Iacopo Chiodini1,2, Agostino Gaudio3, Cristina Eller-Vainicher4, Valentina Morelli4, Carmen Aresta1,2, 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. 1. Unit for Bone Metabolism Diseases and Diabetes & Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy. 2. Department of Clinical Sciences & Community Health, University of Milan, Milan, Italy. 3. Department of Clinical and Experimental Medicine, University of Catania, University Hospital "G. Rodolico," Catania, Italy. 4. Unit of Endocrinology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico Milan, Milan, Italy. 5. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy. 6. San Raffaele Hospital, Milan, Italy. 7. Unit of Epidemiology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico Milan, Milan, Italy. 8. Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy. 9. Unit of Internal Medicine, Ospedale "Casa Sollievo della soffererenza," IRCCS, San Giovanni Rotondo, Italy. 10. Unit of Endocrinology and Diabetology, Ospedale "Casa Sollievo della soffererenza," IRCCS, San Giovanni Rotondo, Italy.
Abstract
CONTEXT: Previous data suggest a possible association between type 2 diabetes (T2D) and fragility fractures (FX) with the degree of glucocorticoid suppressibility (GCS) and peripheral activation or sensitivity even in persons without hypercortisolemia. OBJECTIVE: To investigate whether the degree of GCS, GC sensitivity, and peripheral activation in persons without overt or mild hypercortisolism are associated with hypertension and with the number of the possible consequences of cortisol excess among patients with T2D, fragility FX, and hypertension. DESIGN: Case-control study. SETTING: Outpatient clinic. PATIENTS: A total of 216 postmenopausal women without hypercortisolemia (age, 50 to 80 years; 108 with hypertension); 68 and 99 patients had fragility FX and T2D, respectively. MAIN OUTCOME MEASURES: We assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP). RESULTS: Hypertension was associated with F-1 mgDST [odds ratio (OR), 3.3; 95% CI, 1.5 to 7.5; P = 0.004) and R-UFF/UFE (OR, 101.7; 95% CI, 2.6 to 4004.1; P = 0.014), regardless of age, body mass index, and presence of the N363S single nucleotide polymorphism and of T2D. The progressive increase in the number of possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2 = 0.125; P = 0.04), R-UFF/UFE (R2 = 0.46; P = 0.02), and the prevalence of N363S heterozygous variant (T = 0.46; P = 0.015), after adjustment for age. CONCLUSIONS: In postmenopausal women without hypercortisolemia, hypertension is associated with GCS and GC peripheral activation. The number of possible consequences of cortisol excess (among patients with hypertension, T2D, and fragility FX) is associated with GCS, GC peripheral activation, and the prevalence of the N363S heterozygous variant.
CONTEXT: Previous data suggest a possible association between type 2 diabetes (T2D) and fragility fractures (FX) with the degree of glucocorticoid suppressibility (GCS) and peripheral activation or sensitivity even in persons without hypercortisolemia. OBJECTIVE: To investigate whether the degree of GCS, GC sensitivity, and peripheral activation in persons without overt or mild hypercortisolism are associated with hypertension and with the number of the possible consequences of cortisol excess among patients with T2D, fragility FX, and hypertension. DESIGN: Case-control study. SETTING:Outpatient clinic. PATIENTS: A total of 216 postmenopausal women without hypercortisolemia (age, 50 to 80 years; 108 with hypertension); 68 and 99 patients had fragility FX and T2D, respectively. MAIN OUTCOME MEASURES: We assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP). RESULTS:Hypertension was associated with F-1 mgDST [odds ratio (OR), 3.3; 95% CI, 1.5 to 7.5; P = 0.004) and R-UFF/UFE (OR, 101.7; 95% CI, 2.6 to 4004.1; P = 0.014), regardless of age, body mass index, and presence of the N363S single nucleotide polymorphism and of T2D. The progressive increase in the number of possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2 = 0.125; P = 0.04), R-UFF/UFE (R2 = 0.46; P = 0.02), and the prevalence of N363S heterozygous variant (T = 0.46; P = 0.015), after adjustment for age. CONCLUSIONS: In postmenopausal women without hypercortisolemia, hypertension is associated with GCS and GC peripheral activation. The number of possible consequences of cortisol excess (among patients with hypertension, T2D, and fragility FX) is associated with GCS, GC peripheral activation, and the prevalence of the N363S heterozygous variant.
Authors: L Giovanelli; C Aresta; V Favero; M Bonomi; B Cangiano; C Eller-Vainicher; G Grassi; V Morelli; F Pugliese; A Falchetti; L Gennari; A Scillitani; L Persani; I Chiodini Journal: J Endocrinol Invest Date: 2021-01-04 Impact factor: 4.256