Introduction to Clinical

Endocrinology

Professor Dr. Najat A. Hasan (MB ChB, MSc, PhD in Clinical

Biochemistry, College of Medicine -Alnahrain University, Baghdad. Iraq)
OBJECTIVES:
1. Explain why the endocrine system is so closely related to
the nervous system.
2. Distinguish between an endocrine gland and an exocrine
gland.
3. Define the term hormone and explain its general
characteristics.
4. Distinguish between a steroidal and non-steroidal
hormone, in terms of composition and action.
5. For each of the glands, name the hormone(s) they secrete,
identify the target organ of each hormone, and the effect
of each hormone.
6. Define the term gonadotropin, name of hormones secreted
by the pituitary ,thyroid,adrenal glands,pancreatic gonadal
gland ….
7. Distinguish between dwarfism, giantism, and acromegaly
OBJECTIVES:
7. Describe how calcium levels are maintained in the blood.
8. The hormones that work together to regulate water and
electrolyte levels in the blood and therefore regulate
blood pressure.
9. Describe how glucose levels are maintained in the blood.
10. Compare and contrast cretinism, myxedema, Grave’s
Disease, and goiter.
11. Define the blood ,stimulatory tests, and other diagnostic
procedures to define the disease.
12. To describe secondary sexual characteristics ,differentiate
between virilism and hirsutism, get information about
PCOS and ovulatory cycle.
13. Describe the adipose tissue -derived hormones
( leptin,adiponectin,resistin) and their role in adiposity
 Learning outcomes
1. List the cells and state the hormones secreted by
anterior and posterior pituitary,thyroid
gland,adrenal,pancreas,gonads,…
2. Explain the role of hypothalamus in controlling
anterior & posterior pituitary
3. Describe the regulation of secretion & actions of
different hormones
4. Explain the neural control of hormone release.
5. Describe specific hormonal disorders
6. Describe the role of adipose tissue in regulation
of body metabolism
Further reading:
1. Endocrinology-Basic and Clinical
Principles 2nd ed.
[Link] chemistry: Croock et al.
[Link]-clinical chemistry 6th edition bishop
[Link]'S Textbook of Biochemistry with
Clinical Correlations.
[Link] of Medical Biochemistry 3rd ed
(Dinesh Puri) 2011.
[Link] of adipose tissue, article.
Nervous and Endocrine Systems
• Act together to coordinate functions of all body
systems
• Nervous system
– Nerve impulses/ Neurotransmitters
– Faster responses, briefer effects, acts on specific
target
• Endocrine system Composed of endocrine glands that
produce, store, and secrete hormones.
– HORMONE = a very powerful chemical substance
secreted by an endocrine gland into the
bloodstream, that affects the function of another cell
or "target cell
 Types of Glands
Exocrine Glands are those which release their cellular
secretions through a duct which empties to the outside or
into the lumen of an organ. These include certain sweat
glands, salivary and pancreatic glands, and mammary
glands. They are not considered a part of the endocrine
system.
Endocrine Glands are those glands which have no duct and
release their secretions directly into the intercellular fluid or
into the blood. The collection of endocrine glands makes up
the endocrine system. The main endocrine glands are :
pituitary (anterior and posterior lobes)
thyroid, parathyroid
Adrenal (cortex and medulla)
pancreas and gonads,……
• Hormone types
– Circulating –
circulate in blood
throughout body
– Local hormones –
act locally.
– diffuse over a
relatively short
distanc
•PARACRINE – act
on neighboring cells
•AUTOCRINE – act
on the same cell that
secrete them
General characteristic of hormones
1. needed in very small amounts (potent)
2. produce long-lasting effects in the cells (their targets)
3. regulate metabolic processes (maintain homeostasis)
4. may be steroid (produced from cholesterol = fat-soluble)
or non-steroid (water-soluble).
5. they have specific rates and patterns of secretion
(diurnal, pulsatile, cyclic patterns)
6. they operate within feedback systems, either
positive(rare) or negative, to maintain an optimal
internal environment
7. they affect only cells with appropriate receptors
8. they are excreted by the kidney, deactivated by the liver
or by other mechanisms
Some general effects of hormones

