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Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism
Abstract Background Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (
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| Published in: | The journal of clinical endocrinology and metabolism 2021-02, Vol.106 (2), p.e460-e468 |
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| creator | Lee, Maya E Ortega-Sustache, Yashira M Agarwal, Sunita K Tepede, Aisha Welch, James Mandl, Adel Bansal, Rashika Tirosh, Amit Piaggi, Paolo Cochran, Craig Simonds, William F Weinstein, Lee S Blau, Jenny E |
| description | Abstract
Background
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas ( |
| doi_str_mv | 10.1210/clinem/dgaa501 |
| format | article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7823242</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A702287727</galeid><oup_id>10.1210/clinem/dgaa501</oup_id><sourcerecordid>A702287727</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4700-f01f8a82c20fbccc2391059d6ffcc6f75307f770516d36358e0b7696596ac1d3</originalsourceid><addsrcrecordid>eNqFkd1rFDEUxYModq2--igBX_Rh2ptkkkxehKW0WqgfyKK-hWwm2U2dSdZkRvC_N2XX-kFBQggkv3vuPTkIPSVwQiiBUzuE6MbTfmMMB3IPLYhqeSOJkvfRAoCSRkn65Qg9KuUagLQtZw_REaOSCyXoAl18MFNwcSr4c5i2-O35O4KX2WEzYRPxZbTZmeJ6_DGUr9injD-5mOaCV9ucxnVydQ-hjI_RA2-G4p4czmO0ujhfnb1prt6_vjxbXjW2lQCNB-I701FLwa-ttZQpAlz1wntrhZecgfRSAieiZ4LxzsFa1kG5EsaSnh2jV3vZ3bweXW_r4NkMepfDaPIPnUzQf7_EsNWb9F3LjjLa0irw4iCQ07fZlUmPoVg3DCa6akvTloGSivK2os__Qa_TnGN1p6nigjAQXfeb2pjB6RB9qn3tjaheSqC0k5LKSp3cQdXVuzHYFJ0P9f6uAptTKdn5W48E9E3weh-8PgRfC579-TO3-K-kK_ByD6R59z-xn1dpttI</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2956130688</pqid></control><display><type>article</type><title>Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism</title><source>Oxford Journals Online</source><creator>Lee, Maya E ; Ortega-Sustache, Yashira M ; Agarwal, Sunita K ; Tepede, Aisha ; Welch, James ; Mandl, Adel ; Bansal, Rashika ; Tirosh, Amit ; Piaggi, Paolo ; Cochran, Craig ; Simonds, William F ; Weinstein, Lee S ; Blau, Jenny E</creator><creatorcontrib>Lee, Maya E ; Ortega-Sustache, Yashira M ; Agarwal, Sunita K ; Tepede, Aisha ; Welch, James ; Mandl, Adel ; Bansal, Rashika ; Tirosh, Amit ; Piaggi, Paolo ; Cochran, Craig ; Simonds, William F ; Weinstein, Lee S ; Blau, Jenny E</creatorcontrib><description>Abstract
Background
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and adenocorticotropic hormone-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have an increased risk of venous thromboembolism (VTE).
Methods
We queried a prospective natural history study of germline mutation-positive MEN1 patients (n = 286) between 1991 and 2019 for all lifetime events of VTE. The search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban, and apixaban. Incidence rates were calculated, accounting for age and sex. Comparisons were made to published incidence rates in healthy populations, different types of cancer, and Cushing’s syndrome.
Results
Thirty-six subjects (median age 45 years, range 16–75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age–sex adjusted incidence rate of VTE is 9.11 per 1000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1000 patient-years. MEN1-associated lifetime incidence rates are ~2-fold higher than the estimated annual incidence rate in the general population and are comparable to the known risk in the setting of various types of cancer. Approximately 80% of patients who had a VTE were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced perioperative VTE events.
