# Cushing Syndrome Workup > Cushing syndrome workup for NEET-SS Endocrinology: two screening tests, ACTH stratification, AVS-free discrimination with IPSS and ectopic hunt. - Canonical URL: https://prepelephant.com/topics/neet-ss/endocrinology/cushing-workup-dm - Exam / course: NEET-SS · Subject: Endocrinology - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Cushing Syndrome Workup", PrepElephant, https://prepelephant.com/topics/neet-ss/endocrinology/cushing-workup-dm ## Direct answer At least two concordant screening tests are needed before anyone chases the source of cortisol excess — choose from the 1 mg overnight dexamethasone suppression test (cortisol of 1.8 μg/dL or more at 8 a.m. is abnormal), two late-night salivary cortisols, or two 24-hour urinary free cortisol collections. Once hypercortisolism is proven, plasma ACTH stratifies the disease: below 10 pg/mL means adrenal autonomy and an adrenal CT; 20 pg/mL or more means ACTH-dependent disease, of which Cushing disease (a pituitary corticotroph adenoma) causes roughly 70–80 per cent and ectopic ACTH secretion most of the rest. Pituitary MRI with a clear adenoma and concordant dynamic testing permits transsphenoidal surgery without further steps; discordant or negative imaging moves to inferior petrosal sinus sampling — a central-to-peripheral ACTH gradient of 2 or more at baseline, or 3 or more after desmopressin, confirms Cushing disease. And before all of it: ask about steroids — in India, topical combination creams, oral "joint" medicines and depot injections make exogenous Cushing the commonest form by far. ## What you must remember - **Screening trio, two needed:** overnight 1 mg DST (cut-off 1.8 μg/dL), late-night salivary cortisol on two separate nights, and 24-hour urinary free cortisol twice — concordance protects against the false positives of obesity, depression and alcohol (pseudo-Cushing states). - **Physiology behind the tests:** cortisol's normal circadian nadir at midnight is lost earliest in Cushing — that is what the salivary test exploits; the overnight DST probes glucocorticoid feedback. - **ACTH interpretation:** under 10 pg/mL — ACTH-independent (adrenal CT next); over 20 — ACTH-dependent; 10–20 — repeat, since the zone is unreliable. - **ACTH-dependent split:** Cushing disease 70–80 per cent, ectopic ACTH (small cell lung, bronchial or thymic carcinoid, medullary thyroid carcinoma, phaeochromocytoma) 15–20 per cent, rare ectopic CRH. - **IPSS numbers:** basal central:peripheral ACTH gradient at least 2, or at least 3 post-desmopressin, with prolactin normalisation used for failed cannulation — sensitivity above 90 per cent for Cushing disease; every IPSS is paired because ectopic tumours occasionally grade falsely positive on basal gradients alone. - **Caveat armoury:** renal failure invalidates urinary free cortisol; midnight salivary sampling fails shift workers; oestrogen (oral contraceptive) raises cortisol-binding globulin and falsely elevates total cortisol — stop it or measure free fractions; cyclic Cushing secretes in waves and needs repeated testing. - **Adrenal CT reading:** lipid-rich adenoma under 10 Hounsfield units on non-contrast; indeterminate nodules need washout chemistry; large heterogeneous masses raise adrenocortical carcinoma concern. - **Post-cure reality:** all treated Cushing becomes adrenal-insufficient until the axis recovers — glucocorticoid replacement and education for months to years, with taper guided by morning cortisol. ## Screening to localisation in one patient A 42-year-old woman with centripetal obesity, wide violaceous striae, proximal myopathy and new hypertension and diabetes. Step one — exclude exogenous steroids: none (asked twice, including about skin creams). Step two — screen: 1 mg DST shows 8 a.m. cortisol 9.4 μg/dL; late-night salivary cortisol elevated on both nights; the diagnosis of endogenous hypercortisolism stands. Step three — ACTH: 65 pg/mL, so ACTH-dependent. Step four — MRI pituitary: a 4 mm right-sided microadenoma; consistent so far, but incidental microadenomas exist in a tenth of the population. Step five — confirm the gradient: desmopressin-stimulated testing (ACTH rise favouring corticotroph tumour) concordant; proceed to IPSS in most units for a microadenoma of this size or where any discordance exists, and here the central:peripheral gradient is 4.6 — Cushing disease. Step six — transsphenoidal selective adenomectomy, morning cortisol under 2 μg/dL the day after (biochemical cure), hydrocortisone replacement begun with sick-day rules. Had the MRI been negative, the same pathway runs through IPSS and, if the gradient was peripheral, a CT chest for the ectopic source. The examineable discipline: never image before biochemistry, never localise before ACTH, and never declare cure without postoperative hypocortisolism. ## Where students slip The classic error is diagnosing Cushing on one screening test in an obese, depressed or alcoholic patient — pseudo-Cushing disease states produce mild abnormalities in all three screens, and two concordant positives are the entry price. The second slip is CT-scanning the adrenals of an ACTH-dependent patient and "treating" the bilateral hyperplasia found — the adrenals are victims, not culprits. The third is forgetting the high-dose dexamethasone test's fall from grace: modern practice replaces it with IPSS. Indian viva additions: asking about topical steroid creams (fairness and dermatology combinations) before labelling endogenous disease, and remembering tuberculosis of the adrenal in the differential of adrenal masses — a local twist examiners expect. ## Frequently asked questions ### Which tests screen for Cushing syndrome, and how many are needed? The 1 mg overnight dexamethasone suppression test, late-night salivary cortisol and 24-hour urinary free cortisol — at least two concordant abnormal results are required before proceeding. ### How does plasma ACTH guide the workup? Below about 10 pg/mL the disease is ACTH-independent (image the adrenals); 20 pg/mL or more is ACTH-dependent (pituitary MRI, then IPSS if discordant); values between warrant repetition. ### What gradient on inferior petrosal sinus sampling confirms Cushing disease? A central-to-peripheral ACTH gradient of at least 2 at baseline or at least 3 after desmopressin stimulation, from correctly catheterised sinuses. ### Why has the high-dose dexamethasone test lost favour? Its discrimination between Cushing disease and ectopic ACTH is imperfect; IPSS provides far better diagnostic performance, so dynamic suppression testing now plays only a supporting role. ### What defines biochemical cure after transsphenoidal surgery? Postoperative morning cortisol below about 2 μg/dL (5 μg/dL by some protocols) with clinical recovery — indicating remnant corticotroph suppression — followed by glucocorticoid replacement until the axis recovers.