Aldosterone-producing Multiple Micronodules With Several Different KCNJ5 Pathogenic Variants

Area of Science:

• Endocrinology
• Genetics
• Nephrology

Background:

• Primary aldosteronism (PA) is the most prevalent cause of secondary hypertension.
• Genetic mutations in aldosterone-producing adenomas are increasingly identified as key drivers of PA.
• Understanding the genetic basis of PA is crucial for diagnosis and treatment.

Observation:

• A 27-year-old Japanese female presented with hypertension and hypokalemia, indicative of PA.
• Imaging revealed no single adrenal tumor, but adrenal vein sampling confirmed right-sided aldosterone overproduction.
• Surgical removal of the right adrenal gland normalized blood pressure and potassium levels.

Findings:

• Pathological examination identified multiple aldosterone-producing micronodules (<5 mm) in the affected adrenal gland.
• Genetic analysis of these micronodules revealed distinct pathogenic variants in the KCNJ5 gene (T158A and G151R) in different nodules.
• One micronodule lacked detectable KCNJ5 variants, suggesting other genetic factors may be involved.

Implications:

• This case demonstrates genetic heterogeneity within aldosterone-producing micronodules in a single adrenal gland.
• The findings underscore the importance of comprehensive genetic analysis in complex PA cases.
• Long-term follow-up (17 years) showed no recurrence, supporting the efficacy of surgical intervention.