Adrenal Flashcards
What does ACTH stimulate?
Secretion of Cortisol, aldosterone, and androgens
What are the functions of cortisol?
increases BP (upregulation of alpha adrenergic R in arterioles, vasoconstriction), regulates metabolism (SNS hormone, increases insulin resistance, gluconeogenesis, lipolysis, proteolysis), decreased inflammatory response, bone production, fibroblast activity
What are the functions of aldosterone?
Na+ retained from K, water follows, treats low BP (hypovolemia) + increases K+ secretion (hyperkalemia)
What are causes of primary acute adrenal insufficiency?
massive adrenal hemorrhage (Watershouse-Friderichsen Syndrome) due to Neisseria Meningitis blood infection
What are causes of chronic primary adrenal insufficiency? What is the pathophysiology?
Addison Disease: autoimmune destruction of adrenal gland or by infection w/ HIV, Tb, or other
What are the types of adrenal insufficiencies?
Primary - acute and chronic
Secondary
What are causes of secondary adrenal insufficiency?
pb with anterior pituitary, ACTH secretion, chronic use of exogenous glucocorticoids, autoimmune destruction of PG/, traumatic brain injury of PG/, pituitary hemorrhage
What are the general sxs of adrenal insufficiency?
weakness, fatique, weight loss, muscle aches, hypoglycemia, orthostatic hypotension
What are the sxs seen w/ low aldosterone?
salt-craving, low BP, hypoglycemic episodes leading to dizziness and falls
What are sxs of primary acute adrenal insufficiency?
gingival (hyperpigmentation of skin and mucosal surfaces), hyponatremia, hyperkalemia, metabolic acidosis, high eosinophil counts (w/ addison disease)
What are sxs seen with secondary adrenal insufficiency?
no increased skin pigmentation since low ACTH (and low POMC), no hyperkalemia or metabolic acidosis since aldosterone production preserved, regulated by RAAS
What regulates Aldosterone production?
RAAS
When is serum cortisol highest? What does it mean if it is low?
morning, adrenal gland dysfunction
What is ACTH stimulation test? When is it used?
if borderline-low morning cortisol, give synthetic, compare cortisol levels, should see ACTH, x increase if 2ndary AI (not adrenal pb). If 0-25% increase: primary AI or chronic 2ndary due to adrenal atrophy
What happens w/ chronic AI to adrenal gland?
can atrophy
What imaging modality should be used to dx primary AI? What should be seen?
CT = atrophy, hemorrhage, infection
What imaging modality should be used to dx secondary AI?
look for cause of pituitary insufficiency
What infectious test should be done in all primary AI dx? What hormone deficiencies should be screened for in secondary AI?
HIV testing since common cause of primary AI, consider other infections like Tb. Screen for prolactin, TSH, etc to see ndary AI
What is tx for acute primary AI?
IV cortisol to increase BP, IV dexamethasone to replace steroids, IV saline and dextrose to treat hypotension and hypoglycemia
What is tx for chronic primary AI?
Oral glucocorticoids (short-acting hydrocortisone and long-acting dexamethasone or prednisone)
How should secondary AI be treated?
oral glucocorticoids (short-acting hydrocortisone and long-acting dexamethasone or prednisone)
What should be kept in mind when providing long-term glucocorticoid therapy?
never stop suddenly, avoid acute AI (steroid withdrawal), taper off for weeks-months instead
How do you treat hyperkalemia and hyponatremia seen w/ AI? When is it given?
fludrocortisone (synthetic mineralocorticoids), given if pt remains hypotensive while taking glucocorticoid tx
What is Cushing Syndrome? What is seen w/ it?
