{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:54:57Z","timestamp":1781564097088,"version":"3.54.5"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of\n                        Science","doi-asserted-by":"crossref","award":["JP23H03759, JP25K02899"],"award-info":[{"award-number":["JP23H03759, JP25K02899"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyrotoxicosis is associated with heightened adrenergic activity, arrhythmogenic\n                    susceptibility, and procoagulant alterations; yet, its contribution to sudden\n                    death outside overt thyroid storm remains incompletely understood. We\n                    retrospectively screened 975 consecutive autopsies and identified 7 cases with\n                    biochemical evidence of thyroid hormone excess defined by elevated free T3\n                    and\/or free T4 levels. Clinical background, medication exposure, thyroid-related\n                    biomarkers, including thyroglobulin, thyroid autoantibodies, and interleukin-6,\n                    together with detailed histopathological examination of the thyroid gland and\n                    the cardiovascular system, were integrated to assess the potential contribution\n                    of thyroid hormone excess to the fatal outcome. Targeted genetic analysis was\n                    additionally performed in selected cases. Two cases fulfilled\n                    clinicopathological criteria for thyroid storm and showed markedly elevated IL-6\n                    concentrations, suggesting severe systemic decompensation. In the remaining\n                    cases, death was attributed to structural cardiovascular or cerebrovascular\n                    pathology, including intracerebral hemorrhage, acute coronary thrombosis with\n                    plaque rupture, hydrocephalus, or presumed arrhythmic mechanisms. Biochemical\n                    thyrotoxicosis was observed even in the absence of thyroid-stimulating hormone\n                    suppression, and exogenous or treatment-associated thyrotoxicosis was sometimes\n                    accompanied by thyroid atrophy rather than hyperplasia. These findings indicate\n                    that thyroid hormone excess detected at autopsy represents a clinicopathological\n                    spectrum ranging from primary thyroid-driven death to contexts in which\n                    thyrotoxicosis functions as a physiological modifier that lowers the threshold\n                    for fatal cardiovascular events. Integrative interpretation of biochemical,\n                    pathological, and clinical findings may improve the understanding of thyroid\n                    hormone\u2013mediated vulnerability in sudden death.<\/jats:p>","DOI":"10.1055\/a-2851-8963","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T22:59:41Z","timestamp":1776466781000},"page":"221-228","source":"Crossref","is-referenced-by-count":0,"title":["Thyroid Hormone Excess in Sudden Death: A Clinicopathological\n                    Spectrum in an Autopsy Study"],"prefix":"10.1055","volume":"58","author":[{"given":"Yukiko","family":"Hata","sequence":"additional","affiliation":[{"name":"Legal Medicine, University of Toyama, Toyama,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Saito","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Toyama, Toyama,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Hirono","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Toyama, Toyama,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shojiro","family":"Ichimata","sequence":"additional","affiliation":[{"name":"Legal Medicine, University of Toyama, Toyama,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-1768","authenticated-orcid":false,"given":"Naoki","family":"Nishida","sequence":"additional","affiliation":[{"name":"Legal Medicine, University of Toyama, Toyama,\n                    Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1161\/CIRCULATIONAHA.106.678326","article-title":"Thyroid disease and the heart","volume":"116","author":"I Klein","year":"2007","journal-title":"Circulation"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e7895","DOI":"10.1136\/bmj.e7895","article-title":"The spectrum of thyroid disease and risk of new onset atrial fibrillation: A\n                    large population cohort study","volume":"345","author":"C Selmer","year":"2012","journal-title":"BMJ"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1089\/thy.2017.0243","article-title":"Thyroid storm: A Japanese perspective","volume":"28","author":"T Akamizu","year":"2018","journal-title":"Thyroid"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/jth.13970","article-title":"The influence of thyroid function on the coagulation system and its clinical\n                    consequences","volume":"16","author":"LP B Elbers","year":"2018","journal-title":"J Thromb Haemost"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"233","DOI":"10.4323\/rjlm.2015.233","article-title":"Sudden thyroid death. A systematic review","volume":"23","author":"S Hostiuc","year":"2015","journal-title":"Rom J Leg