na 0.5-1mM/h,10mmol/d, H O-Need (L): Rule of thumb:1L Glc 5% → Na+ 4mM od (S-Na/140 – 1) x 0.5xkgKG,thrombosis prophylaxis
2

- >4l Diuresis / Nycturia: Desmopressin (e.g., Minirin®) 0.5-4g iv/sc  10-80g nasal (1-8 Sprays=0.1-0.8ml; Nocutil® Start: 10g)  Melting-Tbl. “Melt” 60-120ug 1-2 (-3) x daily (Start: 60g)
- Thirst sensation intact? Yes: drink to thirst (routinely omit / delay Desmo. -> hyponatremia); No: Management difficult! (Dysnatraemia)  daily Weight ( fix. Fluid intake)
- AVP-Resistance (nephrog. DI): Comilorid Mepha Tbl 5/50mg 1-2 Tbl qd-bid, NSAID (Indocid 50-150mg po or Brufen ret 800mg qd ), Minirin -40ug/d sc, NaCl po (Stop Lithium?)
Desmopressin-induced Hyponatremia => Educate on the ‘Desmopressin Escape’ Method = Delaying or omitting a dose (up to several times/week) of Desmo until Aquaresis & Strong Thirst occur => Signal for next Desmo Dose

F/U: Weight, Balance P & U Na, K, Crea, (Urea, Osm) daily  1x weekly 3 monthly (cave thirst sensation with Age)
Neurosurgery: 12-24h fluid balance, P&U-“Block I” (Na, K, Crea, Urea & Osm) Stressprophylaxis? PG?

