{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:34:37Z","timestamp":1789097677716,"version":"build-2803163510"},"reference-count":48,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Multiple endocrine neoplasia type 4 (MEN4) is caused by a\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE\n                      <jats:sup>\u00ae<\/jats:sup>\n                      and Web of Science\n                      <jats:sup>TM<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different\n                      <jats:italic>CDKN1B<\/jats:italic>\n                      variants, mostly missense (21\/48, 44%) and frameshift mutations (17\/48, 35%), were reported. The majority of patients were women (36\/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10\u201368, mean 33.7 \u00b1 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5\u201376, mean 44.8 \u00b1 19.9) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009\u2009=\u20090.25). The most frequently affected endocrine organ was the parathyroid gland (36\/48, 75%; uniglandular disease 31\/36, 86%), followed by the pituitary gland (21\/48, 44%; hormone-secreting 16\/21, 76%), the endocrine pancreas (7\/48, 15%), and the thyroid gland (4\/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27\/48, 56%) and the pituitary gland (11\/48, 23%). There were one (27\/48, 56%), two (13\/48, 27%), three (3\/48, 6%), or four (5\/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/ec-22-0411","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T13:21:44Z","timestamp":1671110504000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":38,"title":["Multiple endocrine neoplasia type 4: a new member of the MEN family"],"prefix":"10.1530","volume":"12","author":[{"given":"H\u00e9l\u00e8ne","family":"Singeisen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Endocrinology, Cantonal Hospital Thurgau, M\u00fcnsterlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Melanie Renzulli","sequence":"additional","affiliation":[{"name":"Institute of Radiology, Cantonal Hospital Thurgau, Frauenfeld, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vojtech","family":"Pavlicek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Endocrinology, Cantonal Hospital Thurgau, M\u00fcnsterlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Probst","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Hauswirth","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cantonal Hospital Thurgau, M\u00fcnsterlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus K","family":"Muller","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalene","family":"Adamczyk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology, University Hospital Zurich and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto Martin","family":"Kaderli","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5557-5512","authenticated-orcid":true,"given":"Pietro","family":"Renzulli","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cantonal Hospital Thurgau, M\u00fcnsterlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"PNAS","first-page":"15558","article-title":"Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans","volume":"103","author":"Pellegata","year":"2006","unstructured":"Pellegata NSQuintanilla-Martinez LSiggelkow HSamson EBink KH\u00f6fler HFend FGraw JAtkinson MJ. 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