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Abnormal glucocorticoid activity in subjects with risk factors for cardiovascular disease
1Department of Medicine, Western General Hospital, University of Edinburgh, Scotland, UK.
Insights
Increased sensitivity to cortisol, not higher levels, may explain cardiovascular risk factors like hypertension and insulin resistance. This enhanced tissue sensitivity, linked to metabolic syndrome, appears paradoxical as cortisol secretion isn't suppressed.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Cardiovascular Disease Risk Factors
Background:
- Metabolic syndrome X shares characteristics with Cushing's syndrome, including hypertension, insulin resistance, and obesity.
- Previous research suggested cortisol levels were not elevated in conditions associated with cardiovascular risk.
- Recent findings highlight significant variability in tissue sensitivity to cortisol.
Purpose of the Study:
- To investigate the role of tissue sensitivity to glucocorticoids in cardiovascular risk factors.
- To explore the relationship between dermal glucocorticoid sensitivity and conditions like hypertension and insulin resistance.
Main Methods:
- Measurement of tissue sensitivity to glucocorticoids using a skin vasoconstriction assay.
- Assessment of relationships between dermal glucocorticoid sensitivity and cardiovascular risk markers.
Main Results:
- Demonstrated a relationship between increased dermal glucocorticoid sensitivity and high blood pressure, insulin resistance, glucose intolerance, and hypertriglyceridemia.
- Suggested increased glucocorticoid receptor affinity and impaired cortisol inactivation contribute to enhanced sensitivity.
- Observed no compensatory suppression of cortisol secretion despite enhanced peripheral sensitivity.
Conclusions:
- Enhanced peripheral glucocorticoid sensitivity, rather than elevated cortisol levels, may underlie cardiovascular risk factors.
- The maintenance of normal circulating cortisol concentrations in patients with risk factors could be inappropriate.
- Findings suggest a paradoxical role for cortisol in metabolic and cardiovascular health.
Abstract:
There are striking similarities between Cushing's syndrome and the 'metabolic syndrome X' since both are characterised by hypertension, insulin resistance, glucose intolerance, hyperlipidaemia, and central obesity. The possibility that cortisol contributes to the associations between multiple risk factors for cardiovascular disease was rejected when it was demonstrated that there was no elevation in cortisol secretion or circulating concentration in patients with essential hypertension or type 2 diabetes mellitus. However, in recent years the enormous variability in tissue sensitivity to cortisol has become apparent. We have measured tissue sensitivity to glucocorticoids using an assay of skin vasoconstriction and have demonstrated its relationship with high blood pressure, insulin resistance, glucose intolerance, and hypertriglyceridaemia. Our data suggest that the increase in dermal glucocorticoid sensitivity is not a secondary phenomenon and may be explained by increased glucocorticoid receptor affinity together with impaired inactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase. Importantly, we have not found that enhanced peripheral glucocorticoid sensitivity is associated with compensatory suppression of cortisol secretion, so that the maintenance of normal circulating cortisol concentrations in patients with cardiovascular risk factors may be paradoxical and inappropriate.