Premature Thelarche: An Updated Review

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Abstract

Background: Premature thelarche is the most common pubertal disorder in girls. The condition should be differentiated from central precocious puberty which may result in early epiphyseal fusion and reduced adult height, necessitating treatment.

Objectives: The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty.

Methods: A search was conducted in September 2022 in PubMed Clinical Queries using the key term "Premature thelarche". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article.

Results: Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an "overactivation" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty.

Conclusion: Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow- up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.

Graphical Abstract

[1]
Wilkins L. The diagnosis and treatment of endocrine disorders of childhood and adolescence. Springfield, IL: Charles C Thomas 1957; pp. 1-1278.
[2]
Codner E, Román R. Premature thelarche from phenotype to genotype. Pediatr Endocrinol Rev 2008; 5(3): 760-5.
[PMID: 18367996]
[3]
Leung AK. Premature thelarche. J Singapore Paediatr Soc 1989; 31(1-2): 64-8.
[PMID: 2671495]
[4]
Leung AK, McArthur RG. Recent advances in the treatment of isosexual precocious puberty: Identifying all the problems. Can Fam Physician 1991; 37: 2597-604.
[PMID: 20469522]
[5]
de Vries L, Guz-Mark A, Lazar L, Reches A, Phillip M. Premature thelarche: Age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr 2010; 156(3): 466-71.
[http://dx.doi.org/10.1016/j.jpeds.2009.09.071] [PMID: 19914634]
[6]
Sømod ME, Vestergaard ET, Kristensen K, Birkebæk NH. Increasing incidence of premature thelarche in the central region of denmark: Challenges in differentiating girls less than 7 years of age with premature thelarche from girls with precocious puberty in real-life practice. Int J Pediatr Endocrinol 2016; 2016(1): 4.
[http://dx.doi.org/10.1186/s13633-016-0022-x] [PMID: 26909102]
[7]
Curfman AL, Reljanovic SM, McNelis KM, et al. Premature thelarche in infants and toddlers: Prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol 2011; 24(6): 338-41.
[http://dx.doi.org/10.1016/j.jpag.2011.01.003] [PMID: 22099730]
[8]
Österbrand M, Fors H, Norjavaara E. Prevalence of premature thelarche at 18 months of age: A population- and hospital-based study of prevalence and incidence in girls born at Northern Älvsborg County Hospital in Sweden. Horm Res Paediatr 2019; 91(3): 203-9.
[http://dx.doi.org/10.1159/000500356] [PMID: 31167216]
[9]
Wang Y, Wang A, Kong L, et al. Multi-center study of premature thelarche and gynecomastia in Chinese infants and toddlers. Zhonghua Er Ke Za Zhi 2014; 52(1): 5-10.
[PMID: 24680401]
[10]
Zhang J, Xu J, Liu L, et al. The prevalence of premature thelarche in girls and gynecomastia in boys and the associated factors in children in Southern China. BMC Pediatr 2019; 19(1): 107.
[http://dx.doi.org/10.1186/s12887-019-1426-6] [PMID: 30975105]
[11]
Silver HK, Sami D. Premature thelarche. precocious development of the breast. Pediatrics 1964; 34: 107-11.
[PMID: 14181970]
[12]
Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: A study from the pediatric research in office settings network. Pediatrics 1997; 99(4): 505-12.
[http://dx.doi.org/10.1542/peds.99.4.505] [PMID: 9093289]
[13]
Rosenfield RL, Lipton RB, Drum ML. Thelarche, pubarche, and menarche attainment in children with normal and elevated body mass index. Pediatrics 2009; 123(1): 84-8.
[http://dx.doi.org/10.1542/peds.2008-0146] [PMID: 19117864]
[14]
Diamantopoulos S, Bao Y. Gynecomastia and premature thelarche: A guide for practitioners. Pediatr Rev 2007; 28(9): e57-68.
[http://dx.doi.org/10.1542/pir.28.9.e57] [PMID: 17766590]
[15]
Borges MF, Pacheco KD, Oliveira AA, et al. Premature thelarche: Clinical and laboratorial assessment by immunochemiluminescent assay. Arq Bras Endocrinol Metabol 2008; 52(1): 93-100.
[http://dx.doi.org/10.1590/S0004-27302008000100013] [PMID: 18345401]
[16]
Lee CT, Tung YC, Tsai WY. Premature thelarche in taiwanese girls. J Pediatr Endocrinol Metab 2010; 23(9): 879-84.
