{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:47:07Z","timestamp":1787021227126,"version":"build-2736575974"},"reference-count":36,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK102659"],"award-info":[{"award-number":["DK102659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5U54NS078059"],"award-info":[{"award-number":["5U54NS078059"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Endocrine disorders are common in individuals with mitochondrial disease. To develop evidence-based screening practices in this high-risk population, updated age-stratified estimates of the prevalence of endocrine conditions are needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To measure the point prevalence of selected endocrine disorders in individuals with mitochondrial disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Patients<\/jats:title>\n                    <jats:p>The North American Mitochondrial Disease Consortium Patient Registry is a large, prospective, physician-curated cohort study of individuals with mitochondrial disease. Participants (n = 404) are of any age, with a diagnosis of primary mitochondrial disease confirmed by molecular genetic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures<\/jats:title>\n                    <jats:p>Age-specific prevalence of diabetes mellitus (DM), abnormal growth and sexual maturation (AGSM), hypoparathyroidism, and hypothyroidism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The majority of our sample was pediatric (&amp;lt;18 years; 60.1%), female (56.9%), and white (85.9%). DM affected 2% of participants aged &amp;lt;18 years [95% confidence interval (CI): 0.4% to 5.7%] and 24.4% of adult participants (95% CI: 18.6% to 30.9%). DM prevalence was highest in individuals with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes syndrome (MELAS; 31.9%, of whom 86.2% had the m.3243A&amp;gt;G mutation). DM occurred more often with mitochondrial DNA defects (point mutations and\/or deletions) than with nuclear DNA mutations (23.3% vs 3.7%, respectively; P &amp;lt; 0.001). Other prevalence estimates were 44.1% (95% CI: 38.8% to 49.6%) for AGSM; 0.3% (95% CI: 0% to 1.6%) for hypoparathyroidism; and 6.3% (95% CI: 4% to 9.3%) for hypothyroidism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DM and AGSM are highly prevalent in primary mitochondrial disease. Certain clinical mitochondrial syndromes (MELAS and Kearns-Sayre\/Pearson syndrome spectrum disorders) demonstrated a higher burden of endocrinopathies. Clinical screening practices should reflect the substantial prevalence of endocrine disorders in mitochondrial disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/js.2017-00434","type":"journal-article","created":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T14:00:30Z","timestamp":1519048830000},"page":"361-373","source":"Crossref","is-referenced-by-count":54,"title":["Endocrine Disorders in Primary Mitochondrial Disease"],"prefix":"10.1210","volume":"2","author":[{"given":"Iman S","family":"Al-Gadi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, California"},{"name":"Department of Pediatrics, University of California San Diego, La Jolla, California"},{"name":"Division of Neurosciences, Rady Children\u2019s Hospital, San Diego, California"},{"name":"North American Mitochondrial Disease Consortium, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marni J","family":"Falk","sequence":"additional","affiliation":[{"name":"North American Mitochondrial Disease Consortium, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"},{"name":"Children\u2019s Hospital of Philadelphia Mitochondrial Medicine Frontiers Program, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Goldstein","sequence":"additional","affiliation":[{"name":"North American Mitochondrial Disease Consortium, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Division of Human Genetics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana E","family":"McCormack","sequence":"additional","affiliation":[{"name":"North American Mitochondrial Disease Consortium, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"},{"name":"Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania"},{"name":"Children\u2019s Hospital of Philadelphia Mitochondrial Medicine Frontiers Program, Philadelphia, Pennsylvania"},{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2018,2,19]]},"reference":[{"issue":"1-2","key":"2020071623540750400_B1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2013.06.004","article-title":"Endocrine disorders in mitochondrial disease","volume":"379","author":"Schaefer","year":"2013","journal-title":"Mol Cell Endocrinol"},{"key":"2020071623540750400_B2","first-page":"1993","volume-title":"GeneReviews\u00ae","author":"Chinnery"},{"issue":"1","key":"2020071623540750400_B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/pedi.12223","article-title":"The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes","volume":"16","author":"Karaa","year":"2015","journal-title":"Pediatr