183 - Adrenal Cortex

Question 1

Which types of steroids are produced by each of the layers of the adrenal cortex?

Answer 1

zona fasciculata - glucocorticoids

zona glomerulosa - mineralocorticoids

zona reticularis - androgens

Question 2

What is the process of steroid release from the adrenal gland?

Answer 2

steroids are synthesized and immediately released after stimulation with the stimulatory hormone (ex. ACTH or angiotensin II)

rapid synthetic response facilitated by steroidogenic acute regulary protein that transport cholesterol to the inner mitochondrial membrane (where it meets steroidogenic enzymes)

Question 3

What are the physiologically secreted principal adrenal hormones? What regulates them?

Answer 3

cortisol –> regulated by ACTH

aldosterone –> regulated by renin-angiotensin system, potassium, and ACTH (weakly)

Androgens –> regulated by ACTH

Question 4

What is the action of StAR on steroidogenesis?

Answer 4

transports cholesterol into the mitochondria for steroidogenesis

Question 5

What is the action of P450scc in steroidogenesis?

Answer 5

cleaves cholesterol side chain

Question 6

What is the action of P450c17 on steroidogenesis?

Answer 6

17 alpha hydroxylation

converts pregnenolone to 17 OH-pregnenolone

Question 7

What is the role of P450c11-beta in steroidogenesis?

Answer 7

11 beta-hydroxylation

converts 11-deoxycortisol to cortisol

Question 8

What is the mechanism of 11 beta-hydroxysteroid dehydrogenase?

Answer 8

interconverts cortisol to cortisone

Question 9

What is the mechanism of 17 beta-hydroxysteroid dehydrogenase III?

Answer 9

converts androstenedione to testosterone

Question 10

What is the mechanism of 5 alpha reductase?

Answer 10

converts testosterone to 5 alpha-dihydrotestosterone

implicated in men’s hair loss

Question 11

What is the mechanism of aromatase?

Answer 11

converts testosterone to estradiol

Question 12

What glycoproteins are precursors for ACTH?

Answer 12

POMC

Question 13

What dynamic diagnostic tests are used for assessing a normally functioning CRH-ACTH-adrenal axis?

Answer 13

stimulation of axis: insulin tolerance test (tests the entire axis), CRH test (tests pituitary ACTH secretion), ACTH stimulation (tests the adrenal response)

inhibition of axis: dexamethasone suppression test (suppresses ACTH secretion without interfering with the measurement of cortisol)

Question 14

How is plasma renin regulated?

Answer 14

by perceived volume status in the kidneys (via juxtaglomerular apparatus)

Question 15

What is the relationship between renin, angiotensin, and ACE?

Answer 15

renin cleaves angiotensinogen to angiotensin I

ACE converts angiotensin I to angiotensin II (active hormone that stimulates aldosterone)

Question 16

What tests can stimulate and inhibit the renin-angiotensin axis?

Answer 16

stimulating: upright posture, Na deprivation, diuretics that induce Na loss
inhibiting: supine posture, Na loading, NaCl infusion

Question 17

What is the general effect of steroids binding to steroid receptors?

Answer 17

they are nuclear receptors that lead to DNA transcription of steroid-responsive genes

Question 18

What are the effects of cortisol binding to the cortisol receptor?

Answer 18

protein catabolism, insulin resistance, fat redistribution, hematopoiesis, capillary fragility, CNS effects, Na+ retention, K+/H+ excretion, alkalosis, immunosuppression, epinpehrine production

Question 19

What are the effects of aldosterone binding to the aldosterone receptor?

Answer 19

Na retention, K/H excretion, alkalosis

Question 20

What are the effects of androgen binding to the androgen receptors?

Answer 20

protein anabolism, libido, secondary sex characteristics, hair pattern, genital development during embryogenesis

Question 21

What are primary causes of adrenal underfunction?

Answer 21

autoimmune, TB, fungal disease, HIV, tumor metastases, congenital enzyme deficiencies, genetic ACTH receptor deficiency, glucocorticoid resistance

Question 22

What are secondary causes of adrenal underfunction?

