STEP 1 • 73-SLIDE REVIEW

Adrenal disorders, decoded

Start at the gland, then follow the hormone pattern. Tap the adrenal layers and move through the exam pathways.

ACTIVE LAYER

Zona glomerulosa

Aldosterone • controlled mainly by angiotensin II and serum K⁺, not ACTH.

Outside → inside: GFR = Salt, Sugar, Sex. Medulla makes catecholamines.

ZGAldosterone

ZFCortisol

ZRAndrogens

CUSHING WORKUP

Confirm excess → measure ACTH → localize

Screen with one: 24-hour urinary free cortisol, late-night salivary cortisol, or failure to suppress after 1 mg overnight dexamethasone.

ACTH low: adrenal tumor/hyperplasia or exogenous glucocorticoid exposure. Image adrenals when appropriate.

ACTH high: pituitary disease or ectopic ACTH. Pituitary source classically suppresses with high-dose dexamethasone; ectopic source does not.

Unclear pituitary source: inferior petrosal sinus sampling distinguishes central from ectopic ACTH secretion.

ACTH-dependent

↑ ACTH → bilateral adrenal hyperplasia, hyperpigmentation via POMC/MSH, and ↑ adrenal androgens. Pituitary adenoma = Cushing disease.

ACTH-independent

↓ ACTH → no hyperpigmentation. Adrenal tumor causes ipsilateral mass with atrophy of adjacent/contralateral cortex. Exogenous steroids cause bilateral cortical atrophy.

Classic phenotype: central obesity, moon facies, dorsocervical fat pad, purple striae, thin limbs, proximal weakness, osteoporosis, hypertension, hyperglycemia, infections and mood change.

High cortisol + high ACTH + suppression with high-dose dexamethasone points to:

Pituitary ACTH retains partial feedback sensitivity; ectopic ACTH usually does not suppress.

Aldosterone pattern reader

PRIMARY

↑ Aldosterone, ↓ renin

Autonomous adrenal production: bilateral hyperplasia, aldosterone-producing adenoma (Conn), familial disease, rarely carcinoma. Resistant hypertension, hypokalemia, metabolic alkalosis; little edema because of aldosterone escape.

SECONDARY

↑ Aldosterone, ↑ renin

RAAS activation: renal artery stenosis, heart failure, cirrhosis, nephrotic syndrome, pregnancy or renin-secreting tumor. Edema depends on the underlying state.

Sequence: screen with aldosterone-to-renin ratio → confirm autonomous secretion with salt-loading/saline suppression → CT → adrenal venous sampling when lateralization will change surgery.

ENZYME BLOCK LOGIC

All three lower cortisol → raise ACTH → adrenal hyperplasia

21-hydroxylase

↓ aldosterone · ↓ cortisol · ↑ androgens
Salt wasting, hypotension, hyperkalemia; virilized XX infant. Marker: ↑ 17-hydroxyprogesterone.

11β-hydroxylase

↑ DOC effect · ↓ cortisol · ↑ androgens
Hypertension, hypokalemia plus virilization. Aldosterone itself may be low.

17α-hydroxylase

↑ DOC effect · ↓ cortisol · ↓ androgens
Hypertension, hypokalemia; undervirilized XY infant, absent/delayed puberty.

Fast discriminator: BP low = 21. BP high + androgens high = 11. BP high + androgens low = 17.

Hypertensive child with hypokalemia and virilization:

11β deficiency accumulates DOC (mineralocorticoid effect) and shunts precursors toward androgens.

PRIMARY / ADDISON

Adrenal cortex fails

↓ cortisol, ↓ aldosterone, ↑ ACTH. Hyperpigmentation, hypotension, volume loss, hyponatremia, hyperkalemia, hypoglycemia. Causes: autoimmune adrenalitis, TB/fungal disease, metastasis, infiltrative disease or bilateral hemorrhage.

CENTRAL

ACTH/CRH falls

↓ cortisol, low/inappropriately normal ACTH, but aldosterone is generally preserved by RAAS. No hyperpigmentation and usually no hyperkalemia. Chronic glucocorticoids are the classic cause.

Diagnostic spine

Low early-morning cortisol raises suspicion.

Cosyntropin: inadequate cortisol rise supports adrenal insufficiency.

ACTH separates primary (high) from central (low).

Adrenal crisis: shock/hypotension, vomiting or abdominal pain, fever, weakness, hyponatremia, hyperkalemia and hypoglycemia—often after infection, surgery, hemorrhage or abrupt steroid withdrawal. Waterhouse–Friderichsen = meningococcemia → DIC → bilateral adrenal hemorrhage.

Pheochromocytoma: catecholamine bursts

Painheadache

Pulsepalpitations

Perspirationdiaphoresis

Add paroxysmal hypertension, pallor, panic, hyperglycemia and possible orthostatic hypotension. Screen with plasma free or 24-hour urinary fractionated metanephrines, then localize with CT/MRI. Histology: Zellballen nests; chromogranin and synaptophysin positive.

Management trap: α-blockade before β-blockade. Giving β-blockade first risks unopposed α-mediated vasoconstriction and hypertensive crisis.

MEN 1

MEN1/menin tumor suppressor, chr 11.
3 Ps: Parathyroid, Pituitary, Pancreatic endocrine tumors.

MEN 2A

RET gain-of-function, chr 10.
Medullary thyroid carcinoma + pheochromocytoma + parathyroid hyperplasia.

MEN 2B

RET gain-of-function.
Medullary thyroid carcinoma + pheochromocytoma + mucosal neuromas + marfanoid habitus.

Hereditary pheo associations

Think RET/MEN2, VHL, NF1 and SDH-subunit mutations. Extra-adrenal chromaffin tumors are paragangliomas; malignancy is established by metastasis, not histologic atypia alone.

Adrenal Disorders Map