Hypercortisolism mainly, decreased wound healing, slower bone formation, increased infections, 2ndary form of diabetes
What are the 2 categories of causes of Cushing?
exogenous/iatrogenic (most common, meds taken for lupus or arthritis) or endogenous (abnormal adrenal gland or high ACtH)
What causes primary hypercortisolism (Cushing)?
adrenal adenoma producing cortisol (beign neoplastic overgrowth), bilateral hyperplasia, adrenal carcinoma (rare)
What causes secondary hypercortisolism?
pituitary adenoma (most common), paraneoplastic syndrome (cancer)
What population is most at risk for pituitary adenoma causing Cushing disease?
women and prepubertal boys
What is Cushing disease vs Cushing syndrome?
disease = caused by pit. adenoma, increased ACTH secretion Syndrome = affects associated w/ hypercortisolism, multiple causes
What are sxs seen w/ Cushing syndrome?
moon face, emotional disturbances, cardiac hypertrophy, high BP, steroid-induced acne, buffalo hump, thin, wrinkled skin, hirsutism, obesity/weight gain + abdominal striae, proximal muscle weakness, osteoporosis and osteopenia, skin ulcers, amenorrhea, erectile dysfunction –> hyperglycemia, hypertriglyceridemia, frequent infections, DVT
How do you measure cortisol levels?
24h urine (free cortisol) test late night salivary cortisol low-dose dexamethasone suppression test (ACTH suppressed or elevated in response to exogenous steroid admission)
What should we see during low dose dexamethasone suppression test?
serum cortisol doesn’tdecrease even when synthetic steroid given
How do you differentiate between pituitary gland or ectopic cancer causing hypercortisolism and high ACTH?
high-dose dexamethasone test (8mg) = high ACTH, and high cortisol, both suppressed –> pituitary. Not suppressed –> cancer
CRH stimulation test = give CRH, see higher ACTH and cortisol –> pituitary, no change –> cancer
What imaging modality should be used for lung cancer, carcinoid tumors, and other ectopic sources of hypercortisolism?
Chest and abdominal CT
What is tx for hypercortisolism (Cushing syndrome)? Caused by exogenous drug, adrenal adenoma, pit. adenoma, bilateral adrenal hyperplasia, ectopic cancer?
exogenous = lower/stop drug
adenomas = remove surgerically
Bilateral adrenal hyperplasia = metyrapone, ketoconazole, mitotane, inhibit synthesis of cortisol
Cancer = surgery or chemo
Where does aldosterone act?
collecting ducts of K
- Na+ reabsorbed by epithelial Na+ channels ENaCs
- K+ secreted by Na+-K+-ATPase due to influx of Na+ from ENaCs
- H+ secreted from H+-ATPase in intercalated cells (high blood pH)
If angiotensin II increases, what happens to aldosterone?
increases, regulated by RAAS
What is seen w/ hyperaldosteronism?
hypokalemia, metabolic alkalosis, resistant HTN, increased ANP secretion due to initial volume expansion
What is ANP? What does it do? When is it secreted?
peptide hormone synthesized and secreted by atrial cardiac myocytes in response to atrial wall stretching, promotes renal Na+ and H2O loss → counters aldosterone effects, secreted w/ hyperaldosteronism
What are hypokalemia sxs?
muscle weakness, cardiac changes (T-wave inversions, prominent U waves)
What are the causes of primary hyperaldosteronism?
bilateral hyperplasia of gland, adrenal adenoma (benign, Conn Syndrome), glucocorticoid remediable hyperaldosteronism (rare, genetic abnormality)
What happens in glucocorticoid-remediable hyperaldosteronism? What is the tx?
rare genetic abnormality where aldosterone synthase hyperactivity. Tx = give glucocorticoids
What are the causes of secondary hyperaldosteronism?
renal artery stenosis, edematous disorders (CHF, cirrhosis, chronic renal failure, nephrotic syndrome), juxtaglomerular tumors
What can renal artery stenosis lead to? How?
Secondary hyperaldosteronism, impaired blood flow thyrough renal arteries stimulates release of renin
How do edematous disorders result in hyperaldosteronism?
low renal blood flow, associated w/ edema, can cause high aldosterone levels
What happens w/ juxtaglomerular tumors? What does it result in?
produce renin, results in hyperaldosteronism
What is a normal plasma aldosterone:renin activity level? What is seen w/ primary aldosteronism? Secondary aldosteronism?
normal = 10 primary = >30 since increased aldosterone negatively feedbacks on renin Secondary = high aldosterone and high renin = ratio near normal
How should hyperaldosteronism be confirmed? What should be seen?
