Mifepristone Effects on Tumor Somatostatin Receptor Expression in Two Patients with Cushing's Syndrome due to Ectopic Adrenocorticotropin Secretion

Author:

de Bruin C.1,Hofland L. J.1,Nieman L. K.2,van Koetsveld P. M.1,Waaijers A. M.1,Sprij-Mooij D. M.1,van Essen M.3,Lamberts S. W. J.1,de Herder W. W.1,Feelders R. A.1

Affiliation:

1. Department of Internal Medicine (C.d.B., L.J.H., P.M.v.K., A.M.W., D.M.S.-M., S.W.J.L., W.W.d.H., R.A.F.), 3015 CE Rotterdam, The Netherlands

2. Pediatric and Reproductive Endocrinology Branch (L.K.N.), National Institutes of Health, Bethesda, Maryland 20892-1109

3. Division of Endocrinology, and Department of Nuclear Medicine (M.v.E.), Erasmus Medical Center, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands

Abstract

Context: Two patients presented with Cushing's syndrome due to ectopic ACTH secretion. Initial localization studies included computed tomography, magnetic resonance imaging, and octreoscans (111In-pentreotide scintigraphy), which were negative in both patients. They were treated with the glucocorticoid receptor antagonist mifepristone, with improvement in their clinical symptoms. Follow-up octreoscans after, respectively, 6 and 12 months showed the unequivocal presence of a bronchial carcinoid in both patients. Objective: The objective of the study was to correlate in vivo and in vitro findings in patients with ectopic ACTH-producing syndrome. Methods: We determined the expression of somatostatin and dopamine receptors by immunohistochemistry (patients 1 and 2), quantitative PCR, and in vitro culturing of tumor cells (patient 1 only). In Vitro Results: Both tumors were strongly positive for somatostatin receptor type 2 (sst2) on immunohistochemistry, whereas one of the tumors (patient 1) was also dopamine receptor subtype 2 (D2) positive on both immunohistochemistry and quantitative PCR. Octreotide (a sst2 preferring analog) and cabergoline (D2 agonist) both decreased the ACTH levels in the cultured tumor cells of patient 1. Conclusion: We describe two patients with ACTH-producing bronchial carcinoids, in whom a direct down-regulatory effect of glucocorticoid levels on tumoral sst2 receptor expression is suggested by a remarkable change in octreoscan status after successful mifepristone therapy. Further studies will have to demonstrate whether glucocorticoid lowering or antagonizing therapy may be used to improve the diagnostic accuracy of somatostatin receptor scintigraphy in patients with ectopic ACTH production of unknown primary origin.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

Reference31 articles.

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