Med"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1111\/1556-4029.12247","article-title":"Sudden unexpected death due to Graves\u2019 disease during a physical\n                    altercation","volume":"58","author":"D Wei","year":"2013","journal-title":"J Forensic Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1253\/circj.CJ-22-0397","article-title":"Pathological and comprehensive genetic investigation of autopsy cases of\n                    idiopathic bradyarrhythmia","volume":"87","author":"Y Hata","year":"2023","journal-title":"Circ J"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.1002\/alz.14037","article-title":"Prevalence and clinicopathological features of primary age-related tauopathy\n                    (PART): A large forensic autopsy study","volume":"20","author":"K Yoshida","year":"2024","journal-title":"Alzheimers Dement"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fendo.2016.00057","article-title":"Calculated parameters of thyroid homeostasis: Emerging tools for differential\n                    diagnosis and clinical research","volume":"7","author":"J W Dietrich","year":"2016","journal-title":"Front Endocrinol"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"5380","DOI":"10.1007\/s00415-023-11850-8","article-title":"Comprehensive pathological and genetic investigation of three young adult\n                    myotonic dystrophy type 1 patients with sudden unexpected death","volume":"270","author":"Y Hata","year":"2023","journal-title":"J Neurol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint\n                    consensus recommendation of the American College of Medical Genetics and\n                    Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1365-2265.2011.04023.x","article-title":"What should be done when thyroid function tests do not make sense?","volume":"74","author":"M Gurnell","year":"2011","journal-title":"Clin Endocrinol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1210\/er.2018-00119","article-title":"Interferences with thyroid function immunoassays: Clinical implications and\n                    detection algorithm","volume":"39","author":"J Favresse","year":"2018","journal-title":"Endocr Rev"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1210\/clinem\/dgad681","article-title":"Approach to the patient with raised thyroid hormones and nonsuppressed TSH","volume":"109","author":"C Moran","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s42000-020-00180-3","article-title":"Hyperthyroxinemia with a non-suppressed TSH: How to confidently reach a\n                    diagnosis in this clinical conundrum","volume":"19","author":"J G Timmons","year":"2020","journal-title":"Hormones"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1089\/thy.2009.0205","article-title":"Thyroid function in Japanese adults as assessed by a general health checkup\n                    system in relation with thyroid-related antibodies and other clinical\n                    parameters","volume":"19","author":"K Kasagi","year":"2009","journal-title":"Thyroid"},{"issue":"06","key":"ref17","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1136\/jcp.40.6.631","article-title":"Importance of postmortem changes in measurements of thyroid function in studies\n                    of sudden infant death syndrome","volume":"40","author":"ML Wellby","year":"1987","journal-title":"J Clin Pathol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"104438","DOI":"10.1016\/j.psyneuen.2019.104438","article-title":"Effects of acute psychosocial stress on the hypothalamic-pituitary-thyroid (HPT)\n                    axis in healthy women","volume":"110","author":"S Fischer","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fendo.2017.00163","article-title":"Thyroid allostasis-adaptive responses of thyrotropic feedback control to\n                    conditions of strain, stress, and developmental programming","volume":"8","author":"A Chatzitomaris","year":"2017","journal-title":"Front Endocrinol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e937957","DOI":"10.12659\/MSM.937957","article-title":"Thyroid-stimulating hormone as a biomarker for stress after thyroid surgery: A\n                    prospective cohort study","volume":"28","author":"H Hong","year":"2022","journal-title":"Med Sci Monit"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1172\/JCI29812","article-title":"Deiodinases: Implications of the local control of thyroid hormone action","volume":"116","author":"A C Bianco","year":"2006","journal-title":"J Clin Invest"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1172\/JCI26031","article-title":"Thyrotropin receptor-associated diseases: From adenomata to Graves disease","volume":"115","author":"T F Davies","year":"2005","journal-title":"J Clin Invest"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1172\/JCI119497","article-title":"Familial congenital hypothyroidism due to inactivating mutation of the\n                    thyrotropin receptor causing profound hypoplasia of the thyroid gland","volume":"99","author":"M J Abramowicz","year":"1997","journal-title":"J Clin