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To identify the cause of Cushing's syndrome, a process of elimination is required:
- adrenal CT - adrenal adenomas are usually smaller than 6 cm. The larger carcinomas usually show an irregular outline and radiologic evidence of local invasion or distant metastases. Adrenal tumours show no suppression of plasma cortisol with high dose dexamethasone.
- very high plasma ACTH - above 300 ng/l - is likely to be ectopic ACTH not Cushing's disease. At least two occurrences of low or undetectable ACTH - less than 10 ng/l - confirms non-ACTH dependent disease
- plasma potassium - hypokalaemia in ectopic ACTH secretion but note that about 10% of patients with pituitary disease are hypokalaemic and that careless handling of the blood sample may cause haemolysis and masking of mild hypokalaemia
- glucose intolerance - common in both ectopic ACTH and Cushing's disease
- high dose dexamethasone suppression - 80% of Cushing's disease show more than 50% suppression
- CRH test - i.v. bolus of 100 mcg CRH - exaggerated response of serum cortisol occurs in 80% of pituitary Cushing's disease. Response in ectopic ACTH is extremely rare.
- tumour markers - elevated levels of beta-human chorionic gonadotrophin, calcitonin, carcinoembryonic antigen may occur with ectopic ACTH
- chest X-ray - may detect small cell carcinoma of bronchus
- pituitary CT or MRI - uncommonly detects pituitary macro-adenoma
- whole lung and mediastinal CT - may detect carcinoid tumours if ectopic ACTH suspected
- selective catheterisation of inferior petrosal sinuses draining the pituitary - to identify pituitary source of ACTH - or of the jugular veins - to localise ectopic ACTH
Note - metyrapone, lysine vasopressin and ACTH stimulation
Last reviewed 01/2018