Understanding precocious puberty management and diagnosis: a review

Jitender Prasad; Vijay K. Singh; Kajal Malhotra; Ashish Mudgal; Ritika Shrivastava; Ashima Dabas; Anita Devi; Atul Gupta; Binita Goswami

doi:10.18203/2349-3291.ijcp20261925

Authors

Jitender Prasad Department of Biochemistry, All India Institutes of Medical Science, Deoghar, Jharkhand, India
Vijay K. Singh Department of Biochemistry, Maulana Azad Medical College and Associated Hospital, New Delhi, India https://orcid.org/0000-0002-7299-4660
Kajal Malhotra Department of Pediatrics, Maulana Azad Medical College and Associated Hospital, New Delhi, India
Ashish Mudgal Department of Biochemistry, Maulana Azad Medical College and Associated Hospital, New Delhi, India
Ritika Shrivastava Department of Pediatrics, Maulana Azad Medical College and Associated Hospital, New Delhi, India
Ashima Dabas Department of Pediatrics, Maulana Azad Medical College and Associated Hospital, New Delhi, India
Anita Devi Department of Biochemistry, Dr. Rajendra Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, India
Atul Gupta Department of Pediatrics, Dr. Rajendra Prasad Government Medical College, Kangra at Tanda, Himachal Pradesh, India
Binita Goswami Department of Biochemistry, Maulana Azad Medical College and Associated Hospital, New Delhi, India

DOI:

https://doi.org/10.18203/2349-3291.ijcp20261925

Keywords:

Precocious puberty, Central precocious puberty, Peripheral precocious puberty, Thelarche, Pubarche

Abstract

The precocious puberty (PP) typically defined as the onset of secondary sexual characteristics prior to the age of 8 years in females and 9 years in males. The retrospective studies proved that the rate of PP significantly elevated in last few decades. This can be the result of early activation of the hypothalamic-pituitary-gonadal axis or due to autonomous production of sex steroids, independent of gonadotropin stimulation. The central precocious puberty is more common and is gonadotropin-dependent, whereas peripheral precocious puberty is gonadotropin-independent. Precocious puberty is associated with several challenges, including accelerated secondary sexual transformation, reduced adult height, psychosocial disturbances, and increased risk of certain malignancies. Recent years have witnessed a growing interest in understanding the genetic, environmental, and metabolic underpinnings of this condition, especially with the rising global incidence. In this review, we discuss the mechanism of precocious puberty and explore the epidemiology, etiology, clinical presentation, diagnostic workup, and management of PP, with a focus on recent advances in therapy and molecular insights. A multidisciplinary approach is essential to optimize outcomes and ensure psychological well-being.

References

Palmert MR, Dunkel L. Delayed Puberty. N Engl J Med. 2012;366(5):443-53.

Kim HK, Kee SJ, Seo JY, Yang EM, Chae HJ, Kim CJ. Gonadotropin-releasing hormone stimulation test for precocious puberty. Korean J Lab Med. 2011;31(4):244-9.

Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics. 2005;116(6):1323-8.

Mouritsen A, Aksglaede L, Sørensen K, Mogensen SS, Leffers H, Main KM, et al. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty. Int J Androl. 2010;33(2):346-59.

Papadimitriou A, Papadimitriou DT. Endocrine-Disrupting Chemicals and Early Puberty in Girls. Children (Basel). 2021;8(6):492.

Le Beau J, C TE. An american case report of precocious puberty published in 1832. Pediatrics. 1978;61(2):318-8.

Wyk JJ Van, Grumbach MM. Syndrome of precocious menstruation and galactorrhea in juvenile hypothyroidism: an example of hormonal overlap in pituitary feedback. J Pediatr. 1960;57(3):416-35.

Atta I, Laghari TM, Khan YN, Lone SW, Ibrahim M, Raza J. Precocious puberty in children. J Coll Physicians Surg Pak. 2015;25(2):124-8.

Kim SH, Huh K, Won S, Lee KW, Park MJ. A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010. PLoS One. 2015;10(11):e0141844.

Kang S, Park MJ, Kim JM, Yuk JS, Kim SH. Ongoing increasing trends in central precocious puberty incidence among Korean boys and girls from 2008 to 2020. PLoS One. 2023;18(3):e0283510.

