Lack of influence of somatic mutations on steroid gradients during adrenal vein sampling in aldosterone-producing adenoma patients

Eur J Endocrinol. 2013 Oct 1;169(5):657-63. doi: 10.1530/EJE-13-0551. Print 2013 Nov.

Abstract

Objective: Adrenal vein sampling (AVS) is a technically demanding procedure required for the identification of suitable candidates for unilateral adrenalectomy in primary aldosteronism. Recently, somatic KCNJ5 K(+)-channel mutations in aldosterone-producing adenoma (APA) patients have been shown to influence steroid gradients during AVS. These and other recently identified genetic modifiers (ATP1A1 and ATP2B3) might affect the final diagnosis and treatment of the affected patients.

Design: Fifty-nine patients with APAS who had undergone successful AVS (adrenal vein cortisol:peripheral cortisol ratio 2) and had undergone a mutation analysis of their tumor tissue were studied. the mutation status of the APAS was as follows: 19 KCNJ5 mutations, eight ATPase mutations (five ATP1A1 and three ATP2B3), and 32 patients with none of these mutations.

Methods: The lateralization index (ratio of aldosterone:cortisol on the side of the adenoma to aldosterone to cortisol on the contralateral side) and the contralateral suppression index (ratio of aldosterone:cortisol on the contralateral side to aldosterone to cortisol in the periphery) were calculated for the KCNJ5-mutated, ATPase-mutated, and the KCNJ5/ATPase mutation-negative APA patients.

Results: The lateralization indices of the ATPase mutation carriers had a median of 19.9 compared with a median of 16.0 in the KCNJ5 mutation carriers and that of 20.5 in the KCNJ5/ATPase mutation-negative patients. The contralateral suppression indices of the ATPase-mutated patients had a median of 0.1 compared with a median of 0.4 in the KCNJ5 mutation carriers and that of 0.2 in the KCNJ5/ATPase mutation-negative patients. The differences between the genetic groups were not statistically significant.

Conclusions: We did not find evidence for a clinically important impact of mutation status on steroid gradients during AVS.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adrenal Cortex Neoplasms / metabolism*
  • Adrenal Glands / chemistry
  • Adrenal Glands / metabolism*
  • Adrenocortical Adenoma / metabolism*
  • Age Factors
  • Aged
  • Aldosterone / metabolism*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics
  • Humans
  • Hyperaldosteronism / genetics*
  • Hyperaldosteronism / metabolism*
  • Male
  • Middle Aged
  • Mutation / physiology*
  • Plasma Membrane Calcium-Transporting ATPases / metabolism
  • Sex Factors
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Specimen Handling
  • Steroids / metabolism*
  • Veins / chemistry

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ5 protein, human
  • Steroids
  • Aldosterone
  • ATP1A1 protein, human
  • Adenosine Triphosphatases
  • Plasma Membrane Calcium-Transporting ATPases
  • ATP2B3 protein, human
  • Sodium-Potassium-Exchanging ATPase