Do young patients with premature hypertension have abnormal urinary glucocorticoid and androgen excretion profiles compared to older hypertensive patients and normotensive controls?
Young patients with premature hypertension exhibit abnormally high urinary excretion of glucocorticoid and androgen metabolites, suggesting that partial glucocorticoid receptor resistance may contribute to the pathogenesis of their elevated blood pressure.
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 pressure monitoring before the age of 36 years).In addition, 30 older hypertensive 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 chromatography.Results-Among male patients, those with premature hypertension had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) µg/day) than age matched normal controls (7270 (1788) µg/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) µg/day; p = 0.002).A similar increase was seen among the female patients, although the absolute concentrations were lower.There was no significant diVerence between middle aged hypertensive patients and normal controls.Urinary total androgen excretion profiles in female patients also showed an unusual increase in the premature hypertension group (2958 (1672) µg/ day) compared with the other groups (middle aged hypertensive controls, 1373 (748) µg/day, p = 0.0003; normal controls, 1687 (636) µg/day, p = 0.002).In all subjects, serum sodium and creatinine concentrations were within the normal range; serum potassium concentrations were found to be low before the start of treatment.Conclusions-Individuals presenting with premature hypertension have an abnormally high excretion of glucocorticoid metabolites in the urine.While the mechanism remains uncertain, these findings are compatible with partial resistance of the glucocorticoid receptors, with a compensatory increase in cortisol and androgen metabolites.The mineralocorticoid eVects of the latter (sodium and water retention) may contribute to an abnormally high blood pressure and may have implications for targeted selection of first line treatment in young hypertensive patients.
P. Nihoyannopoulos (Wed,) studied this question.