ADRENAL
INSUFFICIENCY
Dr. Jamil Salman
Assit. prof. Oral and Maxillofacial surgeon
ARAB AMERICAN UNIVERCITY
Adrenal gland
• Small (6-8 g )
• Endocrine gland
• Located at superior pole
of each kidney
• Container an outer
cortex and inner medulla
The adrenal medulla
The adrenal medulla functions as a sympathetic ganglion and secretes catecholamines, primarily epinephrine.
The adrenal cortex
• The adrenal cortex makes up about 90% of the
gland
• consists of three zones.
>outer zone - zona glomerulosa.
>middle zone - zona fasciculata,
>innermost zone- zona reticularis.
• The cortex manufactures three classes of
adrenal steroids.
>mineralocorticoids, aldosterone .
>glucocorticoids, cortisol.
>androgens. sex hormons.
The adrenal cortex
Zone glomerulosa
• The predominant hormone is
aldosterone, a mineralocorticoid
• responds to hormones made by the
kidneys (i.e. renin and angiotensin).
• Aldosterone regulates physiologic
levels of sodium and potassium; mineralcorticoid
these two electrolytes are important
for control of intravascular
volume and blood pressure.
Regulation of
Aldosterone secretion
The adrenal cortex
Zone fasciculata
The predominant hormone is Cortisol
a glucocorticoids,
• insulin antagonist > hepatic gluconeogenesis
and inhibiting glucose uptake
glucocorticoid
• activates lipolysis > free fatty acids into
circulation.
• increases blood pressure > vasoconstrictor
action of catecholamines and angiotensin II.
• anti-inflammatory action > inhibitory action on
(1) lysosome(2) prostaglandin (3)cytokine release,
(4)neutrophils, and (5) leukocyte function.
• activates osteoclasts and inhibits osteoblasts.
Surgery , trauma, illness, mediated by CNS
burns, fever, hypoglycemia,
and emotional upset (e.g.,
anxiety)
Synthetic glucocorticoids (cortisol-like drugs) used in
• treatment of autoimmune and inflammatory diseases (e.g., rheumatoid
arthritis, systemic lupus erythematosus, asthma, hepatitis, inflammatory
bowel disease, dermatoses, mucositis) can affect adrenal function.
• long-term basis in patients during immunosuppressive therapy for
organ transplantation and joint replacement.
• In dentistry, corticosteroids may be used during the perioperative period
for the reduction of pain, edema, and trismus after oral surgical .
The adrenal cortex
Zone reticularis
• Dehydro epi andro sterone (DHEA) is the principal
androgen secreted by the adrenal cortex.
• The effects of adrenal androgens are the same as
those of testicular androgens (i.e., masculinization
and the promotion of protein anabolism and
growth).
• The activity of the adrenal androgens, however, is
only about 20% that of the testicular androgens and
is of relatively minor physiologic importance.
• Estrogen precursors are secreted from the zona
reticularis of the adrenal cortex.
Hyperadrenalism
Hyperadrenalism. Adrenal hyperfunction,
excessive secretion of adrenal cortisol, mineralocorticoids, androgens, or
estrogen in isolation or combination.
• The most common type of overproduction is due to glucocorticoid excess.
• Androgen-related disorders are rare and primarily affect the reproductive
organs.
• Mineralocorticoid excess (primary aldosteronism) is associated with
hypertension, hypokalemia, and dependent edema
glucocorticoid excess
• The most common form of hyperadrenalism
• Cushing disease: When this is caused by pathophysiologic processes (e.g.,
tumor of the pituitary gland or tumor of the adrenal gland).
• Cushing syndrome is a generalized state caused by excessive cortisol in
the body, regardless of the cause.
• The most common cause of elevated cortisol levels in Cushing syndrome is
the medical administration of corticosteroids (e.g., prednisone).
• Both Cushing disease and syndrome produce similar clinical features.
• This syndrome classically produces
>weight gain >a broad and round face (“moon facies”)
>a “buffalo hump” on the upper back, >abdominal striae,
>hypertension >hirsutism >and acne.
• Other findings may include
>glucose intolerance (e.g., diabetes mellitus),
>heart failure >osteoporosis
>bone fractures >impaired healing > psychiatric disorders
• Long- term steroid use also may increase risks for
insomnia, peptic ulceration, cataract formation, glaucoma, growth suppression,
and delayed wound healing.