Aldosterone suppression test, orally administer Na+ and Cl- followed by renin and aldosterone: will see renin and aldosterone levels will not lower
How is renal artery stenosis supposed to be dx? Tx?
CT angiography or Doppler sonography, tx: renal artery stenosis
What meds can be given to treat hyperaldosteronism?
competitive aldosterone R antagonists (K+ sparing diuretics spironolactone and eplerenone)
What is spironolactone? MOA? What is it used for? Side effects?
K+ sparing diuretic, competitive aldosterone R antagonist used to treat hyperaldosteronism. Acts on collecting tubule by binding and inactivating R = reduces K+ loss and improving BP. Can see painful breast swelling (gynecomastia)
What is congenital adrenal hyperplasia? What do you see?
family of different enzyme deficiencies involved in production of adrenal hormones, autosomal recessive = results in hyperplastic/enlargened adrenal gland
Why does adrenal gland enlargen with congenital adrenal hyperplasia?
lack of cortisol hormone leads to high ACTH = promotes growth w/ increase in adrenal size
What is the most common type of CAH? What does it lead to? What is it caused by?
Deficiency of enzyme 21-hydroxylase = decreased cortisol and aldosterone, increased androgenic (DHEA, androstenedione, testosterone) + buildup of progesterone and 17-OH progesterone. Caused by mutation in CYP21A2 gene
What happens w/ high levels of androgens? Low levels?
high = virilization of external genitalia, low = feminization
What are androgens (testosterone, androstenedione) converted to in peripheral tissues?
Estradiol
What are the types of 21-hydroxylase deficiency CAH?
classic-saltwasting (deficiency) and non-saltwasting type (partial 21-OH deficiency)
What is seen with saltwasting CAH?
severe dehydration, hypotension, more feedings of infant initially, develop poor feeding and adrenal crisis eventually, hyponatremia, hyperkalemia, mental status changes and vomiting due to electrolyte imbalances
What are the sxs of non-saltwasting CAH?
no genital ambiguity at birth, no adrenal crisis, increased androgen features later w/ premature onset of puberty, short stature, hirsutism in teen girls, polycystic K disease, abnormal menstrual period
What are sxs seen w/ CAH?
genital ambiguity for girls via virilization of external genitalial, enlarged clitoris w/ or w/o partial fusion of labioscrotal folds, can have testes or uterus, hyperpigmentation due to increased ACTH and MSH
How is CAH diagnosed?
increased 17-OH-progesterone
What is the tx for CAH?
IV fluid resuscitation w/ Na+ containing fluids, electrolyte regulation, cortisol + mineralocorticoid administration
Are adrenal masses usually symptomatic?
No, usually discovered incidentally on abdominal CT/MRI
What is shape and size of adrenal adenoma? CT attenuation? What is seen on contrast CT, MRI?
<4cm, regular shape and borders, CT attenuation <10 HU, Contrast CT: contrast washed out quickly w/ >50% after 10min injection, MRI + isointense w/ liver on T1 and T2
What is shape and size of adrenal malignancy (carcinoma)? CT attenuation? What is seen on contrast CT, MRI?
> 4cm, irregular, can have calcifications, local invasion, necrosis. CT attenuation > 20 HU. CT contrast = increased blood vessels means <50% washed out 10min after injection. MRI = hypointense w/ liver on T1, hyperintense on T2
What should all adrenal adenomas be screened for?
cortisol (Cushing) and catecholamine hypersecretion
What is a pheochromocytoma? Sxs? How do you dx it? What is Tx?
Adrenal mass causing catecholamine hypersecretion = HTN difficult to control w/ meds, headaches, increased sweating, high metanephrine levels, tx w/ surgery
What should be done before surgery for pheochromocytoma?
removal of mass can precipitate severe hypertensive crisis so 2 weeks before surgery, start on alpha blockers to normalize BP, 2-3 days before, start on beta blocker to prevent HTN, right before start on glucocorticoids to prevent adrenal crisis
What are the hereditary primary adrenal carcinoma’s
Li-Fraumeni, Beckwith-Wiedemann, MEN1 syndromes
