Glucocorticoid remediable aldosteronism (GRA) was first described in 1966 by Sutherland et ala. In this family, aldosterone secretion was regulated by ACTH and symptoms and signs were reversed by the administration of exogenous glucocorticoid. GRA is usually characterised by moderate to severe hypertension with early onset. The hypertension is often difficult to control and is associated with greatly increased vascular risk. It is inherited as an autosomal dominant trait and occurs equally among men and women, and has been reported worldwide, but is said to be more common in individuals of Celtic ancestry. No cases have been described in the black population.
Genetic screening for GRA is now possible. A gene expressing aldosterone synthase activity and a second gene involved in adrenal steroidogenesis, steroid 11β-hydroxylase, are located in close proximity on chromosome 8. In affected subjects, a chimeric gene which fuses sequences of the 11β-hydroxylase and aldosterone synthase is present. The presence of this gene duplication is reported to be 100% sensitive and specific for the diagnosis of GRA.
As GRA appears to have an increased incidence in individuals of Irish and Scottish ancestry, we have been concerned that a potentially reversible life threatening condition could be missed in our population. All available members of our large group of primary aldosteronism patients carefully classified, as described previously, as having bilateral adrenal hyperplasia by hormonal assessment, CT scanning and adrenal venous sampling (Harper et al; 1999b) have been systematically screened for GRA. One patient died. Of 24 patients still alive 16 consented to genetic screening. All were negative for the gene duplication responsible for GRA. We conclude therefore that in the regional centre for endocrinology in Northern Ireland, GRA is not being missed and remains a rare cause of hypertension.
aSutherland DJA, Ruse JL, Laidlaw MD. Can Med Assoc J 1966; 95: 1109-1119.
bHarper R, Ferrett JA, McKnight JA, McIlrath EM, Russell CF, Sheridan B, Atkinson AB. Q J Med 1999; 92: 643-650.
08 - 11 Apr 2002
British Endocrine Societies