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Precocious puberty: a comprehensive review of diagnosis and clinical presentation, etiology, and treatment Cover

Precocious puberty: a comprehensive review of diagnosis and clinical presentation, etiology, and treatment

Open Access
|Apr 2025

Figures & Tables

Figure 1.

Development of the HPA and HPG axes during adolescence. ACTH, adrenocorticotropic hormone; CRH, corticotrophin-releasing hormone; FSH, follicular stimulating hormone; GnRH, gonadotropin-releasing hormone; HPA, hypothalamic–pituitary–adrenal; HPG, hypothalamic–pituitary–gonadal; LH, luteinizing hormone.
Development of the HPA and HPG axes during adolescence. ACTH, adrenocorticotropic hormone; CRH, corticotrophin-releasing hormone; FSH, follicular stimulating hormone; GnRH, gonadotropin-releasing hormone; HPA, hypothalamic–pituitary–adrenal; HPG, hypothalamic–pituitary–gonadal; LH, luteinizing hormone.

Figure 2.

Diagnostic guidelines for precocious puberty in girls (MAS). CNS, central nervous system; DLK1, delta-like homolog 1; GnRH, gonadotropin-releasing hormone; KISS1, kisspeptin; KISS1R, kisspeptin receptor; MAS, McCune-Albright syndrome; MKRN3, makorin ring finger 3.
Diagnostic guidelines for precocious puberty in girls (MAS). CNS, central nervous system; DLK1, delta-like homolog 1; GnRH, gonadotropin-releasing hormone; KISS1, kisspeptin; KISS1R, kisspeptin receptor; MAS, McCune-Albright syndrome; MKRN3, makorin ring finger 3.

Figure 3.

Diagnostic guidelines for precocious puberty in boys. CAH, congenital adrenal hyperplasia; CNS, central nervous system; DLK1, delta-like homolog 1; GnRH, gonadotropin-releasing hormone; KISS1, kisspeptin; KISS1R, kisspeptin receptor; LH, luteinizing hormone; MKRN3, makorin ring finger 3.
Diagnostic guidelines for precocious puberty in boys. CAH, congenital adrenal hyperplasia; CNS, central nervous system; DLK1, delta-like homolog 1; GnRH, gonadotropin-releasing hormone; KISS1, kisspeptin; KISS1R, kisspeptin receptor; LH, luteinizing hormone; MKRN3, makorin ring finger 3.

Tanner classification of pubic hair in girls

TannerCharacteristics
1Prepubertal
2Sparse growth of long, slightly pigmented downy hair, straight or slightly curled, chiefly along labia
3Considerably darker, coarser, and more curled. The hair spreads sparsely over the junction of the pubes
4Hair now adult in type, but area covered is still considerably smaller than in the adult. No spread to the medial surface of the thighs
5Adult in quality and type with distribution of the horizontal (or classically “feminine”) pattern. Spread to medial surface of thighs but not up linea alba or elsewhere above the base of the inverse triangle (spread up linea alba occurs late and is rated as stage VI)

Tanner classification of breast development in girls [6]

TannerCharacteristics
1Prepubertal: elevation of papilla only
2Breast bud stage: elevation of breast and papilla as a small mound. Enlargement of areola diameter
3Further enlargement and elevation of breast and areola, with no separation of their contours
4Projection of areola and papilla to form a secondary mound above the level of the breast
5Mature stage: projection of papilla only, due to recession of the general contour of the breast

Tanner classification of pubic hair in boys

TannerCharacteristics
1Prepubertal
2Sparse growth of long, slightly pigmented downy hair, straight or slightly curled, chiefly at the base of the penis
3Considerably darker, coarser, and more curled. The hair spreads sparsely over the junction of the pubes
4Hair now adult in type, but area covered is still considerably smaller than in the adult. No spread to the medial surface of the thighs
5Adult in quality and type with distribution of the horizontal (or classically “feminine”) pattern. Spread to medial surface of thighs but not up the linea alba or elsewhere above the base of the inverse triangle (spread up linea alba occurs late and is rated as stage VI)