[http://dx.doi.org/10.1515/jpem.2010.142] [PMID: 21175086]
[17]
Pasquino AM, Piccolo F, Scalamandre A, Malvaso M, Ortolani R, Boscherini B. Hypothalamic-pituitary-gonadotropic function in girls with premature thelarche. Arch Dis Child 1980; 55(12): 941-4.
[http://dx.doi.org/10.1136/adc.55.12.941] [PMID: 6779715]
[18]
Sizonenko PC. Preadolescent and adolescent endocrinology: Physiology and physiopathology. II. Hormonal changes during abnormal pubertal development. Am J Dis Child 1978; 132(8): 797-805.
[http://dx.doi.org/10.1001/archpedi.1978.02120330069017] [PMID: 150791]
[19]
Crofton PM, Evans NEM, Wardhaugh B, Groome NP, Kelnar CJH. Evidence for increased ovarian follicular activity in girls with premature thelarche. Clin Endocrinol 2005; 62(2): 205-9.
[http://dx.doi.org/10.1111/j.1365-2265.2004.02198.x] [PMID: 15670197]
[20]
Leung AKC. Premature thelarcheCommon Problems in Ambulatory Pediatrics: Symptoms and Signs. New York: Nova Science Publish-ers, Inc. 2011; pp. 273-6.
[21]
Türkyılmaz Z, Karabulut R, Sönmez K, Can Başaklar A. A striking and frequent cause of premature thelarche in children: Foeniculum vulgare. J Pediatr Surg 2008; 43(11): 2109-11.
[http://dx.doi.org/10.1016/j.jpedsurg.2008.07.027] [PMID: 18970951]
[22]
Ilicki A, Lewin RP, Kauli R, Kaufman H, Schachter A, Laron Z. Premature thelarche--natural history and sex hormone secretion in 68 girls. Acta Paediatr 1984; 73(6): 756-62.
[http://dx.doi.org/10.1111/j.1651-2227.1984.tb17771.x] [PMID: 6240890]
[23]
Khokhar A, Mojica A. Premature Thelarche. Pediatr Ann 2018; 47(1): e12-5.
[http://dx.doi.org/10.3928/19382359-20171214-01] [PMID: 29323691]
[24]
Dumic M, Tajic M, Mardesic D, Kalafatic Z. Premature thelarche: A possible adrenal disorder. Arch Dis Child 1982; 57(3): 200-3.
[http://dx.doi.org/10.1136/adc.57.3.200] [PMID: 6462113]
[25]
Harrington J, Palmert MR. Definition, etiology, and evaluation of precocious puberty. UpToDate
[26]
Hartmaier RJ, Walenkamp MJE, Richter AS, et al. A case of premature thelarche with no central cause or genetic variants within the estrogen receptor signaling pathway. J Pediatr Endocrinol Metab 2009; 22(8): 751-8.
[http://dx.doi.org/10.1515/JPEM.2009.22.8.751] [PMID: 19845126]
[27]
Asci A, Durmaz E, Erkekoglu P, Pasli D, Bircan I, Kocer-Gumusel B. Urinary zearalenone levels in girls with premature thelarche and idiopathic central precocious puberty. Minerva Pediatr 2014; 66(6): 571-8.
[PMID: 25336100]
[28]
Andersson AM, Skakkebaek NE. Exposure to exogenous estrogens in food: Possible impact on human development and health. Eur J Endocrinol 1999; 140(6): 477-85.
[http://dx.doi.org/10.1530/eje.0.1400477] [PMID: 10366402]
[29]
Chang SSY, Nagarajan N, Tan JMC. Premature thelarche in an infant girl with failure to thrive related to dietary soy exposure. BMJ Case Rep 2021; 14(3): e239651.
[http://dx.doi.org/10.1136/bcr-2020-239651] [PMID: 33758044]
[30]
Daxenberger A, Ibarreta D, Meyer HH. Possible health impact of animal oestrogens in food. Hum Reprod Update 2001; 7(3): 340-55.
[http://dx.doi.org/10.1093/humupd/7.3.340] [PMID: 11392381]
[31]
Guarneri MP, Brambilla G, Loizzo A, Colombo I, Chiumello G. Estrogen exposure in a child from hair lotion used by her mother: Clinical and hair analysis data. Clin Toxicol 2008; 46(8): 762-4.
[http://dx.doi.org/10.1080/15563650701638941] [PMID: 18763154]
[32]
Chiabotto P, Costante L, de Sanctis C. Premature thelarche and environmental pollutants. Minerva Med 2006; 97(3): 277-85.
