1. Adrenocortical hormones
Cairo University
Faculty of Pharmacy
Department of Pharmacology & Toxicology
Pharmacology III
Practical Sessions
Adrenocortical hormones

2. Mineralocorticoids The adrenal cortex secretes 3 types of hormones:
Pharma-III Practical
The adrenal cortex secretes 3 types of hormones:
Mineralocorticoids
(mainly aldosterone)
Glucocorticoids
(mainly cortisol = hydrocortisol)
Androgens

3. - Regulation of secretion:
Hormones
Pharma-III Practical
- Regulation of secretion: -
Hypothalamus
CRF
Anterior Pituitary
ACTH = Corticotropin
Adrenal cortex
Glucocorticoids

4. Very important Hormones
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Very important
Long-term administration of exogenous GCs  -ve feedback on ACTH & CRH 
Suppression of Adrenal cortices
Too rapid withdrawal of GCs  acute adrenal insufficiency  may lead to death!!!
Hence, GCs should be GRADUALLY withdrawn

5. 1- Glucocorticoids Diurnal (circadian rhythm) Hormones
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1- Glucocorticoids
Diurnal (circadian rhythm)
ACTH is secreted in irregular bursts through out the day
Plasma cortisol tends to rise and fall in response to these bursts
These bursts are most frequent in early morning and least frequent in the evening

6. Actions of GCs: Hormones 1. Metabolism:
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Actions of GCs:
1. Metabolism:
CHO metabolism: maintains an adequate glucose supply within a normal range.
Similar to growth hormone (GH),
 GC has anti-insulin activity  utilization of glucose by peripheral tissues
 GC also  gluconeogenesis   hepatic glucose output
Both hyperglycemia   insulin secretion (hyperinsulinemia)

7. Hormones
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Protein metabolism: pharmacological or therapeutic dose of GC has catabolic effect on protein.
Fat metabolism: pharmacological or therapeutic dose of GC causes peculiar redistribution of fats  thin extremities & central obesity (↑ fat deposition in abdominal area & in face & back of neck & shoulders  moon-face & buffalo hump)

8. Hormones
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2. Electrolyte balance: hydrocortisone has a weak mineralocorticoid-like activity   Na+& H2O reabsorption &  K+ & H+ secretion.
3. CVS:  blood Pressure.
4. CNS: behavioral changes.
GIT:  PGs   HCl &  mucus formation
 predispose to peptic ulcer.
6. Skeletal muscles: GCs are essential for normal muscle work ( GC  muscle weakness due to  protein catabolism and electrolyte imbalance)
7. Anti-inflammatory effect
8. Immunosuppressive effect

9. Clinical disorders Hormones Hypercorticism: Cushing`s syndrome
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Clinical disorders
Hypercorticism:
Cushing`s syndrome
Hypocorticism:
Addison`s disease

10. Clinical state of excess free GCs occurs due to:
Hormones
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Cushing’s syndrome
Clinical state of excess free GCs occurs due to:
Therapeutic administration of ACTH or
GCs for long periods (Iatrogenic CS)
Endocrine disorder
(Pituitary ACTH dependent   ACTH secretion), Known as cushing disease
(Pituitary ACTH independent  adrenal tumor)
Tumor outside  the normal pituitary-adrenal system, which produces ACTH (ectopic Cushing’s syndrome) (small cell lung cancer).

11. The dexamethasone suppression test
Hormones
Pharma-III Practical
The dexamethasone suppression test
 is designed to diagnose and differentiate among the various types of Cushing's syndrome 
Dexamethasone is given at night & plasma cortisol is measured next morning
Cortisol
Interpretation
Not suppressed
Adrenal CS
Ectopic CS
Suppressed
Pituitary CS

12. Features of Cushing`s syndrome :
Hormones
Pharma-III Practical
Features of Cushing`s syndrome :
Hyperglycemia .
Thinning of skin.
Myopathy & muscle weakness
Uneven fat redistribution.
Buffalo hump.
Moon face.
 abdominal fat.

