The ectopic corticotropin syndrome in association with nonpancreatic gastrointestinal tract cancer is rare. We report an unusual case of hyperadrenocorticism in a patient with metastatic esophageal squamous-cell carcinoma.

A 64-year-old man presented with a 3-month history of dysphagia and 11.35-kg weight loss. Physical examination was remarkable for a blood pressure of 160/98 mm Hg, cachexia, numerous ecchymoses, and globally diminished strength and reflexes. Abnormal laboratory values included a hematocrit of 0.34; a serum potassium level of 2.1 mEq/L, a chloride level of 86 mEq/L, a bicarbonate level of 42 mEq/L, and a glucose level of 264 mg/dL.

Esophogastroduodenoscopy revealed a friable lesion in the mid-esophagus. Computed tomography showed an esophageal mass, a low-attenuation hepatic lesion, and bilateral adrenal enlargement. The following findings were diagnostic for the ectopic corticotropin syndrome: elevated urinary free cortisol excretion (4508 µg/24 hours [normal, 20 to 90 µg/24 hours]); increased late-afternoon serum adrenocorticotropic hormone (ACTH) concentration (88 pg/mL [normal, 4 to 52 pg/mL]); low corticotropin-releasing hormone level (20 pg/mL [normal, 24 to 40 pg/mL]); and lack of suppressibility on 2-day, high-dose dexamethasone suppression testing. Pathologic examination of the esophageal tissue revealed poorly differentiated squamous-cell carcinoma. Positive results on immunohistochemical analysis for synaptophysin, keratin, and enolase indicated neuroendocrine differentiation. Staining for ACTH was negative.

Ketoconazole was administered to inhibit adrenal steroid biosynthesis. For widespread metastases, the patient received cisplatinum and 5-fluorouracil. The patient died shortly after leaving the hospital against medical advice. Autopsy was refused.

Neoplasms of the lung, thymus, and pancreas are the main producers of ectopic ACTH. In 1968, Lohrenz and Custer [1] described the only other patient with the ectopic corticotropin syndrome associated with esophageal squamous-cell carcinoma.

Negative staining for ACTH in tumor tissue does not exclude ACTH biosynthesis [2]. Some explanations include a predominance of ACTH precursors that are not immunoreactive to a particular anti-ACTH serum and excessive hormone secretion rates leading to a reduced storage of pro-opiomelanocortin-derived peptides [3].

Neuroendocrine esophageal cancer and no evidence of a pulmonary, thymic, or pancreatic tumor render the former the most probable source of the ectopic ACTH syndrome in our patient.