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Impact of KCNJ5-induced sodium entry on adrenal development in FH-III

Determine whether increased sodium entry caused by germline KCNJ5 mutations affects adrenocortical cell proliferation during adrenal development in familial hyperaldosteronism type III, and assess whether this contributes to bilateral adrenal hyperplasia.

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Background

Familial hyperaldosteronism type III (FH-III) is caused by germline KCNJ5 mutations and can present with severe, bilateral adrenal hyperplasia. KCNJ5 mutations increase sodium influx and activate calcium signaling, driving aldosterone production.

It remains unresolved whether sodium entry during adrenal development alters proliferation programs, potentially explaining bilateral hyperplasia. Establishing this developmental impact would improve understanding and management of FH-III.

References

Finally, in FH-III it cannot be ruled out that Na+ entry induced by KCNJ5 mutations may have an impact on cell proliferation during adrenal development, which could explain the bilateral hyperplasia observed in severe cases8,19.

— Modulation of Calcium Signaling on Demand to Decipher the Molecular Mechanisms of Primary Aldosteronism (2507.15353 - Fedlaoui et al., 21 Jul 2025) in Discussion — FH-III context (late Discussion)