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case_images: Enhanced computerized tomography (CT), pathological and immunohistochemical findings. (A) CT scan revealed bilateral adrenocortical adenomas, with the left adenoma of 38 x 28 mm and the right adenoma of 25 x 21 mm (white arrows). (B) Gross pathology of the resected left adrenal tumor showing a bright yellow well-circumscribed mass arising from the cortex. (C) Gross pathology of the resected right adrenal tumor showing a brownish yellow, relatively solid area. (D, G) H&E stain results, (x200); (E, F, H, I) immunostaining (x200). Left adrenocortical adenoma (left ACA, predominately secreted aldosterone) consisting primarily of clear cells, CYP11B1 (-) and CYP11B2 (+). Right adrenocortical adenoma (right ACA, predominately secreting cortisol) was composed of both eosinophilic compact cells and clear cells, with the former accounting for 60%, CYP11B1 (+) and CYP11B2 (-).
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case_images: Computerized tomography scan revealed bilateral adrenocortical adenomas, with the left adenoma of 38 x 28 mm and the right adenoma of 25 x 21 mm ( Figure 1A ). Pathological examination revealed that the left adrenal mass was a golden-yellow adenoma ( Figure 1B ) mainly composed of clear cells on hematoxylin/eosin stained sections ( Figure 1D ). Immunohistochemical analysis revealed cytoplasm immunoreactivity for aldosterone synthase (CYP11B2) with no expression of 11beta-hydroxylase 1 (CYP11B1;  Figures 1E, F ). Pathological examination revealed that the right adrenal tumor was brownish yellow and relatively solid ( Figure 1C ). This mass was composed of both eosinophilic compact and clear cells, with the former accounting for 60% ( Figure 1G ). Immunohistochemical analysis also revealed cytoplasm immunoreactivity for CYP11B1 with no expression of CYP11B2 ( Figures 1H, I ).
case_images: mRNA expression of steroidogenic enzymes STAR, CYP17A1, CYP11B1, and CYP11B2 in the bilateral adrenal adenomas of the patient and other adrenal adenomas. (A)
  STAR was highly expressed in both bilateral adenomas, (B, C)
  CYP11B1 and CYP17A1 were highly expressed in right adenoma and CPAs, (D)
  CYP11B2 was highly expressed in the left adenoma and APAs compared with other adrenal diseases and nonfunctional adenoma. * P < 0.05 compared with other groups. NFA, nonfunctional adenomas; left ACA, left adrenocortical adenoma of the index patient; right ACA, right adrenocortical adenoma of the index patient; APA, aldosterone-producing adenomas; CPA, cortisol-producing adenomas.
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case_images: CYP11B1 and CYP17A1 were highly expressed in the right adenoma and CPAs, whereas CYP11B2 was highly expressed in the left adenoma and APAs compared with other adrenal diseases and nonfunctional adenoma ( Figure 2 ).
case_images: Effects of nifedipine and verapamil on aldosterone and cortisol secretions, respectively, in the primary cells of bilateral adenomas. (A, B) Effects of verapamil and nifedipine on the secretion of aldosterone and cortisol in the left adenoma. (C, D). Effects of verapamil and nifedipine on the secretion of aldosterone and cortisol in right adenoma. * P < 0.05 compared with the control. left ACA, left adrenocortical adenoma of the index patient; right ACA, right adrenocortical adenoma of the index patient.
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case_images: Moreover, verapamil and nifedipine remarkably inhibited the secretion of bilateral aldosterone and cortisol ( Figure 3 ).
case_images: Sequencing chromatograms of the KCNJ5 variant identified in peripheral blood samples and bilateral adenomas. (A) The germline KCNJ5 variant was not found in peripheral blood samples. (B) Heterozygous KCNJ5 c.503T > G somatic variant was identified in the left adenoma. (C) Normal sequence of the KCNJ5 gene in the right adenoma. (D) Multiple alignment of the KCNJ5 protein sequence in different species, indicating conservation of the residues KCNJ5 c.503T > G affected by this variant.
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case_images: A novel somatic heterozygous missense variant, KCNJ5 c.503T > G (p.L168R), was detected in the left adrenal adenoma, whereas no germline and somatic variants associated with PA and CS were found in the peripheral blood samples or right adrenocortical adenoma ( Figures 4A-C ). The amino acid alignment of KCNJ5 across different species revealed that the leucine residue mutated in our case was conserved across all examined species ( Figure 4D ).