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The purpose of the current study was to investigate whether insulin sensitivity determines levothyroxine action on thyroid antibody titres and hypothalamic\u2013pituitary\u2013thyroid axis activity in young women with autoimmune subclinical hypothyroidism. The study population consisted of three age\u2010, thyroid antibody\u2010 and thyrotropin\u2010matched groups of women with autoimmune subclinical hypothyroidism: metformin\u2010naive women with insulin resistance (group A, n=31), women receiving metformin treatment because of insulin resistance (group B, n=32), as well as metformin\u2010naive women with normal insulin sensitivity (group C, n=35). Throughout the study, all subjects were treated with levothyroxine. Titres of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of glucose, insulin, lipids, thyrotropin, free thyroid hormones, prolactin, high\u2010sensitivity C\u2010reactive protein (hsCRP) and 25\u2010hydroxyvitamin D were determined at the beginning of the study and 6\u00a0months later. Except for two individuals, all patients completed the study. At baseline, group A differed from groups B and C in circulating levels of glucose, HDL\u2010cholesterol, triglycerides, hsCRP, 25\u2010hydroxyvitamin D and the homeostatic model assessment 1 of insulin resistance (HOMA1\u2010IR). Although levothyroxine reduced thyroid antibody titres, decreased thyrotropin levels and increased free thyroid hormone levels in all studied groups, the effect on antibody titres and thyrotropin levels was more pronounced in groups B and C than in group A. The impact of levothyroxine on thyroid antibody titres correlated with baseline and treatment\u2010induced changes in HOMA1\u2010IR, thyrotropin, hsCRP and 25\u2010hydroxyvitamin D. The results of the current study suggest that the impact of exogenous levothyroxine on thyroid autoimmunity and hypothalamic\u2013pituitary\u2013thyroid axis activity is determined by insulin sensitivity.<\/jats:p>","DOI":"10.1111\/1440-1681.13532","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T16:45:54Z","timestamp":1622565954000},"page":"1215-1223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Insulin resistance attenuates the impact of levothyroxine on thyroid autoimmunity and hypothalamic\u2013pituitary\u2013thyroid axis activity in women with autoimmune subclinical hypothyroidism"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5454-2620","authenticated-orcid":false,"given":"Robert","family":"Krysiak","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia  Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0674-5612","authenticated-orcid":false,"given":"Marcin","family":"Basiak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia  Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogus\u0142aw","family":"Okopie\u0144","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia  Katowice Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3280113d1a"},{"issue":"2","key":"e_1_2_9_3_1","first-page":"205","article-title":"Hashimoto\u2019s thyroiditis","volume":"1","author":"Lorini R","year":"2003","journal-title":"Pediatr Endocrinol 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