[PMID: 16855522]
[33]
Paris F, Gaspari L, Servant N, Philibert P, Sultan C. Increased serum estrogenic bioactivity in girls with premature thelarche: A marker of environmental pollutant exposure? Gynecol Endocrinol 2013; 29(8): 788-92.
[http://dx.doi.org/10.3109/09513590.2013.801448] [PMID: 23767830]
[34]
Beccuti G, Ghizzoni L. Normal and abnormal puberty. Endotext. South Dartmouth (MA): MDText.com, Inc. 2000-2015.
[35]
Chen L, Shi J, Fang Y, Liang L, Chen W, Chen X. Serum bisphenol A concentration and premature thelarche in female infants aged 4-month to 2-year. Indian J Pediatr 2015; 82(3): 221-4.
[http://dx.doi.org/10.1007/s12098-014-1548-7] [PMID: 25120062]
[36]
Colón I, Caro D, Bourdony CJ, Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect 2000; 108(9): 895-900.
[http://dx.doi.org/10.1289/ehp.108-2556932] [PMID: 11017896]
[37]
Coppola L, Tait S, Ciferri L, et al. Integrated approach to evaluate the association between exposure to pesticides and idiopathic premature thelarche in girls: The peach project. Int J Mol Sci 2020; 21(9): 3282.
[http://dx.doi.org/10.3390/ijms21093282] [PMID: 32384657]
[38]
Coppola L, Tait S, Fabbrizi E, Perugini M, La Rocca C. Comparison of the toxicological effects of pesticides in non-tumorigenic MCF-12A and tumorigenic MCF-7 human breast cells. Int J Environ Res Public Health 2022; 19(8): 4453.
[http://dx.doi.org/10.3390/ijerph19084453] [PMID: 35457321]
[39]
Deodati A, Sallemi A, Maranghi F, et al. Serum levels of polybrominated diphenyl ethers in girls with premature thelarche. Horm Res Paediatr 2016; 86(4): 233-9.
[http://dx.doi.org/10.1159/000444586] [PMID: 27035145]
[40]
Durmaz E, Asci A, Erkekoglu P, Balcı A, Bircan I, Koçer-Gumusel B. Urinary bisphenol a levels in turkish girls with premature thelarche. Hum Exp Toxicol 2018; 37(10): 1007-16.
[http://dx.doi.org/10.1177/0960327118756720] [PMID: 29405766]
[41]
Durmaz E, Erkekoglu P, Asci A, Akçurin S, Bircan İ, Kocer-Gumusel B. Urinary phthalate metabolite concentrations in girls with premature thelarche. Environ Toxicol Pharmacol 2018; 59: 172-81.
[http://dx.doi.org/10.1016/j.etap.2018.03.010] [PMID: 29625387]
[42]
Freni-Titulaer LW, Cordero JF, Haddock L, Lebrón G, Martínez R, Mills JL. Premature thelarche in puerto rico. Am J Dis Child 1986; 140(12): 1263-7.
[http://dx.doi.org/10.1001/archpedi.1986.02140260065028] [PMID: 3776944]
[43]
Roy JR, Chakraborty S, Chakraborty TR. Estrogen-like endocrine disrupting chemicals affecting puberty in humans: A review. Med Sci Monit 2009; 15(6): RA137-45.
[PMID: 19478717]
[44]
Bosman JM, Bax NMA, Wit JM. Premature thelarche: A possible adverse effect of cimetidine treatment. Eur J Pediatr 1990; 149(8): 534-5.
[http://dx.doi.org/10.1007/BF01957686] [PMID: 2347351]
[45]
White PAM, Singh R, Rais T, Coffey DBJ. Premature thelarche in an 8-year-old girl following prolonged use of risperidone. J Child Adolesc Psychopharmacol 2014; 24(4): 228-30.
[http://dx.doi.org/10.1089/cap.2014.2442] [PMID: 24840046]
[46]
Okdemir D, Hatipoglu N, Kurtoglu S, Akın L, Kendirci M. Premature thelarche related to fennel tea consumption? J Pediatr Endocrinol Metab 2014; 27(1-2): 175-9.
[http://dx.doi.org/10.1515/jpem-2013-0308] [PMID: 24030028]
[47]
Henley DV, Lipson N, Korach KS, Bloch CA. Prepubertal gynecomastia linked to lavender and tea tree oils. N Engl J Med 2007; 356(5): 479-85.
[http://dx.doi.org/10.1056/NEJMoa064725] [PMID: 17267908]
[48]
Ramsey JT, Li Y, Arao Y, et al. Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities. J Clin Endocrinol Metab 2019; 104(11): 5393-405.
