Raised urinary glucocorticoid and adrenal androgen precursors in the urineof young hypertensive patients: possible evidence for partial glucocorticoid resistance

Objective-To evaluate urinary glucocorticoid excretion profiles in a cohort of recently diagnosed young hypertensive patients. Methods-After excluding patients with secondary causes, 60 individuals with premature hypertension were recruited (diagnosed by ambulatory blood press ure monitoring before the age of 36 years). In addition, 30 older hypertens ive controls (age of onset > 36 years, "middle aged hypertensive controls") , and 30 normal controls (age matched to the young hypertensive group) were studied. All provided 24 hour urine collections for mass spectrometry for total cortisol metabolites and total androgen metabolites by gas chromatogr aphy. Results-Among male patients, those with premature hypertension had higher t otal urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) mu g/day) than age matched normal controls (7270 (1788) mug/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) mug/day; p = 0.002). A si milar increase was seen among the female patients, although the absolute co ncentrations were lower. There was no significant difference between middle aged hypertensive patients and normal controls. Urinary total androgen exc retion profiles in female patients also showed an unusual increase in the p remature hypertension group (2958 (1672) mug/ day) compared with the other groups (middle aged hypertensive controls, 1373 (748) mug/day, p = 0.0003; normal controls, 1687 (636) mug/day, p = 0.002). In all subjects, serum sod ium and creatinine concentrations were within the normal range; serum potas sium concentrations were found to be low before the start of treatment. Conclusions-Individuals presenting with premature hypertension have an abno rmally high excretion of glucocorticoid metabolites in the urine. While the mechanism remains uncertain, these findings are compatible with partial re sistance of the glucocorticoid receptors, with a compensatory increase in c ortisol and androgen metabolites. The mineralocorticoid effects of the latt er (sodium and water retention) may contribute to an abnormally high blood pressure and may have implications for targeted selection of first line tre atment in young hypertensive patients.