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Diagnosis and management of precocious sexual maturation: an updated review

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Abstract

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.

Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation.

What is Known:

• The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys.

• Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement.

What is New:

• Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1.

• A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

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Data Availability

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Abbreviations

CNS:

Central nervous system

CPP:

Central precocious puberty

ECL:

Electrochemiluminescence

FMPP:

Familial male-limited precocious puberty

FSH:

Follicle-stimulating hormone

GnRH:

Gonadotropin-releasing hormone

GnRHa:

Gonadotropin-releasing hormone agonist

HPG:

Hypothalamic-pituitary-gonadal

ICMA:

Immunochemiluminescent assay

IFMA:

Immunofluorometric assay

IGF-1:

Insulin-like growth factor-1

IPT:

Isolated premature thelarche

LH:

Luteinizing hormone

MRI:

Magnetic resonance imaging

MAS:

McCune-Albright syndrome

PPP:

Peripheral precocious puberty

TW3:

Tanner-Whitehouse 3

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Financial support was provided by the Hospital de Clínicas de Porto Alegre Research and Events Support Fund (FIPE-HCPA) and Medical Science Program: Endocrinology, Universidade Federal do Rio Grande do Sul, Brazil.

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  1. Post-graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Amanda Veiga Cheuiche, Leticia Guimarães da Silveira, Leila Cristina Pedroso de Paula & Sandra Pinho Silveiro

  2. Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Leila Cristina Pedroso de Paula & Sandra Pinho Silveiro

  3. Radiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Iara Regina Siqueira Lucena

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Sandra Pinho Silveiro had the idea for the article. Amanda Veiga Cheuiche and Leticia Guimarães da Silveira performed the literature search and data analysis. Amanda Veiga Cheuiche wrote the first draft of the manuscript. Leila Cristina Pedroso de Paula, Iara Regina Siqueira Lucena, and SandraPinho Silveiro critically revised the work.

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Cheuiche, A.V., da Silveira, L.G., de Paula, L.C.P. et al. Diagnosis and management of precocious sexual maturation: an updated review. Eur J Pediatr 180, 3073–3087 (2021). https://doi.org/10.1007/s00431-021-04022-1

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