Glucocorticoid remediable aldosteronism: low morbidity and mortality in a four-generation italian pedigree

J Clin Endocrinol Metab. 2002 Jul;87(7):3187-91. doi: 10.1210/jcem.87.7.8647.

Abstract

Glucocorticoid remediable hyperaldosteronism (GRA) is a monogenic form of inherited hypertension caused by a chimeric gene originating from an unequal cross-over between the 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. GRA is characterized by high plasma levels of aldosterone (regulated by ACTH) with suppressed plasma renin activity and the production of two rare steroids, 18hydroxycortisol and 18oxocortisol. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Affected women have a high risk of developing preeclampsia during pregnancy. Here, we describe a 5-generation pedigree from Sardinia in which the presence of the chimeric gene is demonstrated in 4 generations. This family displays a mild phenotype with average blood pressure levels of 131/86 mm Hg for GRA+ patients. The occurrence of stroke is very low, and preeclampsia was not observed in 29 pregnancies from 8 GRA+ mothers. We investigated whether the cross-over site (between the CYP11B1 and CYP11B2 genes) or biochemical characteristics could explain this phenotype. The cross-over site was located at the end of intron 3, in the same region as described in other families. We found a significant correlation between blood pressure and 18hydroxycortisol, 18oxocortisol, and plasma aldosterone levels, but not with kallikrein. However, none of the biochemical or genetic parameters investigated could explain the mild phenotype of the family.

MeSH terms

  • Adult
  • Aldosterone / blood
  • Blood Pressure
  • Crossing Over, Genetic
  • Cytochrome P-450 CYP11B2 / genetics
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hydrocortisone / analogs & derivatives*
  • Hydrocortisone / blood
  • Hyperaldosteronism / drug therapy*
  • Hyperaldosteronism / genetics*
  • Hyperaldosteronism / mortality
  • Hyperaldosteronism / physiopathology
  • Italy
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Pregnancy
  • Pregnancy Complications / physiopathology
  • Steroid 11-beta-Hydroxylase / genetics

Substances

  • Glucocorticoids
  • 18-oxocortisol
  • Aldosterone
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase
  • 18-hydroxycortisol
  • Hydrocortisone