Hyperaldosteronism type 1

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.

Epidemiology

Less than 1% of patients with primary hyperaldosteronism suffer from familial hyperaldosteronism 1, glucocorticoid remediable aldosteronism.

Clinical Findings

Glucocorticoid-remediable aldosteronism becomes apparent in adults. Because of its autosomal dominant inheritance several relatives exist who also suffer from hypertension.

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.

Pathogenesis

Aldosteronism type 1 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.

Management

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. Rarely an additional therapy with spironolacton, potassium, and antihypertensive drugs is required.

Systematic

Hyperaldosteronism
	Conn syndrome
	Glucocorticoid triggered hypertension
	Hyperaldosteronism type 1
		CYP11B1
		CYP11B2
	Hyperaldosteronism type 2
	Hyperaldosteronism type 3
	Hyperaldosteronism type 4

References:

1.	Lifton RP et al. (1992) A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension.

2.	Orphanet article Orphanet ID 235936

3.	OMIM.ORG article Omim 103900

4.	Wikipedia article Wikipedia EN (Glucocorticoid_remediable_aldosteronism)