Cortisol Secretion, Sensitivity, and Activity Are Associated With Hypertension in Postmenopausal Eucortisolemic Women

Iacopo Chiodini, Agostino Gaudio, Cristina Eller-Vainicher, Valentina Morelli, Carmen Aresta, Volha V. Zhukouskaya, Daniela Merlotti, Emanuela Orsi, Anna Maria Barbieri, Silvia Fustinoni, Elisa Polledri, Luigi Gennari, Alberto Falchetti, Vincenzo Carnevale, Luca Persani, Alfredo Scillitani

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)4441-4448
Number of pages8
JournalThe Journal of clinical endocrinology and metabolism
Issue number10
Publication statusPublished - Oct 1 2019

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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