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 25. Rare Diseases & Inborn Errors of Metabolism
Genomes speak biochemistry, not phenotype
Metabolic center USZ 044 266 7111, [Link]
Overview nutrition, Flyers rare diseases (DE, FR, IT, EN)
Newborn Screening (NBS, Guthrie-Test) 72-96h after birth.: TSH, 17-OH-progesterone, PKU, galaktosemia, biotinidase, MCADD
ER-Tx: Glc 1-2L 10-20% per Inf qd, avoid proteins  initially& a 2h VBGA for acidosis & hypo-Na
CAVE: highdose Glc contraindicate in PDH-deficiency a/o lactatacidosis, administer NaCl 0.9% iv)
PhenylKetonUria (PKU): Incidence 1/10’000, >400Mut.; PAH (=Phenylalaninhydroxylase) Phe → Tyr( Dopa, A, NA)
Formen: PKU  diet required; MPH (mild PKU)  no diet if Phe<600uM (except in pregnancy!)
Cave: maternal PKU  fetopathy in mothers with PKU  family planning!; start diet if desire to have children with target Phe<400uM
SY: Adult: diet mal-compliance (social reasons?)  attention & performance (Phe >900-1200um/l (>15-20mg/dl)
Neonatal: mental retardation, seizures, spasticity
Tx: low-protein diet acc. Phe-tolerance, supplement essential aminoacids & trace elements (ERB UKBB)
F/U: 1.-[Link]/pregnancy: Phe 40-250uM (0.7-4mg/dl); after 10/12.Y <600-900uM (<10-15mg/dl), no 50-80 uM
Tx if hosp: assure PKU-diet, rel. calory intake to avoid (protein)-catabolism
Prg: normal development & IQ if early and efficient tx
Maple Syrup Urine Disease (MSUD) mitoch. degradation branched-chain AA (Val, Leu, Ile)   toxic ketone bodies & Alloisoleucin
SY: Adult: metabol. derailment due to catabolism or malcompliance (infection, stress, Op, too much protein)  cerebral edema w vomitus,
apathy, ataxia, evtl focal neurol sy  ketoacidot. coma;  chron. ment. retardation, osteoporosis, [Link]
- Neonatal: metabol. enzephalopathy: lethargia, drinking weakness, somnolence, cerebral edema, aoma
Tx: - low protein diet (Ile, Val, Leu) acc. Leu-tolerance, supplement essential aminoacids & trace elements (ERB UKBB)
- Evtl thiamin (cofactor) (5mg/kg/d po), carnitin po if deficiency documented
Target: Plasma-Leu <300-450uM (4-6mg/dl), acc. to plasma-AA; cave Ile (>75uM resp. 1mg/dl, else addition)
Tx if hosp: if imminent metabol derailment acc Emergency leaflet! (+ consult UKBB, cave: cerebral edema): prot. fasting max. 24h, force
anabolic metabolism (Glc, iv! evtl. Insulin), detox: diuresis, ev. hemodiafiltration
Prg: b rascher (v [Link].) u konsequenter Th normale Entwicklung und IQ
Methylmalonaciduria (MMA) Vit.B12 – dep. mitochondrial degrad.  (Ile, Val, Met, Thr, odd FFA, cholesterol)
 MMA & propionyl-CoA  keto-(lactate)-acidosis/ carnitin / NAGS NH3; ev PG, Tc-, Lc-penia, ca
SY: Adult (& neonatal): metabol. derailment due to catabolism or malcompliance  see MSUD
- Chron. complications: metabolic stroke (basal ganglia), IQ, cardiomyop., pancreatitis, osteoporis, interst. nephritisCKD
Tx:  MSUD (Ile, Val, Met, Thr) acc Val-tolerance, L-carnitin 50-100mg/kg/d gem. carnitinstatus / acylcarnitine; hydroxycobalamin 1mg iv od im 2-3x/w b. Vit.B12
-sens., argininhdrochlorid (up to 1mmol/kg/d iv or po) b. NH3; evtl flagyl (10-20mg/kg/d p.o. x 10d/Mon  endogenous propionacid build-up
Target: Urin MMA <960mmol/mmol crea, acc to plasma-AA (Thr>80, Gln<800, Gly<400, Val>100, Met>25, Ile>25 uM)
odd fatty acids (C15,C17) <2%
Tx if hosp: see MSUD; maximise excretion of MMA (diuresis, carnitin iv, 1mg Vit B12 iv/d)
Prg: depending on the severity of the defect / Th efficiency / frequency of SW derailments (oldest patient to date 45 yrs.)
Medium Chain Acyl-Carnitin Dehydrogenase Deficiency (MCADD): Inc 1/10’000, defect degradation mediumchain fatty acids
Sy: Adult: muscular symptoms, impaired consciousness, vomiting after trigger (fasting, sport, alcohol, op, infection)
Neonatal: «Reye-Sy-like»; encephalopathy, ev. early lethal, NBS since 2005
Lab: metabolic acidosis ↑ ammonium, ↑ lactate, ↑CK, ev. ↓PG (late), acylcarnitin-profile
Tx: Acute: Glucose i.v., long-term therapy: regular meals, know triggers, ev. carnitin
Prg: Normal development with correct therapy
Urea Cycle Defects: Ornithin-Transcarbamylase deficiency (OTC, x-chrom.), Citrullinämie, Arg-Bernsteinsre-KH (ASL), Argininämie, CPS,
NAGS; Inc. cumul. 1/8000. insuff. NH3-detox. from aminoacids decay DG: NH3 (>80M), Glutamin (>700M, Pufferfunktion, «HbA1c des Ammoniaks»)
SY: Adult: metabol. derailment due to catabolism or malcompliance (triggers: Infection, stress, op, birth, protein load)  chron neurol sy
enzephalopathy, behavrioral abnormalities w confusion, psychosis, lethargy. OTC-females may manifest in adulthood only
Tx: - low protein diet acc. NH3 / glutamine, suppl. essent. AA & tracelements (ERB UKBB); arginin a/o citrullin dep. on defect
- Na-benzoate a/o Na-phenylbutyrate po (detox NH3)
Target: NH3<80M, plasma-glutamine <800M, acc. to plasma-AA; Ile>25M (if below endogenous protein catabolism)
Tx if hosp: Emergency leaflet!; in addtion to Na-benzoate ev Na-phenylacetat e& arginine-HCL iv,; if NH3>400M > 4h  hemodiafiltration
Prg: with rapid (< 5days) & consistent tx normal development 6 IQ possible (OTC-boys often lethal, ASL often IQ)
Fructose Intolerance Fructose & Sacharose  ATP-need  uric acid i S , PO4 hepat. phosphorylase
SY: typically apparent when switch form breast milk to formula  vomiting, hypoglycemia, fibrinogen deficiency, NH3, fructosuria
Tx i hosp: Glucose iv, avoid syrup meds, saccharose-containing Tbl-coating usually ok
Prg: normal, if fructose, sacharose, sorbitol avoided: no sweet foods, no fruits: "sweets = disgusting"
Glykogenosis Type I: Mut. Glc-6-phosphatase (Typ Ia, G6PC), resp. trsp in ER (type Ib, Leber, Niere, SLC37A4)
SY: recurrent hypoglycemias w epileptic fits, acidosis, doll’s face, truncal obesity, short stature, failure to thrive, hepato- & nephromegaly, hepat.
adenomas, bleeding tendency; type Ib: & neutropenia (<1500/l), leucocyte functiontbact. infections, diarrhea IBD, type III: & myopathy
DG: Glc (fasting), lactate, uric acid, transaminases , TG (u. chol.) ; oGTT lactate; molecular genetics; enzymatics (liver)
Tx: Emergency leaflet! cont Glc-intake: meals 2-4 hrly: slow resorb. carbs (maltodextrin); at night uncooked cornstarch (Maizena ®, Glycosade ®) or pasta at
bedtime or tube feeding; limited fructose (vegetables, fruits),; ca-containing soy-based milk products; empagliflozin 10mg/d off label ,evtl. allopurinol. Type
Ib: G-CSF (Neupogen®) 2-3g/kg 2-3x/wk
F/U: >60% carb in meals; target PG 4-6, pp<8 mM; lactat e→ (also 24h-urine),TG, uric acids, transaminases; Liver-US 6mthly.; from 14yrs crea
& microalbuminuria, gonadal function & BMD, polyneuropathy, ferritin
Prg.: Leberadenoma (HCC!), osteoporosis, CKD, gout. delayed in optimal conditions, cave: hypo’s vs overnutrition (Obesity & IR)

Galactosemia: → Emergency leaflet!