[http://dx.doi.org/10.1210/jc.2018-01880] [PMID: 31393563]
[49]
Giroux JM, Orjubin M. Letter to the Editor:Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities. J Clin Endocrinol Metab 2020; 105(7): e2677-2678.
[http://dx.doi.org/10.1210/clinem/dgaa226]
[50]
Larkman T. Lavender products associated with premature thelarche and 1 prepubertal gynecomastia: Case reports and endocrine-disrupting chemical activities. J Clin Endocrinol Metab 2020; 105(9): dgaa392.
[http://dx.doi.org/10.1210/clinem/dgaa392]
[51]
Linklater A, Hewitt JK. Premature thelarche in the setting of high lavender oil exposure. J Paediatr Child Health 2015; 51(2): 235.
[http://dx.doi.org/10.1111/jpc.12837] [PMID: 25677490]
[52]
Tyler Ramsey J, Diaz A, Korach KS. Lavender products associated with premature thelarche and prepubertal gynecomastia: Case reports and EDC activities. J Clin Endocrinol Metab 2020; 105(7): e2692-3.
[http://dx.doi.org/10.1210/clinem/dgaa227]
[53]
Hawkins J, Hires C, Dunne E, Baker C. The relationship between lavender and tea tree essential oils and pediatric endocrine disorders: A systematic review of the literature. Complement Ther Med 2020; 49: 102288.
[http://dx.doi.org/10.1016/j.ctim.2019.102288] [PMID: 32147050]
[54]
Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr 2012; 101(2): e71-5.
[http://dx.doi.org/10.1111/j.1651-2227.2011.02444.x] [PMID: 21854448]
[55]
Xu Y, Li Y, Liang S, Li G. Differential analysis of nutrient intake, insulin resistance and lipid profiles between healthy and premature thelarche Chinese girls. Ital J Pediatr 2019; 45(1): 166.
[http://dx.doi.org/10.1186/s13052-019-0758-z] [PMID: 31856872]
[56]
Román R, Johnson MC, Codner E, Boric MA, Ávila A, Cassorla F. Activating GNAS1 gene mutations in patients with premature thelarche. J Pediatr 2004; 145(2): 218-22.
[http://dx.doi.org/10.1016/j.jpeds.2004.05.025] [PMID: 15289771]
[57]
Çatlı G, Erdem P, Anik A, Abaci A, Böber E. Clinical and laboratory findings in the differential diagnosis of central precocious puberty and premature thelarche. Turk Pediatri Ars 2015; 50(1): 20-6.
[http://dx.doi.org/10.5152/tpa.2015.2281] [PMID: 26078693]
[58]
Eugster EA. Update on precocious puberty in girls. J Pediatr Adolesc Gynecol 2019; 32(5): 455-9.
[http://dx.doi.org/10.1016/j.jpag.2019.05.011] [PMID: 31158483]
[59]
Su H, Su Z, Pan L, et al. Factors affecting bone maturation in Chinese girls aged 4-8 years with isolated premature thelarche. BMC Pediatr 2020; 20(1): 356.
[http://dx.doi.org/10.1186/s12887-020-02256-w] [PMID: 32727432]
[60]
Leung AKC, Wong AHC, Hon KL. Childhood obesity: An updated review. Curr Pediatr Rev 2022; 18.
[http://dx.doi.org/10.2174/1573396318666220801093225] [PMID: 35927921]
[61]
Adam MP, Hudgins L, Hannibal M. Kabuki syndromeAdam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH GeneReviews® . Seattle: Seattle (WA): University of Washington 2011.
[62]
Bereket A, Turan S, Alper G, Comu S, Alpay H, Akalin F. Two patients with Kabuki syndrome presenting with endocrine problems. J Pediatr Endocrinol Metab 2001; 14(2): 215-20.
[http://dx.doi.org/10.1515/JPEM.2001.14.2.215] [PMID: 11305802]
[63]
Boniel S, Szymańska K, Śmigiel R, Szczałuba K. Kabuki syndrome: Clinical review with molecular aspects. Genes 2021; 12(4): 468.
[http://dx.doi.org/10.3390/genes12040468] [PMID: 33805950]
[64]
Devriendt K, Lemli L, Craen M, de Zegher F. Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome. Horm Res 1995; 43(6): 303-6.
[http://dx.doi.org/10.1159/000184355] [PMID: 7607617]
[65]
Ito N, Ihara K, Tsutsumi Y, Miyake N, Matsumoto N, Hara T. Hypothalamic pituitary complications in Kabuki syndrome. Pituitary 2013; 16(2): 133-8.
