Glucocorticoid-remediable aldosteronism (GRA) represents a rare, heriditary form of primary aldosteronism which is inherited in an autosomal dominant fashion. GRA is characterized by early onset of moderate-to-severe hypertension and suppressed plasma renin activity. The family history is often positive for a history of early hemorrhagic stroke. However, the clinical and biochemical features that define mineralcorticoid excess states, such as hypokalemia, are not consistently present in GRA. Accordingly, recognition of this syndrome can be difficult. In GRA, aldosterone secretion is solely regulated by adrenocorticotropin. As a result, the administration of exogenous glucocorticoids will suppress the hypothalamic-pituitary axis and suppress aldosterone levels, thereby relieving the mineralocorticoid-excess state. GRA is caused by a chimeric gene duplication that results from unequal crossing over between the highly homologous 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. The chimeric gene represents a fusion of the 5` adrenocorticotropin-responsive regulatory region of the 11β-hydroxylase gene and the 3` coding sequence of the aldosterone synthase gene. This results in ectopic expression of aldosterone synthase activity in the zona fasciculata, the zone of the adrenal gland that normally secretes cortisol. This mutation explains the physiology and genetics of GRA and provides the basis for a simple direct genetic test for this disorder.
* Identify the demographic, pathophysiologic, and genetic features of glucocorticoid-remediable aldosteronism (GRA), emphasizing those that distinguish it from other forms of aldosteronism.
* Recall the phenotypic expression of GRA and the best way to diagnose it.
* Describe and contrast options for treating GRA.
Professor of Medicine, Harvard Medical School, Associate Director, Endocrine Hypertension Division, Brigham and Women’s Hospital, Boston, Massachusetts.
CHIEF EDITOR’S NOTE:
This article is the 18th of 36 that will be published in 2001 for which a total of up to 36 Category 1 CME credits can be earned. Instructions for how credits can be earned appear following the Table of Contents.
Address correspondence to: Robert G. Dluhy, M.D., Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115.
*The author has disclosed that he has no significant relationships with or financial interest in any commercial companies that pertain to this educational activity.