Cushing syndrome - biochemical localisation (ACTH-dependent vs independent, Nelson's, Sheehan's)
Core concept
- Two questions, and never in the reverse order
- 1. Is there hypercortisolism? - screening tests
- 2. Where is it coming from? - plasma ACTH first
- *Never image before biochemistry - incidental adrenal (5-10%) and pituitary (10%) lesions are common enough to mislead*
Step 1 - confirm hypercortisolism (need 2 abnormal tests)
| Test | Abnormal | Caveats |
|---|---|---|
| 1 mg overnight dexamethasone suppression | Cortisol >50 nmol/L | False + with oestrogen (inc CBG), CYP3A4 inducers (phenytoin, rifampicin), malabsorption, non-adherence |
| 24 h urinary free cortisol (x2) | >3x ULN is diagnostic | Falsely low in CKD; falsely high with high fluid intake |
| Late-night salivary cortisol (x2) | Elevated | Loss of the diurnal nadir is the earliest abnormality; invalid in shift workers |
- Exclude the mimics first: exogenous steroid (including topical, inhaled, joint injection, "herbal" preparations), then pseudo-Cushing's - alcohol, severe depression, obesity, poorly controlled diabetes, PCOS
3 more sections, plus exam facts
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