Adrenal Gland Basics Flashcards
adrenal anatomy - overview
- outer adrenal cortex
-3 layers, each producing its own distinct hormone
-derived from mesoderm - inner adrenal medulla
-chromaffin cells derived from NEURAL CREST CELLS
-modified postganglionic nerves: secrete epi/norepi in response to sympathetic stimulation; neurotransmitter is acetylcholine
what cells are the adrenal medulla derived from
*chromaffin cells of the adrenal medulla are derived from NEURAL CREST CELLS
what cells are the adrenal cortex derived from
mesoderm
3 layers of adrenal cortex - mnemonic
GFR:
1. zona Glomerulosa (produces aldosterone)
2. zona Fasciculata (produces cortisol)
3. zona Reticularis (produced androgens: DHEA)
*GFR corresponds with salt (mineralocorticoids: aldosterone), sugar (glucocorticoids: cortisol), and sex (androgens: DHEA); “gets better the deeper you go”
adrenal cortex - outermost layer
*Zona Glomerulosa
*responsible for producing mineralocorticoids: ALDOSTERONE
*action of aldosterone: sodium retention in DCT and collecting ducts, increasing blood pressure
adrenal cortex - middle layer
*Zona Fasciculata
*responsible for producing glucocorticoids: CORTISOL
*action of cortisol: coordinating the body’s response to stress through altering metabolism, blood pressure, immune response
adrenal cortex - inner layer
*Zona Reticularis
*responsible for producing androgens: DHEA-S
*action of DHEA-S: source of > 50% of the androgens in females; much less in males
Zona Glomerulosa
*outermost layer of adrenal cortex
*responsible for producing mineralocorticoids: ALDOSTERONE
*action of aldosterone: sodium retention in DCT and collecting ducts, increasing blood pressure
Zona Fasciculata
*middle layer of adrenal cortex
*responsible for producing glucocorticoids: CORTISOL
*action of cortisol: coordinating the body’s response to stress through altering metabolism, blood pressure, immune response
Zona Reticularis
*innermost layer of adrenal cortex
*responsible for producing androgens: DHEA-S
*action of DHEA-S: source of > 50% of the androgens in females; much less in males
dual control of adrenal cortex
- cortisol and DHEA-S secretion are controlled by ACTH secretion from the pituitary
- aldosterone secretion is controlled by Renin-Angiotensin system from the kidney (RAAS)
stimulation & suppression of aldosterone release
*aldosterone release is stimulated by:
1. RAAS system (activated by low renal BP, decreased NaCl detected by macula densa, sympathetic activation of beta1 receptors)
2. direct stimulation by hyperkalemia
*aldosterone release is suppressed by:
1. renin suppression (increased BP, high sodium diet)
2. hypokalemia
aldosterone - action
*aldosterone binds to mineralocorticoid receptors (MR) in nephron → increased expression of ENaC channels → sodium reabsorption
*potassium and H+ ions are EXCRETED in the urine due to change in transmembrane potential
overall: reabsorbs Na+; wastes K+ and H+
(too much aldosterone → hypokalemia & metabolic alkalosis)
cortisol - regulation of release
- corticotropin-releasing hormone (CRH) is released from hypothalamus and goes to pituitary
- CRH stimulates transcription of pro-opiomelanocortin (POMC)
- POMC is cleaved into corticotropin (ACTH) and melanocyte stimulating hormone (MSH)
- ACTH stimulates cortisol production & secretion from adrenal gland
note - in disease states where ACTH production is significantly increased, pts can become hyperpigmented due to MSH
diurnal variation of cortisol
*peaks around 8am
*nadir (lowest point) around midnight
*this becomes important when ordering and interpreting tests for disease states
cortisol - functions
- metabolism: increase blood glucose through gluconeogenesis, lipolysis, and muscle catabolism; induces insulin resistance in peripheral tissues
- skin, muscle, connective tissue: decreased fibroblast activity and collagen; muscle atrophy
- bone: inhibits osteoblast function
- blood pressure: increased sensitivity to catecholamines and Ang II, decreases nitric oxide → increased BP