Mitochondrial Disorders: → [Link] (Drs. J.-M. Nuoffer & A. Schaller, Inselspital od Prof. M. Baumgartner USZ)
X-chromosomal Hypophosphatemia: Self-help gorup Phosphatdiabetes

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 26. Gender Incongruence & -Dysphoria
Happy is the person who knows how to break with circumstances, before they have broken the person
Amicum esse unum animum in duobus corporibus.
[Link] ; [Link]
Prevalence: 0.5-3% of pop., MF 60/Mio > FM 25/Mio trans-terminologies, legal aspects
DEF Persistent desire to live and be recognized as a member of the opposite sex (= gender incongruence). Is no longer
considered an "illness" per se. However, it is usually accompanied by a feeling of discomfort or not belonging to one's own gender
and psychological distress (= gender dysphoria).
SAB = sex assigned at birth; gender identity = internal sense of own gender (f, m., both, neither); gender incongruence = gender identify differs from SAB;
gender dysphoria = distress with gender incongruence; cisgender = gender identity is concordant with SAB; transgender = umbrella term (i.e., transgender;
gender diverse, gender nonbinary); transgender women (“transfeminine”) = female gender identity, assigned male at birth (AMAB, MF); transgender man
(“transmasculine”) = male gender identity, assigned female at birth (AFAB, FM)
 imperative desire for hormonal & surgical Tx, to adapt one's own body to the preferred gender

DD Endocrinological intersex. (AGS, testicular feminization); psych. dist. (schizophrenia, „self-dg“ transsexualism); Homosexuality
m effeminate behavior, transvestitism (does not categorically reject her own sex, less suffering pressure, "after work transsex")

TH
Interdisciplinary working group due to complexity of the problem & division of responsibility, "Team Basel": psychiatry,
psychology, endocrinology, urology, ENT, plastic surgery, gynecology. Surgery, Gyn. formalized and written patient info &
consent by MD. Individual and stepwise approach. Different DD & tx for adolescents vs adults,
Plast. Surgeon responsible for protocols & scheduling. The following guidelines only apply to adults.

1) First contact In principle, psychiatrists or psychologists belonging to the working group upon written referral by
external MD (usually psychiatrist)  Pat-Info on procedure & obtaining consent for information exchange within working group
& treating MD: female to male (FM, AFAB) D (F); male to female (MF, AMAB) D (F)
Patients “directly assigned to Sx” from outside (ie, levels 2-5 made externally)→“Second look” d members of the working group (files, evtl
consult.)
2) Psycholocial stabilisation Tx by external psychiatrist or psychol. (Dg-security & DD, consistency in desire for gender
reassignment, stabilization of personality)  final report f re-referral to team psychiatrist or psychiatrist

3) Med. clarification of gonads / co-morbidity: Proof of normality & exclusion of endocrinopathy &
contraindication for drug therapy & Sx by endocrinologist, signed patient info on hormonal tx → referral to op with report
Status: Internist. status, incl. endocrine (genitals, testicular volume, gynecomastia, hair growth). FM referral to OBGYN, mens. calendar
Dx: PRL, FSH, LH, Testo, SHBG, E2, 17-OH-Prog, PSA, TSH, BB, Chemogr, PG
evtl 1mg DST HIV, hepatitis-Serol, Lues, chromos. Analyse, Th-Rx, EKG, MRI b. idiop. Kopfsz od Hypogonad., Gerinnungsabkl.

4) Surgical consultation & Pat. Info:

Exclusion of surg. contraindications & patient information as part of a consult  report

5) Opposite-sex Hormonal Tx & „Cross-dressing“ 1-2 years regular F/U on endocrinology, with continuation of
external psychological support (psychological stabilization) & everyday life test (testing the external transsexual viability in
society; wearing opposite-sex clothing privately & professionally), depending on the canton, gender-neutral first name possible
FM: T undecanoate im (Nebido) increasing 500 - 1000 mg 3-mthly evtl. T enanthate (Testoviron Depot) 125-250 mg bi-wkly im
Ziel&SE: Amenorrhoa, voice break (irrev), clitoris, Acne, hirsutism, musculature ,  psychis, breastatrophy; T middle norm
MF: Preoperatively (dual-phase hormonal schedule)
1. Spironolactone Tbl. 100-200mg qd; cyproterone acetate (Androcur ® tbl. 10mg (cave meningeoma; art. hypertension) qd; finasteride
Tbl. 5mg; (Bicalutamid 50mg/d, GnRH-analogues)
Ziel: Suppression erections, ejakulations
2. E2:- transdermal E2 > 40 J (Estradot) 50 – 100 g, 2x/Wo
- E2 (Estrofem) 1-2mg BP – tid;
Ziel: Gynäkomastia (50%<B-cup), erection, testicular atrophy., female fat distribution.,  psychis
SE: Migräne, TVT (Perioperative Management E2 6Wo preop stop? individual decision (associated risk factors (smoking, BMI)?
Long immobility expected?) but basically continuing GAHT seems to be safe), worsening of epilepsy, hepatitis (Androcur),
PRL(>100ug/LMRI), cholelithiasis

6) Interdisciplinary Decision on Sex Reassignment Sx Personal introduction, questions & wishes of pat.,
presentation of alternatives (e.g., epithesis), presentation of the irreversibility of the Sx (sterility, sexuality), evtl phoniatrics.
Preop. Communication of decision to external MD & obtaining cost approval from surgeon; postop. legal name & gender change
via psychiatric report; before Sx discuss patient info with patient again
FM: Colpohysterectomy, mastectomy, evtlibly penile reconstruction surgery
MF: Orchiectomy, neovagina, evtl. breast augmentation plastic surgery & laryngectomy (ENT), postop. Epilation (PoHI)

