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Nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a paradigm for activating mutations causing endocrine

Stephen M Rosenthal1, Brian J Feldman, Gabriel A Vargas

  • 1University of California, San Francisco.

Pediatric Endocrinology Reviews : PER
|January 31, 2007
PubMed

Insights

Gain-of-function mutations in the V2 vasopressin receptor cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). This condition mimics Syndrome of Inappropriate Antidiuretic Hormone secretion but lacks elevated vasopressin levels.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • G protein-coupled receptors, including the V2 vasopressin receptor (V2R), are implicated in numerous diseases.
  • Over 180 inactivating V2R mutations cause nephrogenic diabetes insipidus, a disorder of water balance.
  • Previously, only inactivating V2R mutations were known.

Purpose of the Study:

  • To describe a novel disorder caused by activating V2R mutations.
  • To introduce the term "nephrogenic syndrome of inappropriate antidiuresis" (NSIAD).
  • To characterize the clinical presentation and underlying molecular mechanisms of NSIAD.

Main Methods:

  • Clinical case description of patients with V2R activating mutations.
  • Biochemical analysis to assess vasopressin levels.
  • Molecular studies to investigate V2R constitutive activation (ongoing).

Main Results:

  • Identified the first patients with V2R activating mutations.
  • Described a new clinical entity, NSIAD, characterized by features of SIAD.
  • Patients presented with undetectable arginine vasopressin levels despite NSIAD symptoms.

Conclusions:

  • Activating V2R mutations lead to NSIAD, a distinct clinical syndrome.
  • NSIAD presents similarly to SIAD but is caused by V2R dysfunction, not excess vasopressin.
  • Further research is needed to elucidate the mechanisms of V2R constitutive activation by these mutations.

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