AKT · Endocrine/Adrenal

Cushing syndrome

Chronic glucocorticoid excess (exogenous steroids, or endogenous ACTH-dependent/independent)

Overview

Chronic cortisol excess. Commonest cause is EXOGENOUS (prescribed steroids). Endogenous: ACTH-dependent (pituitary adenoma = Cushing's DISEASE, or ectopic ACTH from small-cell lung/carcinoid) or ACTH-independent (adrenal adenoma/carcinoma). Central obesity, striae, proximal myopathy, hypertension and hyperglycaemia. Confirm cortisol excess, then localise.

Recognise

Central obesity, moon face, interscapular/supraclavicular fat, thin skin with purple STRIAE, easy bruising
PROXIMAL myopathy (can't rise from a chair), hypertension, impaired glucose tolerance/diabetes, osteoporosis, mood change
Hyperpigmentation if ACTH-dependent; hypokalaemic alkalosis (esp. ectopic ACTH, which is often rapid with weight loss not gain)

Red flags

Rapid onset + weight loss + hypokalaemia + pigmentation → ectopic ACTH (often small-cell lung cancer) — investigate for malignancy
Severe hypertension/hyperglycaemia/psychosis from cortisol excess

Differentials & how to tell them apart

Exogenous (iatrogenic) Cushing'ssteroid history; ACTH and cortisol both LOW (suppressed axis) — the commonest cause

Pseudo-Cushing's (alcohol, depression, obesity)mild, with a plausible cause; resolves — overnight dexamethasone helps discriminate

Ectopic ACTHrapid, weight loss, marked hypokalaemia/pigmentation, often small-cell lung cancer

Metabolic syndrome/PCOScentral obesity without striae/proximal myopathy/easy bruising

Cushingoid features — moon face / central adiposity
Ozlem Celik, Mutlu Niyazoglu et al / CC BY 2.5 — Wikimedia Commons

Investigations

First confirm cortisol excess: overnight/low-dose DEXAMETHASONE suppression test (fails to suppress), late-night salivary cortisol, or 24-h urinary free cortisol. Then ACTH (suppressed = adrenal; normal/high = ACTH-dependent) and localise (high-dose dexamethasone, MRI pituitary, CT chest/abdomen, IPSS).

Management

Confirm cortisol excess + localise → treat the cause (surgery; taper exogenous steroids)

1Establish cortisol excess (dexamethasone suppression/late-night salivary/urinary cortisol), then measure ACTH and localise. Commonest cause is exogenous steroids — review and taper.Gate: NEVER stop long-term exogenous steroids abruptly (precipitates adrenal crisis) — taper; a suppressed ACTH points to an adrenal tumour, a normal/high ACTH to pituitary (Cushing's disease) or ectopic source
2Definitive: transsphenoidal surgery (Cushing's disease), adrenalectomy (adrenal tumour), treat the ectopic tumour; medical therapy (metyrapone/ketoconazole) bridges to surgery.

Treat the cause — taper exogenous steroids; transsphenoidal surgery (Cushing's disease); adrenalectomy (adrenal tumour); treat ectopic source

Steroidogenesis inhibitors (metyrapone, ketoconazole) — medical control of cortisol while awaiting definitive treatment

Key points

Central obesity + striae + proximal myopathy + hypertension + hyperglycaemia. Step 1 confirm cortisol excess (dexamethasone), step 2 localise with ACTH. Rapid + weight loss + hypokalaemia = ectopic ACTH (think lung). The commonest cause overall is the steroids you prescribed.

Monitor & prognosis

Cortisol axis post-treatment; replace if hypoadrenal after cure.

Good if treated; cardiovascular/metabolic risk if untreated.

Source: CKS Cushing's; Endocrine Society