Invest"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1089\/thy.2016.0469","article-title":"DUOX2 gene mutation manifesting as resistance to thyrotropin phenotype","volume":"27","author":"P Srichomkwun","year":"2017","journal-title":"Thyroid"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1089\/thy.2018.0587","article-title":"DUOX2\/DUOXA2 mutations frequently cause congenital hypothyroidism that evades\n                    detection on newborn screening in the United Kingdom","volume":"29","author":"C Peters","year":"2019","journal-title":"Thyroid"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1297\/cpe.2023-0059","article-title":"Concurrent THRB and DUOX2 variants in a patient detected via newborn screening\n                    for congenital hypothyroidism: A case of resistance to thyroid hormone","volume":"33","author":"M Hatano","year":"2024","journal-title":"Clin Pediatr Endocrinol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1056\/NEJM198208123070705","article-title":"Low serum thyroglobulin as a clue to the diagnosis of thyrotoxicosis\n                    factitia","volume":"307","author":"S Mariotti","year":"1982","journal-title":"N Engl J Med"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ando.2023.03.008","article-title":"Factitious thyrotoxicosis and thyroid hormone misuse or abuse","volume":"84","author":"L Persani","year":"2023","journal-title":"Ann Endocrinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1515\/dx-2019-0015","article-title":"Factitious thyrotoxicosis: How to find it","volume":"7","author":"P Vorasart","year":"2020","journal-title":"Diagnosis (Berlin)"},{"key":"ref30","first-page":"100196","article-title":"Chemokines in hyperthyroidism","volume":"16","author":"S M Ferrari","year":"2019","journal-title":"J Clin Transl Endocrinol"},{"key":"ref31","first-page":"2976","article-title":"Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor\n                    in patients with Graves\u2019 disease","volume":"81","author":"M Salvi","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"ref32","first-page":"435","article-title":"Serum cytokines in thyrotoxicosis","volume":"84","author":"A Siddiqi","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12902-024-01680-8","article-title":"Generation of a mouse model of thyroid storm and preliminary investigation of\n                    the therapeutic effects of ghrelin","volume":"24","author":"C Kurimoto","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1160\/TH12-07-0496","article-title":"The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic\n                    factors: A systematic review and meta-analysis","volume":"108","author":"D J Stuijver","year":"2012","journal-title":"Thromb Haemost"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1210\/jc.2007-0199","article-title":"Clinical review: Thyroid dysfunction and effects on coagulation and\n                    fibrinolysis: A systematic review","volume":"92","author":"A Squizzato","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1161\/CIRCULATIONAHA.115.020789","article-title":"Thyroid function and sudden cardiac death: A prospective population-based cohort\n                    study","volume":"134","author":"L Chaker","year":"2016","journal-title":"Circulation"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"942971","DOI":"10.3389\/fcvm.2022.942971","article-title":"Minor perturbations of thyroid homeostasis and major cardiovascular\n                    endpoints\u2014physiological mechanisms and clinical evidence","volume":"9","author":"P M\u00fcller","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/joim.13189","article-title":"Abnormal thyroid function is common in takotsubo syndrome and depends on two\n                    distinct mechanisms: Results of a multicentre observational study","volume":"289","author":"A Aweimer","year":"2021","journal-title":"J Intern Med"},{"key":"ref39","volume-title":"Hyperthyroidism in aging. In: Feingold KR, Adler RA, Ahmed SF, et al., editors.\n                    Endotext [Internet]","author":"M H Samuels","year":"2000"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e2848","DOI":"10.1097\/MD.0000000000002848","article-title":"Factors associated with mortality of thyroid storm: Analysis using a national\n                    inpatient database in Japan","volume":"95","author":"Y Ono","year":"2016","journal-title":"Medicine"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1210\/clinem\/dgae124","article-title":"Prospective multicenter registry-based study on thyroid storm: The guidelines\n                    for management from Japan are useful","volume":"110","author":"Y Furukawa","year":"2024","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2851-8963.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T22:35:25Z","timestamp":1781562925000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2851-8963"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":41,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2026,6,15]]},"published-print":{"date-parts":[[2026,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2851-8963","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]}}}