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Primärer Hyperaldosteronismus

Genetik und Pathologie

Primary aldosteronism

Genetics and pathology

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Zusammenfassung

Hintergrund

Der primäre Hyperaldosteronismus, eine Überproduktion des Steroidhormons Aldosteron, ist die häufigste Ursache der sekundären Hypertonie. Häufigste Subformen sind die bilaterale Hyperplasie und das aldosteronproduzierende Adenom.

Fragestellung

In dieser Übersichtsarbeit sollen wichtige Arbeiten zu genetischen Grundlagen des primären Hyperaldosteronismus zusammengefasst werden.

Ergebnisse

Als Ursache aldosteronproduzierender Adenome wurden somatische Mutationen in den Genen KCNJ5, CACNA1D, ATP1A1 und ATP2B3 beschrieben, die letztlich alle zu einem verstärkten Calciumeinstrom in die Zelle und Aldosteronproduktion führen. Der Mechanismus seltener CTNNB1-Mutationen ist weniger gut definiert. Korrelationen von Mutationen mit unterschiedlichen histologischen Charakteristika wie auch mit Geschlecht und Ethnizität sind bisher unverstanden. Neuere Arbeiten weisen darauf hin, dass die bilaterale Hyperplasie zumindest teilweise auf sog. aldosteronproduzierende Zellcluster, häufig mit somatischen Mutationen im Gen CACNA1D, zurückgeht. Bei seltenen familiären Formen wurden Mutationen in den Genen CYP11B2, CLCN2, KCNJ5, CACNA1H und CACNA1D identifiziert.

Schlussfolgerungen

Diese Ergebnisse weisen darauf hin, dass ein erheblicher Anteil der Fälle von primärem Hyperaldosteronismus auf somatische Mutationen in einzelnen Genen zurückgeht.

Abstract

Background

Primary aldosteronism, the excessive production of the steroid hormone aldosterone, is the most common cause of secondary hypertension. Common subforms include bilateral adrenal hyperplasia and aldosterone-producing adenoma.

Objectives

The goal of this review is to summarize important publications on the genetic basis of primary aldosteronism.

Results

Somatic mutations in the KCNJ5, CACNA1D, ATP1A1, and ATP2B3 genes have been described as causes of aldosterone-producing adenomas. They eventually all lead to increased cellular calcium influx and aldosterone production. The mechanisms of rare CTNNB1 mutations are less defined. Correlations between mutations and different histologic characteristics as well as gender and ethnicity remain unexplained. Recent publications suggest that bilateral hyperplasia is at least partially due to so-called aldosterone-producing cell clusters, often with mutations in CACNA1D. Rare familial forms show mutations in the CYP11B2, CLCN2, KCNJ5, CACNA1H, or CACNA1D genes.

Conclusions

These results suggest that a significant fraction of primary aldosteronism is due to somatic mutations in single genes.

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Förderung

Diese Arbeit wurde durch die Stiftung Charité, die Deutsche Forschungsgemeinschaft (SCHO 1386/2‑1, SFB 1365) und die Fritz Thyssen Stiftung (10.16.1.027MN) unterstützt.

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Authors and Affiliations

  1. Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    U. Scholl

  2. Berliner Institut für Gesundheitsforschung, 10178, Berlin, Deutschland

    U. Scholl

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  1. U. Scholl
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Correspondence to U. Scholl.

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Interessenkonflikt

U. Scholl gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Scholl, U. Primärer Hyperaldosteronismus. Pathologe 40 (Suppl 3), 369–372 (2019). https://doi.org/10.1007/s00292-019-00682-x

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  • DOI: https://doi.org/10.1007/s00292-019-00682-x

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