Genetic and Histopathologic Intertumor Heterogeneity in Primary Aldosteronism.

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.

• Authors: Kei Omata, Yuto Yamazaki, Yasuhiro Nakamura, Sharath K Anand, Justine A Barletta, Hironobu Sasano, William E Rainey, Scott A Tomlins, Anand Vaidya
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 102 Issue 6 Pg. 1792-1796 (06 01 2017) ISSN: 1945-7197 [Electronic] United States
• PMID: 28368480 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• CACNA1D protein, human
• Calcium Channels, L-Type
• G Protein-Coupled Inwardly-Rectifying Potassium Channels
• KCNJ5 protein, human
• Steroid 17-alpha-Hydroxylase
• Cytochrome P-450 CYP11B2
• Sulfotransferases
• dehydroepiandrosterone sulfotransferase

Topics

• Adrenal Cortex Neoplasms (genetics, metabolism, pathology, surgery)
• Adrenocortical Adenoma (genetics, metabolism, pathology, surgery)
• Calcium Channels, L-Type (genetics)
• Cytochrome P-450 CYP11B2 (metabolism)
• G Protein-Coupled Inwardly-Rectifying Potassium Channels (genetics)
• Humans
• Hyperaldosteronism (genetics, metabolism, pathology, surgery)
• Immunohistochemistry
• Male
• Middle Aged
• Neoplasms, Multiple Primary (genetics, metabolism, pathology, surgery)
• Steroid 17-alpha-Hydroxylase (metabolism)
• Sulfotransferases (metabolism)
• Zona Fasciculata (pathology)
• Zona Glomerulosa (pathology)
• Zona Reticularis (pathology)