The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes.
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ABSTRACT:
SUBMITTER: Wu VC
PROVIDER: S-EPMC5244399 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes.
Wu Vin-Cent VC Wang Shuo-Meng SM Chueh Shih-Chieh Jeff SJ Yang Shao-Yu SY Huang Kuo-How KH Lin Yen-Hung YH Wang Jian-Jhong JJ Connolly Rory R Hu Ya-Hui YH Gomez-Sanchez Celso E CE Peng Kang-Yung KY Wu Kwan-Dun KD
Scientific reports 20170119
Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The ...[more]
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Project description:Recent discoveries of somatic mutations permit the recognition of subtypes of aldosterone-producing adenomas with distinct clinical presentations and pathological features. Here we describe three women with hyperaldosteronism, two who presented in pregnancy and one who presented after menopause. Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding ?-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas. The mutations stimulate Wnt activation and cause adrenocortical cells to de-differentiate toward their common adrenal-gonadal precursor cell type. (Funded by grants from the National Institute for Health Research Cambridge Biomedical Research Centre and others.).
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Project description:Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identify patients who might benefit from effective and targeted treatment modalities. Effective treatments available include both surgical and medical approaches, usually dependent on the subtype of PA present. Our collective understanding of the pathophysiology of PA is expanded by recent developments in molecular biology and genetics, including understanding the specific somatic and germline mutations involved in pathogenesis. We review the pathophysiology, diagnostic workup, and treatment considerations for this disease process.
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