Elevated adrenocorticotropic hormone and cortisol levels in a patient with medullary carcinoma of the thyroid containing ectopic immunoreactive corticotropin-releasing hormone and bombesin

Abstract

Pituitary adrenocorticotropic hormone-dependent Cushing’s syndrome due to ectopic production of corticotropin-refeasing hormone (CRH) or bombesin (gastrin-releasing peptide) is an extremely rare cause of pituitary adrenocorticotropic hormone (ACTH) hypersecretion. We report a patient with elevated ACTH and cortisol levels due to ectopic secretion of both bombesin and CRH by metastatic medullary carcinoma of the thyroid (MCT). A 45-year-old man was investigated because of diabetes insipidus and visual field disturbances due to suprasellar metastasis of the MCT. On physical examination, he was a chronically ill man with a body mass index of 18.5 and was darkly pigmented but without other features typical of Cushing’s syndrome. Hypogonadotropic hypogonadism, thyroid-stimulating hormone (TSH) deficiency, and hyperprolactinemia were due to pituitary stalk disorder, in light of these deficiencies, we were surprised to find elevated plasma ACTH, cortisol, and growth hormone (GH) levels throughout the day. Plasma ACTH at 9am was 118 pg/ml and plasma cortisol was 859 nmol/L. At 12pm, ACTH was 89 pg/ml whereas plasma cortisol was 540 nmol/L. Urinary 17 OH CS were elevated (38 nmol/24 hr). The mean of the four-point day curve for GH was elevated. Plasma electrolytes were normal. The presence of both CRH and bombesin was documented by immunocytologic studies in the metastases (lymph node and suprasellar biopsy). ACTH was not found in any of the metastases. Because of the close proximity of the suprasellar metastasis to the portal pituitary circulation, CRH and bombesin could have been readily provided to the pituitary corticotrophs.