Too much and too little cortisol
Cushing's syndrome is the picture of chronic cortisol excess. Because cortisol mobilizes and redistributes fat, the result is a rounded face, a fatty pad at the upper back, central weight gain with thin limbs, easy bruising, purple stretch marks, high blood sugar, high blood pressure and muscle weakness. The single most common cause overall is actually iatrogenic — long-term glucocorticoid therapy given for other diseases.
Addison's disease is the mirror image: the adrenal cortex fails and makes too little of everything. Low cortisol brings fatigue, weight loss, low blood sugar and an inability to cope with stress; low aldosterone brings low blood pressure, salt craving, and high potassium. A telltale sign is darkening of the skin — because the failing adrenal releases little cortisol, negative feedback is lost and ACTH climbs, and ACTH's parent molecule also drives pigment cells.
A blocked enzyme and a runaway medulla
Congenital adrenal hyperplasia is the steroidogenesis dam from guide 2 made real. An inherited enzyme deficiency (most often 21-hydroxylase) blocks the cortisol path. With cortisol low, negative feedback is lost, ACTH surges, and the cortex enlarges (the “hyperplasia”) while precursors pile up and divert into the androgen branch. The classic result is excess androgens — which can virilize a newborn girl — often combined with dangerous salt loss from low aldosterone.
Pheochromocytoma is a tumor of the medulla that pours out catecholamines on its own schedule. The classic triad is episodic pounding headache, sweating, and a racing heart, riding on top of severe, often spiky high blood pressure. It is uncommon but important because it is a surgically curable cause of hypertension — and a dangerous one to miss before any operation.
Testing: pull the lever, watch the loop
Because the adrenals sit inside feedback loops, the smartest tests don't just measure a level once — they probe the loop. To check for cortisol excess, the dexamethasone suppression test gives a synthetic glucocorticoid at night and measures morning cortisol. A normal axis reads the dexamethasone as cortisol and suppresses; in Cushing's the source ignores the feedback and cortisol stays high.
The same logic, reversed, finds deficiency. To probe for Addison's, a stimulation test gives synthetic ACTH and watches whether cortisol rises; a healthy gland responds, a failed one barely moves. Pairing a hormone level with its controller — cortisol with ACTH, aldosterone with renin — tells you whether the problem is in the gland itself or in the command chain above it.
READING THE LOOP — cortisol + ACTH together
cortisol HIGH + ACTH LOW -> adrenal making too much on its own
(e.g. adrenal tumor)
cortisol HIGH + ACTH HIGH -> pituitary/ectopic driving it
(ACTH-dependent Cushing's)
cortisol LOW + ACTH HIGH -> adrenal failed (Addison's)
feedback lost, ACTH climbs
cortisol LOW + ACTH LOW -> pituitary/hypothalamus failed
(central / secondary)