A patient with primary aldosteronism and a somatic KCNJ5 mutation was found to have biallelic APC inactivation, supporting a two-hit model for aldosterone-producing adenoma development.
Case Report (n=1)
This case report suggests a two-hit model for aldosterone-producing adenoma development and highlights the potential link between germline APC variants and primary aldosteronism.
CONTEXT: Recurrent somatic mutations in KCNJ5, CACNA1D, ATP1A1, and ATP2B3 have been identified in aldosterone-producing adenomas (APAs). The question as to whether they are responsible for both nodulation and aldosterone production is not solved. CASE DESCRIPTION: We describe the case of a young patient who was diagnosed with severe arterial hypertension due to primary aldosteronism at age 26 years, followed by hemorrhagic stroke 4 years later. Abdominal computed tomography showed bilateral macronodular adrenal hyperplasia. Identification of lateralized aldosterone secretion led to right adrenalectomy, followed by normalization of biochemical and hormonal parameters and amelioration of blood pressure. The resected adrenal showed three nodules, one of them expressing aldosterone synthase and harboring a somatic KNCJ5 mutation. A Weiss revisited index of 3 of the APA prompted us to perform a second 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography after surgery, which revealed abnormal rectal activity despite the absence of clinical symptoms. Gastrointestinal exploration showed multiple polyps with severe dysplasia, and the diagnosis of familial adenomatous polyposis was established in the presence of a germline heterozygous APC gene mutation. Sequencing of somatic DNA from the APA and a second adrenal nodule revealed biallelic APC inactivation due to loss of heterozygosity in both nodules. CONCLUSIONS: This case report underlines the need for establishing the frequency of germline APC variants in patients with primary aldosteronism and bilateral macronodular adrenal hyperplasia because their presence may predispose to APA development and severe hypertension well before the first familial adenomatous polyposis symptoms appear. From a mechanistic point of view, it supports a two-hit model for APA development, whereby the first hit drives increased cell proliferation whereas the second hit specifies the pattern of hormonal secretion.
Vouillarmet et al. (Tue,) conducted a case report in Primary aldosteronism and familial adenomatous polyposis (n=1). Somatic KCNJ5 and germline APC mutations was evaluated. A patient with primary aldosteronism and a somatic KCNJ5 mutation was found to have biallelic APC inactivation, supporting a two-hit model for aldosterone-producing adenoma development.