Chen M, Eugster EA. Central Precocious Puberty: Update on Diagnosis and Treatment. Paediatr Drugs. 2015;17(4):273-81.

Correa Brito L, Rey RA. Taming Idiopathic Central Precocious Puberty: High Frequency of Imprinting Disorders in Familial Forms. J Clin Endocrinol Metab. 2023;108(8):e636-e7.

Chemaitilly W, Merchant TE, Li Z, Barnes N, Armstrong GT, Ness KK, et al. Central precocious puberty following the diagnosis and treatment of paediatric cancer and central nervous system tumours: presentation and long-term outcomes. Clin Endocrinol (Oxf). 2016;84(3):361-71.

Latronico AC, Brito VN, Carel JC. Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol. 2016;4(3):265-74.

Brito VN, Canton APM, Seraphim CE, Abreu AP, Macedo DB, Mendonca BB, et al. The Congenital and Acquired Mechanisms Implicated in the Etiology of Central Precocious Puberty. Endocr Rev. 2023;44(2):193-221.

Tajima T. Genetic causes of central precocious puberty. Clin Pediatr Endocrinol. 2022;31(3):2022.

Zainab Q, Vikas G. Peripheral Precocious Puberty - StatPearls - NCBI Bookshelf. StatPearls. 2023.

Hymavathi K, Tadisetti S, Pusarla D, Devi Gottipati M. Isosexual precocious puberty with primary hypothyroidism: an interesting case report. Int J Reprod Contracept Obstet Gynecol. 2017;6(9):4140.

Leung AKC, Lam JM, Hon KL. Premature Thelarche: An Updated Review. Curr Pediatr Rev. 2024;20(4):500-9.

Yaisilp P, Numsriskulrat N, Sahakitrungruang T. Clinical and epidemiological insights into early puberty in Thai girls: a 5-year study. Ann Pediatr Endocrinol Metab. 2025;30(1):17-24.

Partsch CJ, Sippell WG. Pathogenesis and epidemiology of precocious puberty. Effects of exogenous oestrogens. Hum Reprod Update. 2001;7(3):292-302.

Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross-sectional analysis. J Pediatr Endocrinol Metab. 2014;27(1-2).

Fanaki M, Michala L, Nazari E, Daskalakis G. Central Precocious Puberty During the COVID-19 Pandemic Period: A Systematic Review of Literature. Cureus. 2024;16(10):e71002.

Shim YS, Lee HS, Hwang JS. Genetic factors in precocious puberty. Clin Exp Pediatr. 2022;65(4):172-81.

Bigambo FM, Wang D, Niu Q, Zhang M, Mzava SM, Wang Y, et al. The effect of environmental factors on precocious puberty in children: a case-control study. BMC Pediatr. 2023;23(1):207.

Leonardi A, Cofini M, Rigante D, Lucchetti L, Cipolla C, Penta L, et al. The Effect of Bisphenol A on Puberty: A Critical Review of the Medical Literature. Int J Environ Res Public Health. 2017;14(9):1044.

Shi L, Jiang Z, Zhang L. Childhood obesity and central precocious puberty. Front Endocrinol (Lausanne). 2022;13:1056871.

Yu T, Yu Y, Li X, Xue P, Yu X, Chen Y, et al. Effects of childhood obesity and related genetic factors on precocious puberty: protocol for a multi-center prospective cohort study. BMC Pediatr. 2022;22(1):310.

Kim EY, Lee MI. Psychosocial aspects in girls with idiopathic precocious puberty. Psychiatry Investig. 2012;9(1):25-8.

Teilmann G, Petersen JH, Gormsen M, Damgaard K, Skakkebaek NE, Jensen TK. Early puberty in internationally adopted girls: hormonal and clinical markers of puberty in 276 girls examined biannually over two years. Horm Res. 2009;72(4):236-46.

Ziqin L, Xiaohui L, Xiaobo C. Precocious Puberty in Boys: A Study Based on Five Years of Data from a Single Center in Northern China. J Clin Res Pediatr Endocrinol. 2021;13(4):418-25.

Brown DB, Loomba-Albrecht LA, Bremer AA. Sexual precocity and its treatment. World J Pediatr. 2013;9(2):103-11.

Tanner JM. Growth and maturation during adolescence. Nutr Rev. 1981;39(2):43-55.

