CUSHING'S SYNDROME, NODULAR ADRENAL HYPERPLASIA AND VIRILIZING CARCINOMA

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Abstract
A 48 yr old hypertensive diabetic woman rapidly became virilized. Urine 17-oxo- and oxogenic steroids and plasma testosterone, androstenedione, DHEA [dehydroepiandrosterone], DHEA-sulfate and androstenediol were elevated. Plasma cortisol was constantly high and was not suppressed by dexamethasone. Circulating immunoreactive ACTH was consistently detectable at 18-24 ng/l. A 450 g carcinoma arising from a nodular hyperplastic right adrenal gland was resected. Production by the tumor of 17.alpha.-hydroxypregnenolone, 17.alpha.-hydroxyprogesterone and 5 C-19 steroids, but very little pregnenolone, progesterone or cortisol, was shown by blood sampling, tumor culture and dramatic falls after operation. The plasma cortisol fell to half, with no diurnal variation, consistent with persistent Cushing''s syndrome, and the plasma ACTH rose to 55 ng/l. She died 3 mo. later from a myocardial infarction. Autopsy revealed a pituitary basophil adenoma at a site where radiologically there was an indentation in the fossa floor for at least 7 yr. The left adrenal gland showed nodular hyperplasia. Mild pituitary dependent Cushing''s syndrome may have been present for many years before development of a virilizing carcinoma. Adrenal carcinoma in man can sometimes develop as a consequence of nodular adrenal hyperplasia which may be due to long-standing trophic hyperstimulation.

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