Lecture 8 - Cushing disease, primary aldosteronism, pheochromocytoma

acth dependent cushing syndrome - causes

pituitary adenoma, ectopic acth syndrome (neuroendocrine tumours), ectopic crh secretion (non/hypothalamic tumours)

cushing disease

hypersecretion acth from pituitary microadenoma (basophilic or chromophobe)

acth independent causes of cushing syndrome

adrenocortical adenomas/carcinomas, bilateral adrenal micronodular hyperplasia or acth-independent macronodular hyperplasia, ectopic cortisol secretion (from ovarian/testicular tumours)

Carney complex

familial form cushing syndrome in bilateral adrenal micronodular hyperplasia - pigmented lentigines, blue nevi, multiple neiplasms

clinical features cushing syndrome

obesity (central), linear growth deceleration, skin atrophy + facial plethora, pink striae, slow healing + fungal infections, htn, osteoporosis, behaviour issues, gonadal dysfxn + decreased libido, renal calculi, polyuria, m weak + wasting

when does hyperpigmentation occur in cushings syndrome

ectopic acth syndrome

lab dgx evaluation cushing syndrome to determine hyperocortisolism

• diurnal cortisol secretion + high cortisol @ midnight

• urine free cortisol in 24h urine collection elevated

• overnight 1mg dxm suppression test

• 2 day 2mg dxm test high

2+ tests must be abnormal to dg

test for cause of cushing syndrome (acth in/dependent)

2 site immunoradiometric assay (IRMA), acth test

low acth conc = acth independent

_______ is the investigation of choice once biochem tests have suggested cushings syndrome

pituitary mri, adrenal ct, ct/mri of trunk if carcinoid tumors

routine lab exams results in cushing syndrome

high hb, htc and rbc, wbc

low Ly, eos, neutrophilia

hypercalciuria

serum electrolytes in ectopic acth syndrome

hypokalemia alkalosis

pseudo-cushing’s syndrome

in patients w/ severe obesity (esp in visceral obesity, alcoholism + PCOS)

iatrogenic cushing’s syndrome

acth independent, by exogenous admnisitration gcs

treatment cushings disease

microsurgery, radiation, inhibitors of acth secretion drugs → pituitary control

treatment of ectopic acth syndrome

can only be cured if benign

k+ replacement, spironolactone

adrenal adenoma treatment

unilateral adrenalectomy, gcs therapy during + postop to suppress contralat adrenals

when is bilateral adrenalectomy indicated in cushing

micro + macronodular hyperplasia

when is mitotane indicated

adrenocorticoal carcinoma, cushing syndrome

cushing syndrome drugs treatment

mitotane, ketoconazole, metyrapone, aminoglutethimide, etomidate

combos

complications cushings syndrome

htn, cardiovasc disease, stroke, thromboembolism, infections

Nelson syndrome

after bilaterla adrenalectomy as treatment of cushing - neuro opthalmic syndrome by supra + parasella extension, hyperpigmentation, adrenal failure, high acth levels

primary aldosteronism prevalnce

hypertensive patients, low renin

characteristics primary aldosteronism

htn, suppressed renin, increased aldosterone excretion

etiopathogenesis primary aldosteronism

• aldosterone-producing adenoma - Conn’s

• bilatera idiopathic hyperplasia - increased glomerular sensitivity to ATII

• primary adrenal hyperplasia

• aldosterone-producing adrenocortical carcinoma

• familial hyperaldosteronism

  • ectopic aldosterone-producing adenoma/carcinoma

types familial hyperaldosteronism

1. gcs remediable hyperaldosteronism - AD, ectopic expression aldosterone in zona fasciculata (controlled by acth)

2. aldosterone-producing adenoma or bilateral iodpathic hyperplasia

CYP11B1 gene mutation causes what

type 1 familial hyperaldosteronism

why is there tetany in primary aldosteronism

mg depletion + alkalosis

raas system in primary aldosteronism

suppressed

clinical presentation primary aldosteronism

htn resistant to drugs, hypokalemia → asthenia, tetany, palpitations

left heart hypertrophy

labs primary aldosteronism

hypokalemia, hyperkaliuria, hypernatremia, hyperchloremia, metabolic alkalosis

what to rule out when diagnosing primary aldosteronism

htn in young, w/ adrenal incidentaloma, w/ spontaneous hypokalemia, w/ family history PA

severe htn

hormonal tests results in primary aldosteronism

aldosterone conc - high

PRA - low

PAC/PRA ratio for screening

suppression tests for primary aldosternism

• oral Na+ loading test - high to prove secretion aldosterone

• iv saline infusion test - PAC tested, is high

• captopril test - PAC tested, remains the same level in Conn’s

investigation to establish etiology in dg of primary aldosteronism

abd ct (well defined hypodense tumour)

causes of secondary hyperaldosteronism

congestive heart disease, renovasc htn, malignant htn, diuretics treatment, pheochromocytoma

what to think of when both PRA and PAC values reduced

weak mineralocorticoid excess suspected or cortisol excess - congenital adrenal hyperplasia, DOC-secreting tumours, Liddle syndrome, apparent mineralocorticoid excess (defficiency 11bhsd-2, licorice)

treatment primary aldosteronism

unilateral adrenalectomy for adenoma or unila hyperplasia

idiopathic bilateral or CO for surgery - spironolactone (ald antagonist), K+ sparing diuretics (amiloride, not 1st line bcus doesn’t block cardiovasc effects), ace i for htn (enalapril), low sodium diet

what drugs are used in malignant forms of primary aldosteronism

cisplatin or trilostan

pheochromocytoma

ctch secreting tumorus from chromaffin cells, from adrenal medulla

paraganglioma

non-head neck tumours from symp ganglia, usually intra-abd (perinephric, periaortic, bladder)

familial disorders associated w/ pheochromocytoma

VHL syndrome - pheochromocytoma, paranganglioma

MEN2 - mutations thru RET

neurofibromatosis 1 - neurofibromas, cafe au lait spots, lisch nodules

familial paraganglioma

ad disorder, paragangliomas in head + neck by mutations in SDH genes

clinical manifestations pheochromocytoma

hyper epi, norep, dopa → triad headaches, sweating, tachycardia

essential sustained OR paroxysmal htn, orthostatic hypotension + syncope

anxiety, peripheral vasoconstriction, paresthesia, tremor

cardiomyopathy, congestive hf

hypertensive crises may occur in pheochromocytomas, triggered by

postural change, meds, exercise, foods w/ tyramine

labs pheochromocytoms

urinary + plasma fractionaed metanephrines and ctch (dopa), creatinine

what can influence metanephrine results when testing for pheochromocytoma

metanephrine - smoking increases it

normetanephrine - coffee increases it

what is a test to diagnose nonsecretory medullary tumours

serum chromogranin A

imaging for pheochromocytoma and paraganglioma

ct of adrenals + abd, mri, mibg scintigraphy w/ PET to detect other tumours, octreoscan for paraganglioma or metastases

other routine lab results in pheochroomocytoma

increased wbc, hyperglycemia, hypercalcemia

genetic testing for pheochromoctym and paraganglioma if

paranganglioma

bilateral pheo

nilateral pheo + familyu hisotyr

unilateral pheo + symtpoms <45y

other clinical findings of one of the syndromes