Synonyms: Glucocorticoid Remediable Aldosteronism (GRA)
Genetic Locus: 8q21
Genes Affected:
(1) CYP11B1: beta-hydroxylase
(2) CYP11B2: aldosterone synthase
Gene Mutation: A chimeric gene formed by fusion of CYP11B1 with CYP11B2. Normally CYP11B1 activity is regulated by ACTH and CYP11B2 is not; the activity of the chimeric gene is responsive to ACTH.
Inheritance: autosomal dominant
A patient may have normal adrenal glands, bilateral adrenocortical hyperplasia or adrenocortical adenomas.
Clinical features:
(1) usually hypertension but occasionally normotensive
(2) correction of hypertension by glucocorticoid therapy (dexamethasone, other)
Laboratory findings:
(1) normal or elevated plasma aldosterone levels
(2) increased adrenal production of certain steroids, including 11-beta-hydroxycorticosterone 18-beta-oxycortisol and 18-beta-hydroxycortisol
(3) low plasma renin activity
(4) decline in plasma aldosterone levels when the patient is in an upright posture
(5) demonstration of the chimeric gene by PCR
References
Gates LJ, MacConnachie AA, et al. Variation in phenotype in patients with glucocorticoid remediable aldosteronism. J Med Genetics. 1996; 33: 25-28.
Lifton RP, Dluhy RG, et al. A chimaeric 11-beta-hydroxylase/aldosterone synthase gene causes glucocorticoid remediable aldosteronism and human hypertension. Nature. 1992; 355: 262-265.