7) Lebenslange VerlaufsKo Psychological support, often re-op. necessary, often difficult patients (depression, HIV),
<1% regret op, even if outcome poor; lifelong hormone therapy necessary
F/U: Risk assessment PE & CVD (risk MF>FM) & STDs without stigmatization (HIV risk MF>>FM)
general cancer screening (PAP smear, colo, breast)
FM: HRT: cont. testo (T middle norm); F/U: BP, Hb, LFT, lipids, testo, osteoporosis, risk for MACE 40%
MF: Postoperative E2 low – middle norm ( ½ preop. E2-Ds); evtl Androcur ® 10mg/d; transdermal E2 (Estradot ®) 50 – 100 g, 2x wkly
> 40 yrs.; E2 (Estrofem ®) 1-2 mg BP-tid F/U: Mamma, BRCA2- if at risk, BP, lipids & other cvR, edema, prostate (PSA, if
available), LFT, bone, prolactin (up to 10-fold increase “physiological”)

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 27. Hormones in Polymorbidity
"The good physician treats the disease; the great physician treats the patient who has the disease” W. Osler

- Stress hyperglycemia close PG-monitoring (day, evtl. night) if >10mM → insulin → target PG 7-10mM & AVOID
HYPOGLYCEMIA & PG variability  mortality benefit controversial, causes: stresshormones, cytokines, drugs (steroids, thiazide, -blocker,
prograf ®, CyA, proteaseinh, atyp. antipsychotics)
- Pituitary gland acute stress: HGH, PRL, HPA , other axes supressed; pronlonged stress → also HGH ( growth  in children)
- Pineal gland melatonin-deficit Causes. 1° (congenital, anatomical or synthesis deficit, tumors), 2°: shift work/jet-lag, neurodegenerative
diseases, blindness, drugs (e.g., -blocker, calcium channel blockers) Tx: Circadin ® 2 mg ret ≈1h before sleep
- NNR Cortisol & blunted daily rhythm initial 5d, tissue-specific titration of glucocorticoid rec.  action→ «CIRCI», Stressprophylaxis! (p6)
- Thy Euthyroid sick syndrome (p19) with TSH range 0.1 to 20mU, cave: no T4-Substitution, low T3 = prognostic marker
- Gonads Hypogonadotropic hypogonadism, lipids: Tg, HDL-C & LDL-C (prognostic marker)
- Ca2+: ion. Ca, iPTH, esp. bacterial infection, Procalcitonin (PCT) (ua)  Hormokine-guided antibiotic therapy
in respiratory tract infections“ (evidence grade A, >6000 patients in RCTs, PSI, CURB-65)
< 0.1 ug/L AB NO ! 0.1 - 0.25 ug/L AB no 0.25–0.5 ug/L AB yes >0.5 ug/L AB YES!

PCT control 6-24 h; AB therapy („overruling“) If on AB therapy:

- Respiratory or hemodynamic instability, ICU Reevaluation on 3, 5, 7 d, incl. PCT
severest comorbidity - Stopp AB with same cut offs
- PCT <0.1: CAP w PSI V / CURB>3, COPD GOLD IV - Initially very high PCT (i.e. >5ug/L):
- PCT 0.1-0.25: CAP w PSI IV & V, CURB>2, Stopp when 80-90% decrease of peak PCT
empyema, complicated pneumonia, COPD GOLD - Outpatients: AB Duration (0 to 7d) based on
III, last PCT level
SaO2<90% & 30‘ intensive therapy

