{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:56:12Z","timestamp":1790816172762,"version":"4.1.0"},"reference-count":17,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:sec><jats:title>Context:<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Description:<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2016-1874","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T17:54:24Z","timestamp":1474394064000},"page":"3874-3878","source":"Crossref","is-referenced-by-count":49,"title":["Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis"],"prefix":"10.1210","volume":"101","author":[{"given":"Julien","family":"Vouillarmet","sequence":"first","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fernandes-Rosa","sequence":"additional","affiliation":[{"name":"Inserm, UMRS_970 (F.F.-R., S.B., E.C., M.-C.Z.), Paris Cardiovascular Research Center, 75015 Paris, France;"},{"name":"Universit\u00e9 Paris Descartes (F.F.-R., S.B., E.C., M.-C.Z.), Sorbonne Paris Cit\u00e9, 75006 Paris, France;"},{"name":"Assistance Publique-H\u00f4pitaux de Paris (F.F.-R., M.-C.Z.), H\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, 75015 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Graeppi-Dulac","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Lantelme","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"},{"name":"Hospices Civils de Lyon (P.L.), H\u00f4pital de la Croix-Rousse, Service de Cardiologie, European Society of Hypertension Excellence Center, 69317 Lyon, France;"},{"name":"Universit\u00e9 de Lyon (P.L.), CREATIS; CNRS UMR5220; Inserm U1044; INSA-Lyon; Universit\u00e9 Claude Bernard Lyon 1, 69100 Lyon, France;"},{"name":"Universit\u00e9 Claude Bernard Lyon I (P.L., M.D.-P., C.T.), 69100 Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Decaussin-Petrucci","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"},{"name":"Hospices Civils de Lyon (M.D.-P.), Centre Hospitalier Lyon-Sud, Service d\u2019anatomo-pathologie, universit\u00e9 Claude Bernard Lyon I, 69310 Pierre B\u00e9nite, France;"},{"name":"Universit\u00e9 Claude Bernard Lyon I (P.L., M.D.-P., C.T.), 69100 Lyon, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Thivolet","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"},{"name":"Universit\u00e9 Claude Bernard Lyon I (P.L., M.D.-P., C.T.), 69100 Lyon, France;"},{"name":"Inserm U1060 (C.T.), Facult\u00e9 de m\u00e9decine Lyon sud, 69921 Oullins, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Peix","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (J.V., J.G.-D., C.T.), Centre Hospitalier Lyon-Sud, Service d\u2019Endocrinologie, Diab\u00e8te et Ob\u00e9sit\u00e9, 69310 Pierre B\u00e9nite, France;"},{"name":"Hospices Civils de Lyon (J.-L.P.), Centre Hospitalier Lyon-Sud, Service de chirurgie digestive et endocrinienne, 69495 Pierre B\u00e9nite, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheerazed","family":"Boulkroun","sequence":"additional","affiliation":[{"name":"Inserm, UMRS_970 (F.F.-R., S.B., E.C., M.-C.Z.), Paris Cardiovascular Research Center, 75015 Paris, France;"},{"name":"Universit\u00e9 Paris Descartes (F.F.-R., S.B., E.C., M.-C.Z.), Sorbonne Paris Cit\u00e9, 75006 Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Clauser","sequence":"additional","affiliation":[{"name":"Inserm, UMRS_970 (F.F.-R., S.B., E.C., M.-C.Z.), Paris Cardiovascular Research Center, 75015 Paris, France;"},{"name":"Universit\u00e9 Paris Descartes (F.F.-R., 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