Journal of Clinical Endocrinology & Metabolism, Vol 81, 3168-3172, Copyright © 1996 by Endocrine Society

ARTICLES

Food-dependent Cushing's syndrome resulting from abundant expression of gastric inhibitory polypeptide receptors in adrenal adenoma cells

WW de Herder, LJ Hofland, TB Usdin, FH de Jong, P Uitterlinden, P van Koetsveld, E Mezey, TI Bonner, HJ Bonjer and SW Lamberts
Department of Internal Medicine, University Hospital Rotterdam, The Netherlands.

We studied a 45-yr-old woman with food-dependent Cushing's syndrome. Plasma cortisol levels were subnormal (4-47 nmol/L) after an overnight fast and increased after a mixed meal to values between 500-1000 nmol/L. There was a close correlation between circulating gastric inhibitory polypeptide (GIP) and cortisol levels during normal food intake (r = 0.92; P < 0.0002). Plasma corticotropin (ACTH) levels were undetectable. Nonfasting plasma cortisol levels were not suppressed by low or high doses of dexamethasone. Plasma ACTH and cortisol levels did not increase after human CRH administration, but fasting plasma cortisol levels increased after ACTH treatment. The infusion of GIP increased plasma cortisol levels to 7.8 times above baseline. Radiological and cholesterol uptake studies pointed to a unilateral adrenal adenoma. Treatment with octreotide initially prevented the meal- induced increases in cortisol and GIP levels and decreased urinary cortisol excretion. Unilateral adrenalectomy was performed. Cortisol production by cultured adrenal adenoma cells from the patient was stimulated by GIP and ACTH. In situ hybridization studies using a GIP receptor probe showed an abundant expression of GIP receptor messenger ribonucleic acid in the adrenocortical adenoma. We conclude that food- dependent Cushing's syndrome results from the expression of GIP receptors on adrenocortical adenoma cells.

This article has been cited by other articles:

				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]

				J. Bertherat, V. Contesse, E. Louiset, G. Barrande, C. Duparc, L. Groussin, P. Emy, X. Bertagna, J.-M. Kuhn, H. Vaudry, et al. In Vivo and in Vitro Screening for Illegitimate Receptors in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Causing Cushing's Syndrome: Identification of Two Cases of Gonadotropin/Gastric Inhibitory Polypeptide-Dependent Hypercortisolism J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1302 - 1310. [Abstract] [Full Text] [PDF]

				M. C. B. V. Fragoso, S. Domenice, A. C. Latronico, R. M. Martin, M. A. A. Pereira, M. C. N. Zerbini, A. M. Lucon, and B. B. Mendonca Cushing's Syndrome Secondary to Adrenocorticotropin-Independent Macronodular Adrenocortical Hyperplasia due to Activating Mutations of GNAS1 Gene J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2147 - 2151. [Abstract] [Full Text] [PDF]

				K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [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]

				S. Tsagarakis, C. Tsigos, V. Vassiliou, P. Tsiotra, H. Pratsinis, D. Kletsas, P. Trivizas, A. Nikou, T. Mavromatis, F. Sotsiou, et al. 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 J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 583 - 589. [Abstract] [Full Text]

				H. Mircescu, J. Jilwan, N. N'Diaye, I. Bourdeau, J. Tremblay, P. Hamet, and A. Lacroix Are Ectopic or Abnormal Membrane Hormone Receptors Frequently Present in Adrenal Cushing's Syndrome? J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3531 - 3536. [Abstract] [Full Text]

				J. L. Doppman, G. P. Chrousos, D. A. Papanicolaou, C. A. Stratakis, H. R. Alexander, and L. K. Nieman Adrenocorticotropin-independent Macronodular Adrenal Hyperplasia: An Uncommon Cause of Primary Adrenal Hypercortisolism Radiology, September 1, 2000; 216(3): 797 - 802. [Abstract] [Full Text]

				A. Lacroix, P. Hamet, and J.-M. Boutin Leuprolide Acetate Therapy in Luteinizing Hormone-Dependent Cushing's Syndrome N. Engl. J. Med., November 18, 1999; 341(21): 1577 - 1581. [Full Text] [PDF]

				F. P. Pralong, F. Gomez, L. Guillou, F. Mosimann, S. Franscella, and R. C. Gaillard Food-Dependent Cushing's Syndrome: Possible Involvement of Leptin in Cortisol Hypersecretion J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3817 - 3822. [Abstract] [Full Text] [PDF]

				N. N’Diaye, P. Hamet, J. Tremblay, J.-M. Boutin, L. Gaboury, and A. Lacroix Asynchronous Development of Bilateral Nodular Adrenal Hyperplasia in Gastric Inhibitory Polypeptide-Dependent Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2616 - 2622. [Abstract] [Full Text]

				W W DE HERDER and S W J LAMBERTS Octapeptide somatostatin-analogue therapy of Cushing's syndrome Postgrad. Med. J., February 1, 1999; 75(880): 65 - 66. [Full Text]

				M. C. Lebrethon, O. Avallet, Y. Reznik, F. Archambeaud, J. Combes, T. B. Usdin, G. Narboni, J. Mahoudeau, and J. M. Saez Food-Dependent Cushing's Syndrome: Characterization and Functional Role of Gastric Inhibitory Polypeptide Receptor in the Adrenals of Three Patients J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4514 - 4519. [Abstract] [Full Text]

				J. Newell-Price, P. Trainer, M. Besser, and A. Grossman The Diagnosis and Differential Diagnosis of Cushing's Syndrome and Pseudo-Cushing's States Endocr. Rev., October 1, 1998; 19(5): 647 - 672. [Abstract] [Full Text]

				O. Chabre, P. Liakos, J. Vivier, P. Chaffanjon, F. Labat-Moleur, M. Martinie, S. P. Bottari, I. Bachelot, E. M. Chambaz, G. Defaye, et al. Cushing's Syndrome due to a Gastric Inhibitory Polypeptide-Dependent Adrenal Adenoma: Insights into Hormonal Control of Adrenocortical Tumorigenesis J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3134 - 3143. [Abstract] [Full Text]

				N. N’Diaye, J. Tremblay, P. Hamet, W. W. De Herder, and A. Lacroix Adrenocortical Overexpression of Gastric Inhibitory Polypeptide Receptor Underlies Food-Dependent Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2781 - 2785. [Abstract] [Full Text]

				A. Lacroix, J. Tremblay, G. Rousseau, M. Bouvier, and P. Hamet Propranolol Therapy for Ectopic {beta}-Adrenergic Receptors in Adrenal Cushing's Syndrome N. Engl. J. Med., November 13, 1997; 337(20): 1429 - 1434. [Full Text] [PDF]

				A. Lacroix, J. Tremblay, R. M. Touyz, L. Y. Deng, R. Lariviere, J. R. Cusson, E. L. Schiffrin, and P. Hamet Abnormal Adrenal and Vascular Responses to Vasopressin Mediated by a V1-Vasopressin Receptor in a Patient with Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia, Cushing's Syndrome, and Orthostatic Hypotension J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2414 - 2422. [Abstract] [Full Text] [PDF]