[http://dx.doi.org/10.1007/s11102-012-0386-8] [PMID: 22434255]
[66]
Moon JE, Lee SJ, Ko CW. A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: A case report. BMC Med Genet 2018; 19(1): 102.
[http://dx.doi.org/10.1186/s12881-018-0606-9] [PMID: 29914387]
[67]
Tutar HE, Öcal G, İnce E, Cın Ş. Premature thelarche in Kabuki make-up syndrome. Pediatr Int 1994; 36(1): 104-6.
[http://dx.doi.org/10.1111/j.1442-200X.1994.tb03141.x] [PMID: 8165898]
[68]
Zarate YA, Zhan H, Jones JR. Infrequent manifestations of Kabuki Syndrome in a patient with novel MLL2 mutation. Mol Syndromol 2012; 3(4): 180-4.
[http://dx.doi.org/10.1159/000342253] [PMID: 23239960]
[69]
Ihara K, Kuromaru R, Takemoto M, Hara T. Rubinstein-Taybi syndrome: A girl with a history of neuroblastoma and premature thelarche. Am J Med Genet 1999; 83(5): 365-6.
[http://dx.doi.org/10.1002/(SICI)1096-8628(19990423)83:5<365::AID-AJMG4>3.0.CO;2-P] [PMID: 10232744]
[70]
Kurosawa K, Masuno M, Tachibana K, Imaizumi K, Matsuo M, Kuroki Y. Premature thelarche in Rubinstein-Taybi syndrome. Am J Med Genet 2002; 109(1): 72-3.
[http://dx.doi.org/10.1002/ajmg.10297] [PMID: 11932997]
[71]
Stevens CA, Carey JC, Blackburn BL. Rubinstein-Taybi syndrome: A natural history study. Am J Med Genet 1990; 37(S6): 30-7.
[http://dx.doi.org/10.1002/ajmg.1320370605] [PMID: 2118775]
[72]
Brunetti-Pierri N, Esposito V, Salerno M. Premature thelarche in Coffin-Siris syndrome. Am J Med Genet 2003; 121A(2): 174-6.
[http://dx.doi.org/10.1002/ajmg.a.20158] [PMID: 12910500]
[73]
Flynn MA, Milunsky JM. Autosomal dominant syndrome resembling Coffin-Siris syndrome. Am J Med Genet A 2006; 140A(12): 1326-30.
[http://dx.doi.org/10.1002/ajmg.a.31287] [PMID: 16691594]
[74]
De Silva SR, Painter SL, Hildebrand D. Möbius syndrome associated with obesity and precocious puberty. BMJ Case Rep 2018; 11(1): e219590.
[http://dx.doi.org/10.1136/bcr-2017-219590] [PMID: 30567196]
[75]
Ichiyama T, Handa S, Hayashi T, Furukawa S. Premature thelarche in Möbius syndrome. Clin Genet 1995; 47(2): 108-9.
[http://dx.doi.org/10.1111/j.1399-0004.1995.tb03938.x] [PMID: 7606843]
[76]
Atabek ME, Pirgon O, Sert A. Mayer?Rokitansky?Kuster?Hauser syndrome presenting as premature thelarche in a young child. Pediatr Int 2007; 49(4): 533-5.
[http://dx.doi.org/10.1111/j.1442-200X.2007.02408.x] [PMID: 17587284]
[77]
Ekbote AV, Danda S, Zankl A, Mandal K, Maguire T, Ungerer K. Patient with mutation in the matrix metalloproteinase 2 (MMP2) gene: A case report and review of the literature. J Clin Res Pediatr Endocrinol 2014; 6(1): 40-6.
[http://dx.doi.org/10.4274/Jcrpe.1166] [PMID: 24637309]
[78]
Jeong SY, Kim BY, Kim HJ, Yang JA, Kim OH. A novel homozygous MMP2 mutation in a patient with Torg-Winchester syndrome. J Hum Genet 2010; 55(11): 764-6.
[http://dx.doi.org/10.1038/jhg.2010.102] [PMID: 20720557]
[79]
Johannesen KM, Gardella E, Gjerulfsen CE, et al. PURA-related developmental and epileptic encephalopathy: Phenotypic and genotypic spectrum. Neurol Genet 2021; 7(6): e613.
[http://dx.doi.org/10.1212/NXG.0000000000000613] [PMID: 34790866]
[80]
Reijnders MRF, Janowski R, Alvi M, et al. PURA syndrome: Clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. J Med Genet 2018; 55(2): 104-13.