Conclusions
MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgaa501</identifier><identifier>PMID: 32756962</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; Anticoagulants (Medicine) ; Anticoagulants - therapeutic use ; Aspirin ; Clinical s ; Development and progression ; Embolism ; Enoxaparin ; Female ; Gene mutations ; Genetic aspects ; Health aspects ; Hematology ; History, 20th Century ; History, 21st Century ; Humans ; Incidence ; Male ; Middle Aged ; Multiple endocrine neoplasia ; Multiple Endocrine Neoplasia Type 1 - complications ; Multiple Endocrine Neoplasia Type 1 - drug therapy ; Multiple Endocrine Neoplasia Type 1 - epidemiology ; Neuroendocrine tumors ; Pancreatic cancer ; Patients ; Population Surveillance ; Prevalence ; Pulmonary embolism ; Retrospective Studies ; Risk Factors ; Thromboembolism ; Tumors ; Type 2 diabetes ; United States - epidemiology ; Venous Thromboembolism - epidemiology ; Venous Thromboembolism - etiology ; Venous Thromboembolism - prevention & control ; Young Adult</subject><ispartof>The journal of clinical endocrinology and metabolism, 2021-02, Vol.106 (2), p.e460-e468</ispartof><rights>Published by Oxford University Press on behalf of the Endocrine Society 2020. 2020</rights><rights>Published by Oxford University Press on behalf of the Endocrine Society 2020.</rights><rights>COPYRIGHT 2021 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4700-f01f8a82c20fbccc2391059d6ffcc6f75307f770516d36358e0b7696596ac1d3</citedby><cites>FETCH-LOGICAL-c4700-f01f8a82c20fbccc2391059d6ffcc6f75307f770516d36358e0b7696596ac1d3</cites><orcidid>0000-0003-3794-9634</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32756962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Maya E</creatorcontrib><creatorcontrib>Ortega-Sustache, Yashira M</creatorcontrib><creatorcontrib>Agarwal, Sunita K</creatorcontrib><creatorcontrib>Tepede, Aisha</creatorcontrib><creatorcontrib>Welch, James</creatorcontrib><creatorcontrib>Mandl, Adel</creatorcontrib><creatorcontrib>Bansal, Rashika</creatorcontrib><creatorcontrib>Tirosh, Amit</creatorcontrib><creatorcontrib>Piaggi, Paolo</creatorcontrib><creatorcontrib>Cochran, Craig</creatorcontrib><creatorcontrib>Simonds, William F</creatorcontrib><creatorcontrib>Weinstein, Lee S</creatorcontrib><creatorcontrib>Blau, Jenny E</creatorcontrib><title>Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Abstract
Background
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and adenocorticotropic hormone-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have an increased risk of venous thromboembolism (VTE).
Methods
We queried a prospective natural history study of germline mutation-positive MEN1 patients (n = 286) between 1991 and 2019 for all lifetime events of VTE. The search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban, and apixaban. Incidence rates were calculated, accounting for age and sex. Comparisons were made to published incidence rates in healthy populations, different types of cancer, and Cushing’s syndrome.
Results
Thirty-six subjects (median age 45 years, range 16–75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age–sex adjusted incidence rate of VTE is 9.11 per 1000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1000 patient-years. MEN1-associated lifetime incidence rates are ~2-fold higher than the estimated annual incidence rate in the general population and are comparable to the known risk in the setting of various types of cancer. Approximately 80% of patients who had a VTE were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced perioperative VTE events.
