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A 36-year-old woman presents with a 9-month history of weight gain (central), easy bruising, purple abdominal striae over 1 cm wide, muscle weakness on climbing stairs, secondary amenorrhoea and new-onset hypertension (158/96). She takes a combined oral contraceptive pill. She does not drink alcohol and has no psychiatric history.
Questions
a) What clinical syndrome does this describe, and what is the single most discriminating bedside feature separating it from simple obesity? (2 marks)
Cushing syndrome (chronic cortisol excess). The single most discriminating bedside feature is proximal muscle weakness (difficulty rising from a squat / climbing stairs / shoulder abduction against resistance); wide purple striae over 1 cm and easy bruising are also highly specific.
b) Outline the three first-line screening tests and the diagnostic criterion. (3 marks)
- 1-mg overnight dexamethasone suppression test: dex 1 mg PO at 23:00, serum cortisol at 08:00 — fail if cortisol over 50 nmol/L (1.8 microgram/dL).
- Late-night (midnight) salivary cortisol on two separate nights — elevated above the lab cut-off.
- 24-hour urine free cortisol (two collections) — elevated above the reference limit.
Diagnosis requires two abnormal tests (provided exogenous steroid is excluded). The OCP should be stopped 6 weeks before testing as oestrogen raises cortisol-binding globulin; salivary cortisol or UFC can be used meanwhile.
c) Her ACTH comes back at 68 pg/mL. How does this alter the differential, and what is the next diagnostic step? (3 marks)
ACTH over 22 pg/mL = ACTH-dependent (pituitary or ectopic). Next: differentiate the two with high-dose DST (over 50% suppression = pituitary) and/or CRH stimulation test (cortisol rises over 20% = pituitary), then gadolinium-enhanced pituitary MRI. If imaging is equivocal, bilateral inferior petrosal sinus sampling (gold standard): petrosal-to-peripheral ACTH ratio over 2 basally or over 3 after CRH = pituitary disease. Ectopic ACTH is suggested by hypokalaemic alkalosis, hyperpigmentation, weight loss and a smoker over 50; localise with CT chest/abdomen/pelvis and DOTATATE scintigraphy.
d) She is diagnosed with Cushing disease and undergoes transsphenoidal adenomectomy. Name two complications to anticipate and prevent in the peri-operative period. (2 marks)
- Acute adrenal crisis from HPA suppression — give IV hydrocortisone 100 mg at induction, then 50 mg 8-hourly, tapering to oral replacement over weeks-months (post-op cortisol target under 50 nmol/L defines remission).
- Venous thromboembolism (up to 10-fold increased risk) — pharmacological thromboprophylaxis (enoxaparin 40 mg SC daily) plus mechanical, continued until biochemical remission.