Diabetes"},{"key":"2020071623540750400_B4","doi-asserted-by":"crossref","first-page":"16080","DOI":"10.1038\/nrdp.2016.80","article-title":"Mitochondrial diseases","volume":"2","author":"Gorman","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"2","key":"2020071623540750400_B5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrendo.2016.151","article-title":"Mitochondrial disease and endocrine dysfunction","volume":"13","author":"Chow","year":"2017","journal-title":"Nat Rev Endocrinol"},{"issue":"10","key":"2020071623540750400_B6","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00125-007-0779-9","article-title":"Prevalence and progression of diabetes in mitochondrial disease","volume":"50","author":"Whittaker","year":"2007","journal-title":"Diabetologia"},{"issue":"11","key":"2020071623540750400_B7","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1177\/088307380001501108","article-title":"Endocrine disorders in two sisters affected by MELAS syndrome","volume":"15","author":"Balestri","year":"2000","journal-title":"J Child Neurol"},{"issue":"3","key":"2020071623540750400_B8","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1651-2227.2008.01148.x","article-title":"Abnormal growth in mitochondrial disease","volume":"98","author":"Wolny","year":"2009","journal-title":"Acta Paediatr"},{"issue":"9-10","key":"2020071623540750400_B9","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1515\/jpem-2014-0315","article-title":"Growth hormone deficiency in a patient with mitochondrial disease","volume":"28","author":"Rocha","year":"2015","journal-title":"J Pediatr Endocrinol Metab"},{"issue":"1-2","key":"2020071623540750400_B10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ymgme.2013.07.011","article-title":"Mitochondrial respiratory chain disease discrimination by retrospective cohort analysis of blood metabolites","volume":"110","author":"Clarke","year":"2013","journal-title":"Mol Genet Metab"},{"key":"2020071623540750400_B11","unstructured":"North American Mitochondrial Disease Consortium (NAMDC) Patient Registry and Biorepository\n          . NAMDC website. Available at:https:\/\/www.rarediseasesnetwork.org\/cms\/namdc\/. Accessed 16 October 2016."},{"key":"2020071623540750400_B12","unstructured":"ClinicalTrials.gov. North American Mitochondrial Disease Consortium (NAMDC) Patient Registry and Biorepository. Updated 6 May 2015. Available at: www.clinicaltrials.gov\/ct2\/show\/NCT01694940. Accessed 16 October 2016. NLM Identifier: NCT01694940."},{"key":"2020071623540750400_B13","unstructured":"The United Mitochondrial Disease Foundation. NAMDC. Available at:\n          www.umdf.org\/namdc\/. Accessed 16 October 2016."},{"key":"2020071623540750400_B14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.biocel.2013.12.011","article-title":"Mitochondria: impaired mitochondrial translation in human disease","volume":"48","author":"Boczonadi","year":"2014","journal-title":"Int J Biochem Cell Biol"},{"key":"2020071623540750400_B15","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-3722-2","volume-title":"Mitochondrial Disorders Caused by Nuclear Genes","author":"Wong","year":"2013"},{"issue":"9","key":"2020071623540750400_B16","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1172\/JCI19435","article-title":"Mitochondrial DNA mutations in human colonic crypt stem cells","volume":"112","author":"Taylor","year":"2003","journal-title":"J Clin Invest"},{"key":"2020071623540750400_B17","unstructured":"MITOMAP: a human mitochondrial genome database. 2016. Available at: www.mitomap.org. Accessed 5 October 2016."},{"issue":"6","key":"2020071623540750400_B18","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/humu.22974","article-title":"MSeqDR: a centralized knowledge repository and bioinformatics web resource to facilitate genomic investigations in mitochondrial disease","volume":"37","author":"Shen","year":"2016","journal-title":"Hum Mutat"},{"key":"2020071623540750400_B19","unstructured":"National Center for Biotechnology Information. Gene. Bethesda, MD: National Center for Biotechnology Information; 2005\u20132016. Available at: www.ncbi.nlm.nih.gov\/gene\/. Accessed 5 October 2016."},{"key":"2020071623540750400_B20","unstructured":"National Center for Biotechnology Information.\n          \n            ClinVar\n          . Bethesda, MD: National Center for Biotechnology Information; 2012\u20132016. Available at: www.ncbi.nlm.nih.gov\/clinvar\/. Accessed 5 October 2016."},{"key":"2020071623540750400_B21","unstructured":"Online Mendelian Inheritance in Man\n          . OMIM. Baltimore, MD: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University; 2016. Available at: http:\/\/omim.org\/. Accessed 5 October 2016."