Adrenal insufficiency
• Primary adrenocortical insufficiency: also known as Tertiary
Addison disease, occurs when the adrenal cortex is
destroyed or the gland is removed.
• Secondary adrenocortical insufficiency: is the result of
secondary
pituitary disease or a lack of responsiveness of the adrenal
glands to ACTH (corticotrophin) or caused by critical
illness.
Primary
addison
• Tertiary adrenal insufficiency: results from processes
that impair function of the hypothalamus, which is most
commonly caused by chronic use of corticosteroids.
Primary adrenal insufficiency
Addison disease
Etiology :caused by progressive destruction of the adrenal cortex,
• primarily because of autoimmune disease in adults
• less frequently from chronic infectious disease (tuberculosis, [HIV] infection,
cytomegalovirus infection, and fungal infection)
• malignancy.
• hemorrhage (e.g., heparin)
• sepsis
• adrenalectomy
• genetic mutations (e.g. familial glucocorticoid deficiency),
• drugs (e.g., that increase cortisol metabolism, inhibit gene transcription, or alter
tissue resistance to glucocorticoids)
SIGNS AND SYMPTOMS
• The most common complaints are
weakness, fatigue, abdominal pain,
hyperpigmentation of the skin and mucous membranes
• Additional commonly associated features.
Hypotension, anorexia, salt craving, myalgia,
hypoglycemia, and weight loss .
• If a patient with Addison disease is challenged by emotional or physical stress
(e.g., illness, infection, surgery), an adrenal crisis may be precipitated.
PATHOPHYSIOLOGY AND COMPLICATIONS
lack of the major hormones of the adrenal cortex.
Lack of cortisol results in
• impaired metabolism of glucose, fat, and protein
• hypotension,
• increased ACTH secretion,
• impaired fluid excretion,
• excessive pigmentation,
• inability to tolerate stress.
Aldosterone deficiency
• results in an inability to conserve sodium and eliminate potassium and hydrogen ions, leading to
>hypovolemia, >hyperkalemia, and >acidosis.
Medical management
Primary adrenal insufficiency
• The primary medical needs of patients with Addison disease are
(1) management of the adrenal disease (e.g., elimination of the infectious agent or malignant
disease)
(2) lifelong hormone replacement therapy.
> Glucocorticoid replacement , usually about 20 to 25 mg/day of hydrocortisone or cortisone
acetate, with a range of 12.5 to 50 mg/day.
>Mineralocorticoid replacement is accomplished by single administration of 9α-fludrocortisone
(0.05–0.2 mg) each morning.
• Patients also are encouraged to ingest adequate sodium and to monitor their blood pressure closely.
• Steroid supplementation during surgery .
Secondary adrenal insufficiency
caused by structural lesions of the pituitary gland
• tumor
• removal of the pituitary gland,
• cranial irradiation of the pituitary gland,
• head trauma,
• and lack of responsiveness of the adrenal glands to ACTH
(corticotrophin)
• critical illness (e.g., sepsis, liver cirrhosis).
Tertiary adrenal insufficiency
Etiology results from
• defective hypothalamus function.
• more commonly, as a result of chronic administration of exogenous
corticosteroids. (suppresses the hypothalamic– pituitary axis).
• specific drugs .
• or a critical illness (burns, trauma, systemic infection).
Pathophysiology and complications
• Secondary and tertiary adrenal insufficiency are
associated with low levels of cortisol.
• Unlike primary adrenal insufficiency, aldosterone is
not impaired with secondary or tertiary adrenal
insufficiency. This is because aldosterone secretion
is ACTH independent.
SIGNS AND SYMPTOMS
• Secondary and tertiary adrenal insufficiency may cause a partial
insufficiency that is limited to glucocorticoids.
• The condition usually does not produce hyperpigmentation or any
symptoms unless the patient is significantly stressed and does not have
adequate circulating cortisol during times surrounding stress. In this
event, an adrenal crisis is possible.
• However, an adrenal crisis is rare and tends not to be as severe as that
seen with primary adrenal insufficiency because aldosterone secretion is
normal.
