{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:06:48Z","timestamp":1778033208080,"version":"3.51.4"},"reference-count":17,"publisher":"Walter de Gruyter GmbH","issue":"5","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2024-0602_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Familial Male-Limited Precocious Puberty (FMPP) is a rare autosomal-dominant genetic condition with sexual dimorphism. We aim to summarize the clinical characteristics of FMPP patients and emphasize the use of a therapeutic regimen involving letrozole, spironolactone, and GnRHa, to augment clinician\u2019s understanding of the disease, thus enhancing patient care.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0602_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively analyzed the clinical data of 10 FMPP patients and conducted follow-up assessments of adult height in six patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0602_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Out of the 10 FMPP cases, five had the <jats:italic>LHCGR M398T<\/jats:italic> mutation, three exhibited the <jats:italic>LHCGR A564G<\/jats:italic> mutation, and two had the <jats:italic>LHCGR T577I<\/jats:italic> mutation. All patients initially presented with symptoms like penile enlargement, frequent erections, and rapid growth. Their median age at diagnosis was 4.67 years with bone age being 9 years. Four patients were untreated with a median adult height of 162\u202fcm. Six patients underwent treatment between ages 3.58 and 5.5 years noting decreased frequency of erections, slower growth rate, and delayed bone age progression. Secondary Central Precocious Puberty (CPP) developed between ages 5 and 6.5 years in all cases, necessitating additional GnRHa treatment. Two treated cases reached an adult height of 176\u202fcm and 173\u202fcm, respectively, without any significant adverse effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0602_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The most prevalent genotype among FMPP patients in this study was the <jats:italic>LHCGR M398T<\/jats:italic> mutation. Early intervention using a regimen including letrozole and spironolactone, and later GnRHa, appears beneficial in limiting physical signs and improving adult height without major side effects. However, the longer-term effects on fertility require further investigation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2024-0602","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:20:40Z","timestamp":1741728040000},"page":"488-493","source":"Crossref","is-referenced-by-count":2,"title":["The clinical characteristics of 10 cases and adult height of six cases of rare familial male-limited precocious puberty"],"prefix":"10.1515","volume":"38","author":[{"given":"Dandan","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"},{"name":"Department of Pediatrics , The First People\u2019s Hospital of Hangzhou Lin An District , Hangzhou , Zhejiang , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huamei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rujiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuli","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , The First Affiliated Hospital, Sun Yat-sen University , Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"2025082013043672006_j_jpem-2024-0602_ref_001","doi-asserted-by":"crossref","unstructured":"Atay, Z, Yesilkaya, E, Erdeve, SS, Turan, S, Akin, L, Eren, E, et al.. The etiology and clinical features of non-CAH gonadotropin-independent precocious puberty: a multicenter study. J Clin Endocrinol Metab 2016;101:1980\u20138. https:\/\/doi.org\/10.1210\/jc.2015-3500.","DOI":"10.1210\/jc.2015-3500"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_002","unstructured":"Yan, C, Wang, MD. Pediatric endocrinology, 2nd ed. Jing: People\u2019s Medical Publishing House; 2006."},{"key":"2025082013043672006_j_jpem-2024-0602_ref_003","unstructured":"Chen, RM. Research progress on the etiology of peripheral precocious puberty. J Appl Clin Pediatr 2012;27:1545\u20137. https:\/\/doi.org\/10.3969\/j.issn.1003-515X.2012.20.001."},{"key":"2025082013043672006_j_jpem-2024-0602_ref_004","doi-asserted-by":"crossref","unstructured":"Casarini, L, Santi, D, Brigante, G, Simoni, M. Two hormones for one receptor: evolution, biochemistry, actions, and pathophysiology of LH and hCG. Endocr Rev 2018;39:549\u201392. https:\/\/doi.org\/10.1210\/er.2018-00065.","DOI":"10.1210\/er.2018-00065"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_005","doi-asserted-by":"crossref","unstructured":"Lane, LC, Flowers, J, Johnstone, H, Cheetham, T. Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management. J Pediatr Endocrinol Metab 2018;31:551\u201360. https:\/\/doi.org\/10.1515\/jpem-2017-0363.","DOI":"10.1515\/jpem-2017-0363"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_006","doi-asserted-by":"crossref","unstructured":"Holland, FJ, Kirsch, SE, Selby, R. Gonadotropin-independent precocious puberty (\u201ctestotoxicosis\u201d): influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab 1987;64:328\u201333. https:\/\/doi.org\/10.1210\/jcem-64-2-328.","DOI":"10.1210\/jcem-64-2-328"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_007","doi-asserted-by":"crossref","unstructured":"Almeida, MQ, Brito, VN, Lins, TS, Guerra-Junior, G, de Castro, M, Antonini, SR, et al.. Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole. Clin Endocrinol 2008;69:93\u20138. https:\/\/doi.org\/10.1111\/j.1365-2265.2007.03160.x [Epub 2008 Jul 1].","DOI":"10.1111\/j.1365-2265.2007.03160.x"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_008","doi-asserted-by":"crossref","unstructured":"Bertelloni, S, Baroncelli, GI, Lala, R, Cappa, M, Matarazzo, P, De Sanctis, C, et al.. Long-term outcome of male-limited gonadotropin-independent precocious puberty. Horm Res 1997;48:235\u20139. https:\/\/doi.org\/10.1159\/000185521.","DOI":"10.1159\/000185521"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_009","doi-asserted-by":"crossref","unstructured":"Ito, Y, Yano, K, Mitamura, R, Oka, R, Okuno, A, Kataoka, N, et al.. Sporadic testotoxicosis in Japanese children: report of 4 cases. Horm Res 1992;1:95\u2013100. https:\/\/doi.org\/10.1297\/cpe.1.95.","DOI":"10.1297\/cpe.1.95"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_010","doi-asserted-by":"crossref","unstructured":"Soriano-Guill\u00e9n, L, Lahlou, N, Chauvet, G, Roger, M, Chaussain, JL, Carel, JC. Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty. J Clin Endocrinol Metab 2005;90:147\u201351. https:\/\/doi.org\/10.1210\/jc.2004-1438.","DOI":"10.1210\/jc.2004-1438"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_011","doi-asserted-by":"crossref","unstructured":"Leschek, EW, Flor, AC, Bryant, JC, Jones, JV, Barnes, KM, Cutler, GBJr. Effect of antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog on adult height in familial male precocious puberty. J Pediatr 2017;190:229\u201335. https:\/\/doi.org\/10.1016\/j.jpeds.2017.07.047.","DOI":"10.1016\/j.jpeds.2017.07.047"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_012","doi-asserted-by":"crossref","unstructured":"Yoshizawa-Ogasawara, A, Katsumata, N, Horikawa, R, Satoh, M, Urakami, T, Tanaka, T. Third-generation aromatase inhibitor improved adult height in a Japanese boy with testotoxicosis. Clin Pediatr Endocrinol 2014;23:53\u20138. https:\/\/doi.org\/10.1297\/cpe.23.53.","DOI":"10.1297\/cpe.23.53"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_013","doi-asserted-by":"crossref","unstructured":"Jeha, GS, Lowenthal, ED, Chan, WY, Wu, SM, Karaviti, LP. Variable presentation of precocious puberty associated with the D564G mutation of the LHCGR gene in children with testotoxicosis. J Pediatr 2006;149:271\u20134. https:\/\/doi.org\/10.1016\/j.jpeds.2006.03.017.","DOI":"10.1016\/j.jpeds.2006.03.017"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_014","doi-asserted-by":"crossref","unstructured":"Partsch, CJ, Krone, N, Riepe, FG, Gromoll, J, Sippell, WG. Long-term follow-up of spontaneous development in a boy with familial male precocious puberty. Horm Res 2004;62:177\u201381. https:\/\/doi.org\/10.1159\/000080887.","DOI":"10.1159\/000080887"},{"key":"2025082013043672006_j_jpem-2024-0602_ref_015","unstructured":"Li, ML, Bai, GG, Hu, SW, Wang, ZH. Clinical and genetic analysis of five cases of familial male precocious puberty. Chin J Endocrinol Metabol 2022;38:887\u201392. https:\/\/doi.org\/10.3760\/cma.j.cn311282-20211229-00823."},{"key":"2025082013043672006_j_jpem-2024-0602_ref_016","unstructured":"Su, Z, Ma, HM, Du, ML, Li, YH. Familial male-limited precocious puberty caused by heterozygous mutation (M398T) in LHCGR gene. J Sun Yat-sen Univ (Soc Sci Ed) 2012;33:639\u2013643,654."},{"key":"2025082013043672006_j_jpem-2024-0602_ref_017","doi-asserted-by":"crossref","unstructured":"McGee, SR, Narayan, P. Precocious puberty and Leydig cell hyperplasia in male mice with a gain of function mutation in the LH receptor gene. Endocrinology 2013;154:3900\u201313. https:\/\/doi.org\/10.1210\/en.2012-2179.","DOI":"10.1210\/en.2012-2179"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0602\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:05:15Z","timestamp":1755695115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0602\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":17,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3,20]]},"published-print":{"date-parts":[[2025,5,26]]}},"alternative-id":["10.1515\/jpem-2024-0602"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2024-0602","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}