SM151 Adrenal Cortex Pathophysiology

Question 1

What are the 3 types of steroids made in the cortex and where are they made?

Answer 1

Glucocorticoids (C-21) - zona fasciculata

Mineralcorticoids (C-21) - zona glomerulosa Androgens (C-19) - zona reticularis

Question 2

What precursor protein does ACTH come from? What tissues is it expressed in? What else is made from this precursor?

Answer 2

POMC cascade. Also produces a-MSH (responsible for pigmentation).

ACTH is expressed in anterior pituitary and skin, MSH is expressed in skin only.

Question 3

How do you test for ACTH insufficiency?

Answer 3

ACTH stimulation test (should see rise in cortisol production)

Insulin tolerance test (causes release of ACTH and GH)

CRH stimulation test (hypothalamic hormone that releases ACTH)

Question 4

How do you test for aldosterone insufficiency?

Answer 4

Administer low salt diet, upright posture, or diuretic and check for increased production of aldosterone

Question 5

How do you test for an excess ACTH state?

Answer 5

Dexamethasone suppression test: normally endogenous production is suppressed to almost 0 with dex administration.

Question 6

How do you test for an excess aldosterone state?

Answer 6

Give high salt diet or supine posture and check for decreased production of aldosterone

Question 7

Effects of cortisol?

Answer 7

BBIIG mnemonic

Blood pressure (up-regulates alpha receptors)
Bone formation is stopped
Immunosuppression/anti-inflammation
Insulin resistance (diabetogenic) 
Gluconeogenesis, lipolysis, proteolysis

Question 8

Effects of mineralocorticoids?

Answer 8

Na+ retention, K+ excretion, H+ excretion

Question 9

Effects of androgens?

Answer 9

Hair growth, temporal balding, sebum production (acne), anabolism (more muscle mass), penile/clitoral growth, erythropoiesis, anti-estrogen effects

Question 10

Etiologies of adrenal insufficiency?

Answer 10

Primary (adrenal problem): autoimmune (Addison’s), infectious/granuloma (TB), hemorrhage, metastases, ACTH-R or MRAP mutations

Secondary (ACTH problem): pituitary dx (tumor, granuloma, autoimmune, hemorrhage)

Congenital adrenal hyperplasia (mixed hypo- and hyper- syndrome). Defect in the cortisol synthesis pathway. Get a build up of whatever comes before the enzyme that is mutated

Question 11

Clinical features of cortisol insufficiency?

Answer 11

Anorexia, weakness, hypoglycemia, hyponatremia, hyperkalemia, dehydration, death if let untreated

Question 12

Clinical features of aldosterone insufficiency?

Answer 12

Hyponatremia, hyperkalemia, dehydration, hypotension

Question 13

Clinical features of androgen insufficiency?

Answer 13

Axillary and pubic hair loss, loss of libido (women only - no testes supplementation)

Question 14

Clinical features of ACTH excess?

Answer 14

Primary: pigmentation, secondary: no pigmentation

Question 15

What do you see in isolated hypoaldosteronism? What is the most common cause of this?

Answer 15

Cortisol levels are normal, aldosterone is low 
Hyporeninemic hypoaldosteronism (complication of diabetes)

Question 16

Clinical features of glucocorticoid excess/Cushing’s syndrome?

Answer 16

Weight gain, redistribution of fat to face and trunk, buffalo hump, moon facies

HTN: Na+/fluid retention, hypokalemia

Hyperglycemia, (insulin resistance)

Derm: ruddy complexion, purple striae

Osteoporosis, amenorrhea, immune suppression

Question 17

Clinical features of androgen excess?

Answer 17

Hirsutism, acne, temporal balding
Ruddy complexion, purple striae
Increased RBC mass
Irregular menstruation

Question 18

Etiologies of Cushing’s syndrome?

Answer 18

Exogenous steroids (most common)
Pituitary adenoma (this is Cushing’s disease)
Adrenal tumor
Nodular adrenal hyperplasia
Ectopic ACTH syndrome (small cell carcinoma)

Question 19

Etiologies of Cushing’s syndrome?

Answer 19

Pituitary adenoma (this is Cushing’s disease)
Adrenal tumor
Nodular adrenal hyperplasia
Ectopic ACTH syndrome (small cell carcinoma)
Exogenous steroid administration (most common)

Question 20

What are the hallmarks of adrenal insufficiency vs. excess?

Answer 20

Insufficiency: non-stimulability
Excess: non-suppressibility

Question 21

How do people with Cushing’s disease test on dexamethasone suppression?

Answer 21

Start at higher cortisol levels than normal. Can be suppressed, but require higher levels of dex than normal.

Note: ectopic ACTH-tumors and cortisol tumors are never suppressed by dex suppression

Question 22

How do people with Cushing’s disease test on dexamethasone suppression?

Answer 22

Start at higher cortisol levels than normal. Can be suppressed, but require higher levels of dex than normal.

Question 23

Etiologies of mineralocorticoid excess?

Answer 23

Primary: aldosterone-producing adenoma, bilateral nodular hyperplasia

Secondary: renin overproduction due to hypovolemia

Question 24

Etiologies of mineralocorticoid excess?

Answer 24

Primary: aldosterone-producing adenoma, bilateral nodular hyperplasia (aldosterone synthase or KCNJ5 mutations)

Secondary: renin overproduction due to hypovolemia

Question 25

How can you distinguish primary and secondary mineralocorticoid excess?

Answer 25

Primary: renin low, aldosterone high. Renin can’t be stimulated (by Na+/volume depletion or standing up). Aldosterone not suppressible (by Na+ loading or high volume)

Secondary: renin and aldosterone both high, both suppressible

Question 26

How can you distinguish primary and secondary mineralocorticoid excess?

Answer 26

Primary: renin low, aldosterone high. Renin can’t be stimulated (by Na+/volume depletion or standing up). Aldosterone not suppressible (by Na+ loading)

Secondary: renin and aldosterone both high. Renin and aldosterone both suppressible (by Na+ loading or high volume)

Question 27

Clinical signs of congenital adrenal hyperlasia?

Answer 27

Ambiguous genitalia, short stature, tomboyish, hirsutism, amenorrhea