Glucocorticoid-remediable aldosteronism.

Abstract

GRA is an inherited disorder of aldosterone biosynthesis. To date, all cases have been the result of chimeric gene duplications in which the regulatory region of the 11-beta hydroxylase gene is fused to more distal coding sequences of the aldosterone synthase gene. This results in ectopic expression of aldosterone synthase in fasciculata cells. Genetic testing has been remarkably precise in identifying these individuals with 100% concordance of the presence of the chimeric gene with increases in 18-oxygenated cortisol products. Several implications follow from these findings. First, GRA may be more common in the hypertensive population than had been previously estimated, and second, genetic testing of subsets of the essential hypertensive population (e.g., those who have low plasma renin activity) may allow the identification of GRA patients who could then be treated specifically. We recommend that hypertensive patients with signs of aldosteronism and no radiologic evidence of an aldosteronoma, especially young hypertensive subjects with low renin activity, be genetically screened for GRA. To track the success of this approach and to identify responses to various therapeutic programs, a central international registry for GRA has been established. This registry not only provides access to screening for GRA, but also informational resources for patients and physicians.