Key result
Sequencing identifies somatic GNAS and CACNA1D mutations in concurrent primary aldosteronism and mild autonomous cortisol secretion.
Case Report (n=1)
No
This case demonstrates that concurrent primary aldosteronism and mild autonomous cortisol secretion can be associated with somatic GNAS and CACNA1D mutations in a cortisol-producing adenoma with adjacent aldosterone-producing micronodules.
Rare GNAS/CACNA1D-mutant adenoma with MAPM in PA+MACS; leaves open molecular drivers and management strategies.
Background The concurrent presence of primary aldosteronism (PA) and mild autonomous cortisol secretion (MACS) caused by adrenal lesions of a solitary cortisol-producing adenoma, accompanied by multiple aldosterone-producing micronodules (MAPM), is exceptionally rare. Moreover, there is a notable paucity of data regarding the molecular pathogenesis of this disease. Case presentation We report a unique case of a somatic GNAS / CACNA1D -mutant cortisol-producing adenoma accompanied by MAPM and an aldosterone-producing nodule (APN) in the adjacent adrenal cortex. The patient was a 63-year-old woman with a 25-year history of hypertension and had a mass in the right adrenal gland. Detailed endocrine examinations revealed the concomitant occurrence of PA and MACS. Histologically, the main tumor was a well-circumscribed, encapsulated mass composed of neoplastic cells arranged in trabecular and nested patterns, exhibiting eosinophilic to vacuolated cytoplasm with uniformly round nuclei. Adjacent to the main tumor, a histologically similar 0.4 cm cortical nodule rich in clear cells was observed. Immunohistochemical analysis revealed diffuse CYP11B1 staining in the main tumor, whereas adjacent scattered cortical cell clusters and nodules exhibited distinctively diffuse CYP11B2 positivity. Next-generation sequencing results revealed missense mutations in the GNAS (p.R201H) and CACNA1D genes (p.F1131L). Conclusion Our molecular findings from bulk tissue analysis identified somatic mutations in the GNAS and CACNA1D genes. Although the lack of microdissection precludes definitively assigning each variant to a specific pathological component, we hypothesize that these mutations may serve as key drivers for concurrent PA and MACS associated with cortisol-producing adenoma and adjacent MAPM/APN. Furthermore, our data support the emerging concept that primary aldosteronism can originate from MAPM rather than just from conventional adrenal cortical adenomas.
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Deng et al. (2026) conducted a case report in Concurrent primary aldosteronism and mild autonomous cortisol secretion (n=1). Somatic GNAS and CACNA1D mutations was evaluated. Somatic missense mutations in the GNAS (p.R201H) and CACNA1D (p.F1131L) genes were identified in a patient with concurrent primary aldosteronism and mild autonomous cortisol secretion.
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