Aldosterone-producing nodules and CYP11B1 signaling correlate in primary aldosteronism

in Endocrine-Related Cancer
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  • 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • | 2 TAIPAI, Taiwan Primary Aldosteronism Investigation (TAIPAI) Study Group, Taipei, Taiwan
  • | 3 Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • | 4 Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
  • | 5 Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • | 6 Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • | 7 Division of Colon and Rectal Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • | 8 Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • | 9 Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan, Taiwan
  • | 10 Department of Neurosurgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • | 11 Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
  • | 12 Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
  • | 13 Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

Correspondence should be addressed to V-C Wu: q91421028@ntu.edu.tw
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Autonomous cortisol secretion (ACS) could be found in some patients with unilateral primary aldosteronism (uPA). However, the histopathological patterns of uPA with concurrent ACS have not been well elucidated. The adrenal gland with the adenoma from 61 uPA patients who underwent unilateral adrenalectomy were assessed by immunohistochemistry. Bioinformatics analysis, including the Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes, was applied. The prevalence of multiple aldosterone-producing nodules or micronodules (mAPN/mAPM) was 65.6% (40/61) among our uPA patients. Concurrent ACS was identified in 32% of this uPA cohort; they were associated with the interaction of larger tumor size (>1.98 cm) and mAPN/mAPM (odds ratio = 3.08, P  = 0.004). Transcriptome analysis uncovered a dominant enrichment of HSD3B7 overexpression (P  = 0.004) in the adenomas of the histopathologically classical adrenal uPA lesions with concomitant mAPN/mAPM, compared with those uPA adenomas without concurrent surrounding mAPN/mAPM. We identified a novel linkage of enhanced steroidogenic genes of HSD3B7 expression concurrent with the downstream higher CYP11B1 expression; further relationship was confirmed by immunohistochemical staining and validated by TCGA bioinformatics. The presence of mAPN/mAPM in uPA patients had lower rate for biochemical success after adrenalectomy (P  = 0.047). In summary, two-thirds of uPA patients had concomitant mAPN/mAPM; 1/3 of uPA patients had concurrent ACS. Steroidogenic HSD3B7/CYP11B1 signaling was associated with uPA adenomas with surrounding mAPN/mAPM. Interaction of larger adenoma size with the presence of mAPN/mAPM was linked to co-existing ACS. Such uPA patients with concomitant mAPN/mAPM had lower rate of biochemical success.

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