Adrenal Cortex

Question 1

What does the adrenal cortex do?

Answer 1

secretes hormones derived from cholesterol

Question 2

What is Waterhouse-Friderichsen syndrome

Answer 2

ACUTE primary adrenal insuffienciency due to adrenal hemorrhage associated with Neisseria meningitidis septicemia

Question 3

what does cholesterol do in the different layers of the cortex

Answer 3

aldo in glomerulosa, cortisol and glucocorticoids in fasiculata, and sex steroids in the reticularis

Question 4

What is cushing syndrome and what are clinical features? Include mechanisms

Answer 4

excess cortisol
muscle weakness with thin extremities 
moon facies, buffalo hump, and turncal obesity 
abdominal striae
HTN
osteoporosis
immune suppression
amneorrhea

Question 5

How does excess cortisol cause muscle weakness and moon faceis, buffalo hump, and truncal obesity?

Answer 5

cortisol normally raises blood sugar by breaking down muscles- too much cortisol = muscle breakdown
it also promotes gluconeogenesis (gluconeogenesis = high glucose, which causes excess insulin, which causes storage of fat)

Question 6

How does excess cortisol cause abdominal striate

Answer 6

cortisol impairs synthesis of collagen

Question 7

How does excess cortisol cause HTN

Answer 7

upregulates alpha 1 receptors on arterioles, and normally helps maintain vascular tone

Question 8

How does excess cortisol cause immune suppression?

Answer 8

3 mechanisms:

1. inhibitis phospholipase A2. you can’t generate arachidonic acid metabolites, which are needed for inflammation
2. inhibits IL-2: important growth factor
3. inhibits release of histamine from mast cells (less vasodilation and vascular permeability)

Question 9

Dx of cushing syndrome

Answer 9

24 hr urine

Question 10

causes of cushing syndrome. How do you differentiate between them

Answer 10

1. exogenous corticosteroids. most common cause. both adrenal glands will become atrophic.
2. adrenal problem: adenoma, hyperplasia, or carcinoma. one adrenal will be big, and the opposite adrenal will be atrophic (via ATCH axis)
3. ACTH secreting pituitary adenoma: both are big
4. paraneoplastic ACTH secretion: classically from small cell carcinoma of the lungs. both adrenals are large.
   to distinguish 3 from 4, you should do a high dose dexamethasone test. this is a cortisol analog- it can suppress ACTH production by a pituitary adenoma, but not ectopic ACTH production by small cell lung CA.
   follow the effect of this test by following cortisol levels

Question 11

What is hyperaldosteronism? what does aldo do?

Answer 11

too much aldo
works on late distal region and collecting duct. principle cells grab sodium and dump K in response to aldo.
Alpha intercalated cells dump protons in response to aldo

Question 12

what are clinical manifestations of hyperaldosteronism?

Answer 12

hypernatremia, hypokalemia, and metabolic alkalosis

HTN (you’ve retained Na)

Question 13

What are causes of primary hyperaldosteronism? Characteristics of primary hyperaldosteronism?

Answer 13

usually due to adrenal adenoma
sporatic hyperplasia and CA are much less common
see a high Aldo and low renin.

Question 14

What are causes of secondary hyperaldosternonism? Characteristics?

Answer 14

activation of renin angiotensin system.
classically, in young woman, you can get fibromuscular dysplasia. thickened blood vessel wall decr. blood flow to kidney
or, atherosclerosis in elderly males- also decr. blood flow to kidney
CHF, nephrotic syndrome.
activates juxtoglomerulo apparatus
characterized by high aldo and high renin

Question 15

What is congenital adrenal hyperplasia

Answer 15

excess sex steroids with hyperplasia of both adrenal glands due to a congenital defect in enzymes necessery for steroidogenesis

Question 16

biochemistry of congenital adrenal hyperplasia

Answer 16

cholesterol is made into pregmenolone. preg can make mineralocorticoids, cortisol, or sex steroids
you need 21 hydroxylase to make mineralocorticoids and cortisol
with 21 hydroxylase deficiency, you see shunting towards the sex steroids and incr. sex steroids
if XX, you may see cliterol enlargement. if male, you get precocious puberty
also, you see a lack of cortisol: decr. cortisol:
1. life threatening hypotension
2. decr. inhibitory feedback on anterior pituitary. excess ACTH- both adrenals get big in response to excess ACTH
Also, no mineralocorticoids:
no aldo:
1. loose Na and hold K. (hyponatremia and hyperkalemia)
2. hypovolemic

Question 17

clinical features of congenital adrenal hyperplasia

Answer 17

salt wasting with hyponatremia, hyperkalemia, and hypovolemia
life-threatening hypotension
clitoral enlagement or precocious puberty (I think we learned “ambiguous genitalia” in XX babies)

Question 18

What is the significance of 11 hydroxylase?

Answer 18

can’t make cortisol, and some shunting towards sex steroids.
however, a patient who has normal 21-hydroxylase can make a weak mineralocorticoid. 11-hydroxylase usually converts this to a stronger mineralicorticoid.
if the patient has classic story for 21 hydroxylase deficiency, but patient doesn’t have salt wasting, hyperkalemia, hypovolemia , it is probably an 11-hydroxylase problem.

Question 19

What is the significance of 17-hydroxylase?

Answer 19

without it, youc can only produce mineralocorticoids
excess mineralocorticoids, no cortisol, and no sex steroids
you will still have congenital adrenal hyperplasia

Question 20

adrenal insufficiency: acute

Answer 20

lack of adrenal hormones
acutely: Waterhouse-Friderichsen syndrome
arises in young kid with N. meningitis infection who gets DIC and then gets bilateral necrosis of both adrenal glands. acute lack of cortisol- exacerbates hypotension. looks like a sac of blood adrenal gland.

Question 21

adrenal insufficency: chronic causes

Answer 21

progressive destruction:

1. autoimmune destruction
2. TB
3. Metastatic carcinoma in the adrenals. Lung cancer loves to go to the adrenals

Question 22

clinical features of chronic adrenal insufficiency

Answer 22

hypotension, hyponatremia, hypovolemia, hyperkalemia you don’t have aldo.
weakness
hyperpigmentation:
vomiting and diarrhea

Question 23

Why do we see hyperpigmentation in adrenal insufficiency?

Answer 23

excess ACTH in response to low cortisol levels. ACTH is derived from a molec called POMC. Derivative of POMC is melanocyte stimulating hormone- hyperpigmentation