Autoimmune adrenal disease and exogenous glucocorticoids are the most common cause of primary and secondary adrenal insufficiency (AI), respectively.

The initial manifestations of autoimmune polyglandular syndrome type 1 (APS-1) include hypoparathyroidism and mucocutaneous candidiasis followed by AI and primary hypogonadism.

The manifestations of autoimmune polyglandular syndrome type 2 (APS-2) include AI, autoimmune thyroid disease, type 1 diabetes mellitus (DM-1), primary hypogonadism and hypopituitarism. Hypoparathyroidism does not occur in APS-2.

Hyperkalemia is commonly seen in patients with primary AI, but it is absent in patients with secondary AI since adrenocorticotropic hormone (ACTH) plays a minor role in regulation of aldosterone secretion.

Early morning cortisol or ACTH stimulation test is the initial test of choice for evaluation of AI.

The 24-hour urine-free cortisol, midnight salivary cortisol, and 1-mg dexamethasone suppression test are reasonable initial screening tests for Cushing syndrome (CS). Two abnormal initial tests are required to diagnose CS.

Once the diagnosis of CS is established, ACTH level should be measured to differentiate between ACTH-dependent and ACTH-independent CS.

The inferior petrosal sinus sampling is the gold standard test to differentiate between pituitary and ectopic source of ACTH secretion when pituitary MRI and dynamic studies do not point toward a pituitary source.

The therapy of choice for patients with CS is surgery depending on the primary etiology (pituitary adenomectomy/adrenalectomy/ectopic tumor removal).

Most patients with aldosterone-producing adenomas are normokalemic and, therefore, a normal serum potassium should not preclude further evaluation.

The measurement of plasma aldosterone to renin ratio (ARR) is the best initial test for evaluation of primary aldosteronism.

The initial screening test (ARR) may be done while patients are on all antihypertensive agents except aldosterone receptor blockers (spironolactone and eplerenone); these need to be discontinued for at least 4 weeks.

Patients with primary hyperaldosteronism (PA) should undergo CT of the adrenals for adrenal imaging. Bilateral adrenal vein sampling may be necessary to confirm the presence of a unilateral source of hyperaldosteronism.