Answer 22

ACTH or renin deficiency (pituitary disease, exogenous steroid therapy, renal disease with juxtaglomerular apparatus dysfunction)

Question 23

What are the symptoms of adrenal underfunction?

Answer 23

weakness, hypotension, pigmentation (high ACTH levels), hypoglycemia, hyperkalemia, hyponatremia, dehydration

Question 24

What are the symptoms of 21-hydroxylase deficiency?

Answer 24

salt loss and virilization

due to deficiency of both cortisol and aldosterone deficiency and accumulation of precursors that are shunted to the androgen pathway

Question 25

What are the symptoms of 11-hydroxylase deficiency?

Answer 25

virilization and salt retention/hypertension ## Footnote *accumulation of precursors shunted to androgen pathway, accumulation of the mineralocorticoid 11-deoxycorticosterone*

Question 26

What are the symptoms of isolated aldosterone deficiency?

Answer 26

hyperkalemia ## Footnote *due to hyporeninemic hypoaldosteronism*

Question 27

Is pigmentation a symptom of secondary adrenal insufficiency?

Answer 27

no - ACTH is not elevated in secondary adrenal insufficiency

Question 28

What is the treatment for adrenal underfunction?

Answer 28

steroid replacement therapy

Question 29

What are causes of adrenal overfunction?

Answer 29

pituitary ACTH overproduction (corticotroph adenoma), ectopic ACTH production, adrenal adenoma/carcinoma, bilateral macronodular adrenal hyperplasia, bilateral micronodular adrenal hyperplasia, exogenous steroids, primary hyperaldosteronism, renin overproduction, licorice ingestion

Question 30

What are the symptoms of glucocorticoid excess?

Answer 30

moon face, truncal obesity, plethora, purple striae, muscle wasting, osteoporosis, glucose intolerance, increased appetite, mood changes ACTH --\> Cushing's disease

Question 31

What are the symptoms of androgen excess?

Answer 31

facial hair, acne, balding, plethora, oligo- or amenorrhea, virilization

Question 32

What are the symptoms of mineralocorticoid excess?

Answer 32

hypertension, hypokalemia, alkalosis

Question 33

What are the cortisol and ACTH levels for pituitary cushing's disease, ectopic ACTH, and adrenal tumors?

Answer 33

Pituitary Cushing's disease --\> high cortisol, ACTH normal to high Ectopic ACTH --\> very high cortisol, very high ACTH Adrenal tumor --\> high cortisol, low ACTH

Question 34

What is the cause of congenital adrenal hyperplasia?

Answer 34

genetic defects in steroidogenic enzymes (ex. 21-hydroxylase or 11-hydroxylase deficiency)

Question 35

What is the treatment for congenital adrenal hyperplasia?

Answer 35

replacement therapy with hydrocortisone, possible surgical correction of ambiguous genitalia

Question 36

A 34 yo woman comes to your endocrine clinic for follow-up care of partial anterior hypopituitarism. She initially presented with amenorrhea, fatigue, weight loss, orthostasis, and several syncopal episodes. Initial lab results of note included profoundly low gonadotropins and a low morning ACTH and cortisol. A MRI of her pituitary revealed a 3 cm pituitary adenoma impinging on the optic chiasm. She underwent a successful transsphenoidal resection of the nonfunctional mass. What impact does secondary adrenal insufficiency due to lack of ACTH have on the zona glomerulosa?

Answer 36

mineralocorticoids are synthesized in the zona glomerulosa. While there is some increase in synthesis in response to ACTH, the main drivers are angiotensin II and hyperkalemia. So ACTH deficiency does not have a significant impact on ZG function.

Question 37

How does black licorice cause hypertension?

Answer 37

licorice blocks 11 beta-hydroxysteroid dehydrogenase type II (responsible for inactivation of cortisol in the kidney), allowing cortisol to stimulate mineralocorticoid receptors leading to hypertension