[http://dx.doi.org/10.1136/jmedgenet-2017-104946] [PMID: 29097605]
[81]
Rezkalla J, Von Wald T, Hansen KA. Premature thelarche and the pura syndrome. Obstet Gynecol 2017; 129(6): 1037-9.
[http://dx.doi.org/10.1097/AOG.0000000000002047] [PMID: 28486374]
[82]
Trau SP, Pizoli CE. PURA syndrome and myotonia. Pediatr Neurol 2020; 104: 62-3.
[http://dx.doi.org/10.1016/j.pediatrneurol.2019.09.008] [PMID: 31911028]
[83]
Azurara L, Marçal M, Vieira F, Tuna ML. DPG-plus syndrome: New report of a rare entity. BMJ Case Rep 2015; 2015(nov12 1): bcr2015212416.
[http://dx.doi.org/10.1136/bcr-2015-212416] [PMID: 26564114]
[84]
Prezioso G, Petraroli M, Bergonzani M, et al. Duplication of the pituitary gland (DPG)-plus syndrome associated with midline anomalies and precocious puberty: A case report and review of the literature. Front Endocrinol 2021; 12: 685888.
[http://dx.doi.org/10.3389/fendo.2021.685888] [PMID: 34122353]
[85]
Klein KO, Mericq V, Brown-Dawson JM, Larmore KA, Cabezas P, Cortinez A. Estrogen levels in girls with premature thelarche compared with normal prepubertal girls as determined by an ultrasensitive recombinant cell bioassay. J Pediatr 1999; 134(2): 190-2.
[http://dx.doi.org/10.1016/S0022-3476(99)70414-2] [PMID: 9931528]
[86]
Lee DS, Ryoo NY, Lee SH, Kim S, Kim JH. Basal luteinizing hormone and follicular stimulating hormone: Is it sufficient for the diagnosis of precocious puberty in girls? Ann Pediatr Endocrinol Metab 2013; 18(4): 196-201.
[http://dx.doi.org/10.6065/apem.2013.18.4.196] [PMID: 24904877]
[87]
Poomthavorn P, Khlairit P, Mahachoklertwattana P. Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty. Horm Res Paediatr 2009; 72(2): 114-9.
[http://dx.doi.org/10.1159/000232164] [PMID: 19690429]
[88]
de Souza KBF, Veiga MSP, Martins GRF, et al. Assessment of gonadotropin concentrations stimulated by gonadotropin-releasing hormone analog by electrochemiluminescence in girls with precocious puberty and premature thelarche. Horm Res Paediatr 2021; 94(11-12): 433-40.
[http://dx.doi.org/10.1159/000521593] [PMID: 34933304]
[89]
Ibáñez L, Potau N, Zampolli M, et al. Use of leuprolide acetate response patterns in the early diagnosis of pubertal disorders: Comparison with the gonadotropin-releasing hormone test. J Clin Endocrinol Metab 1994; 78(1): 30-5.
[http://dx.doi.org/10.1210/jc.78.1.30] [PMID: 7507123]
[90]
Seymen Karabulut G, Atar M, Çizmecioğlu Jones FM, Hatun Ş. Girls with premature thelarche younger than 3 years of age may have stimulated luteinizing hormone greater than 10 IU/L. J Clin Res Pediatr Endocrinol 2020; 12(4): 377-82.
[http://dx.doi.org/10.4274/jcrpe.galenos.2020.2019.0202] [PMID: 32349465]
[91]
Ouyang L, Yang F. Combined diagnostic value of insulin-like growth factor-1, insulin-like growth factor binding protein-3, and baseline luteinizing hormone levels for central precocious puberty in girls. J Pediatr Endocrinol Metab 2022; 35(7): 874-9.
[http://dx.doi.org/10.1515/jpem-2022-0161] [PMID: 35635485]
[92]
Almasi N, Zengin HY, Koç N, et al. Leptin, ghrelin, nesfatin-1, and orexin-A plasma levels in girls with premature thelarche. J Endocrinol Invest 2022; 45(11): 2097-103. Online ahead of print [http://dx.doi.org/10.1007/s40618-022-01841-3
[PMID: 35764868]
[93]
Çatlı G, Anık A, Küme T, et al. Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche. J Endocrinol Invest 2015; 38(8): 909-13.
[http://dx.doi.org/10.1007/s40618-015-0277-8] [PMID: 25833360]
[94]
Dundar B, Pirgon O, Sangun O, Doguc DK. Elevated leptin levels in nonobese girls with premature thelarche. J Investig Med 2013; 61(6): 984-8.