Physical examination of precocious puberty

Physical examinationDetailsReasons
BreastAccording to Tanner stagingAssess breast development
TestesEvaluate size using Prader orchidometerAssess testicular development to differentiate causes
PenisAccording to Tanner stagingAssess penile development
ClitorisMeasure length in centimetersAssess clitoral development, especially in heterosexual precocity cases
Pubic hairAccording to Tanner stagingAssess pubic hair development
Vulvar mucosaColor of mucosaAssess vulvar mucosa appearance which reflect estrogenic effect
RashCheck for café-au-lait spots (irregular border)Consider McCune Albright syndrome
Visual fieldAssess visionPituitary gland tumors may affect vision
Abdominal massPalpate abdominal areaDetect abdominal tumors capable of hormone production
Dysmorphic featuresAll dysmorphic features should be observed and recordedPallister–Hall syndrome, William syndrome, Temple syndrome are the examples of syndrome associated with precocious puberty

Etiology of CPP [18]

SystemDiseases
CNS lesionsCongenital
– Hypothalamic hamartoma– Suprasellar arachnoid cysts– Hydrocephalus– Glioma or neurofibromatosis type 1– Tuberous sclerosis– Septo-optic dysplasia– Chiari malformations and myelomeningocele Acquired– Tumors: astrocytoma, ependymoma, pinealoma, hypothalamic or optic glioma– Post-insults (perinatal, infection, trauma, radiotherapy)– Granulomatous disease– Cerebral palsy
No CNS lesions– Idiopathic– Endocrine disruptors– Genetic changes: gain-of-function mutations in the genes encoding KISS1 and KISS1R: formerly called GPR54: G-protein coupled receptor, loss-of-function mutation in MKRN3 and DLK1– Early exposure to sex steroids (secondary CPP)

Etiology of PPP [19]

SystemDiseases
Boys–Beta-HCG secreting tumor (CNS/outside CNS)– Androgen secretion by adrenal glands and testes–CAH– Virilizing adrenal neoplasm– Leydig cell tumor– Familial testotoxicosis
Girls– Ovarian cyst– Estrogen secreting ovarian or adrenal glands
Both sex– MAS (PPP, irregular border café au lait spot & fibrous dysplasia)– Hypothyroidism– Exogenous sex steroid

Genetic mutation in CPP

GeneProteinDiseases
MKRN3 [20]MKRN3Suppression of GnRH secretion
KISS1KISS1Disruption of puberty regulation
KISS1R [21]KISS1 receptorImpair response to KISS1 signaling
DLK1 [5]DLK1Imprinting disorder affecting pubertal timing
LIN28BLin 28 Homolog BUnknown, homolog of Caenorhabditis elegans protein may play in GnRH secretion
NPYR1NPYR1Inhibitory effect on GnRH pulse activity
TAC3 [22]Neurokinin BPlay role in GnRH release
TACR3Neurokinin B receptorNeurokinin receptors, which is G protein-coupled receptor that bind to neurokinin B may play a role in GnRH release.
GABRA1 [23]Gamma amino butyric acid A1 receptor α-1 subunitGABA-A receptor α-1 subunit that binds to GABA may inhibit GnRH release.

Tanner classification of genital development in boys [7]

TannerCharacteristics
1Prepubertal
2Enlargement of scrotum and testes. Skin of scrotum reddens and changes in texture
3Enlargement of penis, which occurs at first mainly in length. Further growth of testes and scrotum
4Increased size of penis with growth in breadth and development of glans. Testes and scrotum larger; scrotal skin darkened
5Genitalia adult in size and shape
DOI: https://doi.org/10.2478/abm-2025-0009 | Journal eISSN: 1875-855X | Journal ISSN: 1905-7415
Language: English
Page range: 69 - 77
Published on: Apr 30, 2025
In partnership with: Paradigm Publishing Services
Publication frequency: 6 issues per year

© 2025 Khomsak Srilanchakon, Vichit Supornsilchai, Suttipong Wacharasindhu, Martin O. Savage, published by Chulalongkorn University
This work is licensed under the Creative Commons Attribution 4.0 License.