{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:27:49Z","timestamp":1780525669292,"version":"3.54.1"},"reference-count":27,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2015\/17049-8"],"award-info":[{"award-number":["2015\/17049-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["403256\/2016-0"],"award-info":[{"award-number":["403256\/2016-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["302849\/2015"],"award-info":[{"award-number":["302849\/2015"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303002\/2016-6"],"award-info":[{"award-number":["303002\/2016-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the VHL gene. Guidelines recommend pheochromocytoma (PHEO) biochemical screening should start at age 5 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Genotype\u2013phenotype correlations in VHL, focusing on PHEO penetrance in children, were studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We retrospectively evaluated 31 individuals (median age at diagnosis was 26 years) with diagnosed VHL disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PHEO was diagnosed in six children with VHL. A large PHEO (5 cm) was detected in a 4-year-old boy with p.Gly114Ser mutation. PHEO penetrance was 55% starting at age 4 years. VHL missense mutations were identified in 11 of 22 families (50%), frameshift mutations in four (18.2%), stop codon in three (13.6%), splicing site in two (9.1%), and large gene deletion in two (9.1%). The codon 167 (n = 10) was a hotspot for VHL mutations and was significantly associated with PHEO (90% vs. 38%; P = 0.007). PHEOs and pancreatic neuroendocrine tumors (PNETs) were strongly associated with VHL missense mutations compared with other mutations (89.5% vs. 0% and 73.7% vs. 16.7%; P = 0.0001 and 0.002, respectively). In contrast, pancreatic cysts (91.7% vs. 26.3%; P = 0.0001), renal cysts (66.7% vs. 26.3%; P = 0.027), and central nervous system hemangioblastomas (91.7% vs. 47.3%; P = 0.012) were more frequent in VHL with nonmissense mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>VHL missense mutations were highly associated with PHEO and PNETs. Our data support that in children with VHL harboring missense mutations, biochemical screening for PHEO should be initiated at diagnosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/js.2019-00225","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T09:02:59Z","timestamp":1562058179000},"page":"1682-1692","source":"Crossref","is-referenced-by-count":25,"title":["New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations"],"prefix":"10.1210","volume":"3","author":[{"given":"Gustavo F C","family":"Fagundes","sequence":"first","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaina","family":"Petenuci","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Delmar M","family":"Lourenco","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Gen\u00e9tica, LIM\/25, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"},{"name":"Servi\u00e7o de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ericka B","family":"Trarbach","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Gen\u00e9tica, LIM\/25, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adelaide A","family":"Pereira","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Geral, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joya Emilie","family":"Correa D\u2019Eur","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Gen\u00e9tica, LIM\/25, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana O","family":"Hoff","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio M","family":"Lerario","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Claudia N","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Anatomia Patol\u00f3gica, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Anatomia Patol\u00f3gica, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Departamento de Radiologia e Oncologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Srougi","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Y","family":"Tanno","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Chambo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Urologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Latronico","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice B","family":"Mendonca","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Candida B V","family":"Fragoso","sequence":"additional","affiliation":[{"name":"Unidade de Suprarrenal, Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM\/42, Servi\u00e7o de Endocrinologia e Metabologia, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brasil"},{"name":"Servi\u00e7o de Endocrinologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo, 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