Tumor-specific KCNJ5 mutation in an aldosterone-producing adenoma not detected in adrenal venous plasma cell-free DNA.

Circulating tumor DNA (ctDNA) can be detected in adrenocortical carcinoma; however, its detectability in benign adrenal tumors, such as aldosterone-producing adenoma (APA), remains unclear. We investigated whether tumor-specific mutations could be detected in plasma cell-free DNA (cfDNA) obtained from peripheral and adrenal venous blood in a 34-year-old man with APA. The patient was evaluated for secondary hypertension, and screening and confirmatory tests established the diagnosis of primary aldosteronism. Computed tomography revealed an 11-mm left adrenal mass, and adrenal venous sampling demonstrated left-sided aldosterone hypersecretion. The patient subsequently underwent left adrenalectomy, and pathological examination confirmed an APA. Targeted next-generation sequencing of 18 adrenal disease-related genes identified a somatic KCNJ5 mutation in the tumor tissue. However, the corresponding mutation was not detectable in cfDNA from either peripheral or adrenal venous plasma, despite sampling under clinically favorable conditions. Postoperatively, blood pressure and serum potassium levels normalized. This case illustrates the challenges of detecting tumor-derived mutations in plasma from small benign adrenal tumors using standard sequencing approaches and highlights how tumor burden, sampling conditions, and assay sensitivity influence ctDNA detectability. Further studies employing highly sensitive, mutation-targeted methods are warranted to elucidate the biological and technical factors affecting ctDNA detection in APA.