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Cortisol secretion, sensitivity, and activity are associated with hypertension in postmenopausal eucortisolemic women.

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 non-hypercortisolemic subjects.


OBJECTIVE
To investigate if in subjects without overt or mild hypercortisolism the degree of GCS, GC sensitivity and peripheral activation are associated with hypertension (Hy) and with the number of the possible consequences of cortisol excess among T2D, fragility FX and Hy.


DESIGN
Case-control study.


SETTING
Outpatient basis.


PATIENTS
216 non-hypercortisolemic postmenopausal females (age 50-80 years, 108 with Hy); 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), cortisol after 1mg-overnight-dexamethasone (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP).


RESULTS
Hy was associated with F-1 mgDST (odds ratio, OR, 3.3, 95% confidence interval, 95%CI, 1.5-7.5, p=0.004) and R-UFF/UFE (OR 101.7, 95%CI 2.6-4004.1, p=0.014), regardless of age, BMI and presence of the N363S-SNP and of T2D. The progressive increase of the number of the possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2=0.125, p=0.04), with R-UFF/UFE (R2 =0.46, p=0.02) and with the prevalence of N363S heterozygous variant (T=0.46, p=0.015), after adjusting for age.


CONCLUSIONS
In postmenopausal non-hypercortisolemic females Hy is associated with GCS and GC peripheral activation. The number of the possible consequences of cortisol excess (among Hy, T2D and fragility FX) are associated with GCS, GC peripheral activation and with the prevalence of N363S heterozygous variant.