This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsagarakis, S. Articles by Thalassinos, N. Search for Related Content PubMed PubMed Citation Articles by Tsagarakis, S. Articles by Thalassinos, N.

Food-Dependent Androgen and Cortisol Secretion by a Gastric Inhibitory Polypeptide-Receptor Expressive Adrenocortical Adenoma Leading to Hirsutism and Subclinical Cushing’s Syndrome: In Vivo and in Vitro Studies

Department of Endocrinology, Diabetes and Metabolism (S.T., V.V., P.Tr., A.N., N.T.), Department of Surgery (T.M.) and Department of Pathology (F.S.), Evangelismos Hospital; 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University and Hellenic National Diabetes Center (C.T., P.Ts., S.R.); and Institute of Biology National Center for Scientific Research Democritos (H.P., D.K.), 106 76 Athens, Greece

Address all correspondence and requests for reprints to: S. Tsagarakis, M.D., Ph.D., Department of Endocrinology, Evangelismos Hospital, 106 76 Athens, Greece.

Aberrant gastric inhibitory polypeptide (GIP) receptor expression in bilaterally hyperplastic adrenals or unilateral adrenal adenomas is a rare form of adrenal hyperfunction. So far, only few cases have been described. In all these cases, cortisol was the predominant steroid released in a food-dependent manner, leading to the development of non-ACTH-dependent Cushing’s syndrome. In the present study, we describe a novel case of a GIP receptor-expressive adrenocortical adenomatous nodule, detected incidentally by computed tomography scanning in a 41-yr-old lady with hirsutism but no clinical signs of Cushing’s syndrome, on physical examination. Hormonal investigations in morning fasting samples showed slightly elevated androgen levels, low-normal baseline cortisol, normal suppression of cortisol after dexamethasone administration, and ACTH levels that were not suppressed and did stimulate after CRH administration. The elevated urinary free cortisol excretion, in conjunction with an atypical cortisol diurnal rhythm, raised the possibility of an aberrant stimulation of cortisol production by the adrenal tumor. Further studies demonstrated food-dependent secretion of cortisol, which was abolished by prior octreotide administration. Notably, substantial amounts of adrenal androgens were also secreted after food consumption. Removal of the tumor resulted in undetectable cortisol and androgen levels that did not respond to food consumption. Histological examination of the excised tumor revealed an adrenocortical adenomatous nodule originating from the inner zona reticularis, consisting mainly of compact cells. A steroidogenic secretory pattern, indicating the concomitant release of adrenal androgens and cortisol, was also observed in vitro from tumor cells cultured in the presence of GIP. The in vitro secretory response to GIP was higher for the adrenal androgen DHEA, compared with cortisol. The expression of the GIP receptor in tumor cells, but not in the adjacent normal adrenal, was demonstrated by RT-PCR), using specific oligonucleotide probes for this receptor.

In summary, we describe a patient with a GIP-expressive cortisol and androgen oversecreting adrenocortical nodule with the unusual presentation of hirsutism and not the typical clinical signs of Cushing’s syndrome. It is of note that food intake in this patient provoked a substantial increase in both adrenal androgen and cortisol levels that, together with the histological appearance of this nodule, was compatible with a zona reticularis-derived tumor. Thus, aberrant expression of the GIP receptor does not exclusively involve cells of a zona fasciculata phenotype, as previously reported, but may also occur in other types of differentiated adrenocortical cells.

This article has been cited by other articles:

				A. Lampron, I. Bourdeau, S. Oble, A. Godbout, W. Schurch, P. Arjane, P. Hamet, and A. Lacroix Regulation of Aldosterone Secretion by Several Aberrant Receptors Including for Glucose-Dependent Insulinotropic Peptide in a Patient with an Aldosteronoma J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 750 - 756. [Abstract] [Full Text] [PDF]

				M. H. S. Costa, A. C. Latronico, R. M. Martin, A. S Barbosa, M. Q Almeida, C. F. P. Lotfi, H. P Lima Valassi, M. Y. Nishi, A. M. Lucon, S. A. Siqueira, et al. Expression profiles of the glucose-dependent insulinotropic peptide receptor and LHCGR in sporadic adrenocortical tumors J. Endocrinol., February 1, 2009; 200(2): 167 - 175. [Abstract] [Full Text] [PDF]

				N M Albiger, G Occhi, B Mariniello, M Iacobone, G Favia, A Fassina, D Faggian, F Mantero, and C Scaroni Food-dependent Cushing's syndrome: from molecular characterization to therapeutical results Eur. J. Endocrinol., December 1, 2007; 157(6): 771 - 778. [Abstract] [Full Text] [PDF]

				T. L. Mazzuco, O. Chabre, N. Sturm, J.-J. Feige, and M. Thomas Ectopic Expression of the Gastric Inhibitory Polypeptide Receptor Gene Is a Sufficient Genetic Event to Induce Benign Adrenocortical Tumor in a Xenotransplantation Model Endocrinology, February 1, 2006; 147(2): 782 - 790. [Abstract] [Full Text] [PDF]

				V. Baldacchino, S. Oble, P.-O. Decarie, I. Bourdeau, P. Hamet, J. Tremblay, and A. Lacroix The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome J. Mol. Endocrinol., August 1, 2005; 35(1): 61 - 71. [Abstract] [Full Text] [PDF]

				F. M. Swords, S. Aylwin, L. Perry, J. Arola, A. B. Grossman, J. P. Monson, and A. J. L. Clark The Aberrant Expression of the Gastric Inhibitory Polypeptide (GIP) Receptor in Adrenal Hyperplasia: Does Chronic Adrenocorticotropin Exposure Stimulate Up-Regulation of GIP Receptors in Cushing's Disease? J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3009 - 3016. [Abstract] [Full Text] [PDF]

				M. O. Goodarzi, D. W. Dawson, X. Li, Z. Lei, P. Shintaku, C. V. Rao, and A. J. Van Herle Virilization in Bilateral Macronodular Adrenal Hyperplasia Controlled by Luteinizing Hormone J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 73 - 77. [Abstract] [Full Text] [PDF]

				L. Groussin, K. Perlemoine, V. Contesse, H. Lefebvre, A. Tabarin, P. Thieblot, J. L. Schlienger, J. P. Luton, X. Bertagna, and J. Bertherat The Ectopic Expression of the Gastric Inhibitory Polypeptide Receptor Is Frequent in Adrenocorticotropin-Independent Bilateral Macronodular Adrenal Hyperplasia, but Rare in Unilateral Tumors J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 1980 - 1985. [Abstract] [Full Text] [PDF]

				A. Lacroix, N. N'Diaye, J. Tremblay, and P. Hamet Ectopic and Abnormal Hormone Receptors in Adrenal Cushing's Syndrome Endocr. Rev., February 1, 2001; 22(1): 75 - 110. [Abstract] [Full Text]