- immune system: immunosuppression
- mood: important for normal mood
- endocrine effects: downregulates other axes, esp. gonadal
adrenal androgens - overview
*DHEA, DHEA-S, and androstenedione are the primary androgens from adrenal gland
*these are converted to testosterone → dihydrotestosterone and estrogen in peripheral tissues
*serve as an important pool of potential androgens, particularly in females
*production is under control of ACTH
steroid synthesis pathway - general principles
*adrenal steroids are derived from cholesterol
*rate limiting step: first step - conversion of cholesterol to pregnenolone via StAR; blocked by ketonazole
*each layer of adrenal cortex produces its own specific steroid due to differential expression of enzymes
*when there is a genetic deficiency in one enzyme, this results in: 1) buildup of precursors; 2) diversion to other, unaffected pathways; 3) congenital adrenal hyperplasia (CAH)
congenital adrenal hyperplasias (CAHs) - overview
*autosomal RECESSIVE group of disorders characterized by deficient cortisol synthesis due to mutations in one of the enzymes in the steroidogenesis pathway
*results in either partial or complete blockage at the level of the enzyme → shunting of precursors to the other 2 pathways (androgens and/or mineralocorticoids)
*reduced cortisol synthesis → reduced negative feedback on pituitary → increased ACTH → adrenal hyperplasia
*due to ACTH increase, pts can be hyperpigmented (due to increased MSH)
CAH: 21-hydroxylase deficiency - overview
*most common congenital adrenal hyperplasia (90-95% of CAH)
*due to increased androgens in utero, females experience virilization (clitoral enlargement, labial fusion) and can have ambiguous genitalia (even with inappropriate sex assignment)
*included in the newborn screening labs now
CAH: 21-hydroxylase deficiency - 2 forms
- classic CAH: salt-wasting or simple virilizing
- nonclassical (late-onset)
CAH: 21-hydroxylase deficiency - SALT-WASTING form
*loss of CORTISOL and ALDOSTERONE (adrenal crisis)
*infants present at 2 weeks of life with severe hypotension, low Na+, high K+
*symptoms include failure to thrive, lethargy, vomiting, sepsis-like syndrome
*mortality is high
CAH: 21-hydroxylase deficiency - SIMPLE VIRILIZING form
*experience excess androgens, but still able to make some aldosterone, so do not present with adrenal crisis
*females may have ambiguous genitalia, but males are phenotypically normal
*can present with early puberty, growth accelaration
*if untreated, excess androgens lead to premature epiphyseal closure, not reaching adult height
CAH: 21-hydroxylase deficiency - diagnosis
*test for elevated levels of precursor: 17-hydroxyprogesterone
CAH: 21-hydroxylase deficiency - treatment
*replace missing cortisol and/or aldosterone with medications
*reduce adrenal androgen synthesis by suppressing ACTH (crinecerfont: oral CRH antagonist)
*surgery to correct ambiguous genitalia
CAH: 11-beta hydroxylase deficiency - overview
*less common than 21-hydroxylase
*in addition to virilization, patients are hypertensive due to buildup of 11-deoxycortisol
*lab diagnosis: 11-deoxycortisol levels are elevated
CAH: 17-alpha hydroxylase deficiency - overview
*pts present with low cortisol and low androgens
*often have severe HTN due to excess aldosterone
*inability to make androgens also occurs in gonads, resulting in hypergonadotropic hypogonadism
memory aid for congenital adrenal hyperplasias
*if the deficient enzyme STARTS with 1, it causes HYPERTENSION: 11-beta hydroxylase; 17-alpha hydroxylase
*if the deficient enzyme ENDS with 1, it causes VIRILIZATION: 21-hydroxylase, 11-beta hydroxylase
steroid replacement options
*hydrocortisone
*prednisone
*dexamethasone
in a patient with hypothyroidism and adrenal insufficiency, which hormone should you replace first?
*must give the STEROID prior to the thyroid replacement because the thyroid hormone could otherwise precipitate an adrenal crisis