13. Features of Cushing`s syndrome….. contd.
Hormones
Pharma-III Practical
Features of Cushing`s syndrome….. contd.

14. Hormones Pharma-III Practical Hypertension. Poor wound healing.
Features of Cushing`s syndrome…… contd.
Hypertension.
Poor wound healing.
 susceptibility to infection.
 in hair growth.
Osteoporosis. (Why?)
Euphoria, psychosis or depression.

15. Hormones
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Features of Cushing`s syndrome …… contd.
Purple or red stria (the weight gain in Cushing's syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage)

16. ☺ Treatment of Cushing’s syndrome:
Hormones
Pharma-III Practical
☺ Treatment of Cushing’s syndrome:
 or stop exogenous GC gradually
(risk vs benefit)
Surgical removal of the tumor
Using inhibitors of biosynthesis, e.g.:
Aminoglutethimide (inhibit the 1st step in steroid hormones synthesis from cholesterol).
Trilostane (3β- dehydrogenase inhibitor),
Metyraponore. (11β-hydroxylase inhibitor)
Using GCs receptor antagonists , e.g.:
Mifepristone

17. Addison’s disease Hormones This clinical state occurs due to:
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Addison’s disease
This clinical state occurs due to:
1ry adrenal insufficiency:
Adrenal cortex dysfunction ( GCs  ACTH)
2ry adrenal insufficiency:
pituitary disorder ( ACTH  GCs)
3ry adrenal insufficiency:
hypothalamic disorder ( CRF  ACTH  GCs)

18. Features of Addison`s disease :
Hormones
Pharma-III Practical
Features of Addison`s disease :
Weakness & fatigue.
Hypotension.
Anorexia & , weight loss.
Hyperpigmentation (bronzing of skin) Why?
Due to ↑ ACTH, which has structural similarity with MSH  ↑ melanin production by melanocytes also MSH is a by product of ACTH synthesis from common precursor.

19. ☺ Treatment of Addison’s disease:
Hormones
Pharma-III Practical
☺ Treatment of Addison’s disease:
Replacement therapy with:
GCs as prednisolone &
Mineralocorticoids as fludrocortisone
N.B. Immune mediated destruction of the adrenal glands often occurs in conjunction with other autoimmune endocrine diseases such as thyroiditis (hypothyroidism), diabetes mellitus or hypoparathyroidism or non endocrine disease as vitiligo (autoimmune polyendocrine syndrome )

20. Physical examination Diagnosis: Hormones Laboratory tests:
Pharma-III Practical
Diagnosis:
Physical examination
Laboratory tests:
Laboratory tests
Cushing’s syndrome
Addison’s disease
Serum cortisol
( mmol/l) ↑ ↓
Serum ACTH
(10-47 ng/l)
↑ or ↓
Na+ K+
Fasting BGL
( mg/dl)

21. 2- Mineralocorticoids Actions: Hormones
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2- Mineralocorticoids
Actions:
- ↑ Na+ & H2O reabsorption and ↑ K+ & H+ secretion.
- Regulation of aldosterone secretion:
↓ plasma Na+ , ↑ K+  ↑ aldosterone.
↓ Na+ , ↓ BP  ↑ renin  ↑ Ang II  ↑ aldosterone.
ACTH also stimulates secretion but to a much smaller extent.

22. 1ry hyperaldosteronism
Hormones
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Clinical disorders
Hyperfunction:
1ry hyperaldosteronism
(CONN`s disease)
Hypofunction:
Hypoaldosteronism
Hypotension
Hyponatremia
Hyperkalemia
Acidosis
Hypertension
Hypernatremia
Hypokalemia
Alkalosis
ttt: Aldosterone antagonist
e.g. Spironolactone
ttt: RT with fludorocortisone

23. 2ry hyperaldosteronism
Hormones
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Hyperfunction:
2ry hyperaldosteronism
(hyperreninism, or hyperreninemic hyperaldosteronism)
due to overactivity of the renin-angiotensin system. As in Juxtaglomerular cell tumor. Renal artery stenosis. Hyporeabsorption of sodium from kidney tubulues (as seen in Bartter and Gitelman syndromes).

24. Assessment
Chrousos syndrome

25. Thank You!