A German family with glucocorticoid-remediable aldosteronism

Abstract

The prevalence of primary hyperaldosteronism (PHA) in the hypertensive population has increased in recent years. Glucocorticoid-remediable aldosteronism (GRA) is a rare monogenic form of PHA. Here we report a German family with GRA. Since the phenotype of GRA varies widely, we asked whether recommended algorithms for PHA diagnosis distinguish GRA from other forms of PHA. Plasma aldosterone (pg/ml) and renin (pg/ml) levels were determined in three hypertensive family members with GRA before and after sodium loading with 2 l of saline (0.9%), during posture and after 1 week of 2 mg dexamethasone daily. 24 h blood pressure and urinary excretion of aldosterone, cortisol precursors and metabolites were measured before and after dexamethasone. Southern blot hybridization and long-range PCR were performed to identify the chimeric gene. All three affected patients had normal potassium levels but markedly increased aldosterone/renin ratios of 472, 213 and >322 (normal range<50) indicating PHA. Sodium loading failed to lower plasma aldosterone below the threshold of 50 pg/ml in all patients. During posture, aldosterone increased in one but decreased in both other GRA patients. Elevated 18-hydroxycortisol, free aldosterone and its main metabolite aldosterone-18-glucuronid and tetrahydroaldosterone returned to normal range after 1 week dexamethasone in all patients, but blood pressure was reduced only in one patient. The chimeric gene was identified in affected family members by Southern blot and PCR. The aldosterone/renin ratio is a valid screening and sodium loading a valid confirmation test in GRA. Determination of elevated urinary excretion of specific aldosterone metabolites and identification of the chimeric gene are mandatory since a lacking blood pressure response to dexamethasone can be misleading.