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The Ectopic Adrenocorticotropin Syndrome: Clinical Features, Diagnosis, Management, and Long-Term Follow-Up

Departments of Endocrinology (A.M.I., G.A.K., C.P., V.F., P.J.J., J.P.M., A.B.G., G.M.B.) and Academic Radiology (R.H.R.), St. Bartholomew’s Hospital, London EC1A 7BE, United Kingdom; and Department of Endocrinology (J.N.-P.), Division of Clinical Sciences, University of Sheffield, Sheffield S5 7AU, United Kingdom

Address all correspondence and requests for reprints to: Professor A. B. Grossman, Department of Endocrinology, St. Bartholomew’s Hospital, London EC1A 7BE, United Kingdom. E-mail: a.b.grossman{at}qmul.ac.uk.

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.

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