Endocrine-metabolic changes in chronic diseases

HIV/AIDS Wasting-Sy  Euthyroid sick, gynecomastia w 1°& 2° hypogonad, 1° adrenal insufficiency, hypoglycemia (drug-related p10)
- Lipodystrophy RF: visceral obesity: protease inhibitors (40% a >1J esp. age, HIV duration, tx-response); Lipoatrophy: nucleoside analogues (Stavudine, Zidovudine);
PG: PPAR u/o SREBP1c, SY: fat face, extremities, fat (neck „buffalo hump“); insulin resistance, dyslipidemia (TGpancreatitis, HDL), PG, MASH; rarely PCO,
acanthosis nigricans, acromegaly (IgF1/Insulin); TH: adapt HIV-Tx, nutr. counselling (fat, „fast“ carbs, OH), sport, metformin, pioglizatone (Competact® 850mg bd),
fenofibrate (Lipanthyl ® 200Mg qid), rosuvastatin (Crestor ® Tbl 10-20mg (Cyp4504A4w HIV-Tx), Acipimox, HGH od GnRH (PoHI)
Cystic Fibrosis Hypogonadism, osteoporosis (leaflet); maldigestion / exocrine pancreatic insufficiency Tx: Creon®, supp. fat-soluble vit ADEK , CF-
related Dm (CFRD): Dg 2h-1.75g/KG-oGTT w 0, (1,) 2h, HbA1c, CGM (educational but not diagnostic), Tx: Insulin (prandial often sufficient, anabolic), trial w oral agents (Ripaglinid®, Sitagliptin®) in
mild forms, CSII, Closed-loop.
Tumors Breast & pulmonary Ca: Cushing-Sy (ACTH/CRH), prim. Adrenal insuff. (bilat. adrenal metastases), SIADH, tumor cachexia (p14)
Liver failure: E2 & SHBG, fTesto, ascites→ Hypo-Na→sek. hyperaldosteronism, Tx: Spironolactone (Aldactone 25-200mg/d)
Renal insufficiency / dialysis (ClCrea <50ml/’) renal osteopathy (rarely fractures), hypogonadism, HGH ( & Thy), PRL,
- 1-25-VitD Ca sec. HPT: calcitriol (Rocaltrol ®, evening, PTH<300pg/ml: 3x0.25ug wkly; PTH>300pg/ml: 0.25-0.5ug/d), ViDe 3 ® 3 8-10Trpf/d if ClCrea>40ml/’),
- Ca-CO3 (3x1-2g w meals), "Pseudogout" (uric acid, CaxPO4>2.5mM) PO4 (goal <1.6mM): sevelamercarbonate (Renagel ®), cinacalcet (Mimpara ®)
goal PTH < 300pg/ml; if >>400pg/ml  ad Sx (resection of all parathyroid glands w retransplantation of 1/8 in forearm);
- Hypoproteinemia, met. acidosis, S-K  nutritional counselling: diet low on potassium, protein-adapted (chron CKD (<0.8g/kg/d), normal protein amount if nephrot. Sy)
- Anemia: Erythropoietin (Epo ®, substitution at dialysis
Alcohol (C2, OH): = "PanTissueToxin"  sec. hypogonadism, infertility, pankreatoprive Dm, PRL, cortisole  (Pseudo-Cushing, p5); TBG
 TT4, Vitamins: B12, folic acid, D  Ca&PO4 (a HypoPTH due to Mg) Tx: Vit B1 (Benerva ® 100mg iv), Ca, Mg, PO4, anti-addictive effects of GLP-1 Agonists?
Psychol./Psychiatr.-Sy Depression/asthenia DD: Hypothyroidism, hyperthyroidism in elderlies, Cushing Sy, M. Addison, PRL, Hypogonadism, pHpt,
acromegaly, Mania: Cushing (incl. Steroidtx), hyperthyroidism, Panic attacks: Pheochromcytoma (p4), Aggress: Testosteronprod Tu
Hemochromatosis: Dm (p7, pankreatopriv & insulin-resistance), hypopituitarismus (p23), hypogonadism (p17), osteoporosis (p16)
Porphyrie: when & how to diagnose [Link]@[Link], SIADH (p24),
Short bowel Sy: DD: M. Crohn, mesenteric infarction / trauma / Sx / radiation, bariatric surgery, Sy per intestinal section Duodenum: Ca
(osteoporosis), Mg, PO4, zinc, Fe (anemia), folic acid; Jejunum: Na, K, Glc, amino acids, water-soluble vitamins, trace elements, ulcers (Gastrin) & gall stones;
Ileum: Vit B12 (esp. 50cm before ileocecal valve), bile acids (diarrhea, E’lyte losse, esp. Na, K, Mg)  cholestyramine, fat (steatorrhea), essential fatty acids a
fat-soluble vitamins; Colon: H2O (dehydratation), E’lyte (Na, Mg, Ca  steatorrhea & calcium soaps, oxalate if colon intact  nephrolithiasis), medium-chain TG
(MCT) Tx: Stage I (hypersecretion (weeks to months); typ diarrhea, H2O & E’lyte loss, somatostatin 100mg sc tid; omeprazole 40mg qd) TPN (requirement:
25-30kcal/kg/d; Glc 5g/kg/d, fat 1.5g/kg/d (30% of energy); AA 1.5g/; 6-8L 0.9% NaCl/d (Na 300mmol, K 150mmol, target urine >1L/d). Stage II (adaptation, stool
volume <3L/d, months to years); combination / transition TPN /drinking food / elective food (p14, steps 6 →1, „slowly but surely“, 30-50kcal/kg/d, 50%
CH, 20% prot, 30% fat (evtl. MTC). Stage III Stabilisation. Long-term complications: Anemia, osteoporosis, if colon → fluid loss, evtl. loperamide before
meals & bed rest, 6-20mg/d, evtl. opiates, sandostatin, Ca-rich diet (nephrolithiasis); F/U: 3-monthly chemogramm, iron status, PG, HCO3, lactate, blood count,
INR, , Zn, Se, folic acid, Vit B12, B1, A, D, E. Stoma daily weight, losses of fluids- Na- & Mg- w Ileostomy, Tx: Boullion, omeprazoel Tbl. 40 qd - bd; loperamide
(Imodium ®) Tbl. 2mg, -8Tbl./d, sandostatin; fatty stools -> Quantalan ® Sach. 1-2 tid, distal ileum: Vit B12, folic acid, proximal ileum: vit. C, B, ADEK, Zn, Cu, Ca,
Mg, Fe u evtl subst. (sa), Ca-po due Oxalate kidney stones, evtl. PoHI f GLP-2 Analogon (Revestive®) to increase resorbtive capacity (expensive!)

Drugs: patient information, e.g., Lithium: Hyper- (p20) & hypothyroidism (p19), goiter (p21; Tx: T4, surgery), SIADH od nephrogenic D.i. (p24 -> Tx: amiloride (if
hypercalcemic), evtl. + thiazide (Comilorid ® 5/50mg qd-bd; ); hypercalcemia (p16-> Tx: cinacalcet, PTx); F/U: before start & 6-12mthly:: TSH, fT4, TPO-Ab, Ca, creatinine,
Cordarone (p21), Neuroleptics (PRL (p23), Dm (p7f), obesity (p13), -blocker: hypoglycemia-awareness
mTOR/Tyrosinkinase-Inhibitors: Glc & LDL-C , Tyrosinkinase- & Immunecheckpoint-Inhibitors: hypophysitis,; dysthyroidism (mostly destructive
thyroiditis, rarely Graves disease, p22 & 19); IDDM, adrenal insufficiency. Alemtuzumab b. MS: dysthyroidism (Graves diseases w (inh.) TRAK) Abirateronacetat:
adrenal Insuff → steroid substitution, emergency card, Ferinject: hypophosphatemia (Fe-carboxymaltose (75%)>Fe-cerisomaltose (8%, Monofer®); mostly
transient, FGF23 mediated). Cytochrome-drug-interactions

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 28. This & That
"It takes considerable knowledge just to realize the extent of your own ignorance." → basic literature

Before you examine a patient in the clinic, the corresponding page / section in the pocket guide must be read & understood!

