183 - Adrenal Cortex Flashcards
Which types of steroids are produced by each of the layers of the adrenal cortex?
zona fasciculata - glucocorticoids
zona glomerulosa - mineralocorticoids
zona reticularis - androgens
What is the process of steroid release from the adrenal gland?
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)
What are the physiologically secreted principal adrenal hormones? What regulates them?
cortisol –> regulated by ACTH
aldosterone –> regulated by renin-angiotensin system, potassium, and ACTH (weakly)
Androgens –> regulated by ACTH
What is the action of StAR on steroidogenesis?
transports cholesterol into the mitochondria for steroidogenesis
What is the action of P450scc in steroidogenesis?
cleaves cholesterol side chain
What is the action of P450c17 on steroidogenesis?
17 alpha hydroxylation
converts pregnenolone to 17 OH-pregnenolone
What is the role of P450c11-beta in steroidogenesis?
11 beta-hydroxylation
converts 11-deoxycortisol to cortisol
What is the mechanism of 11 beta-hydroxysteroid dehydrogenase?
interconverts cortisol to cortisone
What is the mechanism of 17 beta-hydroxysteroid dehydrogenase III?
converts androstenedione to testosterone
What is the mechanism of 5 alpha reductase?
converts testosterone to 5 alpha-dihydrotestosterone
implicated in men’s hair loss
What is the mechanism of aromatase?
converts testosterone to estradiol
What glycoproteins are precursors for ACTH?
POMC
What dynamic diagnostic tests are used for assessing a normally functioning CRH-ACTH-adrenal axis?
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)
How is plasma renin regulated?
by perceived volume status in the kidneys (via juxtaglomerular apparatus)
What is the relationship between renin, angiotensin, and ACE?
renin cleaves angiotensinogen to angiotensin I
ACE converts angiotensin I to angiotensin II (active hormone that stimulates aldosterone)
What tests can stimulate and inhibit the renin-angiotensin axis?
stimulating: upright posture, Na deprivation, diuretics that induce Na loss
inhibiting: supine posture, Na loading, NaCl infusion
What is the general effect of steroids binding to steroid receptors?
they are nuclear receptors that lead to DNA transcription of steroid-responsive genes
What are the effects of cortisol binding to the cortisol receptor?
protein catabolism, insulin resistance, fat redistribution, hematopoiesis, capillary fragility, CNS effects, Na+ retention, K+/H+ excretion, alkalosis, immunosuppression, epinpehrine production
What are the effects of aldosterone binding to the aldosterone receptor?
Na retention, K/H excretion, alkalosis
What are the effects of androgen binding to the androgen receptors?
protein anabolism, libido, secondary sex characteristics, hair pattern, genital development during embryogenesis
What are primary causes of adrenal underfunction?
autoimmune, TB, fungal disease, HIV, tumor metastases, congenital enzyme deficiencies, genetic ACTH receptor deficiency, glucocorticoid resistance
What are secondary causes of adrenal underfunction?
ACTH or renin deficiency (pituitary disease, exogenous steroid therapy, renal disease with juxtaglomerular apparatus dysfunction)
What are the symptoms of adrenal underfunction?
weakness, hypotension, pigmentation (high ACTH levels), hypoglycemia, hyperkalemia, hyponatremia, dehydration
What are the symptoms of 21-hydroxylase deficiency?
salt loss and virilization
due to deficiency of both cortisol and aldosterone deficiency and accumulation of precursors that are shunted to the androgen pathway
What are the symptoms of 11-hydroxylase deficiency?
virilization and salt retention/hypertension
accumulation of precursors shunted to androgen pathway, accumulation of the mineralocorticoid 11-deoxycorticosterone
What are the symptoms of isolated aldosterone deficiency?
hyperkalemia
due to hyporeninemic hypoaldosteronism
Is pigmentation a symptom of secondary adrenal insufficiency?
no - ACTH is not elevated in secondary adrenal insufficiency
What is the treatment for adrenal underfunction?
steroid replacement therapy
What are causes of adrenal overfunction?
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
What are the symptoms of glucocorticoid excess?
moon face, truncal obesity, plethora, purple striae, muscle wasting, osteoporosis, glucose intolerance, increased appetite, mood changes
ACTH –> Cushing’s disease
What are the symptoms of androgen excess?
facial hair, acne, balding, plethora, oligo- or amenorrhea, virilization
What are the symptoms of mineralocorticoid excess?
hypertension, hypokalemia, alkalosis
What are the cortisol and ACTH levels for pituitary cushing’s disease, ectopic ACTH, and adrenal tumors?
Pituitary Cushing’s disease –> high cortisol, ACTH normal to high
Ectopic ACTH –> very high cortisol, very high ACTH
Adrenal tumor –> high cortisol, low ACTH
What is the cause of congenital adrenal hyperplasia?
genetic defects in steroidogenic enzymes (ex. 21-hydroxylase or 11-hydroxylase deficiency)
What is the treatment for congenital adrenal hyperplasia?
replacement therapy with hydrocortisone, possible surgical correction of ambiguous genitalia
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?
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.
How does black licorice cause hypertension?
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