1. they influence of ionic transport across

the cell membrane.
2. they stimulate transport of glucose and
amino acids.
3. they influence of epithelial transporting
mechanisms
4. they stimulate or inhibit of cellular
enzymes
5. they influence the cells - genetic
information
 Control of Hormone Secretion
Control of secretion is in the form of neural, hormonal, or humoral stimuli.
1. Neural: Signals from nervous system
The adrenal medulla is directly stimulated by the sympathetic nervous system.
Epinephrine and norepinephrin reinforce the actions of the sympathetic
nervous system.
2. Hormonal
Occurs when hormones from one endocrine gland stimulate the secretion of
hormones from another endocrine gland.
E.g. TRH,TSH, TH
E.g. CRH, ACTH,Cortisol
3. Humoral :
- Occurs when substances other than hormones control the secretion of
endocrine glands.
E.g. Insulin secretion by the pancreas is determined by several factors.
Rise in glucose after a meal triggers insulin secretion.
Rise in amino acids after a meal triggers insulin secretion.
In addition hormonal and neural stimuli also play a role in insulin secretion.
- or change in osmolarity (ADH release)
 Chemical classes of hormones
1. Amino acid-derived: Hormones that are modified
amino acids (catecholamines, thyroid hormones,
dopamine, serotonin, GABA, melatonin)
2. Polypeptide and proteins: Hormones that are formed
of chains of amino acids of less than or more than about
100 amino acids, respectively. Some protein hormones
are actually glycoproteins, containing glucose or other
carbohydrate groups. (insulin, GH, Leptin...)
3. Steroids: Hormones that are lipids synthesized from
cholesterol. a) Corticoids (cortisol, aldosterone, b) sex
hormones (androgen, estrogen, progesterone),
4. Eicosanoids: Are lipids synthesized from the fatty acid
chains of phospholipids found in plasma membrane.
Eicosanoids
Another groups of hormones

A. gastrointestinal hormones (more than 26 GI

polypeptides)
B. opioid peptides (endogenic opioids
C. tissue growth factors (epidermal growth factor,
nerve growth factor, PDGF, insulin-like growth
factor ...)
D. atrial natriuretic hormone (ANF)
E. transforming growth factors and
hematopoietic
and other growth factors (FGF....)
F. endothelial factors (endothelins, EDGRF...)
G. cytokines (interleukines, interferón, TNF....)
Hormones activate target cells by
depending upon the chemical nature of the hormone.
I- Lipid-soluble hormones (steroid hormones) and
hormones of the thyroid gland diffuse through the cell
membranes of target cells. The lipid-soluble hormone
then binds to a receptor protein that, in turn, activates a
DNA segment. The proteins produced as result of the
transcription of the genes and subsequent translation of
mRNA act as enzymes that regulate specific physiological
cell activity.
•Lipid-soluble hormones are bound to plasma proteins
and are less easily metabolized and excreted from the
body.
E.g. TH has a half-life of several days.
E.g. Cortisol has a half-life of about 90 minutes
 Free hormone Blood capillary

1 1Lipid-soluble
Lipid-soluble
Transport Transport hormone
hormone
protein protein diffuses
diffuses
intointo
cellcell

Lipid-
2 Activated2 Activated soluble
Nucleus
Nucleus
receptor-hormone
receptor-hormone
Receptor
Receptor
complex alters
complex alters
gene expression
gene expression

DNA
DNA
Cytosol Cytosol
mRNA
mRNA
3 Newly formed
3 Newly formed
mRNA directs mRNA directs Ribosome
Ribosome
synthesis of synthesis of
specific proteins
specific proteins New
on ribosomes on ribosomes protein

4 New proteins alter

cell's activity

Target cell
II. Water-soluble hormones (polypeptide, protein, and
most amino acid hormones) bind to a receptor on the
plasma membrane of the cell. The receptor- protein
complex, in turn, stimulates the production of one of
chemical messengers.
• Water-soluble hormones are easily degraded by
enzymes in the blood stream and are also excreted
very quickly from the kidneys.
E.g. insulin has a half-life of about 10 minutes in the
body.
E.g. Epinephrine has a half-life of about 10 seconds
in the body.
 Blood capillary Blood capillary

1 1 Binding
Binding of
of hormone
hormone (first
(first
Binding
messenger)
messenger)
of hormone (first messenger)
to
to its
its receptor
receptor activates
activates
to G
its
G protein,
protein,
receptor activates G protein,
Water-soluble
Water-soluble which
which activates
activates adenylate
adenylate
which cyclase
cyclase
activates adenylate cyclase
Water- hormone
hormone
Adenylate
Adenylate cyclase
cyclase Adenylate cyclase
soluble ReceptorReceptor

