{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:54:16Z","timestamp":1792788856770,"version":"4.5.0"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","funder":[{"name":"Clinical Research Center of Child Health Care and Developmental & Behavioral Disorders, Wuhan Children\u2019s Hospital","award":["2025FEYJS009"],"award-info":[{"award-number":["2025FEYJS009"]}],"id":[{"id":"https:\/\/ror.org\/047c53f83","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2026-0397_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether mildly elevated thyroid stimulating hormone (TSH) (&lt;10\u202fmIU\/L) is associated with height in children independently of the growth hormone\u2013insulin-like growth factor 1 (GH\u2013IGF-1) axis, and to assess sex differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0397_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cross-sectional study included 2,447 children aged 2\u201310\u00a0years presenting for slow growth evaluation (2022\u20132024). Multivariable linear regression was used with adjustment for age, sex, and IGF-1 SDS; restricted cubic splines (RCS) were used to assess the dose\u2013response relationship. Sex-stratified and sensitivity analyses were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0397_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mildly elevated TSH was present in 96 (3.92\u202f%) children. Overall, TSH was inversely associated with height SDS (\u03b2=\u22120.03, p&lt;0.001) independently of IGF-1; RCS confirmed linearity. The association was significant in boys (\u03b2=\u22120.03, p=0.002) and borderline in girls. Boys with elevated TSH had lower height SDS (\u03b2=\u22120.18, p=0.025). Sensitivity analyses: the association persisted after excluding low IGF-1 (\u03b2=\u22120.02, p=0.004) but not in children with short stature (height SDS\u00a0\u2264\u22122).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2026-0397_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mildly elevated TSH is independently associated with reduced height in children aged 2\u201310 years, independent of IGF-1. The association was significant in boys and borderline in girls, with no significant interaction. The absence of bone age and parental height data is a major limitation. These findings support growth monitoring rather than routine levothyroxine therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2026-0397","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:55:53Z","timestamp":1791878153000},"source":"Crossref","is-referenced-by-count":0,"title":["Mild TSH elevation is independently associated with height in children"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5884-7577","authenticated-orcid":false,"given":"Mengying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Child Health Care , Clinical Research Center of Child Health Care and Developmental & Behavioral Disorders, Institute of Maternal and Child Health, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College, Huazhong University of Science & Technology , Wuhan City , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5976-4355","authenticated-orcid":false,"given":"Mengqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Child Health Care , Clinical Research Center of Child Health Care and Developmental & Behavioral Disorders, Institute of Maternal and Child Health, Wuhan Children\u2019s Hospital (Wuhan Maternal and Child Health Care Hospital), Tongji Medical College, Huazhong University of Science & Technology , Wuhan City , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"2026101307554630276_j_jpem-2026-0397_ref_001","doi-asserted-by":"crossref","unstructured":"Cammisa, I, Rigante, D, Cipolla, C. Growth outcomes and final height in children with acquired hypothyroidism: a systematic review. Children 2024;11:1510. https:\/\/doi.org\/10.3390\/children11121510.","DOI":"10.3390\/children11121510"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_002","doi-asserted-by":"crossref","unstructured":"Salerno, M, Improda, N, Capalbo, D. Management of endocrine disease subclinical hypothyroidism in children. Eur J Endocrinol 2020;183:R13\u201328. https:\/\/doi.org\/10.1530\/eje-20-0051.","DOI":"10.1530\/EJE-20-0051"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_003","doi-asserted-by":"crossref","unstructured":"Hirtz, R, Keesen, A, H\u00f6lling, H, Hauffa, BP, Hinney, A, Grasemann, C. No effect of thyroid dysfunction and autoimmunity on health-related quality of life and mental health in children and adolescents: results from a nationwide cross-sectional study. 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Thyroid Res 2011;4:6. https:\/\/doi.org\/10.1186\/1756-6614-4-6.","DOI":"10.1186\/1756-6614-4-6"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_019","doi-asserted-by":"crossref","unstructured":"Nesi-Fran\u00e7a, S, Silveira, RB, Rojas Ramos, JCR, Cardoso-Demartini, AA, Lima Cat, MN, de Carvalho, JAR, et al.. Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil. J\u00a0Pediatr Endocrinol Metab 2020;33:1449\u2013555. https:\/\/doi.org\/10.1515\/jpem-2020-0285.","DOI":"10.1515\/jpem-2020-0285"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_020","doi-asserted-by":"crossref","unstructured":"Julian, C, Lui, JB. Effects of glucocorticoids on the growth plate. Endocr Dev 2011;20:187\u201393.","DOI":"10.1159\/000321244"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_021","doi-asserted-by":"crossref","unstructured":"Zhang, J, Luo, Z, Zhang, J, Zhang, R, Liu, X, Wang, J, et al.. 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Horm Res Paediatr 2011;76:1\u20139. https:\/\/doi.org\/10.1159\/000329372.","DOI":"10.1159\/000329372"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_026","doi-asserted-by":"crossref","unstructured":"Jonklaas, J, Bianco, AC, Bauer, AJ, Burman, KD, Cappola, AR, Celi, FS, et al.. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014;24:1670\u2013751. https:\/\/doi.org\/10.1089\/thy.2014.0028.","DOI":"10.1089\/thy.2014.0028"},{"key":"2026101307554630276_j_jpem-2026-0397_ref_027","doi-asserted-by":"crossref","unstructured":"Gannag\u00e9-Yared, M-H, Balech, N, Farah, V, Antar, M, Saliba, R, Chahine, E. Pediatric TSH reference intervals and prevalence of high thyroid antibodies in the Lebanese population. 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