Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations

N Engl J Med. 2015 Oct 8;373(15):1429-36. doi: 10.1056/NEJMoa1504869. Epub 2015 Sep 23.

Abstract

Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).

Publication types

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

MeSH terms

  • Adenoma / genetics*
  • Adenoma / metabolism
  • Adenoma / pathology
  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Adult
  • Aldosterone / metabolism
  • Female
  • Humans
  • Hyperaldosteronism / etiology*
  • Hypertension / etiology
  • Hypokalemia / etiology
  • Middle Aged
  • Postmenopause
  • Pregnancy
  • Pregnancy Complications, Neoplastic / genetics*
  • Receptors, LH / metabolism
  • Receptors, LHRH / metabolism
  • Up-Regulation
  • beta Catenin / genetics*

Substances

  • CTNNB1 protein, human
  • Receptors, LH
  • Receptors, LHRH
  • beta Catenin
  • Aldosterone