Familial hyperaldosteronism

J Steroid Biochem Mol Biol. 2001 Sep;78(3):215-29. doi: 10.1016/s0960-0760(01)00097-8.

Abstract

Primary aldosteronism (PAL) may be as much as ten times more common than has been traditionally thought, with most patients normokalemic. The study of familial varieties has facilitated a fuller appreciation of the nature and diversity of its clinical, biochemical, morphological and molecular aspects. In familial hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing has greatly facilitated diagnosis. Hypertension severity varies widely, demonstrating relationships with gender, affected parent's gender, urinary kallikrein level, degree of biochemical disturbance and hybrid gene crossover point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone regulation and (2) correction of hypertension in FH-I requires only partial suppression of ACTH, and much smaller glucocorticoid doses than those previously recommended. Familial hyperaldosteronism type II is not glucocorticoid-remediable, and is clinically, biochemically and morphologically indistinguishable from apparently sporadic PAL. In one informative family available for linkage analysis, FH-II does not segregate with either the CYP11B2, AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in chromosome 7. As has already occurred in FH-I, elucidation of causative mutations is likely to facilitate earlier detection of PAL and other curable or specifically treatable forms of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aldosterone / biosynthesis
  • Cytochrome P-450 CYP11B2 / genetics
  • Female
  • Genetic Linkage
  • Glucocorticoids / therapeutic use
  • Humans
  • Hyperaldosteronism / classification
  • Hyperaldosteronism / diagnosis
  • Hyperaldosteronism / drug therapy
  • Hyperaldosteronism / genetics*
  • Hyperaldosteronism / physiopathology
  • Male
  • Mutation
  • Neoplasm Proteins / genetics
  • Pedigree
  • Phenotype
  • Proto-Oncogene Proteins*
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin / genetics
  • Renin / blood
  • Steroid 11-beta-Hydroxylase / genetics

Substances

  • Glucocorticoids
  • MEN1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptors, Angiotensin
  • Aldosterone
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase
  • Renin