• Thus, hypotension, dehydration, and shock are seldom encountered
Medical management
Secondary adrenal insufficiency
• Treatment involves glucocorticoid replacement,
• Hydrocortisone dosages of 10 to 20 mg are generally
sufficient, with stress-dose hydrocortisone coverage provided
as needed.
• Mineralocorticoid replacement is not required.
Medical management
Tertiary adrenal insufficiency
resulting from corticosteroids being administered on a chronic basis.
Higher and divided daily doses are more suppressive
>alternate-day regimen.
>A tapered dosage schedule often is implemented for the
discontinuation of steroid usage.
Adrenal Crisis
• life-threatening complication.
• resulting from adrenal insufficiency.
• triggered by emotional and physical stress (e.g.,
infection, fever, sepsis, surgery).
• The condition occurs at a rate of 5 to 6 events per 100
patient-years among those with primary adrenal
insufficiency, with older affected adults at higher risk.
• This medical emergency evolves over a few hours
manifests as
severe exacerbation of the patient’s condition, sunken eyes,
profuse sweating, hypotension, weak pulse, cyanosis, nausea,
vomiting, weakness, headache, dehydration, fever,
dyspnea, myalgias, arthralgia, hyponatremia, and eosinophilia.
• If not treated rapidly, the patient may develop hypothermia, severe
hypotension, hypoglycemia, confusion, and circulatory collapse that
can result in death .
Medical management
Adrenal crisis
This condition requires timely diagnosis and immediate treatment,
• proper patient positioning (i.e., head lower than feet)
• IV injection of a glucocorticoid—usually a 100-mg hydrocortisone bolus—or 4 mg of dexamethasone IV .
• fluid and electrolyte replacement to reverse the hypotension, cortisol deficiency, and electrolyte abnormalities.
• After the initial bolus, 50 mg of hydrocortisone is administered by IV slowly every 6 to 8 hours for 24 hours
for a typical total dose of 100 to 200 mg per 24 hours along with fluid replacement,
• vasopressors.
• correction of hypoglycemia.
The need for corticosteroid
supplementation
• only patients with primary adrenal insufficiency receive
supplemental doses of steroid, and those with secondary adrenal
insufficiency who take daily corticosteroids, should receive only
their usual daily dose of corticosteroid before the surgery.
The rationale for these new recommendations is that the majority of
patients who take daily steroid maintain adrenal function and do not
experience adverse outcomes after minor or even major surgical
procedures.
Factors that influence the need for corticosteroid supplementation
• the overall physical status of the patient,
• level of pain,
• liver dysfunction,
• febrile illness,
• sepsis,
• fluid loss,
• nausea and vomiting,
• drugs taken.
Laboratory and diagnostic
finding
• presence of clinical features together with low serum cortisol level.
• Pairing the basal cortisol tests with plasma corticotropin concentration.
• The most common and reliable provocation test is the standard-dose
corticotropin test.
• The insulin tolerance test to assess the entire HPA axis when secondary adrenal
insufficiency is suspected.
• Patients with adrenal insufficiency may also experience low aldosterone
concentration, hyponatremia, hyperkalemia, hypoglycemia, and high renin levels.
• Imaging of the adrenal gland and pituitary gland
Dental managment
• Identification .signs and symptoms , laboratory testing and diagnostic imaging
• Risk assessment determined by
medical history, physical examination, laboratory tests and medical consultation.
>past or present history of tuberculosis, histoplasmosis, or HIV infection increases the risk for
primary adrenal disease (insufficiency) because opportunistic infectious agents may attack the adrenal
glands.
>adrenal crisis is more likely in patients with adrenal insufficiency who have the following
comorbidities: malignancy, major traumatic injury, severe pain, infection or sepsis, liver cirrhosis,
administration of medications that alter cortisol metabolism or production, recent emergency or
hospitalization visits, or need for stress-related corticoid dose self-adjustments.
>patients with tertiary adrenal insufficiency are at low risk for adrenal crisis unless they receive
an invasive procedure and have one of the above mentioned comorbidities in combination with
recently discontinued high-dose corticosteroid treatment, simply do not take their glucocorticoid before
a stressful surgical procedure, or present with low blood pressure before an invasive procedure.
??If uncertain of the functional reserve of the patient, laboratory testing and medical consultation
are advised before the performance of an invasive or prolonged (>1 hour) procedure.
