Endocrinology of the Adrenal Cortex

Question 1

What is another hormone that can aid in Na reabsorption other than aldosterone?

Answer 1

Cortisol has some mineralocorticoid function.

Question 2

What are the 6 steps involved in the stress hormone cascade?

Answer 2

1) Hypothalamic PVN produces CRH, axonal flow
2) Reaches Median Eminence, released into portal blood vessels
3) Stimulates corticotropes in anterior pituitary
4) Pituitary releases ACTH into circulation
5) Stimulates adrenal cortex to make cortisol
6) Cortisol secreted, long-loop negative feedback inhibits hypothalamic CRH release & pituitary ACTH release

Question 3

What is POMC?

Answer 3

• Proopiomelanocortin: a preprohormone

- Main derivatives ACTH & a-MSH

Question 4

What tissues are the 2 parts of the adrenal gland derived from?

Answer 4

Adrenal cortex: mesoderm

Adrenal medulla: neuroectoderm

Question 5

Why does 21-hydroxylase deficiency cause virilization?

Answer 5

Progesterones build up and are shunted to androgenic pathway: DHEA and androstenedione

Question 6

What 8 factors stimulate ACTH secretion?

Answer 6

1) Decreased cortisol
2) Sleep-wake transition
3) Stress
4) Psychiatric disturbance
5) a-Adrenergic agonists (norepinephrine)
6) b-Adrenergic antagonists
7) Serotonin
8) ADH

Question 7

Which 4 factors inhibit ACTH release?

Answer 7

1) Cortisol increase
2) Enkephalins*
3) Opiates*
4) ACTH*

*Exert weak short-loop negative feedback

Question 8

What are 2 possible reasons for decreased cortisol levels?

Answer 8

1) Adrenalectomy

2) Drugs inhibiting cortisol (metyrapone)

Question 9

When should cortisol deficiency be tested?

Answer 9

Around 8am or time of waking - cortisol should normally spike.

Question 10

How does norepinephrine trigger an increase in cortisol production?

Answer 10

There are norepinephrine neurons in the brain that directly stimulate CRH neurons in hypothalamus to stimulate ACTH production

Question 11

How do SSRIs work? 4 steps.

Answer 11

1) Prevent reuptake of serotonin - more available in synaptic cleft
2) Serotonin stimulates CRH release - anxiety/depression worsens initially
3) Serotonin receptors are downregulated due to excess ligand availability
4) CRH levels drop, and patients feel better

Question 12

How does ADH/AVP stimulate ACTH secretion?

Answer 12

1) There is a subpopulation of ADH neurons in PVN
2) CRH and ADH both released in ME
3) Act synergistically to stim ACTH
4) Cortisol rises, thus ADH acts as stress hormone

Question 13

What effects do different levels of cortisol have on metabolism?

Answer 13

Low levels: anabolic
-increase gluconeogenesis & glycogen storage
High levels: catabolic
-proteolysis, lipolysis, inhibits glucose uptake

Question 14

Which organs produce ACE, angiotensinogen, renin, and aldosterone?

Answer 14

ACE: lungs
Angiotensinogen: liver
Renin: kidney
Aldosterone: Adrenal cortex

Question 15

What are the main symptoms of Cushing’s disease?

Answer 15

(pituitary tumor, primary effect is high ACTH)

1) Moon face - from edema
2) Dorsal-cervical & truncal fat deposition
3) Hyperglycemia –> type 2 diabetes
4) Thin legs from lipolysis for gluconeo

Question 16

What is Cushing’s syndrome?

Answer 16

Same symptoms of Cushing’s disease, but caused by adrenal tumor rather than pituitary

• Primary effect is excess cortisol
• Very low ACTH due to negative feedback

Question 17

How can 21-hydroxylase deficiency be treated? What is the effect of this deficiency?

Answer 17

21-hyroxylase deficiency causes excess androgen production & virilization via uncontrolled ACTH secretion.

• Treat patient with cortisol to reinstate negative feedback - reduce ACTH
• Restores normal androgen levels, patient returns to normal development

Question 18

What are the causes and symptoms of Addison’s disease?

Answer 18

Autoimmune attack destroys adrenal cells, leading to reduced cortisol

1) Hyperpigmentation (excess ACTH, MSH)
2) Hypoglycemic (low cortisol)
3) Hypovolemic & hyponatremic (low aldosterone)
4) Can lead to death if untreated: lack of increased BP during stress, if pt jumps up or runs, may lack blood to brain.