STEPTRACKERENDOCRINE | PATHOLOGY + PHYSIOLOGY + PHARMACOLOGY | HIGH-YIELD REVIEW

Adrenal Cortex Excess

Too much cortisol or too much mineralocorticoid — find the source with ACTH, renin and dexamethasone.

FOCUS ON
Cushing syndrome: most often exogenous steroids. Endogenous: screen (24-h urine cortisol, late-night salivary cortisol, low-dose dex) → ACTH: low = adrenal; high = pituitary (suppresses with high-dose dex) or ectopic (doesn't). Primary aldosteronism: hypertension + hypokalemia + ↓ renin + ↑ aldosterone. Low renin + low aldosterone = licorice, Liddle, other mineralocorticoids.
DISORDER
MECHANISM
FEATURES · LABS
CLUE · TREATMENT
Cushing syndrome — features
Excess cortisol: catabolic, gluconeogenic, immunosuppressive, mineralocorticoid at high levels
Central obesity, moon face, buffalo hump, wide purple striae, thin skin, bruising, proximal myopathy, HTN, hyperglycemia, osteoporosis, infections, depression
Androgen signs (hirsutism, acne) if ACTH-driven
Exogenous glucocorticoids
most common
Suppressed CRH/ACTH
↓ ACTH, bilateral adrenal atrophy
Taper slowly — abrupt stop → adrenal crisis
Cushing disease
most common endogenous
Pituitary ACTH microadenoma → bilateral adrenal hyperplasia
↑ ACTH; cortisol suppresses with high-dose dexamethasone; ↑ ACTH with CRH
Transsphenoidal surgery · IPSS localizes
Ectopic ACTH
ACTH from small cell lung cancer, bronchial carcinoid, medullary thyroid, pancreatic NET
↑↑ ACTH, no suppression; rapid onset, hypokalemic alkalosis, hyperpigmentation, weight loss
Look in the chest
Adrenal adenoma / carcinoma
Autonomous cortisol production
↓ ACTH, contralateral atrophy; carcinoma: large mass, mixed cortisol + androgen excess (virilization)
Adrenalectomy
Cushing — testing
Confirm excess, then localize
Screen: 24-h urine free cortisol, late-night salivary cortisol, 1 mg overnight dex → measure ACTH → high-dose dex, CRH test, IPSS, imaging
Image only after biochemical localization
Primary hyperaldosteronism
Bilateral adrenal hyperplasia (most) or aldosterone-producing adenoma (Conn)
Resistant HTN, hypokalemia (may be normal), metabolic alkalosis, no edema (aldosterone escape); ↑ aldosterone, ↓ renin
↑ aldosterone:renin ratio → saline suppression → adrenal vein sampling
Primary aldosteronism — treatment
Block or remove the source
Unilateral adenoma → adrenalectomy · bilateral hyperplasia → spironolactone or eplerenone
Spironolactone → gynecomastia
Secondary hyperaldosteronism
↑ renin drives aldosterone: renal artery stenosis (fibromuscular dysplasia in young women, atherosclerosis in older), HF, cirrhosis, renin-secreting tumor
↑ renin, ↑ aldosterone; renal bruit in RAS
ACE inhibitor → AKI in bilateral RAS
Glucocorticoid-remediable aldosteronism
Chimeric CYP11B1/CYP11B2 → ACTH drives aldosterone synthase (AD)
Early-onset HTN, family history of early stroke
Dexamethasone suppresses
Low-renin, low-aldosterone HTN
11β-HSD2 deficiency or licorice (cortisol acts on MR) · Liddle (ENaC gain of function) · 11β- or 17α-hydroxylase CAH
HTN, hypokalemia, alkalosis with both renin and aldosterone ↓
Liddle → amiloride or triamterene

Mechanism — localizing Cushing

Confirmed hypercortisolism
→
ACTH low
→
Adrenal tumor or exogenousCT adrenals
ACTH high
→
High-dose dex
→
SuppressesPituitary (Cushing disease)
No suppressionEctopic (chest CT)

Pituitary adenomas still respond partly to negative feedback; ectopic tumors and adrenal tumors don't.

Hypertension with hypokalemia

CAUSE
RENIN
ALDOSTERONE
CLUE
Primary aldosteronism
↓
↑
Adrenal adenoma/hyperplasia
Renovascular / renin tumor
↑
↑
Bruit, young woman (FMD)
Licorice, 11β-HSD2 defect
↓
↓
Cortisol on MR
Liddle syndrome
↓
↓
ENaC; amiloride works
Cushing (severe/ectopic)
↓
↓ / normal
Cortisol excess

How it's tested

COMMON CONFUSION"Cushing syndrome" is cortisol excess from any cause; "Cushing disease" is only the pituitary ACTH adenoma.
THE TRAPAldosterone escape (pressure natriuresis) is why primary aldosteronism causes hypertension without edema. Edema with high aldosterone points to secondary causes (HF, cirrhosis).
YOUR APPROACHCortisol excess → ACTH → dex suppression → image. HTN + low K⁺ → renin and aldosterone → pattern → confirm → treat.

If you see… think…

Purple striae, proximal weakness, buffalo hump on long-term prednisone → exogenous Cushing
↑ cortisol, ↑ ACTH, suppression with high-dose dex → Cushing disease (pituitary)
Smoker with rapid weight loss, hypokalemia, very high ACTH → ectopic ACTH (small cell)
↑ cortisol, ↓ ACTH, unilateral adrenal mass → adrenal adenoma
Resistant HTN, K⁺ 3.0, ↓ renin, ↑ aldosterone → primary aldosteronism
Bilateral adrenal hyperplasia with aldosteronism → spironolactone
Young woman with HTN, abdominal bruit, ↑ renin → fibromuscular dysplasia
HTN and hypokalemia in a heavy licorice eater → 11β-HSD2 inhibition
Teen with HTN, hypokalemia, ↓ renin and aldosterone, responds to amiloride → Liddle syndrome
Family with early hypertension suppressed by dexamethasone → glucocorticoid-remediable aldosteronism