{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:13:27Z","timestamp":1787022807278,"version":"build-2736575974"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      In recognition of its primary role in pituitary\u2013thyroid feedback, TSH determination has become a key parameter for clinical decision\u2013making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T\n                      <jats:sub>4<\/jats:sub>\n                      ) therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods<\/jats:title>\n                    <jats:p>\n                      We have examined the interrelationships between free triiodothyronine (FT\n                      <jats:sub>3<\/jats:sub>\n                      ), free T\n                      <jats:sub>4<\/jats:sub>\n                      (FT\n                      <jats:sub>4<\/jats:sub>\n                      ) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of\n                      <jats:sc>l<\/jats:sc>\n                      -T\n                      <jats:sub>4<\/jats:sub>\n                      and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT\n                      <jats:sub>3<\/jats:sub>\n                      and FT\n                      <jats:sub>4<\/jats:sub>\n                      between untreated patients and\n                      <jats:sc>l<\/jats:sc>\n                      -T\n                      <jats:sub>4<\/jats:sub>\n                      groups. Total deiodinase activity (G\n                      <jats:sub>D<\/jats:sub>\n                      ) was positively correlated with TSH in untreated subjects. However, G\n                      <jats:sub>D<\/jats:sub>\n                      was significantly altered and the correlation was lost under increasing\n                      <jats:sc>l<\/jats:sc>\n                      -T\n                      <jats:sub>4<\/jats:sub>\n                      doses. Ninety-five per cent confidence intervals for FT\n                      <jats:sub>3<\/jats:sub>\n                      and FT\n                      <jats:sub>4<\/jats:sub>\n                      , when assessed in defined TSH concentration bands, differed significantly for\n                      <jats:sc>l<\/jats:sc>\n                      -T\n                      <jats:sub>4<\/jats:sub>\n                      -treated compared with untreated patients. Higher doses were often needed to restore FT\n                      <jats:sub>3<\/jats:sub>\n                      levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The data reveal disjoints between FT\n                      <jats:sub>4<\/jats:sub>\n                      \u2013TSH feedback and T\n                      <jats:sub>3<\/jats:sub>\n                      production that persist even when sufficient T\n                      <jats:sub>4<\/jats:sub>\n                      apparently restores euthyroidism. T\n                      <jats:sub>4<\/jats:sub>\n                      treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/eje-12-0819","type":"journal-article","created":{"date-parts":[[2012,11,26]],"date-time":"2012-11-26T23:37:39Z","timestamp":1353973059000},"page":"271-280","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":49,"title":["Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?"],"prefix":"10.1093","volume":"168","author":[{"given":"Rudolf","family":"Hoermann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E M","family":"Midgley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Larisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes W","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"issue":"7","key":"2_39932117","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1210\/er.2008-0019","volume":"29","year":"2008","journal-title":"Endocrine Reviews","ISSN":"https:\/\/id.crossref.org\/issn\/0163-769X","issn-type":"print"},{"key":"3_43885011","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.biocel.2011.05.016","volume":"43","year":"2011","journal-title":"INTERNATIONAL JOURNAL OF BIOCHEMISTRY CELL BIOLOGY"},{"key":"4_31246200","first-page":"E715","volume":"258","year":"1990","journal-title":"American Journal of Physiology -- Legacy Content","ISSN":"https:\/\/id.crossref.org\/issn\/0002-9513","issn-type":"print"},{"key":"5_37315670","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1089\/105072503321087015","volume":"13","year":"2003","journal-title":"Thyroid : official journal of the American Thyroid Association","ISSN":"https:\/\/id.crossref.org\/issn\/1050-7256","issn-type":"print"},{"issue":"6","key":"6_21747716","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1210\/jc.2005-1833","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology &amp; 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