Glucocorticoid-remediable aldosteronism.
Glucocorticoid remediable aldosteronism (GRA) appears to be the most common monogenic form of human hypertension. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the zona fasciculata of the adrenal gland under the control of adrenocorticotropin (ACTH). Affected individuals are typically hypertensive, often with onset in youth, and demonstrate refractoriness to standard antihypertensives such as angiotensin-converting enzyme inhibitors and beta-blockers. GRA subjects are normokalemic but often develop hypokalemia when treated with a potassium-wasting diuretic. Analysis of affected kindreds has demonstrated a high prevalence of early cerebral hemorrhage, largely as a result of aneurysms. Identification of affected individuals should allow direct neurovascular screening and targeted antihypertensive therapy.
McMahon
Graham T
GT
Division of Endocrinology, Diabetes & Hypertension, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA. gmcmahon@partners.org
Dluhy
Robert G
RG
D000450:Aldosterone / Q000096:biosynthesis*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D003907:Dexamethasone / Q000627:therapeutic use*; D020440:Gene Duplication; D005938:Glucocorticoids / Q000627:therapeutic use*; D006706:Homeostasis; D006801:Humans; D006929:Hyperaldosteronism / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology; D007008:Hypokalemia / Q000209:etiology; D010641:Phenotype; D011188:Potassium / Q000378:metabolism; D020521:Stroke / Q000209:etiology
D005938:Glucocorticoids; D000450:Aldosterone; D003907:Dexamethasone; D019405:Cytochrome P-450 CYP11B2; D011188:Potassium