{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:30:45Z","timestamp":1785180645190,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,12,19]],"date-time":"2014-12-19T00:00:00Z","timestamp":1418947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005405","name":"Ritsumeikan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> is a sensitive indicator of thyroid function. In subclinical hypothyroidism, however, serum <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> concentrations are elevated despite normal thyroid hormone levels, and macro <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> is one of the causes. This study aimed to clarify the prevalence and nature of macro <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> in patients with subclinical hypothyroidism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We conducted a 2\u2010year cross\u2010sectional observational study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>We included 681 patients with subclinical hypothyroidism and 38 patients with overt hypothyroidism (controls).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Macro <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> was screened by polyethylene glycol (<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>) method and analysed by gel filtration chromatography and bioassays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 681 serum samples, 117 exhibited PEG\u2010precipitable TSH ratios greater than 75% (mean\u00a0+\u00a01\u00b75 SD in controls) and were subjected to gel filtration chromatography. TSH was eluted at a position greater than 100\u00a0kDa in 11 patients with subclinical hypothyroidism (1\u00b762%); these patients were diagnosed with macro TSH. The nature of macro TSH included eight anti\u2010TSH autoantibodies of IgG class, two non\u2010IgG\u2010associated and one human anti\u2010mouse antibody (HAMA). Macro TSH showed low bioactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Macro TSH was heterogeneous, but it is mostly comprised of TSH and anti\u2010TSH autoantibodies. When PEG\u2010precipitable TSH exceeds 90% in serum samples with TSH above 10\u00a0mU\/l, clinicians should strongly suspect the presence of macro TSH and confirm it by gel chromatography. Because macro TSH exhibited low bioactivity, thyroid hormone replacement therapy may not be required in patients with subclinical hypothyroidism due to macro TSH except for those with high serum free TSH levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12643","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T12:19:49Z","timestamp":1415708389000},"page":"923-930","source":"Crossref","is-referenced-by-count":65,"title":["Macro <scp>TSH<\/scp> in patients with subclinical hypothyroidism"],"prefix":"10.1111","volume":"83","author":[{"given":"Naoki","family":"Hattori","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Ritsumeikan University Shiga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Kobe City General Hospital Kobe 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