Adrenal Gland Flashcards
what is the embryological origin of the adrenal cortex and what does it secrete?
mesoderm
glucocorticoid and androgens (zona fasciculata and reticularis) and mineralcorticoid (zona glomerulosa)
what happens if you lose adrenal cortex function?
you die
what is the adrenal medulla derived from and what does it secrete?
neural crest cells
epinephrine, norepinephrine, dopa and dopamine
what is the precursor of all adrenal cortical hormones? what family of enzymes makes the hormones?
cholesterol
cytochrome P 450 oxidases
which enzyme in steroid hormone synthesis is not a cytochrome P450 oxidase?
3 beta- hydroxysteroid dehydrogenase
what is the rate limiting step in steroid hormone synthesis?
cholesterol -> pregnenolone
what is secretion of aldosterone limited by?
the rate that the glomerulosa cells can synthesize it (not stored)
how does aldosterone travel in the blood and what does it do?
travels free (30%) or bound to CBG and albumin stimulates kidney, colon, salivary glands and sweat glands to reabsorb sodium and water and enhances K secretion
how does aldosterone change the electrolyte balance?
by increasing the transcription of Na/K pump and expression of apical sodium channels
describe cortisol transport in plasma
most bound to CBT (cortisol binding protein), little bound to albumin and only 3% is free in sln
what are two adrenal androgens. how do they compare to testosterone?
DHEA and androstenedione
less potent than testosterone but can be converted to it
what is the female implication of DHEA?
it maintains the sex drive of females after menopause
how does cortisol demonstrate feedback inhibition?
it inhibits the expression of CRH receptor and ACTH in corticotrophs
what is the mechanism of action of cortisol?
it migrates into the nucleus and alters transcription by binding to a transcription factor
what are the metabolic effects of cortisol?
stimulates gluconeogenesis, proteolysis, lipolysis and decreases osteoblastic activity in trabecular bone and interferes with Ca absorption in the gut
causes central fat deposition
what are the anti inflammatory effects of cortisol?
inhibits cytokines and chemokines production, stabilizes lysosomal enzymes, and contributes to vasoconstriction and decreased capillary permeability
what are the immunosuppressive effects of cortisol?
decreased lymphocyte proliferation and inhibits hypersensitivity reaction
what are other effects of cortisol?
causes emotional instability
what is the cellular action of CRH?
increases cyclic AMP> PKA activation> CRH vesicular release
what is the cellular action of ACTH?
cAMP> PKA> increased synthesis of cytochrome P450 and stimulates the rate limiting step in cortisol formation
what is pro-poiomelanocortin?
the precursor for ACTH
post translationally processed to ACTH and beta- lipotrophin
during fetal life and pregnancy- yields different hormones
when are cortisol levels the highest? the lowest?
highest in the morning and lowest in the evening
how is the diurnal cycle of cortisol levels controlled?
light information is transmitted to the suprachiasmatic nucleus of the hypothalamus which controls CRH levels
what is the most common form of congenital adrenal hyperplasia?
21 alpha hydroxylase deficiency
decreased production of cortisol and aldosterone
increased production of androgens
why is there adrenal hyperplasia with the deficiency of cortisol and aldosterone?
there is no negative feedback to the pituitary so an abundance of ACTH is released-trophic factor for the adrenal gland
how is 21 alpha hydroxylase deficiency diagnosed?
elevation of 17-hydroxyprogesterone before and after ACTH stimulation tests. confirmed with genetic analysis of the gene
how is 21 alpha hydroxylase deficiency treated?
glucocorticoids provide the negative feedback for ACTH and mineralcorticoids are given if there is elevated renin or infants with salt wasting
what is caused by 17- alpha hydroxylase deficiency?
reduced cortisol and androgen synthesis with increased corticosterone and aldosterone
reduced estrogen synthesis
what are the clinical signs of 17- alpha hydroxylase deficiency?
hypertension, hypokalemia, sexual infantilism in males and females and pseudohermaphroditism in males
how is 17- alpha hydroxylase deficiency treated?
hypertension and mineralcorticoid excess- glucocorticoids
females need estrogen treatment. males may need surgery or testosterone treatment
what is cushing’s syndrome?
hyperadrenal function- excess cortisol for a long time due to any cause
what causes cushing’s syndrome?
prolonged use of immunosuppression drugs, adrenal tumors and tumors that increase ACTH
how is cushing’s syndrome different from cushing’s disease?
cushing’s syndrome refers only to elevated cortisol levels. cushing’s disease refers to hypercortisolism secondary to excess production of adrenocorticotrophin from a pituitary gland adenoma
what are the symptoms of cushing’s syndrome?
moon face, upper body obesity, red complexion, increased fat around the neck and thinning arms and legs.
osteopenia, increased infections, glucose intolerance and hypokalemia and hypertension
what is the dexamethasone supression test?
dexamethasone is a glucococrticoid that should inhibit ACTH release. given a night time dose and the serum cortisol levels and ACTH are measured in the morning
determines between adrenal and ACTH producing tumor depending upon if ACTH is low or high
what is another test for cushing’s disease?
24 hour urinary cortisol measurements or saliva sampling
if a pituitary tumor is suspected, what other tests should be done/
levels of other pituitary hormones
what is the treatment for cushing’s disease?
surgery to remove the adrenal or ACTH producing adenoma. replace cortisol if both adrenals are removed
or can inhibit cortisol synthesis with limited efficacy
what is Addison’s disease?
hypoadrenal function- failure to produce enough cortisol
primary adrenal insufficiency also deficient in aldosterone
what are many of the symptoms of Addison’s disease attributed to?
reduced aldosterone synthesis- hyperkalemia
what is the most common cause of Addison’s disease?
autoantibodies directed against adrenal cells containing 21-hydroxylase (in cortisol and aldosterone synthesis)
how is Addison’s disease diagnosed?
test cortisol levels, do ACTH stimulation test and CRH stimulation tests
positive if there is appropriate ACTH response but low cortisol levels
what is the treatment for Addison’s disease?
replacing cortisol and aldosterone if necessary
