ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 OC7.1 | DOI: 10.1530/endoabs.63.OC7.1

Cortisol suppression or peripheral sensitivity and activation are associated with diabetes, hypertension and fragility fractures in postmenopausal eucortisolemic women

Carmen Aresta1,2, Iacopo Chiodini1,2, Agostino Gaudio3, Cristina Eller-Vainicher4, Valentina Morelli4, Volha V Zhukouskaya5, Daniela Merlotti6, Emanuela Orsi4, Anna Maria Barbieri2,4, Silvia Fustinoni2,7, Elisa Polledri2,7, Luigi Gennari8, Alberto Falchetti1, Vincenzo Carnevale9, Luca Persani1,2 & Alfredo Scillitani10

1Department of Endocrinology and Metabolism, Istituto Auxologico Italiano, IRCCS, Milan, Italy; 2Department of Clinical Sciences & Community Health, University of Milan, Milan, Italy; 3Department of Clinical and Experimental Medicine, University of Catania, University Hospital ’G. Rodolico’, Catania, Italy; 4Unit of Endocrinology Fondazione IRCCS Cà Granda – Ospedale Maggiore Policlinico, Milan, Italy; 5Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 6San Raffaele Hospital, Milan, Italy; 7Unit of Epidemiology Fondazione IRCCS Cà Granda – Ospedale Maggiore Policlinico, Milan, Italy; 8Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 9Unit of Internal Medicine Ospedale ‘Casa Sollievo della sofferenza’ IRCCS, San Giovanni Rotondo (FG), Italy; 10Endocrinology and Diabetology, Ospedale ‘Casa Sollievo della sofferenza’ IRCCS, San Giovanni Rotondo (FG), Italy.

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 50–80 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, 1.8–25.2, P=0.005; 129.1, 1.8–9108, P=0.025; 8.8, 1.7–45.9, 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 1.97–10.53, 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.