adrenal steroids Flashcards
where is aldosterone produced
in the glomerulosa
where is cortisol produced?
in the fasciculata
where are androgens produced?
in the reticularis
what are the two precursors to all pathways in the adrenal
cholesterol and pregnenolone
what is the aldosterone pathway?
21-beta hydroxylase, 11-beta hydroxylase and aldosterone synthase.
what is the cortisol pathway?
requires the precursor made by 17 alpha hydroxylase (17-hydroxpregnenolone). then it is 21 hyrox, 11 hydrox, to cortisol
what is the androgen pathway?
requires precursors made by 17 alpha, DHEA androstenedione, testosterone, estradiol (androgen).
what is the role of glucocorticoids?
cortisol allows the body to handle stress. theres re receptors everywhere through out the body. the best known functions are immune function and carbohydrate metabolism
what are the metabolic effects of glucocorticoids.
increase gluconeogenesis in the liver, release amino acids through muscle breakdown, inhibits peripheral glucose uptake. stimulates lipolysis.
what is the goal of glucocorticoid metabolic modulation?
producing food for the brain! it is a counter regulatory hormone.
what does cortisol do tot he immune system
it has potent antiinflammatory effects. it up regulates anti-inflammatory proteins, down regulates proinflam proteins, and causes decreased leukocyte presence at the sites of inflammation.
what other roles does cortisol have>
fetal lung development. cognitive functions throughout the nervous system., also has weak mineralocorticoid function
what is the mechanism of action of mineralocorticoid>
binds the Aldosterone receptor in cytoplasm. active in the principle cells of the collecting tubules in the kidney. increases na/kATPase expression and the epithelial sodium channel expression.
what is the job of aldosterone?
to maintain the vascular volume. there is increased reabsorption of sodium and water, and increased renal excretion of potassium.
what is the significance of 11-beta-hydroxysteroid dehydrogenase?
it breaks down cortisol in cells that are responsive to aldosterone. because cortisol has weak mineralocorticoid stimulation this is required to stop cortisol from overwhelming the entire system,
what regulates aldosterone secretion?
concentration of potassium in the extracellular fluid. angiotensin II. ACTH and sodium deficiency have a small effect
symptoms of cushings
weight gain, menstrual irregularity, hirsutism, psychiatric dysfunction, backache, muscle weakness, fractures, loss of scalp hair.
what are sign of cushing’s
truncal obesity, plethora, moon face, HTN, bruising, thin skin, red-purple striae, proximal myopathy, ankle edema.
diagnosis of cushing’s
ACTH, 24hr urine free cortisol excretion, low dose dexamethisone suppression test. midnight salivary cortisol. diagnosis requires at least two of these to be positive.
what characterizes an ACTH dependent process
when there is high ACTH and high cortisol
what characterizes an ACTH independent process?
when there is low ACTH and high cortisol.
aminoglutethimide?
treats cushing’s by inhibiting the conversion of cholesterol to pregnenolone.
ketoconazole
treats cushing’s by inhibiting adrenal and gonadal synthesis. this is an anti fungal derivative. it is a nonselective inhibitor
mitotane
cushing’s treatment. related to DDT insecticide, nonselective cytotoxic action on the adrenal cortex. has a bad side effect panel.
metyrapone
inhibitor of 11hydroxylase. thus inhibits cortisol synthesis. tests anterior pituitary function. ACTH levels should rise in compensatory response. the levels of precursor should also rise in response.
mifepristoine
glucocorticoid receptor antagonist activity at higher doses. higher affinity than dexamethysone and does not bind the aldosterone receptor. creates a general glucocorticoid resistance in the body.
mifepristone side effect
fatigue, nausea, headache, hypokalemia, arthralgias, edema, endometrial thickening in women. there is adrenal insufficiency
pasireotide
treatment for cushing’s. somatostatin analog thus blocks the release of ATCH.
side effects of pasireotide.
hyperglycemia and GI problems.
primary adrenal insufficiency
caused by the anatomical destruction of the adrenals. there is decreased production of cortisol and aldosterone. HIGH ACTH levels.
secondary adrenal insufficiency
there is decreased pituitary secretion of ACTH. there is typically decreased production of cortisol.
what are the symptoms of adrenocortical insufficiency?
there is an inability to cope with physiological stress such as trauma and infection. can lead to life-threatening shock.
