Cushing's syndrome due to phaeochromocytoma secreting the precursors of adrenocorticotropin

Adrenal phaeochromocytoma rarely causes ectopic ACTH syndrome. We describe a 44-yr-old hypertensive woman who was Cushingoid and markedly pigmented. L aboratory studies indicated severe hypokalaemia, abnormal liver function te sts, and random serum cortisols greater than 1660 nmol/L. Urinary catechola mines were markedly increased. An abdominal computed tomography scan showed a 4-cm left adrenal mass and an hypertrophied right adrenal. ACTH levels were elevated at 200 pmol/L, but ACTH precursors, which cross-r eact in the ACTH assay, were more highly elevated at 1625 pmol/L. The tumor cells cultured in vitro also secreted ACTH precursors, whereas ACTH levels were undetectable. Because the patient was highly pigmented, we measured circulating concentra tions of a-MSH, which were undetectable and certainly insufficient to stimu late melanogenesis, suggesting that tumor-derived ACTH precursors or ACTH w ere responsible for the pigmentation. A laparoscopic adrenalectomy resulted in remission of the Gushing's syndrome and dramatic reduction in the pigme ntation. Before operation, treatment of the patient with metyrapone and replacement dexamethasone decreased cortisol from more than 1660 to less than 20 nmol/L . Surprisingly, this resulted in a decrease in ACTH precursors to 100 pmol/ L and ACTH to 9.0 pmol/L. In vitro treatment of the tumor cells with dexame thasone for 24 or 40 h increased ACTH precursor secretion. In summary, this phaeochromocytoma causing Gushing's syndrome secreted prim arily ACTH precursors, which seemed to cause the marked pigmentation. In vi vo and in vitro evidence suggests that glucocorticoids induced ACTH precurs or secretion.