Gene Expression Analysis of Glucose Transporter GLUT1 and HEXOKINASE II in ACTH-Independent Macronodular Adrenocortical Hyperplasia

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 17-28-Adrenal Tumors & Pheochromocytoma
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-25
Isadora Pontes Cavalcante*1, Beatriz Marinho Mariani2, Maria Candida Barisson Villares Fragoso3, Guilherme Asmar Alencar4, André Faria Murad2, Antonio Marcondes Lerario2, Madson Q Almeida4, Carlos Alberto Buchpiegel5, Ana Claudia Latronico6 and Berenice Bilharinho Mendonca7
1Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, 3University of Sao Paulo, Sao Paulo-SP, Brazil, 4Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brazil, 5Hospital das Clínicas, São Paulo, Brazil, 6Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil, 7Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
Introduction: ACTH-Independent Macronodular Adrenocortical Hyperplasia (AIMAH) is a disease characterized by the presence of functioning macronodules in both adrenal glands and increased production, autonomous and sustained by cortisol, a rare cause of Cushing's syndrome. A better characterization of clinical, laboratory and radiological findings of AIMAH is currently a key point to improve the understanding of the disease. The pathophysiological process that would culminate with AIMAH and any predisposing genetic alterations has not been elucidated yet. Positron emission tomography (PET) imaging test is the most widely used in oncology to detect increased glucose metabolism in tumors from different cell lines. The marker used in most PET is the glucose analogue 2 - [18F] fluoro-2-deoxy-D-glucose (18F-FDG). 18F-FDG, like glucose, is actively transported into cells by glucose transporters. The accumulation of 18F-FDG forms the basis of using 18F-FDG as a functional marker of glucose for quantitative interpretation of PET scans through the standard uptake value (SUV). The transport of glucose across the cell membrane by glucose transporters (GLUTs) and intracellular phosphorylation by hexokinases (HK), especially HK II, were identified as critical to the subsequent accumulation. HK II is overexpressed in many types of cancer, increasing their ability to metabolize glucose, a phenotype used clinically to detect tumor cells by PET. Recently it was described three non-related patients with AIMAH demonstrating increased uptake of 18F-FDG. However, it is still unclear the mechanism by which AIMAH, a benign adrenal disease, exhibit an intense uptake of 18F-FDG in PET / CT. Objectives: To investigate whether increased expression of glucose transporter GLUT1 and HK II is associated with increased uptake of the 18 F-FDG FDG-PET/CT in patients with AIMAH, adrenocortical carcinoma and adenoma. Methods: Expression analysis of SLC2A1 that codifies GLUT1 protein and HKII that codifies hexokinase 2 protein, by real time PCR in 5 adult patients with AIMAH, 3 patients with adenoma and 5 patients with carcinoma using normal adrenal gland tissue as the control tissue. Results: Patients with high SUV demonstrated overexpression of both genes. SLC2A1 was found overexpressed in 2 patients with adrenocortical carcinoma (SUV>11). A reduced expression was found in 2 patients with adenoma (SUV=5,2) and 1 with AIMAH (SUV=5,5). The other patients demonstrated the same expression as the control; the analyses of HKII showed an overexpression on 3 carcinoma patients (SUV>10) and a reduced expression on 2 AIMAH (SUV=5,6) patients. The other patients demonstrated the same expression as the control tissue. Conclusion: Patients with AIMAH appear not to demonstrate an overexpression in SLC2A1 and HKII. The increased uptake of 18F-FDG in PET / CT in patients with AIMAH could result from another methabolic pathway.

1)Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia and aberrant hormone receptors. Horm Res 2005; 64:119-131. 2)Lacroix A. ACTH-independent macronodular adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009; 23: 245–259. 3)Joost HG, Thorens B. 2001. The extended GLUT-family of sugar/polyol transport facilitators: Nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol 18(4):247–256. 4)Marzzoco A, Torres BB. 1999. Bioquímica Básica 5)Alencar GA, Fragoso MC, Yamaga LY, Lerario AM, Mendonca BB. (18)F-FDG-PET/CT imaging of ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) demonstrating increased (18)F-FDG uptake. J Clin Endocrinol Metab. 2011 Nov;96(11):3300-1.

Nothing to Disclose: IPC, BMM, MCBVF, GAA, AFM, AML, MQA, CAB, ACL, BBM

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