Hyper adrenalism
Patients with hyperadrenalism or who take corticosteroids for prolonged periods have an increased likelihood
of having
• Hypertension: blood pressure should be taken at baseline and monitored during dental appointments.
• Diabetes, Blood glucose levels should be determined, and invasive procedures should be performed
during periods of good glucose control.
• Delayed wound healing, Follow-up appointments should be arranged to assess proper wound healing.
• Osteoporosis, Because osteoporosis has a relationship with periodontal bone loss, implant placement, and
bone fracture, periodic measures of periodontal bone loss are indicated. Also, promote bone mineralization,
and extensive neck manipulation should be avoided if osteoporosis is severe.
• Peptic ulcer disease. Because of the risk of peptic ulceration, postoperative analgesics for long-term
steroid users should not include aspirin and other NSAIDS drugs.
ADRENAL
INSUFFICIENCY
Antibiotics: Risk of Infection. No issues.
Bleeding: Generally, this is not an issue.
An exception is patients who take heparin or an other
anticoagulant, which places them at increased risk for adrenal
hemorrhage, postsurgical bleeding, and hypotension.
Blood Pressure.
• Monitoring of blood pressure through- out invasive dental procedures.
• During surgery, evaluated at 5-minute intervals and before the patient
leaves the office.
• A systolic below 100 mm Hg or a diastolic at or below 60 mm Hg
represents hypotension.
• take corrective action.
> proper patient positioning (i.e., head lower than feet),
>fluid replacement,
>administration of vasopressors,
> evaluation for signs of adrenal dysfunction versus hypoglycemia.
> If adrenal crisis is determined to be occurring, a steroid bolus is required.
risk for an adrenal crisis.
• The risk is highest in those with primary adrenal insufficiency,
especially those who are undiagnosed or untreated.
• majority of patients with secondary or tertiary adrenal insufficiency may
undergo routine dental treatment without the need for supplemental
glucocorticoids.
• Patients at risk are those who have a fever, intercurrent illness, or
sustained trauma or who are undergoing stressful surgical procedures or
general anesthesia.
supplemental corticosteroids:
(1) type of adrenal insufficiency,
(2) medical status and stability, and
(3) level and type of stress.
• Currently, only patients with primary adrenal insufficiency are recommended to
receive corticosteroid supplementation, and this recommendation applies only when
surgery or general anesthesia is being performed or in the management of a dental or
systemic infection
• Routine dental procedures do not require supplementation.
• Patients are returned to their usual glucocorticoid dosage as soon as their vital signs are
stabilized
Additional measures
• Surgery should be scheduled in the morning when cortisol levels are
highest.
• Proper stress reduction should be provided because fear and anxiety increase
cortisol demand. Nitrous oxide–oxygen inhalation and benzodiazepine
sedation are helpful in minimizing stress and reducing cortisol demand.
• Surgeries that last longer than 1 hour are more stressful than shorter
surgeries and should be considered major surgical procedures that can require
the need for steroid supplementation.
• It is recommended to delay treatment for these patients and any patient who
is undiagnosed or untreated until the patient has been medically stabilized.
• Blood and fluid volume loss exacerbate hypotension, thereby
increasing the risk for development of adrenal insufficiency–like
symptoms. Thus, methods that reduce blood loss are important in
this setting.
• a fasting state can contribute to hypoglycemia, which can mimic
features of an adrenal crisis but does not require glucocorticoids for
resolution.
Drug Considerations and Interactions.
• good pain control with long acting local anesthesia and analgesics is
recommended.
• general anesthesia increases glucocorticoid demand for these patients.
• Barbiturates enhance the metabolism of cortisol and reduce blood
levels of cortisol.
• inhibitors of corticosteroid production (phenytoin, rifampicin)should
be discontinued at least 24 hours before surgery, with the consent of
the patient’s physician.
Oral Manifestations
• Diffuse or focal brown macular pigmentation of the
oral mucous membranes is a common finding in
primary adrenal insufficiency
• Pigmentation of sun-exposed skin in areas of friction
generally occurs after the appearance of oral
pigmentation
• Patients with secondary or tertiary adrenal insufficiency
may be prone to delayed healing and may have
increased susceptibility to infection but do not develop
hyperpigmentation.
Thank you
Dr. Jamil salman
