Adrenal Flashcards
Fascicata
Secretes cortisol
Glomerulosa
Secretes aldosterone
Reticula
Secretes DHEA
Rate limiting step
Cholesterol conversion is ACTH dependent
ACTH production and release of cortisol
Downstream production of cortisol and aldosterone via 11beta
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
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
Secondary adrenal insufficiency
Defect in hypothalamus/pituitary
Etiology: prolonged glucocorticoid therapy > 2 weeks
Aldosterone system still functional
Electrolytes should be ok
Mineral corticoids
Involve the retention of sodium
Endogenous: aldosterone
Fludrocortisone
Acutely critical for life!
Glucocorticoids
Bind to glucocorticoid receptor (nuclear receptor)
Decreases inflammation
Transactivation, transrepression
Hydrocortisone
Hypothalamus
Secretes CRH (corticotropin releasing)
Pituitary gland
Secretes ACTH
Adrenal cortex
Secretes aldosterone and cortisol
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
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
Steroid coverage for surgery (stress)
Hydrocortisone 100mg IM
Increase to 200mg if fever, hypotension
Taper to maintenance dose
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
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