Hormones Second messenger Second messenger

G protein
G protein
ATP
ATP cAMP 2 Activated adenylate
cAMP 2 Activated adenylate
cyclase converts cyclase converts
ATP to cAMP ATP to cAMP
Protein
Proteinkinases
kinases 6 Phosphodiesterase
inactivates cAMP
3 3 cAMP
cAMPserves
servesasasaa Activated Activated
second
secondmessenger
messenger protein protein
totoactivate
activateprotein
protein kinases kinases
kinases
kinases
4 Activated protein
4 Activated protein
Protein
Protein kinases kinases
phosphorylate phosphorylate
ATP ATP cellular proteins cellular proteins

ADP ADP

Protein—
Protein—
P P

55 Millions of phosphorylated
Millions of phosphorylated
proteins cause reactions
proteinsthat
cause reactions that
produce physiological
produce
responses
physiological responses

Target cell
second messengers: The small molecule generated inside
cells in response to binding of hormone or other mediator
to cell surface receptors
• Calcium (Ca2+)
– Target: calmodulin
– Ca2+-Calmodulin  protein kinases
• Cyclic nucleotides
– cAMP & cGMP
– Target: protein kinases
• Diacylglycerol (DAG) & IP3
– Phosphoipase C act on the Phosphatidylinositol 4,5-
bisphosphate(PIP2 )From membrane lipids
–DAG  Protein Kinase C (membrane)
–IP3  triggers the release of Ca2+from the endoplasmic
reticulum, which then activates enzymes that generate cellular
changes.)
 General Characteristics of Receptors
1. Specific Binding (structural & steric specificity)
2. High Affinity (at physiological concentrations)
3. Saturation (limited, finite # of binding sites)
4. Signal Transduction (early chemical event)
5. Cell Specificity (target organ specificity).

Three types of cell surface receptors:

1. Ion channel receptors :Ionotropic
2. Transmembrane receptors: G-protein-coupled receptors,
Metabotropic
3. Receptors that are kinases or bind kinases: Protein kinases 
phosphorylation
Neurotrophin
Receptors are proteins.
They are present in
cell membranes
Intracellular receptors:
cytoplasmic receptors
nuclear receptors

receptors functional domains:

1. Recognition domain: it binds the hormone
2. Coupling domain: it generates a signal that
couples the hormone recognition to some
intracellular function.
Coupling means signal transduction.
 Cell surface receptors: G- protein receptors
A. Basic G-protein Receptor
a. ligand binds to receptor (outer surface of cell).
b. receptor changes shape (inner surface of cell).
shape change allows receptor to bind inactive G-
protein
c. inactive G-protein binds to receptor
d. receptor activates G-protein
a. G-alpha drops GDP, picks up GTP
b. when G-α binds GTP --> G β and G ᵞ are released
c. G- α + GTP is released from receptor into cytoplasm
d. G- α + GTP = active G-protein.
e. activated G-protein binds to target, protein target
protein's activity is altered - might be stimulated or might
be inhibited .
f. G- α + GTP is released from receptor into cytoplasm
g. The G protein activates adenylate cyclase, the enzyme
that catalyzes the production of cAMP from [Link]
AMP then triggers an enzyme that generates specific
cellular changes - might be stimulated or might be
inhibited .
Negative Feedback in the Hypothalamus.
• Most hormonal regulation by negative feedback
– Few examples of positive feedback
• hypothalamus maintains fairly constant levels of hormones
because it operates through a negative feedback system.
E.g:
excitatory
Hypothalamus

inhibitory Thyroid Stimulating Hormone-Releasing

Hormone

Anterior pituitary

Thyroid Stimulating Hormone

Thyroid gland

Thyroid hormones
positive feedback.
• is uncommon
• the hormone production increases.
• occur during childbirth, where hormone levels build with
increasingly intense labor contractions.
• in lactation, hormone levels increase in response to nursing,
which causes an increase in milk production.
• The hormone oxytocin is produced by the hypothalamus causing the milk
let down and uterine contraction is

-prostaglandins can be
identified as positive
feedback agents, as they
further enhance estrogen-
induced expression of
oxytocin receptors.
During the menstrual cycle a
gradual increase in plasma
LH levels stimulate the ovary
to produce estradiol. After
reaching a certain level,
estradiol induces an abrupt
increase in LH secretion,
known as the preovulatory
surge of LH, because it
induces ovulation. Upon
reaching maximal levels
plasma LH declines despite
the continued presence of
elevated estrogen
concentrations. 
Mechanisms of hormonal alterations
E n d o c r in e d is e a s e s

