{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:04:49Z","timestamp":1758845089193,"version":"3.44.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Hypothalamic hamartoma (HH) is an important cause of central precocious puberty (CPP) in young children but is rarely described in infants. Interpretation of laboratory data could be difficult because gonadotropins and estradiol levels often overlap in healthy infants with mini-puberty and children with HH. Extremely elevated estradiol levels are mostly described in girls with peripheral precocious puberty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We present a 5.5-month-old girl with vaginal bleeding, significantly elevated estradiol levels (up to 3,974 pmol\/L), elevated gonadotropins, and right ovarian cyst. Laboratory and radiologic evaluation revealed the HH as a cause of CPP. Immediately after the start of treatment with depot gonadotropin-releasing hormone analogue, age-appropriate undetectable levels of estradiol were achieved, with ovarian cyst regression and cessation of pubertal changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>If observed in the period of mini-puberty, high levels of estradiol accompanied by unsuppressed gonadotropins can complicate the discrimination between central and peripheral precocious puberty. This challenge emerges particularly due to the absence of the negative feedback mechanism in children with HH. This is the first report identifying extremely high estradiol levels as part of the phenotypic spectrum of HH in infants.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1598734","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:17:40Z","timestamp":1758773860000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Exaggerated estradiol secretion in an infant with hypothalamic hamartoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Maja","family":"Vinkovic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duje","family":"Braovac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Dumic Kubat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Jovanovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Banovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevena","family":"Krnic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.ecl.2024.01.002","article-title":"Females with breast development before three years of age","volume":"53","author":"Kaplowitz","year":"2024","journal-title":"Endocrinol Metab Clin North Am"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00410","article-title":"Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life","volume":"9","author":"Lanciotti","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14241","article-title":"Neuropsychiatric profile of paediatric hypothalamic hamartoma: systematic review and case series","volume":"61","author":"Corbet Burcher","year":"2019","journal-title":"Dev Med Child Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106076","article-title":"Hypothalamic hamartomas: A comprehensive review of the literature - Part 1: Neurobiological features, clinical presentations and advancements in diagnostic tools","volume":"197","author":"Alomari","year":"2020","journal-title":"Clin Neurol Neurosurg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgz196","article-title":"Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS\/MS","volume":"105","author":"Frederiksen","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12902-022-00956-1","article-title":"Ovarian steroid cell tumor causing isosexual pseudoprecocious puberty in a young girl: an instructive case and literature review","volume":"22","author":"Chu","year":"2022","journal-title":"BMC Endocr Disord"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2022-0179","article-title":"Exaggerated mini-puberty in a preterm girl: a case report and review of literature","volume":"35","author":"Lattuada","year":"2022","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1159\/000023189","article-title":"An association of hypothalamic hamartoma, central precocious puberty and juvenile granulosa cell tumour in early childhood","volume":"49","author":"Feilberg J\u00f8rgensen","year":"1998","journal-title":"Horm Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnae003","article-title":"Mini-puberty, physiological and disordered: consequences, and potential for therapeutic replacement","volume":"45","author":"Rohayem","year":"2024","journal-title":"Endocr Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e20153561","DOI":"10.1542\/peds.2015-3561","article-title":"Transient postnatal gonadal activation and growth velocity in infancy","volume":"138","author":"Kiviranta","year":"2016","journal-title":"Pediatrics"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2013-0166","article-title":"Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report","volume":"27","author":"Altuntas","year":"2014","journal-title":"J Pediatr Endocrinol Metab"},{"key":"B12","doi-asserted-by":"publisher","first-page":"695","DOI":"10.17219\/acem\/25212","article-title":"Ovarian hyperstimulation caused by gonadotroph pituitary adenoma\u2013review","volume":"24","author":"Halupczok","year":"2015","journal-title":"Adv Clin Exp Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-1783","article-title":"Consensus statement on the use of gonadotropin-releasing hormone analogs in children","volume":"123","author":"Carel","year":"2009","journal-title":"Pediatrics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.893139","article-title":"Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty","volume":"21","author":"Bourayou","year":"2015","journal-title":"Med Sci Monit"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0515-y","article-title":"Central precocious puberty due to hypothalamic hamartoma in a 7-month-old infant girl","volume":"167","author":"Rousso","year":"2008","journal-title":"Eur J Pediatr"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1598734\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:17:41Z","timestamp":1758773861000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1598734\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":15,"alternative-id":["10.3389\/fendo.2025.1598734"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1598734","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]},"article-number":"1598734"}}