The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up.

Context: There are few large series of patients with ectopic, nonpituitary, corticotropin (ACTH) secretion (EAS).

Objective: The objective of this study was to analyze the clinical, biochemical, and radiological features, management, and treatment outcome of patients with EAS.

Design: This was a retrospective case-record study.

Setting: The setting for this study was a tertiary referral hospital center.

Patients: Forty patients with EAS were studied.

Main Outcome Measures: Clinical, biochemical, and radiological features and response to therapy and survival were measured.

Results: The median follow-up was 5 yr (range, 2-30 yr). None of the dynamic tests achieved 100% accuracy, but bilateral inferior petrosal sinus sampling showed an absent central gradient in all but one case (one of 12). Imaging correctly identified the lesion at first investigation in 65% of cases. Bronchial carcinoid tumors were the most common cause of EAS (n = 12; 30%), followed by other neuroendocrine tumors (n = 13, 32.5%). In 12.5% of patients, the source of EAS was never found. Octreotide scintigraphy and whole-body venous sampling were of limited value. Surgical attempt at curative resection was successful in 83% (10 of 12) of patients with bronchial carcinoid tumors; others responded generally well to adrenolytic therapy or bilateral adrenalectomy. Tumor histology and the presence of distant metastases were the main predictors of overall survival (P < 0.05).

Conclusions: A variety of tests and imaging studies are necessary for the correct diagnosis of the EAS, but even then, up to 20% of cases present a covert or occult EAS syndrome. These cases require a prolonged follow-up, review, and repetition of diagnostic tests and scans.