Ab Rahim SN, Omar J, Tuan Ismail TS. Gonadotropin-releasing hormone stimulation test and diagnostic cutoff in precocious puberty: a mini review. Ann Pediatr Endocrinol Metab. 2020;25(3):152-5.

Jung G, Oh SB, Lee WY, Kim HR, Nam HK, Kim JH, et al. Thyroid function in girls with central precocious puberty. Ann Pediatr Endocrinol Metab. 2019;24(2):124-8.

Lee HS. Central precocious puberty: is routine brain MRI screening necessary for girls? Commentary on "Brain magnetic resonance imaging (MRI) findings in central precocious puberty patients: is routine MRI necessary for newly diagnosed patients?". Ann Pediatr Endocrinol Metab. 2023;28(3):155-6.

Talarico V, Rodio MB, Viscomi A, Galea E, Galati MC, Raiola G. The role of pelvic ultrasound for the diagnosis and management of central precocious puberty: An update. Acta Biomed. 2021;92(5):e2021480.

Satoh M. Bone age: assessment methods and clinical applications. Clin Pediatr Endocrinol. 2015;24(4):143-52.

Hashemipour M, Moaddab MH, Nazem M, Mahzouni P, Salek M. Granulosa cell tumor in a six-year-old girl presented as precocious puberty. J Res Med Sci. 2010;15(4):240-2.

Haddad NG, Eugster EA. Peripheral precocious puberty including congenital adrenal hyperplasia: causes, consequences, management and outcomes. Best Pract Res Clin Endocrinol Metab. 2019;33(3):101273.

Li CD, Luo SQ, Gong J, Ma ZY, Jia G, Zhang YQ, et al. Surgical treatment of hypothalamic hamartoma causing central precocious puberty: long-term follow-up. J Neurosurg Pediatr. 2013;12(2):151-4.

Palma-Lozano D, Tapia-Sequeiros G, Galeas-Torre MK, Roman-Lazarte V. Global production and research trends on precocious puberty in the Web of Science database from 2000 to 2023: A bibliometric approach. Pediatr Endocrinol Diabetes Metab. 2024;30(4):190-7.

Roberts SA, Kaiser UB. Genetics in endocrinology: Genetic etiologies of central precocious puberty and the role of imprinted genes. Eur J Endocrinol. 2020;183(4):R107-17.

Lee HS. Genetic etiologies of central precocious puberty. Precis Futur Med. 2021;5(3):117-24.

Kwon A. Genetic and epigenetic aspects of the KISS1 and KISS1R genes in pubertal development and central precocious puberty: A review. Precis Futur Med. 2023;7(4):137-46.

Shen Y, Hu Y, Yang T, Shen H, Shen G, Orlov YL, et al. Development of Serum Cell-Free miRNA Panel for Identification of Central Precocious Puberty and Premature Thelarche in Girls. Biochemistry (Mosc). 2024;89(10):1834-43.

Qin W, Xie T, Chen Y, Zeng D, Meng Q, Lan D. Osteocalcin: may be a useful biomarker for early identification of rapidly progressive central precocious puberty in girls. J Endocrinol Invest. 2025;48(3):721-30.

Kılınç Uğurlu A, Özdemir Gökce A, Çakır Gündoğan S, Ekşioğlu AS, Boyraz M. MRI evaluation of cranial pathologies in rapidly progressive early puberty cases aged 8-9. Front Endocrinol (Lausanne). 2024;14:1316333.

Kaplowitz PB, Backeljauw PF, Allen DB. Toward More Targeted and Cost-Effective Gonadotropin-Releasing Hormone Analog Treatment in Girls with Central Precocious Puberty. Horm Res Paediatr. 2018;90(1):1-7.

Sims EK, Garnett S, Guzman F, Paris F, Sultan C, Eugster EA; Fulvestrant McCune-Albright study group. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome. Int J Pediatr Endocrinol. 2012;2012(1):26.

Soliman A, Alaaraj N, Alyafei F, Hamed N, Mohamed S. Early puberty and abnormal bone health: a comprehensive review. Endocr Abstr. 2024;99.

Hill JW, Alreja M, Elias CF. From precocious puberty to infertility: metabolic control of the reproductive function. Front Endocrinol (Lausanne). 2013;4:43.

Özen S, Darcan Ş. Effects of environmental endocrine disruptors on pubertal development. J Clin Res Pediatr Endocrinol. 2011;3(1):1-6.