A) Start in the outpatient clinic (EDM KSA):

Concept for continuing medical education CME EDM KSA: continuing education contract incl. catalogue of learning objectives, logbook, [Link] --> SWIF
Congresses / external continuing education (KSA template for reimbursement of costs; guide for completion; regulations)
Wednesday Swiss Grand Rounds (every intern 1x per year, in English, topics according to Pocket Guide);
EndoDiabNet continuing education for interns & residents every 3 months Thursday afternoon (presence in person desired).
Rotation planning for interns: Checklist KSA for the start in the outpatient clinic:
Read out apps for blood glucose (BG) devices to computer, necessary passwords and accesses, etc. -> please check before the first consultation whether
everything is available and functioning.
Meeting minutes of (tumor) boards & colloquiae (templates for KSA)
B) Consultation of out-patients (“Sprechstunde”):
Registration of out-patients (Wegleitung “Anmeldungen” KISIM → Dashboard),
Discussion of questions “how to” if possible in the evening report preceeding the consultation, otherwise via supervisor “ad hoc”
Laboratory orders (in principle already in registration, as an exception following consultation, then phone request to outpatient nursing team (KSA Ambipflege)
6819/6813/6815) and order directly in KISIM curve), genetic tests (duration of evaluation up to 4 months),
Interpreters (“Dolmetscher” a) in person: organize via administrative staff b) alternatively digital tool: POCKETALK
Missed consultations: 1) SMS E-call; 2) in case of repeated (inexcused) no-shows: case closure after writing final report with copy to referring physician (KSA:
KISIM templates stored common favourites EDM)
Patient refuses relevant exam or treamtment: statement of refusal waiver "Verzichtserklärung" (D/F), have it signed by patient.
Report to referring physician: After initial consultation, then once a year or when therapy is adapted (KSA KISIM: report templates → common favourites, mail
report to secretary for correction & billing, secretary starts workflow for signature/visa)
C) Consultation service of in-patients (“Consultien”):
“On-call” phone KSA 6885 from 8:00-8:00 a.m.; supervisor available at any time for any questions if required, consults on MIC/IPS consult supervisor if in doubt,
Daily online blood glucose (BG) screen on neurology & surgery wards with KISIM (KSA): limits BG value >10 and <3.5mmol/l -> document in KISIM curve.
Thyroid-Board ENT (“HNO”) Wed afternoon H60.
Background duty during the night (for telephone no. for supervision, see list of secretaries). Consili-report: KKK (short, concise and clear), in particular procedure
prescription-like, clearly formulate who checks when and where; tel. feedback to consili-provider whenever possible; when completed: create direct work-flow (in
contrast to outpatient reports).
D) Billing:
Billing of consultation hours via IBI-Care (KISIM → [Link])
-> list ALL materials, incl. dressings / sample sensors / ketone bodies; important: credit insulin pump therapy if available; diagnosis codes for statistical purposes;
In each case indicate complete time needed (i.e.,reading of consult & referral letter, check lab results, preliminary discussion, way to ward & back, looking for and
studying of files, trying to reach ward physician, debriefing (general “rule of thumb” new cons. 60min; follow-up consult 45min.
Also charge for unscheduled telephone consults and/or e-mails, dated correctly
If no inpatient case exists: report as "work in absence" (or have case opened) -> discussion with therapist OR (depending on case) have EDM case opened;
List of relevant TARMED codes.
Requests for reimbursement of costs to health insurance companies ("PoHI"): It is important to state that the assumption of costs is made within the
framework of KVV Art 71 ("imminent danger") and that previous therapies did not help (most medical officers of health insurers will ask that).
Most medical officers of health insurers (“Vertrauensärzte”) do a benefit assessment according to the 9-field model
(for details see here: [Link]
In case of rejection, it is advisable to persevere and talk to the medical officer in person. It may be possible to get a therapy trial (i.e. first three/six months paid by
the pharmaceutical company, then the costs are covered).
Procedure for patients with of a suspension of services of health care insurances (“Leistungssperre”).
E) Emergencies:
Rapid HbA1c (for ambulatory care); ketone bodies capillary (KSA device in large US room 03); Diabetic foot -> see Pocket Guide p.7
“Hypo-Box” for ad hoc help in case of evident hypoglycemia (in cupboard between room 25 / room 24); Addison set (ambulatory care).
Emergency transfer from outpatient clinic to INZ: tel. service OT INZ MED 1900, CHIR 1950 (tel. no. transport service: 4780,
REA alarm 999 - ONLY possible via landline!.
F) Journals
[Link]; [Link], [Link], [Link]; ongoing studies: (according to updated list)
G) EDM-Drugs dynamic endocrine function tests, compassionate use , administration & crushability of pills.