[http://dx.doi.org/10.2310/JIM.0b013e31829cbe20] [PMID: 23838698]
[95]
Lee MM, Donahoe PK, Hasegawa T, et al. Mullerian inhibiting substance in humans: Normal levels from infancy to adulthood. J Clin Endocrinol Metab 1996; 81(2): 571-6.
[http://dx.doi.org/10.1210/jcem.81.2.8636269] [PMID: 8636269]
[96]
Muratoğlu Şahin N, Bayramoğlu E, Nursun Özcan H, et al. Antimüllerian hormone levels of infants with premature thelarche. J Clin Res Pediatr Endocrinol 2019; 11(3): 287-92.
[http://dx.doi.org/10.4274/jcrpe.galenos.2019.2018.0293] [PMID: 30859797]
[97]
Sahin NM, Kinik ST, Tekindal MA, Bayraktar N. AMH levels at central precocious puberty and premature thelarche: Is it a parameter? J Pediatr Endocrinol Metab 2015; 28(11-12): 1351-6.
[http://dx.doi.org/10.1515/jpem-2014-0521] [PMID: 26226120]
[98]
Sahin NM, Ozcan HN, Yilmaz AA, Erdeve SS, Cetinkaya S, Aycan Z. The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche. J Pediatr Endocrinol Metab 2021; 34(11): 1385-91.
[http://dx.doi.org/10.1515/jpem-2021-0343] [PMID: 34344062]
[99]
Akıncı A, Çetin D, İlhan N. Plasma kisspeptin levels in girls with premature thelarche. J Clin Res Pediatr Endocrinol 2012; 4(2): 61-5.
[http://dx.doi.org/10.4274/jcrpe.615] [PMID: 22672861]
[100]
Parlak M, Türkkahraman D, Ellidağ HY, Çelmeli G, Parlak AE, Yılmaz N. Basal serum neurokinin B levels in differentiating idiopathic central precocious puberty from premature thelarche. J Clin Res Pediatr Endocrinol 2017; 9(2): 101-5.
[http://dx.doi.org/10.4274/jcrpe.3817] [PMID: 28008860]
[101]
Kutlu E, Özgen İT, Bulut H, Koçyiğit A, Otçu H, Cesur Y. Serum irisin levels in central precocious puberty and its variants. J Clin Endocrinol Metab 2021; 106(1): e247-54.
[http://dx.doi.org/10.1210/clinem/dgaa720] [PMID: 33034623]
[102]
Abacı A, Çatlı G, Anık A, et al. Significance of serum neurokinin B and kisspeptin levels in the differential diagnosis of premature thelarche and idiopathic central precocious puberty. Peptides 2015; 64: 29-33.
[http://dx.doi.org/10.1016/j.peptides.2014.12.011] [PMID: 25572302]
[103]
De Vries L, Shtaif B, Phillip M, Gat-Yablonski G. Kisspeptin serum levels in girls with central precocious puberty. Clin Endocrinol 2009; 71(4): 524-8.
[http://dx.doi.org/10.1111/j.1365-2265.2009.03575.x] [PMID: 19508611]
[104]
García CJ, Espinoza A, Dinamarca V, et al. Breast US in children and adolescents. Radiographics 2000; 20(6): 1605-12.
[http://dx.doi.org/10.1148/radiographics.20.6.g00nv171605] [PMID: 11112814]
[105]
Youn I, Park SH, Lim IS, Kim SJ. Ultrasound assessment of breast development: Distinction between premature thelarche and precocious puberty. AJR Am J Roentgenol 2015; 204(3): 620-4.
[http://dx.doi.org/10.2214/AJR.14.12565] [PMID: 25714294]
[106]
Nguyen NN, Huynh LBP, Do MD, Yang TY, Tsai MC, Chen YC. Diagnostic accuracy of female pelvic ultrasonography in differentiating precocious puberty from premature thelarche: A systematic review and meta-analysis. Front Endocrinol 2021; 12: 735875.
[http://dx.doi.org/10.3389/fendo.2021.735875] [PMID: 34539579]
[107]
Haber HP, Wollmann HA, Ranke MB. Pelvic ultrasonography: Early differentiation between isolated premature thelarche and central precocious puberty. Eur J Pediatr 1995; 154(3): 182-6.
[http://dx.doi.org/10.1007/BF01954267] [PMID: 7758513]
[108]
Herter LD, Golendziner E, Flores JAM, et al. Ovarian and uterine findings in pelvic sonography: Comparison between prepubertal girls, girls with isolated thelarche, and girls with central precocious puberty. J Ultrasound Med 2002; 21(11): 1237-46.
