Cushing's syndrome caused by paraneoplastic ACTH secretion 11 years after occurence of a medullary thyroid carcinoma

Abstract

A 47-year-old man, with known and treated hypertension for 2 years, was admitted because of recent marked weight gain. Eleven years before a medullary thyroid carcinoma had necessitated removal of his thyroid and parathyroids. He was not receiving levothyroxine, calcium and vitamin D. Physical examination revealed florid Cushing's syndrome with a "buffalo hump", plethora, truncal obesity and red striae. Both his mother and a maternal male cousin were reported to have had a medullary thyroid carcinoma. Plasma ACTH was 80 pg/ml (normal 10-70 pg/ml), urinary cortisol 764 microgram/24 h (normal 20-100 microgram/24 h). ACTH rose to 93.1 pg/ml after dexamethasone, with little suppression of serum cortisol (reduced from 34.4 to 22.1 microgram/dl; normal 7-25 microgram/dl. Magnetic resonance imaging did not detected an abnormal hypophysis. Petrosal sinus catheterization revealed hypophyseal suppression of ACTH, without evidence of focal peripheral ACTH production. Calcitonin was 24 000 pg/ml (normal < 8.8 pg/ml). Computed tomography showed multiple round lesions in the liver (histology: metastasis of a C-cell carcinoma). Genetic test showed a multiple endocrine neoplasm type IIa. The findings indicated Cushing's syndrome, most likely due to paraneoplastic ACTH secretion from a metastasis of the C-cell carcinoma. In the absence of a site of paraneoplastic ACTH secretion, bilateral adrenalectomy was performed. The plethora and striae regressed postoperatively and it was possible to reduce markedly the antihypertensive medication. An ectopic site of ACTH should be included in the differential diagnosis of Cushing's syndrome. This is the first reported case of a medullary thyroid carcinoma and ectopic ACTH production in which the paraneoplastic ACTH secretion had been delayed for 11 years.