23 Adrenal cortex physiology Flashcards
ACTH is formed from post-translational processing of a prohormone named ______________.
POMC (proopiomelanocortin)
also give rise to beta-LPH
What is used in the stimulation test of adrenal cortex? What is the expected result?
Synacthen (synthetic ACTH)
In normal subjects, ACTH will stimulate cortisol release, and serum cortisol will then fall back to normal levels due to negative feedback
Why will a high concentration of ACTH cause hyperpigmentation?
This is because the first 13 amino acids of ACTH is identical to a-MSH, thus ACTH possesses a-MSH activity, which will stimulate synthesis of melanin in high concentrations
What is the hypothalamic hormone of ACTH?
What is the hormone causing negative feedback of ACTH?
CRH (corticotropin);
cortisol
When will ACTH peak?
6-8 am
What are the stimulatory causes of ACTH release?
A. Hypoglycemia
B. Stress
C. Circadian rhythm
D. AVP
All of the above
State the 3 zones of adrenal cortex, their products and their major control mechanisms.
1. Zona glomerulosa: aldosterone (mineralocorticoid) 2. Zona fasciculata: cortisol (glucocorticoid) 3. Zona reticularis: adrenal androgens
Control mechanism:
Zone G: by renin-angiotensin
Zone F and R: by ACTH
State the mechanism of peripheral control of cortisol.
Deficiency of what will cause apparent mineralocorticoid excess?
From cortisol to cortisone by 11beta-HSD2 (11beta-hydroxysteroid dehydrogenase type 2) ;
vice versa by 11 beta- HSD1
Deficiency of 11beta-HSD2
Which of the following incorrectly describes ACTH action on glucocorticoid biosynthesis?
A. ACTH stimulates the activity and expression of steroidogenic acute regulatory protein to accelerate cholesterol uptake into mitochondria
B. ACTH stimulates the activity of cholesterol esterase to speed up the breakdown of cholesterol esters to release cholesterol
C. ACTH induce the expression of LDL receptors
D. ACTH Induce increased expression of side chain cleavage enzyme and other steroidogenic enzymes
E. Chronic stimulation of ACTH induces hypertrophy and hyperplasia of zona glomerulus and zone fasciculata.
E
only zona fasciculata and zona reticularis
What are the effects of chronic exogenous use of glucocorticoid?
- suppression of hypothalamic-pituitary adrenal axis, and eventually atrophy of the zona fasciculata and zone reticularis
- Chapter 19: Glucocorticoid suppresses GH as it stimulates somatostatin and suppresses GHRH, thus for children, glucocorticoid treatment may affect their growth
- Endogenous glucocorticoid secretion in response to stress is reduced or absent
What will happen when there is abrupt discontinuation of glucocorticoid treatment?
What should be done instead?
Tertiary adrenal insufficiency (insufficiency glucocorticoid).
This is because the endogenous glucocorticoid secretion is absent when exogenous is given for a long time;
Should gradually taper the withdrawal of exogenous glucocorticoids (>2 weeks) to remove the negative feedback inhibition
Which of the following are correct effects of glucocorticoids? A. raise blood glucose levels by promoting gluconeogenesis B. induce insulin resistance C. helps to cope with stress D. mineralocorticoid activity E. induction of glycogen synthetase F. increase in muscle breakdown G. Induce hormone-sensitive lipase
All of the above
*E is correct! there is an increase in glycogen synthesis
F: for releasing amino acids
G: to increase lipolysis
What does it mean by the permissive action of cortisol?
Cortisol was weak action on its own in stimulating gluconeogenesis and lipolysis. Through its permissive action in inducing expression of enzymes (gluconeogenic enzymes and hormone-sensitive lipase), it allows glucagon and catecholamines to working in stimulating gluconeogenesis and lipolysis
***Permissive action of cortisol is also required for the direct action of GH, and other gluconeogenic and lipolytic hormones
Which of the following is/are not the correct effects of glucocorticoids?
