Adrenocortical Hormone Diseases

Mineralocorticoid pathway

Cholesterol → Pregnenolone → Progesterone → 11-DOC → Corticosterone → Aldosterone

Glucocorticoid pathway

Cholesterol → Pregnenolone → 17a pregnenolone → 17a progesterone → 11 deoxycortisol → Cortisol

Sex hormone pathway

Cholesterol → Pregnenolone → 17a pregnenolone → DHEA → Androstenediol/androstenedione → Testosterone → Estrogen

17a hydroxylase def symptoms

No sex hormone → High cortisol + aldosterone → Hypertension

21 hydroxylase def symptoms

Cannot make cortisol or aldosterone → High sex hormones → Virilization + salt wasting + hypoaldosteronism

11 hydroxylase def symptoms

High sex hormone + high 11 DOC and 11 deoxycortisol → Virilization + mild hypertension

What is metyrapone stimulation test

Inhibit 11 deoxycortisol → No cortisol production → Should increase ACTH and CRH secretion → 11 deoxycortisol should increase

On metyrapone stimulation test 11b deoxycortisol is low what does this mean

Indicate ACTH def or Primary AI

What is Liddle syndrome

Mimic hyperaldosterone but aldosterone level is actually low

What is pseudohypoaldosterone

Aldosterone resistance → Symptoms of hypoaldosterone when levels are high

S&S adrenal insufficiency

Low grade fever, hyperpigmentation (Primary only), hypotension, hyponatremia

Causes of secondary AI

Withdrawal of glucocorticoid therapy, hypothalamic/pituitary disease

Causes of primary AI

Addison, TB, amyloidosis

What drugs commonly cause AI

Ketoconazole, metyrapone, etomidate

Ketoconazole mechanism of action

Anti-fungal → Inhibit cell wall synthesis that uses cholesterol → blocks cholesterol conversion to hormone

When does cortisol peak

In the morning; tests should be done in the morning

What is adrenal crisis

Sing of shock + unconsciousness that resolve 1-2 hrs after given glucocorticoid and hypoglycemia

Management of acute AI

Fluid resuscitation, give hydrocortisone 20mg, prednisolone 5mg or dexamethosone 0.5mg

Why is fluid resuscitation needed in adrenal crisis

Hypotension from low blood volume caused by low aldosterone leads to shock → give fluid

Management in long term therapy of AI

Hydrocortisone + glucocorticoid supplement if indicated

What is Nelson’s syndrome

Suspected Cushing → Bilateral adrenalectomy → Low cortisol with high ACTH from tumor that was missed

Cushing syndrome treatment

Cabergoline and pasireotide → Inhibit ACTH

Ketoconazole → Inhibit cortisol synthesis

Mifepristone → Block cortisol action

Ketoconazole drug interaction

Increased toxic effect of atorvastatin, QT prolonging effect

What is the difference between primary and secondary hyperaldosteronism

Primary → Low renin; secondary → High renin; both cause hypertension, hypokalemia and met alkalosis