Hypertension Linked to Glucocorticoid Sensitivity in Women Without Hypercortisolism

Hypertension may be associated with degree of glucocorticoid suppression and peripheral activation in postmenopausal women, according to study results published in The Journal of Clinical Endocrinology & Metabolism. In addition, researchers found an association between the number of possible consequences of cortisol excess and glucocorticoid suppression and peripheral activation.

Previous studies have reported that the degree of cortisol secretion can have an impact on skeletal health and glucose metabolism even in people without hypercortisolism. There are very limited data regarding the role of glucocorticoid suppression and peripheral activation and sensitivity in patients with hypertension.

In this study, the researchers sought to assess the association among the degree of glucocorticoid suppression, glucocorticoid sensitivity, and peripheral activation in patients with normal cortisol levels and hypertension. They also studied the consequences of cortisol excess, including fragility fracture, type 2 diabetes (T2D), and hypertension.

The case-control study enrolled 216 postmenopausal women (age 37-80 years) without hypercortisolism. The sample was subdivided to 108 participants with hypertension and 98 participants without hypertension. Of the entire cohort, 99 women were previously diagnosed with T2D and 54 had fragility fracture.

In patients with hypertension, levels of cortisol were higher (after 1-mg overnight dexamethasone), 24-hour urinary free cortisone levels were lower, and the ratio between 24-hour urinary free cortisol/cortisone was higher compared with patients without hypertension. In addition, T2D was more common in patients with hypertension. The adjusted difference in ratio of 24-hour urinary free cortisol/cortisone levels was confirmed even after excluding patients with T2D.

The regression analysis showed that hypertension was associated with levels of cortisol after 1-mg overnight dexamethasone (odds ratio [OR], 3.29; 95% CI, 1.45-7.46; P =.004), ratio of 24-hour urinary free cortisol/cortisone levels (OR, 125.9; 95% CI, 3.29-4909.4; P =.01), age (OR, 1.06; 95% CI, 1.01-1.11; P =.022), and body mass index (OR, 1.1; 95% CI, 1.02-1.18; P =.01) after adjusting for the presence of T2D or N363S polymorphism variant of the glucocorticoid receptor gene, which may increase glucocorticoid sensitivity.

In addition, a progressive increase in the number of possible consequences of cortisol excess (including diabetes, hypertension, and fragility fracture) was associated with cortisol secretion and glucocorticoid peripheral activation and sensitivity. The simultaneous presence of T2D, hypertension, and fragility fracture was independently associated with levels of cortisol after 1-mg overnight dexamethasone (OR, 5; 95% CI, 1.6-15.2; P =.005), ratio of 24-hour urinary free cortisol/cortisone (OR, 131.6; 95% CI, 2.3-7417.8), and prevalence of N363S heterozygous variant (OR, 12.4; 95% CI, 2.9-53.1) after adjusting for age and body mass index.

The investigators noted several limitations of the study, including its cross-sectional design, relatively small sample size, and lack of measurement for plasma dexamethasone concentration. In addition, as the study sample included only white participants, the results may not apply to other populations.

“Further studies on a larger sample of patients are needed to confirm the present findings and to assess whether or not, it would be possible to hamper the risk of developing [hypertension], T2D, and fragility fracture by modulating cortisol secretion and peripheral [glucocorticoid] activation,” wrote the investigators.

Reference

Chiodini I, Gaudio A, Eller-Vainicher C, et al. Cortisol secretion, sensitivity, and activity are associated with hypertension in postmenopausal eucortisolemic women [published online May 21, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00037

This article originally appeared on Endocrinology Advisor