Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma

We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaechromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.