},{"key":"2020071623540750400_B22","unstructured":"NAMDC Clinical Manifestations of Mitochondrial Diseases. Mito-PhenoTips, human phenotype ontology. MSeqDR: The mitochondrial disease sequence data resource consortium. 2013-2017. Available at: https:\/\/mseqdr.org\/hpo_namdc_review.php. Accessed 5 December 2017."},{"issue":"1","key":"2020071623540750400_B23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1365-2265.1992.tb02289.x","article-title":"Endocrine dysfunction in Kearns-Sayre syndrome","volume":"37","author":"Harvey","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"17","key":"2020071623540750400_B24","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1001\/jama.2014.3201","article-title":"Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009","volume":"311","author":"Dabelea","year":"2014","journal-title":"JAMA"},{"issue":"10","key":"2020071623540750400_B25","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1001\/jama.2015.10029","article-title":"Prevalence of and trends in diabetes among adults in the united states, 1988-2012","volume":"314","author":"Menke","year":"2015","journal-title":"JAMA"},{"issue":"4","key":"2020071623540750400_B26","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1089\/ars.2009.2531","article-title":"Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities","volume":"12","author":"Sivitz","year":"2010","journal-title":"Antioxid Redox Signal"},{"issue":"3","key":"2020071623540750400_B27","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4274\/jcrpe.2288","article-title":"Endocrine dysfunctions in patients with inherited metabolic diseases","volume":"8","author":"Erd\u00f6l","year":"2016","journal-title":"J Clin Res Pediatr Endocrinol"},{"issue":"5","key":"2020071623540750400_B28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.pediatrneurol.2007.12.001","article-title":"Presentation and diagnosis of mitochondrial disorders in children","volume":"38","author":"Koenig","year":"2008","journal-title":"Pediatr Neurol"},{"issue":"8","key":"2020071623540750400_B29","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.15252\/emmm.201707604","article-title":"GDF15 is a heart-derived hormone that regulates body growth","volume":"9","author":"Wang","year":"2017","journal-title":"EMBO Mol Med"},{"issue":"2","key":"2020071623540750400_B30","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1210\/jcem.87.2.8182","article-title":"Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)","volume":"87","author":"Hollowell","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2020071623540750400_B31","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ajhg.2015.12.008","article-title":"Recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic TANGO2 mutations","volume":"98","author":"Lalani","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"2","key":"2020071623540750400_B32","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.ajhg.2015.12.009","article-title":"Bi-allelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy","volume":"98","author":"Kremer","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2020071623540750400_B33","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0002-9343(91)90153-O","article-title":"Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults","volume":"91","author":"Rallison","year":"1991","journal-title":"Am J Med"},{"issue":"3","key":"2020071623540750400_B34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1136\/adc.83.3.207","article-title":"Prevalence and aetiology of hypothyroidism in the young","volume":"83","author":"Hunter","year":"2000","journal-title":"Arch Dis Child"},{"issue":"1","key":"2020071623540750400_B35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1001\/jama.2014.7184","article-title":"Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies","volume":"312","author":"Taylor","year":"2014","journal-title":"JAMA"},{"issue":"2","key":"2020071623540750400_B36","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s13311-012-0174-1","article-title":"Molecular genetic testing for mitochondrial disease: from one generation to the next","volume":"10","author":"McCormick","year":"2013","journal-title":"Neurotherapeutics"}],"container-title":["Journal of the Endocrine Society"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/2\/4\/361\/24461253\/js.2017-00434.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jes\/article-pdf\/2\/4\/361\/24461253\/js.2017-00434.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T09:43:09Z","timestamp":1594978989000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jes\/article\/2\/4\/361\/4874252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,19]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/js.2017-00434","relation":{},"ISSN":["2472-1972"],"issn-type":[{"value":"2472-1972","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,4]]},"published":{"date-parts":[[2018,2,19]]}}}