A. elevated hormones level H o rm o n e e x c e s s H o r m o n e d e fic ie n c y H o r m o n e r e s is t a n c e

B. depressed hormones level may be caused by:

1. failure of feedback systems

2. dysfunction of endocrine gland or endocrine function of cells:

a) secretory cells are unable to produce or due to in adequate

quantity of required hormone precursors

b) secretory cells are unable to convert the precursors to the

appropriate active form of hormone
c) secretory cells may synthesize and release excessive amounts
of hormone
 3. degradation of hormones at an altered rate or they may be
inactivated by antibodies before reaching the target cell
4. ectopic sources of hormones

C. Hormone resistance (failure of the target cells to respond to hormone)

May be caused by:
1. receptor-associated disorders:

a. decrease in the number of receptors   hormone - receptor binding

b. impaired receptor function  sensitivity to the hormone
c. antibodies against specific receptors
d. unusual expression of receptor function
2. intracellular disorders:-
a) inadequate synthesis of the second messengers
b) number of intracellular receptors may be decreased or they may
have altered affinity for hormones, or) alterations in generation of
new messenger RNA or absence of substrates for new protein
synthesis
Primary & secondary endocrine diseases
Based on site of hormone defect (either increase or
decreased secretion), Endocrine disorders are classified
as:
• A) Primary Disease: If defect is in the target gland from
which hormone has originated
• B) Secondary Disease: If defect is in the Anterior Pituitary
or Hypothalamus

E.g.,
• Primary hypothyroidism means decreased secretion of
thyroid hormone from the Thyroid gland
• Secondary hypothyroidism means deficiency of Anterior
pituitary/ Hypothalamic hormone which stimulates
production of thyroid hormone from the thyroid gland
(defect not in the thyroid gland)
Investigations for Endocine Disorders
I. Basal hormonal concentrations
1. Basal plasma levels (one-time examination)
2. Diurnal dynamics of hormone concentrations (e.g.
cortisol,growth H)
3. Other hormonal cycles (e.g. menstrual phase dynamics:
cyclic changes of LH, FSH, estrogens and progesterone)
4. Urinary output: 24 hr Is alternative method for hormones
with diurnal dynamics (cortisol, aldosterone) or pulsate
secretion (catecholamines),
5. Hormonal metabolites - plasma, urine (e.g. C-peptide), 5-
HIAA (hydroxyindole acetic acid), Vinylmandelic acid
(VMA) for catecholamines.

6. Indirect evaluation - measurement of a metabolic response

(ADH ... Diuresis ,sp. gravity. ,volume ,osmolarity;
insulin ... Glycemic control, etc.)
 II. Functional tests
 Basal hormonal concentration very often doesn´t allow
to establish a diagnosis of hypo- or hyperfunction.
Functional tests:-
1. Stimulatory tests
2. Inhibitory tests

Suspect hypofunction  Stimulatory tests

= quantification of functional reserve of endocrine
gland, Insulin hypoglycemia test, Arginine infusion test,
TRH test, GnRH test, CRH test

Suspect hyperfunction  Inhibitory tests

= quantification of response of endocrine gland to
inhibitory factors, e.g. Dexamethazone suppression
test, Dopaminergic drugs test
 III. Tumor markers in endocrinology
Thyroglobulin (Tg), anti-Tg antibodies
Markers of non-medullar thyroid carcinoma.

CEA (carcinoembryonic antigen)

Marker of non-medullar thyroid carcinoma (and other malignancy – e.g.
colorectal ca)

Calcitonin, procalcitonin
Hormonal product and diagnostic marker of medullary thyroid
carcinoma (lower sensitivity than Tg for non-medullar thyroid ca)

newborn screening :
1. Congenital hypothyroidism - incidence 1 : 5000
screening based on elevation of TSH
2. Congenital adrenal hyperplasia (CAH) - incidence 1 : 10-14000
screening based on elevation of 17-OH-progesterone
IV. Imaging methods
1. Native X-ray exams
2. Ultrasonography
3. CT / MRI
4. Scintigraphy
5. Angiography

V. Biopsy and Histopathological exam

Thyroid gland – Biopsy for unclear solitary
nodule, tumors
- Fine needle aspiration biopsy
(FNAB)
 O U
K Y
A N
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