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Glucocorticoid-remediable aldosteronism
Clinical feature:
Definition: Glucocorticoid-remediable hypertension is an autosomal dominant disease characterized by hyperaldosteronism that is ACTH dependent, so with glucocorticoid administration ACTH is suppressed and hypertension treated.
Pathogenesis: Glucocorticoid-remediable aldosteronism results from anti-Lepore-type fusion of the CYP11B2 and CYP11B1 genes. The 5-prime portion of the downstream gene (CYP11B1) is fused with 3-prime portion of the upstream gene (CYP11B2). As a result, aldosterone synthesis of the CYP11B2 gene is controlled by the ACTH-dependent promotor of the CYP11B1 gene.
Epidemiology: Only in 2% of cases, hypertension is due to primary aldosteronism, which largely results from aldosterone-producing adenoma or bilateral adrenal hyperplasia. Glucocorticoid-remediable aldosteronism is the rarest of all forms of primary aldosteronism.
Clinical picture: Glucocorticoid-remediable aldosteronism becomes apparent in adults. Because of its autosomal dominant inheritance several relatives exist who also suffer from hypertension. The therapy consists of glucocorticoid substitution at levels that mimic normal cortisol secretion. As in Addison disease, dosage has to be increased during stress. The aim of this continuous substitution is adrenal atrophy, so a therapeutic effect in respect to blood pressure can be observed not before several weeks of therapy.
Diagnostics:
Diagnosis: Low plasma renin and elevated aldosterone levels responsive to glucocorticoids are the diagnostic hallmarks of this disease. Paradoxically, baseline aldosterone levels decrease in upright position. Although difficult to measure routinely, abnormal adrenal steroids 18-oxocortisol and 18-hydroxycortisol are typically increased in plasma and urine.
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