Background: Cortisol excess is associated with a higher prevalence of hypertension (Hy), type 2 diabetes (T2D) and fragility fractures (FX). A possible association between T2D and fragility FX with the degree of glucocorticoid (GC) suppression and peripheral activation or sensitivity even in non-hypercortisolemic subjects has been previously suggested.
Aim: To assess if the degree of GC suppression or peripheral sensitivity and activation are associated with Hy and the simultaneous presence of fragility FX, T2D and Hy in eucortisolemic postmenopausal females.
Patients and Methods: We studied 216 non-hypercortisolemic postmenopausal females (age 5080 years, 99 with T2D, 108 with Hy, 68 with fragility FX). In all subjects, we assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), cortisol after 1mg-overnight-dexamethasone (F-1mgDST) and the presence of the N363S single-nucleotide polymorphism (N363S-SNP) in GC receptor gene that is thought to increase GC sensitivity.
Results: In Hy patients, the T2D prevalence and F-1mgDST and R-UFF/UFE levels were higher (64.6%, 1.25±0.43 μg/dL, 0.24±0.13, respectively) while UFE levels were lower (86.9±20.1 μg/24 h) than in non-Hy subjects (35.7%, 1.02±0.41 μg/dL, 0.20±0.08, 94.5±21.9 μg/24 h, respectively, P<0.05 for all comparisons). Hy was independently associated with F-1mgDST and with R-UFF/UFE (OR, 95% CI: 6.02, 2.01-17.98, P=0.001; 63.3, 1.2-3326.6, P=0.04) regardless for N363S-SNP and age. The simultaneous presence of Hy, T2D and fragility FX was associated with F-1mgDST, R-UFF/UFE and N363S-SNP (OR, 95%CI: 6.67, 1.825.2, P=0.005; 129.1, 1.89108, P=0.025; 8.8, 1.745.9, P=0.010, respectively). The progressive increase of the number of the GC-related comorbidities (i.e. Hy, T2D and fragility FX) was significantly associated with F-1mgDST levels, R-UFF/UFE and with the prevalence of N363S-SNP. A eu-cortisolemic postmenopausal female with ≥2 out of N363S-SNP, F-1mgDST >0.9 μg/dL (24.8 nmol/L) and R-UFF/UFE >0.18 has a 4.5-fold increased risk of having ≥2 out of T2D, Hy and fragility FX (OR 4.55, 95% CI 1.9710.53, P<0.0001) regardless of age.
Conclusions: In postmenopausal eucortisolemic females, Hy is associated with GC suppression and peripheral activation; the combination of Hy, T2D and fragility FX is associated with GC suppression, peripheral activation and sensitivity.
18 - 21 May 2019
European Society of Endocrinology