Elevated urinary glucocorticoid and adrenal androgens precursors in the urine of young hypertensives: Possible evidence for partial glucocorticoid resistance

Abstract

Glucocorticoid receptor resistance (GRR) has been described in several clinicopathological states. GRR may be of relevance in the pathogenesis of essential hypertension in young individuals. We examined the 24-hour urinary cortisol and androgen excretion as a measure of GRR in 46 young premature hypertensives, 18 hypertensive controls and 18 healthy controls. The values for serum sodium, potassium, urea, and creatinine were normal in all subjects. Both premature hypertensives and hypertensive controls were extensively investigated and found to have no identifiable cause. Blood pressure was assessed by 24-hour ambulatory blood pressure monitoring. 24-hour urine was analysed for cortisol and androgen metabolites by gas chromatography and mass spectrometry. Results: Total 24-hr urinary cortisol metabolites in males were significantly higher in premature hypertensives than in hypertensive controls (14009±7158 vs 7473±2466 μg/day; p = 0.009) or normal controls (14009±7158 vs 8010±1925 μg/day; p = 0.01). There was a similar increase in urinary cortisol in premature hypertensives compared to hypertensive controls (11424±4632 vs 7098±2913μg/day; p = 0.006) or normal controls (11424±4632 vs 5062±1684 μg/day; p=0.0006) in females. In contrast to cortisol, 24-hr urinary excretion of androgen metabolites showed no significant difference among males. However, premature hypertensive females demonstrated a significantly higher 24-hr urinary excretion of androgen metabolites compared to their hypertensive (3434±1622 vs 1187±706μg/day; p = <0.0001) and normal (3434±1622 vs 1820±417μg/day ; p = 0.007) controls. Conclusion: The increased 24-hr urinary cortisol metabolite in both male and female premature hypertensives may indicate excess adrenal production presumably due to GRR. Further elevated urinary androgens may be of additional pathogenetic relevance in premature female hypertensives.