{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:20:26Z","timestamp":1791930026517,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":190,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Case Reports in Pediatrics"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>The primary manifestations of chronic hypothyroidism in children include growth arrest, delayed skeletal maturity, and delayed puberty. In 1960, Van Wyk and Grumbach reported three girls with hypothyroidism and a combination of incomplete isosexual precocious puberty (early breast development, menstruation, and absence of pubic hair), galactorrhea, delayed bone age, and pituitary enlargement. All abnormalities regressed after appropriate thyroid hormone replacement therapy. Over the years, an increasing number of reported cases has allowed for a more precise understanding of the clinical, biochemical, and radiological phenotypes of the Van Wyk\u2013Grumbach syndrome (VWGS). These varying clinical manifestations are thought to result from a unique pathophysiological process where the thyroid\u2010stimulating hormone (TSH) is a key element. We describe the cases of two patients (a boy and a girl) with severe autoimmune thyroiditis and VWGS. The clinical, biochemical, and radiological imaging characteristics were similar in both patients and included growth failure, absence of clinical goiter, markedly elevated TSH concentrations &gt;100\u2009mIU\/L, undetectable free thyroxine levels, \u201cnormal\u201d thyroglobulin levels, high follicle\u2010stimulating hormone (FSH) and prolactin levels, prepubertal levels of luteinizing hormone (LH), delayed bone age, and hyperplasia of the pituitary gland. The two patients displayed differences, especially in the absence of clinical pubertal development, moderate anemia, abnormal renal function, and moderate goiter detected via ultrasonography (in the female patient). Thyroxine replacement therapy reversed the VWGS phenotype and hypothyroidism, with satisfactory growth velocity, strictly normal thyroid function, and normal pituitary size detected via magnetic resonance imaging at the 6\u2010month follow\u2010up visit.<\/jats:p>","DOI":"10.1155\/2024\/8919177","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T12:36:00Z","timestamp":1720528560000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Severe Acquired Hypothyroidism and Van Wyk\u2013Grumbach Syndrome in Two Children"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7197-3078","authenticated-orcid":false,"given":"Corina Ramona","family":"Nicolescu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Bazus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Stephan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0370"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.4274\/Jcrpe.855"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(60)80250-8"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12994"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/000992288102001102"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej11-0096"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.104093"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.10.050"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/08035259950168973"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2021.03.008"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-002-1033-9"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0167"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-024-01641-w"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.1.276"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.1.11"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-3574"},{"key":"e_1_2_11_17_2","article-title":"Primary hypothyroidism presenting as bilateral ovarian torsion","volume":"55","author":"Agarwala S.","year":"2018","journal-title":"Indian Pediatrics"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1580"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2086"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpag.2010.08.003"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21920"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2007.01616.x"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0041"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0403"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.09.003"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000489264"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-108-4-1333"},{"key":"e_1_2_11_28_2","article-title":"Trait\u00e9 du Go\u00eetre et du Cr\u00e9tinisme","volume":"1852","author":"Niepce E. 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