Conclusions
MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Anticoagulants</subject><subject>Anticoagulants (Medicine)</subject><subject>Anticoagulants - therapeutic use</subject><subject>Aspirin</subject><subject>Clinical s</subject><subject>Development and progression</subject><subject>Embolism</subject><subject>Enoxaparin</subject><subject>Female</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>History, 20th Century</subject><subject>History, 21st Century</subject><subject>Humans</subject><subject>Incidence</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple endocrine neoplasia</subject><subject>Multiple Endocrine Neoplasia Type 1 - complications</subject><subject>Multiple Endocrine Neoplasia Type 1 - drug therapy</subject><subject>Multiple Endocrine Neoplasia Type 1 - epidemiology</subject><subject>Neuroendocrine tumors</subject><subject>Pancreatic cancer</subject><subject>Patients</subject><subject>Population Surveillance</subject><subject>Prevalence</subject><subject>Pulmonary embolism</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Thromboembolism</subject><subject>Tumors</subject><subject>Type 2 diabetes</subject><subject>United States - epidemiology</subject><subject>Venous Thromboembolism - epidemiology</subject><subject>Venous Thromboembolism - etiology</subject><subject>Venous Thromboembolism - prevention & control</subject><subject>Young Adult</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkd1rFDEUxYModq2--igBX_Rh2ptkkkxehKW0WqgfyKK-hWwm2U2dSdZkRvC_N2XX-kFBQggkv3vuPTkIPSVwQiiBUzuE6MbTfmMMB3IPLYhqeSOJkvfRAoCSRkn65Qg9KuUagLQtZw_REaOSCyXoAl18MFNwcSr4c5i2-O35O4KX2WEzYRPxZbTZmeJ6_DGUr9injD-5mOaCV9ucxnVydQ-hjI_RA2-G4p4czmO0ujhfnb1prt6_vjxbXjW2lQCNB-I701FLwa-ttZQpAlz1wntrhZecgfRSAieiZ4LxzsFa1kG5EsaSnh2jV3vZ3bweXW_r4NkMepfDaPIPnUzQf7_EsNWb9F3LjjLa0irw4iCQ07fZlUmPoVg3DCa6akvTloGSivK2os__Qa_TnGN1p6nigjAQXfeb2pjB6RB9qn3tjaheSqC0k5LKSp3cQdXVuzHYFJ0P9f6uAptTKdn5W48E9E3weh-8PgRfC579-TO3-K-kK_ByD6R59z-xn1dpttI</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Lee, Maya E</creator><creator>Ortega-Sustache, Yashira M</creator><creator>Agarwal, Sunita K</creator><creator>Tepede, Aisha</creator><creator>Welch, James</creator><creator>Mandl, Adel</creator><creator>Bansal, Rashika</creator><creator>Tirosh, Amit</creator><creator>Piaggi, Paolo</creator><creator>Cochran, Craig</creator><creator>Simonds, William F</creator><creator>Weinstein, Lee S</creator><creator>Blau, Jenny E</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3794-9634</orcidid></search><sort><creationdate>20210201</creationdate><title>Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism</title><author>Lee, Maya E ; Ortega-Sustache, Yashira M ; Agarwal, Sunita K ; Tepede, Aisha ; Welch, James ; Mandl, Adel ; Bansal, Rashika ; Tirosh, Amit ; Piaggi, Paolo ; Cochran, Craig ; Simonds, William F ; Weinstein, Lee S ; Blau, Jenny E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4700-f01f8a82c20fbccc2391059d6ffcc6f75307f770516d36358e0b7696596ac1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Anticoagulants</topic><topic>Anticoagulants (Medicine)</topic><topic>Anticoagulants - therapeutic use</topic><topic>Aspirin</topic><topic>Clinical s</topic><topic>Development and progression</topic><topic>Embolism</topic><topic>Enoxaparin</topic><topic>Female</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>History, 20th Century</topic><topic>History, 21st Century</topic><topic>Humans</topic><topic>Incidence</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple endocrine neoplasia</topic><topic>Multiple Endocrine Neoplasia Type 1 - complications</topic><topic>Multiple Endocrine Neoplasia Type 1 - drug therapy</topic><topic>Multiple Endocrine Neoplasia Type 1 - epidemiology</topic><topic>Neuroendocrine tumors</topic><topic>Pancreatic cancer</topic><topic>Patients</topic><topic>Population Surveillance</topic><topic>Prevalence</topic><topic>Pulmonary embolism</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Thromboembolism</topic><topic>Tumors</topic><topic>Type 2 diabetes</topic><topic>United States - epidemiology</topic><topic>Venous Thromboembolism - epidemiology</topic><topic>Venous Thromboembolism - etiology</topic><topic>Venous Thromboembolism - prevention & control</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Maya E</creatorcontrib><creatorcontrib>Ortega-Sustache, Yashira M</creatorcontrib><creatorcontrib>Agarwal, Sunita K</creatorcontrib><creatorcontrib>Tepede, Aisha</creatorcontrib><creatorcontrib>Welch, James</creatorcontrib><creatorcontrib>Mandl, Adel</creatorcontrib><creatorcontrib>Bansal, Rashika</creatorcontrib><creatorcontrib>Tirosh, Amit</creatorcontrib><creatorcontrib>Piaggi, Paolo</creatorcontrib><creatorcontrib>Cochran, Craig</creatorcontrib><creatorcontrib>Simonds, William F</creatorcontrib><creatorcontrib>Weinstein, Lee S</creatorcontrib><creatorcontrib>Blau, Jenny E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Maya E</au><au>Ortega-Sustache, Yashira M</au><au>Agarwal, Sunita K</au><au>Tepede, Aisha</au><au>Welch, James</au><au>Mandl, Adel</au><au>Bansal, Rashika</au><au>Tirosh, Amit</au><au>Piaggi, Paolo</au><au>Cochran, Craig</au><au>Simonds, William F</au><au>Weinstein, Lee S</au><au>Blau, Jenny E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>106</volume><issue>2</issue><spage>e460</spage><epage>e468</epage><pages>e460-e468</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Abstract
Background
Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder predisposing the development of multiple functional and nonfunctional neuroendocrine tumors (NETs). Only uncommon MEN1-associated functional NETs such as glucagonomas (<1%) and adenocorticotropic hormone-producing tumors (<5%) are known to be associated with hypercoagulability. It is unknown if patients with MEN1 generally have an increased risk of venous thromboembolism (VTE).
Methods
We queried a prospective natural history study of germline mutation-positive MEN1 patients (n = 286) between 1991 and 2019 for all lifetime events of VTE. The search terms were: DVT, thromb, embol, PE, pulmonary embolism, clot, hematology consult, anticoagulant, coumadin, lovenox, xarelto, warfarin, aspirin, rivaroxaban, and apixaban. Incidence rates were calculated, accounting for age and sex. Comparisons were made to published incidence rates in healthy populations, different types of cancer, and Cushing’s syndrome.
Results
Thirty-six subjects (median age 45 years, range 16–75) experienced a VTE event, yielding a prevalence rate of 12.9%. The age–sex adjusted incidence rate of VTE is 9.11 per 1000 patient-years, with a sex-adjusted lifetime incidence rate of 2.81 per 1000 patient-years. MEN1-associated lifetime incidence rates are ~2-fold higher than the estimated annual incidence rate in the general population and are comparable to the known risk in the setting of various types of cancer. Approximately 80% of patients who had a VTE were diagnosed with pancreatic NETs, of which 24% were insulinomas. Fourteen patients (42%) experienced perioperative VTE events.
Conclusions
MEN1 patients have an increased risk of VTE. Further mechanistic investigation and validation from other MEN1 cohorts are needed to confirm the increased prevalence of VTE in MEN1.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>32756962</pmid><doi>10.1210/clinem/dgaa501</doi><orcidid>https://orcid.org/0000-0003-3794-9634</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Oxford Journals Online |
| subjects | Adolescent Adult Aged Aged, 80 and over Anticoagulants Anticoagulants (Medicine) Anticoagulants - therapeutic use Aspirin Clinical s Development and progression Embolism Enoxaparin Female Gene mutations Genetic aspects Health aspects Hematology History, 20th Century History, 21st Century Humans Incidence Male Middle Aged Multiple endocrine neoplasia Multiple Endocrine Neoplasia Type 1 - complications Multiple Endocrine Neoplasia Type 1 - drug therapy Multiple Endocrine Neoplasia Type 1 - epidemiology Neuroendocrine tumors Pancreatic cancer Patients Population Surveillance Prevalence Pulmonary embolism Retrospective Studies Risk Factors Thromboembolism Tumors Type 2 diabetes United States - epidemiology Venous Thromboembolism - epidemiology Venous Thromboembolism - etiology Venous Thromboembolism - prevention & control Young Adult |
| title | Patients With MEN1 Are at an Increased Risk for Venous Thromboembolism |
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