what are the causes of primary adrenal insufficiency
autoimmune, infection, hemorrhage or meningococcal sepsis. metastatic tumor, infiltration by amyloidosis or hemochromatosis. adrenoleukodystrophy.
causes of secondary insufficiency
suppression of exogenous glucocorticoids, hypopituitarism from a number of causes.
what are the symptoms of primary Adrenal insuf.
weakness, fatigue, nausea, vomiting, salt craving, postural dizziness, anorexia.
what are the signs of adrenal insuf?
weight loss, skin pigmentation, hyperpoigment of the mucous membranes. hypertension, vitiligo.
what would the labs show for adrenal insuf?
hyponatremia, hyperkalemia, anemia, eosinophilia, azotemia.
what is the biggest difference between primary and secondary? the easiest way to tell them apart?
secondary has NO hyperpogmentation.
also near normal aldosterone levels.
what is acute adrenal insuf. or adrenal crisis
volume depletion, lassitude, nausea, vomiting, hyperkalemia, hyponatremia. caused by mineralocorticoid deficiency and increased ADH.
what can cause adrenal crisis?
sepsis, surgical stress and trauma. hemorrhagic destruction of the gland. or rapid withdrawal of the steroids.
what is maintenance therapy for chronic primary adrenal insuf?
glucocorticoid replacement in an effort to remain physiological. hydrocortisone often given. monitor the clinical symptoms and the morning levels of ACTH. mineralocorticoid also needed. fludrocortisone and liberal salt intake
how do we monitor mineralocorticoid function?
supine and standing BP, pulse, edema, serum potassium, and renin activity,
what do we do for chronic primary adrenal insuf. when the patient has a minor febrile illness>
increase the dose 2-3 fold. for the few days of illness but not the mineralocorticoid. patient needs to contact if vomiting or lasts longer than 3 days.
what do we do if a chronic adrenal insuf patient undergoes acute trauma or severe stress?
inject dexamethysone intramuscularly.
do you wait to treat or treat before the results are back for serum analysis?
DO NOT WAIT, TREAT
how to treat adrenal crisis?
large doses of IV fluids. 1-3 liters in 12-24 hrs.and high dose glucocorticoids
why do we not give hypotonic saline to patients in adrenal crisis>
because this will worsen the hyponatremia.
what does primary aldosteronism labs look like
increased aldosterone and decreased renin. there will be hypokalemia and hypertension.
what are the causes of primary aldosteronism,
aldosterone producing tumor, bilateral adrenal hyperplasia, adrenocoritcal carcinoma. unilateral adrenal hyperplasia
when to screen for conn syndrome
when there is HTN and hypokalemia, refractory HTN, adrenal incedentaloma. early onset HTN, severe HTN, or whenever considering secondary HTN
what is the screen for primary hyperaldosteronism
aldosterone concentration, plasma renin secretion, 24 hour urine collection of aldo and sodium
what is the medical treatment for primary hyper aldo?
spironolactone. eplerenone.
congenital adrenal hyperplasia
inherited AR disorders that cause deficient corticosteroid production and thus hyperplasia of the gland. these are enzyme deficiencies. there is diminished negative feedback.
what are the common enzyme deficiencies?
21-beta hydroxylase, 11-beta hydroxylase, 17 alpha hydroxylase. 3BHD, aldosterone synthase.
21 beta H deficiency
most common form of CAH, reduced cortisol leads to reduced feedback inhibition on the ACTH pathway. there is hyper secretion of ACTH. there are increased adrenal androgens secreted that cause hirsutism and virilization in females.
characteristics of early onset 21 beta H deficiency
neonatal period. virilizing clitoral enlargement, labial fusion, urogenital sinus, sexual ambiguity. salt wasting within the 1st year of life because there is concomitant glucocorticoid and aldosterone deficiency. this causes salt wasting and hypotensive crises early
CAH late onset.
usaully present in early adulthood, elevated DHEAS with sexual precocity or hirsutism or irregular menstruation. there is hyponatremia, hyperkalemia, increased renin (if salt-wasting),.
how do we diagnose CAH late onset?
there is increased response to a syncortin stimulation test.
what is the treatment for 21 H deficiency
steroids. usually dexamethysone, prednisone or hydrocortisone. in salt wasting need fludrocortisone as well.
acute side effects of steroid use
insomnia, behavioral changes, acute peptic ulcers, acute pancreatitis.
