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Genetic and Histopathologic Intertumor Heterogeneity in Primary Aldosteronism

Year: 2017
Type: article
Study design: Case Report
Abstract: Context: Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear. Case Description: A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas. Two zona fasciculata (ZF)-like aldosterone-producing adenomas (APAs) each harbored distinct known somatic KCNJ5 mutations (L168R and T158A). A zona glomerulosa-like APA harbored a known CACNA1D G403R somatic mutation, whereas a zona reticularis-like adenoma, which was grossly black in pigmentation with histologic characteristics more associated with cortisol-producing adenomas, expressed CYP11B2, CYP17, and DHEA-ST by immunohistochemistry (IHC) and harbored no known somatic mutations. The fifth adenoma was ZF-type, negative for CYP11B2 and CYP17 IHC, and harbored no known somatic mutations. Conclusions: This case highlights complex intertumor heterogeneity in histology, steroidogenesis, and somatic mutations in multiple adrenocortical adenomas arising in a single patient with PA. These findings suggest that the syndrome of PA can involve heterogeneous and multiclonal functional adrenal adenomas.
DOI: 10.1210/jc.2016-4007
Authors: Kei Omata, Yuto Yamazaki, Yasuhiro Nakamura, Sharath K. Anand, Justine A. Barletta, Hironobu Sasano, William E. Rainey, Scott A. Tomlins, Anand Vaidya
Institutions: Tohoku University, University of Michigan, Tohoku Medical and Pharmaceutical University, Brigham and Women's Hospital, Harvard University, Michigan Center for Translational Pathology
Language: English
Field: Medicine
Open Access status: bronze
Funders: Doris Duke Charitable Foundation, Brigham and Women's Hospital, University of Michigan, A. Alfred Taubman Medical Research Institute, National Institutes of Health, College of Pharmacy, University of Michigan, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G2351744653, Identification of aldosterone-producing cells: Explore the novel mechanism of the hypertension-induced organ damages, G314124149, Adrenal Origins of Aldosterone Excess, G4148011228, Interactions Between Adrenal and Parathyroid Hormones in Human Health, G7253949684, Vitamin D and Hormonal Mechanisms of Cardiovascular Disease in Obesity, G871564352
OpenAlex ID: W2605251296
FWCI: 3.461
Cites: 7
Cited by: 25
Related to: 10