Endocrine Abstracts

Interindividual variations in tissue sensitivity to glucocorticoids have been partly attributed to polymorphisms in the glucocorticoid receptor (GR) gene. The aim of this study was to investigate the prevalence of subclinical hypercortisolism (SH) in women with adrenal incidentaloma (AI), and whether BclI variant of the GR gene may contribute to metabolic abnormalities frequently present in these patients. We evaluated 106 women with AI. Anthropometric characteristics included BMI, waist and hip circumference. SH was diagnosed in the presence of serum cortisol levels after 2-day low-dose dexamethasone suppression test (LDDST) >50 nmol/l with at least one of the following parameter (midnight serum cortisol >208 nmol/L, 24-h urinary free cortisol (UFC) >245 nmol/24 h, or adrenocorticotropin (ACTH) <10 ng/l). Non-diabetic patients underwent an oral glucose tolerance test with 75 g glucose. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR) index. DNA was obtained from peripheral blood leucocytes. The polymorphism was detected using PCR, RFLP and DNA sequencing. The overall prevalence of SH was 20.2%. Carriers of the larger C allele of BclI polymorphism had significantly less suppression of cortisol levels after 0.5 mg dexametasone (126.4±111.4 vs 80.9±75.7 nmol/l, P=0.026), indicating relative GC resistance. No difference was noted in midnight and post LDDST serum cortisol concentrations, UFC, and ACTH levels. The mean age, BMI, waist circumference and waist-to-hip ratio did not differ between carriers and non-carriers. Most patients had central obesity. The prevalence of hypertension and dyslipidemia occurred with similar frequency in both groups. There was no significant difference in mean values of systolic and diastolic blood pressure and HOMA-IR index. The presence of the BclI polymorphism was associated with a reduced prevalence of type 2 diabetes in carriers compared with wild type (9.1% vs 26%, P=0.034). We demonstrated that female carriers of the larger C allele of BclI polymorphism display relative glucocorticoid resistance of the hypothalamic-pituitary adrenal axis and peripheral tissue. This polymorphism has a protective role and reduces the risk of diabetes in patients with AI especially in a state od subtle cortisol excess.