Endocrine Abstracts

Most of adrenal incidentalomas (AI) are nonfunctional, although some of those demonstrate an autonomous subtle cortisol hypersecretion that could lead to increased risk for osteoporosis. Several polymorphisms of glucocorticoid receptor (GR) gene have been found to alter glucocorticoid tissue sensitivity. The aim of this study was toinvestigate whether subclinical hypercortisolism (SH) and BclI variant of the GR gene have an impact on bone mineral density (BMD) in women with AI. In 106 women with AI, we evaluated BMD with dual-energy X-ray absorptiometry at lumbar spine (LS) and hip. The hypothalamic-pituitary-adrenal axis activity was evaluated using ACTH, midnight cortisol level, 24-h urinary free cortisol, and dexamethasone suppression tests. DNA was obtained from peripheral blood leucocytes. The polymorphism was detected using PCR, RFLP and DNA sequencing. Patients with SH had increased frequency of osteoporosis (61.1% vs 22%, P = 0.002). They had significantly lower BMD at the LS (0.83 ± 0.15 vs 0.93 ± 0.13, P = 0.005), and total hip (0.79 ± 0.13 vs 0.72 ± 0.11, P = 0.022). Femoral neck BMD was also lower but the difference did not reach statistical significance (0.66 ± 0.12 vs 0.72 ± 0.11, P = 0.069). Presence of osteoporosis was associated with SH [odds ratio (OR) = 5.775, 95% confidence interval (CI) 1.423-23.426, P = 0.014] and lower body mass index (OR = 1.226, 95% CI 1.071-1.405, P = 0.003), after adjusting for age, menopause and vitamin-D. Carriers of the C allele of BclI 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). Osteoporosiswas more prevalent in carriers than non-carriers (26.5% vs 7.7%, P = 0.031). The present study shows that women with AI and SH have higherprevalence of osteoporosis. Although individual bone sensitivity to glucocorticoid is not only influenced by polymorphism, carriers of the longer C allele of BclI polymorphism exhibit increased sensitivity with enhanced risk of bone density reduction.