Suggestions / Wishes / Criticism welcome, also positive ones

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 29. Laboratory Reference Values
Hormones can only be interpreted with knowledge of assay, pathophysiology, age, gender, drug interactions & co-morbidity
Emergency determination possible, take & centrifuge samples on ice, thyroid & gonadal hormones from serum or heparin plasma, waiting times
Pituitary Gland Gonads (F 3rd day of cycle (follicular phase; Adrenal Gland
S-IGF-1 (1nM=7.6ug/l, F luteal > M) if amenorrhoeic 3d after gestagen test) Cortisol (27.6nM=1ug/dl) 85 - 638nM
16-39Y 16 - 52nM LH 23.30Uhr i Saliva <1 - 2.5nM
40-54Y 10 - 40nM prepubertal 0.2-5mU/L 8h n 1 mg Dexamethasone < 50 (90)nM

ab 55Y 6 - 30nM F follicular 3d (0-8d) 2.4 - 12.6mU/L Urin (FUC, 2.76nmol/d=1ug/d) < 500nM/24h
Susp of GH-Mangel <11 (<17)nM F midcycle 9-14d 14 - 96mU/L FUC/U-Creatinine <70nmol/mmol
S-HGH (1ug/l=2.6mU/l=46pM, IF-assay) <11.5mU/L F luteal 15-30d 1.0 - 11.4mU/L 30' n 1/250ug Synacthen® >500/550nM
1 or 2h after 75g Glc <2.6mU/L F postmenopausal 7.7 - 58.5mU/L 11-Deoxycortisol (CS, 1nM=29ug/dl) <12nM
M 1.7 - 8.6mU/L 8h n Metopirone >130nM
Peak n ITT >13mU/L
Peak n GRF&Arg Stimul >11mU/L Peak a GnRH (30’ od 60’) >15mU/L ACTH Plasma (1pM=4.5ng/L) 7 – 50ng/L
GHRH <60ng/L FSH basal, Morgens, no Stress <20ng/L
S-Prolactin (PRL) (1ug/L = 21.2 mU/L) prepubertal <2mU/L Aldosterone (2.77pM = 1ng/L)
M/F 86 – 324 / 102 – 496 mU/L F follicular 3d (0-8d) 3.5 - 12.5mU/L upright / 60’ supine 110 - 870 / 80 - 450pM
Gestational-Trimester I:1000; II:2000, III:4000mU/L F midcycle (9-14 d) 4.7 - 21.5mU/L n NaCl <240pM
20’ n 0.2mg TRH iv (30’ nasal) <2x F luteal (15-30d) 1.7 - 7.7 mU/L Urin <33nmol/d
F postmenopausal 25.8 - 135.0mU/L aPR (active P-Renin: 1ng/L=1.67mU/L=0.0237pM)
Water, Elektrolytes, Acid/Base M 1.5 - 12.4mU/L (aPR [pg/ml] = PRA[ng Ang I / ml/h] x 8.8 + 6.6)
P-Sodium (“Na”) 131-142mM Peak a GnRH (30’ od 60’) >10mU/L upright / 60’ supine 2-20 / 2-10mU/L
Balance (5-15g/d) 40-150mmol/d -HCG <4.5mU/ml ARR=S-Aldo/aPR-ratio <30 (>35)pM/mU/L
P-Potassium (“K”) 3.5 – 4.7mM Testosterone, total (1nM=28.57ng/dl) PRA (PlasmaRenin Activity) 0.98-4.18ng/ml/h
Balance (3g/d) 60-100mmol/24h M 40s / 50s 8.7 – 31.7 / 7.5 – 30.4nM S-Aldo/PRA < 20 pg/ml / ng/ml/h
Urine in hypokalemia <30mmol/24h M 60s / 70s 6.8 – 29.8 / 5.4 – 28.4nM resp. < 555 pM / ng/ml/h
aBGA pH / -Range 7.40 / 7.35-7.45 M Pregnyltest (max. d4) 1.8-2.8 Metanephrine (NM)
PO2 70 – 100 mmHg bzw. 10.7-12kPa F 0.2 - 2.9nM Plasma, free 0.012-0.12ug/L = 0.06-0.61nM
PCO2 35 – 45 mmHg bzw. 4.7-6kPa FTI = Free Testosteron Index (%) Urine, total <1500nmol/24h
(Testosterone (nM) / SHBG (nM) ) x 100
Bicarbonate (HCO3-) 22-26mM M/F 20 – 81 / 0.5 – 8%
Urine/Crea 10 - 200nmol/mmol
Lactate 0.5-1.4mM Testosterone, bioavailable (NH4-Sulfate Precipitation) Normetanephrine (NMN)
Chloride (Cl-) 97-110mM M. / F 2.3 – 14.6 / 0.02 – 0.2pM Plasma, free 0.022-0.17ug/L = 0.12-0.92nM
Base Excess (BE) -2 bis +2mM Testosterone, free (Equlibrium Dialysis) Urine <4500nmol/24h
M/F 38.1 – 142 / 2.1 - 11.1pM
Aniongap (AG) 8-12mM Urine/Crea 40 - 250nmol/mmol
Estradiol (E2) (3.7pM=1ng/L) Adrenalin (A), Epinephrine
P-ADH / Vasopressin (AVP) 2 - 12pg/mL F follicular 3d (0-8d) 90 - 716pM
S-Osm 280-300mOsm/kg Plasma 4-83pg/ml = 0.02 – 0.45nM
F midcycle 9-14d 243 - 1509pM
