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

Isidori, Andrea M.
Kaltsas, Gregory A.
Pozza, Carlotta
Frajese, Vanni
Newell-Price, John
Reznek, Rodney H.
Jenkins, Paul J.
Monson, John P.
Grossman, Ashley B.
Besser, G Michael

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

First Published Online November 22, 2005

Abbreviations: BIPSS, Bilateral inferior petrosal sinus sampling; CS, Cushing’s syndrome; CT, computerized tomography; CXR, chest radiograph; EAS, ectopic ACTH secretion; HDDST, high-dose dexamethasone suppression test; ¹²³I-MIBG, ¹²³I-meta-iodobenzylguanidine; MRI, magnetic resonance imaging; MTC, medullary carcinoma of the thyroid; NET, neuroendocrine tumor; SCC, small-cell carcinoma; SCLC, small-cell lung carcinoma; WBCS, whole-body venous catheterization and sampling.

Journal of Clinical Endocrinology & Metabolism 91(2):p 371-377, February 2006.

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.