2. Physiology of the adrenal gland
• The adrenal gland is composed of two endocrine tissues:
the medulla and the cortex
• The adrenal cortex consists of three zones
• zona glomerulosa - outer most zone
• zona fasciculata - the middle zone;
• zona reticularis - the inner most zone
• The zona glomerulosa synthesizes aldosterone
• The zona fasciculata produces cortisol
• Zona fasciculata & reticularis produce androgens
• Adrenal medulla- catecholamines
3. Regulation of the Adrenal Cortex
• Glucocorticoid secretion is regulated mainly by
adrenocorticotropic hormone (corticotropin, ACTH), that is
produced in the anterior pituitary
• ACTH is released in secretory bursts of varying amplitude
throughout the day and night
• Are highest at about the time of waking, are low in late
afternoon and evening
• Corticotropin-releasing hormone (CRH), synthesized by
neurons of the hypothalamic is the most important
stimulator of ACTH secretion
• Cortisol exerts a negative feedback effect on the synthesis
and secretion of ACTH,CRH
4. • The rate of aldosterone synthesis, is regulated mainly by
the renin-angiotensin system with ACTH having only a
short-term effect
• In response to decreased intravascular volume, renin is
secreted by juxtaglomerular apparatus of the kidney
resulting in increased secretion of aldostrone
• The mechanisms by which the adrenal androgens are
regulated are not completely understood.
• Adrenarche begins before the earliest signs of puberty and
continues throughout the years when puberty is occurring
• ACTH and additional factors are involved in adreal
androgen synthesis
6. Result of a 21-Hydroxylase Deficiency
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7. Physiologic role of cortisol
• Increases blood glucose by gluconeogenesis and decrease
glucose utilization by cells through insulin resistance
• Redduction in cellular protein by increased protein catabolism
plus decreased protein synthesis .
• Mobilization of fatty acids
• Affects adipocytes differently according to their anatomic
locations
• Decreases inflammation and increases during stressful
conditions
• A positive inotropic influence on the heart, increasing the left
ventricular work index
• Inhibit fibroblasts, leading to increased bruising and poor
wound healing through cutaneous atrophy
8. Cushing Syndrome
• Cushing syndrome is the result of abnormally high blood
levels of cortisol
• This can be iatrogenic or the result of endogenous cortisol
secretion
• Causes of cushing syndrome can be ACTH dependent or
ACTH independent
9. ACTH dependent cushing syndrome
• Are associated with bilateral adrenocortical hyperplasia
• pituitary hypersecretion of ACTH [cushing disease] e.g,
pituitary adenoma,carcinoma
• Ectopic secretion of ACTH by non pituitary tumors
• Ectopic secretion of CRH by non hypothalamic tumors
• Exogenous ACTH
10. ACTH independent cushing syndrome
• Exogenous administration of glucocorticoids is most
common cause of cushing syndrome
• Adrenocortical adenomas , carcinomas – can be isolated
adrenal tumors or as part of multi organ involvement of
tumors
11. Clinical Manifestations
• Progressive central or generalized obesity
• Growth failure
• Moon face(rounded with prominent cheeks)
• Nuchal fat (buffalo hump)
• Signs of abnormal masculanizations such as hirsutism,
pubic hair, acne, deepening of the voice, and
enlargement of the clitoris in girls
• Hypertension ,hyperglycemia,head ach
• striae on the hips, abdomen, and thighs
• Osteoporesis and pathologic fracture
12. Investigation
• Late evening serum and salivary cortisol levels
• Midnight cortisol levels >4.4 micro g/dL strongly suggest
the diagnosis
• Urinary cortisol
• Serum ACTH and CRH
• Dexamethasone suppression test
• Fasting blood sugar
• Adrenal CT scan
• Pituitary MRI
13. Treatment
• Trans sphenoidal Pitutary microsurgery for pitutary tumors
• Adrenal ectomy for adrenal tumors
• Excision of ectopic ACTH producing tumor
• Discontinuation of exogenous steroid adminstration
14. Adrenal insufficiency
• Adrenal insufficiency results from impaired synthesis and
release of adrenocortical hormones.
Primary adrenal insufficiency
• In primary adrenal insufficiency, congenital or acquired
lesions of the adrenal cortex prevent production of cortisol
and often aldosterone
16. Causes of secondary adrenal insufficiency
• Pituitary tumors
• Tumors of the hypothalamic-pituitary region
• Pituitary irradiation
• Hypophysitis
• Congenital isolated ACTH or combined pituitary
hormone deficiency
• Pituitary apoplexy (Sheehan's syndrome)
• Pituitary infiltration or granuloma
• Head trauma ,exogenous steroid adminstration
17. Clinical Manifestation
• Primary adrenal insufficiency leads to cortisol and
often aldosterone deficiency
• Hypoglycemia
• Hypotension/orthostatic hypotension
• Hyponatheremia ,hyperkalemia
• Hypopigmentation (excess ACTH)
• Aldosterone secretion is unaffected in secondary
adrenal insufficiency thus, signs and symptoms are
those of cortisol deficiency
• Associated deficiencies of other pituitary hormones in
secondary adrenal insufficiency
19. Treatment
• Adrenal crisis should be treated aggressively
• Fluid resuscitation
• Treatment of hypoglycemia
• Electrolyte balance
• Replacement of cortisol or mineralocorticoid
• Treatment of underlying disease