U-Osm 200-1200mOsm/kg Urine (pmol / 6  ng/L) <130nmol/24h
F luteal 15-30d 147 -958pM
ClCrea (>40J 1ml/J) M 97-140; F 75 -125ml/’ Urine/Crea 1 - 22nmol/mmol
F postmenopausal 37 - 145pM
 (140-Alter) x kg x 1.23 / SCrea [uM]; F x 0.85 M 40 - 161pM Noradrenalin (NA), Norepinephrine
M Pregnyltest (max. d5) 2.3-2.9x Plasma 80-498pg/ml = 0.5 – 3nM
Thyroid Gland Estrone (E1) (3.7pM=1ng/L) Urine <610nmol/24h
TSH basal peak 24h, nadir 12h 0.33 - 4.49mU/L F nadir: Menses; peak: "midcycle" Urine/Crea 5 - 45nmol/mmol
n. TRH 20' n 0.2mg iv / 30' n 2mg nasal / 3h n 40mg po: 2 – 25 / 3.5 – 30 / 5 - 35mU/L
M & postmenop. F (E1>E2) 55 - 240pM P-A a/o NA
fT4 11.6 - 22.0pM SHBG (: Age, Thy, Cirrhosis: Obesity, DM2) 3h n Clonidine um >40% / <2,75nM
fT4-Index 62 – 164 nM M (Testo Th) 13 – 71nM 2’ n Glucagon <3x / <10nM
GW – 12 / 13 – 25 / 26 – 40 83 – 166 / 76 – 159 / 66 – 160nM VMS (Vanillin Mandelic Acid) <33umol/24h
F (PCO, SS & E2) 18 - 114nM
T4 64 - 163nM Urin/Crea <5ummol/mmol
DHEA-S (1uM=38.7ug/L)
T3 1.2 – 3.2nM
fT3 2.6 - 5.6pM
F 6-29/30-39/40-69J. 2.5-10.3/2.4-6.9/1-5µM Diabetes mellitus
M
PG fasting (=8h pp; BG = 0.89 x PG) <5.6 (7)mM 2.0 - 11.0µM
Thyreoperoxydase (TPO)-AK) <100U/mL DHEA >18Y 5.6-28nM
2h a 75g OGTT <7.8 (11.1)mM
Thyreoglobulin-(Tg)-AK <100U/ml Progesterone (3.2nM=1ug/L)
PG Gravida fasting / 2h pp <5.3 / <7mM
TSH-Receptor-AK (TRAK) <1.5U/L F 0-14d 0.5 - 1.7nM HbA1c Norm DCA / HPLC 5.7 / 6.1%
Tg (n tot. Stx) <0.2ng/ml F Luteal 15-30d (21d) 4.9 - 72.0nM (%-value x 10,93) – 23,5 = mmol/mol-value
Iodine i Urine (*7.7=nmol/d) 50-200mg/d M 0.3 - 0.9nM (mmol/mol-value x 0,0915) + 2,15 = %-value
Calcitonin pg/ml x 0.28=pM, < 2.8pM 17-OH-Progesterone (3.03nM=1ug/L) Target in Dm: no hypoglycemia & <7.5%
2',5',10' n Pentagastrin <28pM M & F basal / n ACTH <6 (3) / 7.5nM Fructosamine <285uM
F luteal <9nM) C-Peptide 200 – 933pM
Calcium & Bones Heterozygous < 30 / 50nM C-Peptide/PG (Restsekretion) >50
Calcium Ca2+ (1mM=4mg/dl) 2.12 - 2.65mM AMH (Anti Müllerian Hormone) (7.14pM=1ug/L) IR (HOMA) PG mM x Insulin mU/L / 22.5 <1
ionized Calcium 1.15-1.3mM F 25 → 45LY (PCOS 2-3x) >35 → 3.5 pM Insulin-Ak (Insulin-Th n 1000-5000) <50nU/ml
Albumin 35-52g/L Alb / Crea i spot urine <2.4mg/mmol
Correct for Alb 10g/L Ca2+ 0.25mM Lipide (TG nü) (x10 = [Link]/d)
Phosphate P043-
(1mM=3.1mg/dl) 0.8-1.5mM Triglyderide (1mM=89mg/dl) 0.5-2.3mM Other VBGA "free" ionCa, PG, Na, K
PTH intact (1pM=10ng/L) 12 - 72pg/ml Cholesterol (1mM=38.7mg/dl) 3.0-5.2mM Creatinine (88.4uM=1mg/dl) 60-117uM
Alkaline Phosphatase 31-108 U/L HDL-C 0.9-2.2mM Urea (1mM=2.8mg/dl) 3.4-8.7 mM
Osteocalcin 8-52ug/L LDL-C 1.6-3.4mM Uric Acid (59.5uM=1mg/dl) 258-491uM
U-Calcium/Crea 0.1 - 0.3mmol/mmol Friedewald (TG<4) LDL=TC - HDL - 0.45xTG Homocysteine 5-15uM
U-Phosphor/Crea 2.2 - 6mmol/mmol -Carotene 0.76-3.34uM
U-Pyridinoline/Crea 40 - 100nmol/mmol „Inborn errors of metabolism”
age-dependent reference values for amino acids Procalcitonin “normal” <0.06ng/ml
U-Deoxypy./Creat 8 - 20nmol/mmol Antibiotic stewardship in LRTI: GP/AECB>0.1;
25-OH-Vit. D (1ug/L=2.4nM) 24-132nM
Endo-Funktionsteste CAP>0.25; Sepsis>0.5; Follow-up a 6-24h if
“Vit D-Insufficiency” (e.g., in sek. Hpt)<50-75nM see overview
withholding antibiotics;; Stop antibiotics after 3-7d
1-25-OH-Vit D 43-149pM

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 30. EndoDiabNET

Version 4/23/2025 250101 Pocket-Guide ©[Link]@[Link]