Cushing's Syndrome: Investigations

Key points

• Cushing's syndrome: investigations Investigations are divided into confirming Cushing's syndrome and then localising the lesion. A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance.
• FIRST EXCLUDE EXOGENOUS GLUCOCORTICOIDS — by far the commonest cause of Cushing's syndrome is prescribed steroid, and no biochemical test is needed to make that diagnosis.
• CONFIRMING CUSHING'S SYNDROME — NICE and endocrine guidance recommend ANY ONE of three screening tests, and at least two abnormal results before proceeding: the 1 mg OVERNIGHT DEXAMETHASONE SUPPRESSION TEST, LATE-NIGHT SALIVARY CORTISOL, or 24-HOUR URINARY FREE CORTISOL. The overnight DST is the usual first-line screening test because it is highly SENSITIVE — but it has poor SPECIFICITY, so a positive result screens IN rather than confirms.
• FALSE POSITIVES on the overnight DST are common: oestrogens and the combined oral contraceptive (raised cortisol-binding globulin), CYP3A4-inducing drugs, alcohol, depression, obesity and other pseudo-Cushing states. Repeat or use an alternative test rather than acting on one abnormal result.
• ONLY THEN LOCALISE. The first localisation step is plasma ACTH: SUPPRESSED ACTH indicates an ACTH-INDEPENDENT (adrenal) cause — image the adrenals. NORMAL OR RAISED ACTH indicates ACTH-DEPENDENT disease — pituitary (Cushing's DISEASE) or ectopic.
• if pituitary source then cortisol rises
• if ectopic/adrenal then no change in cortisol Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion