Adrenal Flashcards by Nicholas Leung

Fascicata

Secretes cortisol

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Glomerulosa

Secretes aldosterone

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Reticula

Secretes DHEA

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Rate limiting step

Cholesterol conversion is ACTH dependent

ACTH production and release of cortisol

Downstream production of cortisol and aldosterone via 11beta

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Cortisol (glucocorticoid) influences

Hemodynamics
Metabolism: gluconeogenesis, uptake
Immune system: antiinflammatory, immunosuppressive, moderate inflammation
Body water distribution

If impaired, deranged metabolism and inability to deal with stressors

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Primary adrenal insufficiency

Addison’s Disease

Defect in adrenal gland

Etiology: hemorrhage, ketoconazole, rifampin, phenytoin
Suspect with thyroid failure

Causes hyperpigment, hypotension, weight loss, weakness, salt craving
HypoNa, hyperK

Reduced CO -> vasopressin secrete -> water retention more hyponatremia

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Secondary adrenal insufficiency

Defect in hypothalamus/pituitary

Etiology: prolonged glucocorticoid therapy > 2 weeks

Aldosterone system still functional
Electrolytes should be ok

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Mineral corticoids

Involve the retention of sodium

Endogenous: aldosterone

Fludrocortisone

Acutely critical for life!

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Glucocorticoids

Bind to glucocorticoid receptor (nuclear receptor)

Decreases inflammation
Transactivation, transrepression

Hydrocortisone

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Hypothalamus

Secretes CRH (corticotropin releasing)

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Pituitary gland

Secretes ACTH

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Adrenal cortex

Secretes aldosterone and cortisol

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Adrenal insufficiency (addisons)

Decrease aldosterone, hyperkalemia
Decrease cardiac output, weakness, hyperpigmentation

Response to secrete vasopressin (ADH)

Acute Treat with normal saline
IV hydrocortisone 100mg q 8

Chronic hydrocortisone (dexa or prednisone are longer acting) and Fludrocortisone replacement if primary

Minor stress 3x replacement dose for 3 days. Major stress IV hydrocortisone

Dexamethasone at home for emergency, high salt diet, med bracelet

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Rapid ACTH stimulation test

Give Cortrosyn

Adrenal/HPA insufficiency suspected

Primary cortisol not getting produced/released

Abnormal if cortisol does not rise > 18

Should go up by 9 points

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Steroid coverage for surgery (stress)

Hydrocortisone 100mg IM

Increase to 200mg if fever, hypotension

Taper to maintenance dose

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Adrenal crisis

Cortisol is essential for survival in times of stress

HypoNa, hyper K, volume depletion, hypotension

Unable to increase steroid during stress
COPD, asthma,
hypothyroidism treatment

Tx: fluids NS, steroid replacement 200mg hydrocortisone or dexamethasone IV.
First time: dexa doesn’t influence lab cortisol levels

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Cushing’s syndrome

Too much cortisol, ACTH tumor

Hypertension, moon face, obesity, glucose intolerance, osteoporosis

Treat: ketoconazole, etomidate if ICU
Cabergoline for refractory 3rd line

Surgery for adrenal adenoma

Cushing diagnosis

Exclude exogenous glucocorticoid before testing:

Late night saliva
Overnight dexamethasone suppression
24 hour urine cortisol >90

DST error of excess estrogen, 3A4
DST should be <1.8

Cortisol levels

Should be high in the morning, low at night

Cortisol: active
Cortisone: inactive

Aldosterone

Na retention

Potassium excretion

Hyperaldosteronism

Hypertension, hypokalemia , muscle weakness, polyuria

HTN resistant to treatment

High PAC low PRA (aldosterone:renin) ratio >20 (neg feedback on renin)

Treat spironolactone (gynecomastia)
Eplerenone better side effect profile

Congenital adrenal hyperplasia

Impaired cortisol synthesis
21 hydroxylase deficiency

Genital ambiguity excess testosterone
Early puberty
Neonatal low aldosterone death

Confirm with 17OHP test
Goal: decrease adrenal androgens
Tx: hydrocortisone, Fludrocortisone, NaCl supplement

Adrenal enzyme inhibitors

For Cushing’s syndrome, non respectable tumor

Ketoconazole, fluconazole
Inhibit testosterone, cortisol production
Caution 3A4 inhibition
Requires acidic stomach

Etomidate for ICU intubation

Metyrapone

Treat Cushing for cortisol control

Inhibit gluco/mineralcorticoid synthesis by inhibiting 11Bhydroxylase

AE: Decrease cortisol, increase ACTH, increase androgen precursors acne

Etomidate

Ultrashort acting hypnotic Blocks adrenal steroid synthesis ICU IV only for rapid control

Mitotane

Inhibits 11hydroxylase Destroys adrenocortical cells Use for 5-6 years Obliterate adrenal gland function for inoperable adrenal carcinoma Spares zone glomerulosa MinC Need to add statin, GC replacement: dexamethasone or prednisone

Mifepristone

Progesterone antagonist (abort) High dose-glucocorticoid antagonist For cortisol induced psychosis Does not influence synthesis pathway

Taper steroids

Up to 3 weeks Withdrawal possible for if >3 week prednisone

Septic shock Supply right antibiotic, fluid, IV vasopressor

Major stress, surgery, severe infection Want to supply glucocorticoid Can cause reduced cortisol breakdown Renal impairment more cortisol Give IV 50mg hydrocortisone & PO Fludrocortisone (pressor dependent) Improved shock reversal unclear benefit in mortality

Pheochromocytoma Chromaffin tumors

Adrenal medulla tumor causing HTN Catecholamine production Tx: tumor surgery high risk! Prior to surgery meds Alpha blocker: phenoxybenzamide (irreversible) Don't use alpha with beta blockers

Hypertensive crisis during surgery

Sodium nitroprusside fastest acting Phentolamine (IV alpha blocker) Nicardipine (IV CCB) PO conversion

Diabetes insipidus

Inability to conserve water, polyuria, thirst, dilute urine Central: Decreased ADH secretion Nephrogenic: ADH resistance High plasma sodium due to water loss Primary polydipsia h2o overload low Na, low urine osmolality Tx: desmopressin ADH replacement Nephro: give thiazide

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Inappropriate ADH secretion (water retention) at hyponatremic levels, Concentrated urine, cerebral edema Can be caused by carbamazepine, clofibrate, chlorpropamide Hyponatremia in the absence of peripheral edema or dehydration Tx: fluid restriction, IV saline ADH a antagonist conivaptan Loop diuretic

SIADH treatment

Acute treat hyponatremia if Na <0.5 mEq/L/hour Or else osmotic brain injury Chronic: restrict fluids Furosemide and increased Na intake

Catecholamines

Synthesized:phenylalanine and tyrosine Metabolized by COMT, MAO in liver Short t1/2=60sec Activate GPCRs

Ketoconazole

Inhibits P450c17, specific for glucocorticoid synthesis, 11beta, p450 scc Decreases testosterone, libido AE: hepatotoxicity

Gaq

Alpha 1 PLC/IP3

Gas, Gai

AC/cAMP Beta Gas Alpha 2 Gai

Cabergoline

Target pituitary, Dopamine agonist Treat high prolactin Make pituitary more functional 3rd line

Osteoporosis

Effect of Cushing cortisol excess Long term steroid use Supplement calcium

Aminoglutemide

Inhibit P450scc cholesterol conversion to Pregnenolone Inhibit corticoids synthesis

Bilateral adrenal hyperplasia

Treat with spironolactone Or eplerenone for less gynecomastia