[http://dx.doi.org/10.7863/jum.2002.21.11.1237] [PMID: 12418765]
[109]
Kaplowitz PB. For premature thelarche and premature adrenarche, the case for waiting before testing. Horm Res Paediatr 2020; 93(9-10): 573-6.
[http://dx.doi.org/10.1159/000512764] [PMID: 33352558]
[110]
Sivasankaran S, Itam P, Ayensu-Coker L, et al. Juvenile granulosa cell ovarian tumor: A case report and review of literature. J Pediatr Adolesc Gynecol 2009; 22(5): e114-7.
[http://dx.doi.org/10.1016/j.jpag.2008.08.001] [PMID: 19576820]
[111]
Palmert MR, Malin HV, Boepple PA. Unsustained or slowly progressive puberty in young girls: Initial presentation and long-term follow-up of 20 untreated patients. J Clin Endocrinol Metab 1999; 84(2): 415-23.
[http://dx.doi.org/10.1210/jc.84.2.415] [PMID: 10022394]
[112]
Leung AKC, Leung AAC. Gynecomastia in infants, children, and adolescents. Recent Pat Endocr Metab Immune Drug Discov 2017; 10(2): 127-37.
[http://dx.doi.org/10.2174/1872214811666170301124033] [PMID: 28260521]
[113]
Takakuwa S. Premature thelarche in later childhood demonstrates a pubertal response to GnRH stimulation test at one year after breast development. Clin Pediatr Endocrinol 2011; 20(4): 81-7.
[http://dx.doi.org/10.1297/cpe.20.81] [PMID: 23926400]
[114]
Varimo T, Huttunen H, Miettinen PJ, et al. Precocious puberty or premature thelarche: Analysis of a large patient series in a single Tertiary center with special emphasis on 6- to 8-year-old girls. Front Endocrinol 2017; 8: 213.
[http://dx.doi.org/10.3389/fendo.2017.00213] [PMID: 28878739]
[115]
Mills JL, Stolley PD, Davies J, Moshang T Jr. Premature thelarche. Am J Dis Child 1981; 135(8): 743-5.
[http://dx.doi.org/10.1001/archpedi.1981.02130320057019] [PMID: 7270520]
[116]
Van Winter JT, Noller KL, Zimmerman D, Melton LJ III. Natural history of premature thelarche in Olmsted County, Minnesota, 1940 to 1984. J Pediatr 1990; 116(2): 278-80.
[http://dx.doi.org/10.1016/S0022-3476(05)82891-4] [PMID: 2299502]
[117]
Midyett LK, Moore WV, Jacobson JD. Are pubertal changes in girls before age 8 benign? Pediatrics 2003; 111(1): 47-51.
[http://dx.doi.org/10.1542/peds.111.1.47] [PMID: 12509553]
[118]
Pasquino AM, Pucarelli I, Passeri F, Segni M, Mancini MA, Municchi G. Progression of premature thelarche to central precocious puberty. J Pediatr 1995; 126(1): 11-4.
[http://dx.doi.org/10.1016/S0022-3476(95)70492-2] [PMID: 7815198]
[119]
Verrotti A, Ferrari M, Moyese G, Chiarelli F. Premature thelarche: A long-term follow-up. Gynecol Endocrinol 1996; 10(4): 241-7.
[http://dx.doi.org/10.3109/09513599609012315] [PMID: 8908524]
[120]
Zhu SY, Du ML, Huang TT. An analysis of predictive factors for the conversion from premature thelarche into complete central preco-cious puberty. J Pediatr Endocrinol Metab 2008; 21(6): 533-8.
[http://dx.doi.org/10.1515/jpem-2008-210607] [PMID: 18717239]
[121]
Uçar A, Saka N, Baş F, Bundak R, Günöz H, Darendeliler F. Is premature thelarche in the first two years of life transient? J Clin Res Pediatr Endocrinol 2012; 4(3): 140-5.
[http://dx.doi.org/10.4274/Jcrpe.709] [PMID: 22985613]
[122]
Çiçek D, Savas-Erdeve S, Cetinkaya S, Aycan Z. Clinical follow-up data and the rate of development of precocious and rapidly progres-sive puberty in patients with premature thelarche. J Pediatr Endocrinol Metab 2018; 31(3): 305-12.
[http://dx.doi.org/10.1515/jpem-2017-0247] [PMID: 29373318]