A. Stimulate lipogenesis (central) B. Increase protein catabolism C. inhibit inflammatory response D. Reduce vascular responsiveness to catecholamines E. Decrease GFR
D and E
D: glucocorticoid maintains the adrenergic receptors, thus respond to the vasoconstrictive effects of catecholamine with a1 receptors
E: should be increase GFR
Comparing stress induced release of cortisol and chronically elevated levels of cortisol, what are the insulin/glucagon ratio and epinephrine/norepinephrine levels in each case respectively?
What are the major effects on carbohydrate, fat and protein metabolism?
Stress-induced:
insulin/glucagon ratio decreases, increased epinephrine and norepinerphine release from sympathoadrenal output.
It will cause gluconeogenesis, lipolysis and proteolysis.
Chronic:
insulin/glucagon ratio increases (as usual), decreased epinephrine and norepinephrine release from sympathoadrenal output.
It will cause glycogenesis, lipogenesis, proteolysis
Why is there central obesity in patients with Cushing’s syndrome? (3 marks)
Visceral fat has high activity of 11beta-HSD1 enzyme activity which allows to activate cortisone into cortisol.
Cortisol then stimulates differentiation of preadipocytes to adipocytes. With high insulin, lipogenesis increases visceral adipose tissue.
Glucocorticoid deficiency - effect on renal system?
Give rise to inability to excrete a water load due to SIADH-like condition
-loss of permissive effect in limiting production of vasodilators > hypotension > triggers ADH release from the posterior pituitary
What is Cushing’s disease?
Hypersecretion of ACTH
Which of the following is true?
A. Glucocorticoid excess can be ACTH-dependent or ACTH-independent
B. Ectopic ACTH syndrome may give rise to hypopigmentation
C. Dexamethasone is a synthetic glucocorticoid used as a stimulatory test for ACTH
A only
B: should be hyperpigmentation (due to uncontrolled release of ACTH) similar to Addison’s disease due to primary adrenal insufficiency
C: Dexamethasone is a synthetic glucocorticoid used as a suppression test for ACTH
Give 3 signs and symptoms of Cushing’s disease.
- Protein degradation - thinning of skin, easy bruising, striae formation, poor wound healing, muscle wasting
- Lipogenesis in central part of body (11 beta-HSD1)
- Anti-insulin effect, resulting in diabetes.
- Renal: mineralocorticoid effect, causing Na+ and water retention, hypokalemia
- Hypertension
- osteoporosis
etc
Which of the following are signs/ symptoms of Cushing’s disease?
A. Hypotension B. increased susceptibility to infections C. Deficiency in adrenal androgen D. Temporal hairline recession in women E. Hirsutism (abnormal growth of hair) F. Hypogonadism
All except A and C
A. should be hypertension
C. should be excess adrenal androgen/ glucocorticoid
Which of the following is true about glucocorticoids?
A. It suppresses GnRH and thus LH/FSH release
B. It suppresses thyroid activity by inhibiting 5’-deiodination
C. It suppresses GH and IGF-1 production by decreasing GHRH
D. It increases the risk of peptic ulcer by inhibiting the production of prostaglandins which are cytoprotective
All of the above
What is Addison’s disease? What are the common signs/ symptoms?
Primary adrenal insufficiency. (thus a lot of ACTH for stimulation, thus hyperpigmentation)
- hypotension
- SIADH-like condition
- poor tolerance to stress
Aldosterone is stimulated by? (4 things)
And it is inhibited by?
- angiotensin
- hyperkalemia
- ACTH
- Hyponatremia
inhibited by ANP (main function is to increase excretion)
What is Conn’s syndrome?
Primary hyperaldosteronism (high sodium retention, hypokalemia, metabolic alkalosis)
Why prolonged hypokalemia will result in polyuria?
- Hypokalemia and hypercalcemia give rise to nephrogenic DI.
- Unclear mechanism, but associated with reduced expression of Aquaporin 2 in collecting duct and NaK2Cl transporters
