Precocious Puberty

Precocious puberty is defined as the appearance of secondary sexual characteristics before 8 years of age in girls and 9 years in boys (in Caucasian populations of developed countries). This includes breast development or testicular enlargement, as well as the premature appearance of pubic and axillary hair (typically between 8 and 13 years in girls and 9 and 14 in boys). This condition may lead to medium- and long-term complications, making timely treatment advisable.

Although often confused, early puberty is not synonymous with precocious puberty; it refers to cases in which girls show pubertal development around 8 years and boys around 9 years. While not considered pathological per se, treatment is recommended to prevent potential adverse effects in the future.

Precocious puberty is a rare disorder, although its incidence has increased significantly in recent years, likely due to lifestyle changes and environmental factors that cause hormonal imbalances, such as exposure to pollutants. Prognosis varies, but with timely and appropriate treatment, most complications can be mitigated.

Symptoms

The most common symptoms of precocious puberty include:

• Pubarche: growth of pubic hair.
• Adrenarche: emergence of axillary hair.
• Strong body odor.
• Acne.
• Accelerated bone age.
• In girls:
• Thelarche: onset of breast budding.
• Menarche: first menstruation.
• In boys:
• Testicular and penile enlargement.
• Appearance of facial hair.
• Deepening of the voice.

When only one secondary sexual characteristic appears prematurely, it is considered acceptable pubertal development if it persists until the normal age or even regresses until true puberty occurs. It can present in three distinct forms:

• Isolated premature thelarche: breast tissue development in girls without other pubertal signs.
• Isolated premature pubarche: appearance of pubic hair without other pubertal characteristics.
• Isolated premature menarche: cyclical vaginal bleeding in girls without other secondary sexual characteristics.

Causes

The main causes of precocious puberty include, although they are not always precisely identifiable:

• Central precocious puberty: early activation of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in the release of gonadotropin-releasing hormones (GnRH) that regulate reproductive function.
• Congenital:
• Hypothalamic hamartoma: benign tumor in the hypothalamus at the base of the brain.
• Neurofibromatosis type 1: genetic disorder producing benign nerve tumors.
• Arachnoid cysts: cerebrospinal fluid-filled sacs in the meninges surrounding the brain.
• Hydrocephalus: fluid accumulation in the brain.
• Tuberous sclerosis: genetic condition causing hamartomas in the brain, heart, lungs, or kidneys.
• Septo-optic dysplasia: congenital neurological disorder affecting the optic nerve, midline structures, and pituitary, causing hormonal dysfunctions.
• Chiari malformation: brain tissue protrudes into the spinal canal.
• Acquired:
• Astrocytomas: brain tumors arising from astrocytes, support cells of the CNS.
• Gliomas: tumors originating in glial cells surrounding neurons.
• Craniopharyngiomas: benign cysts near the hypothalamus and pituitary.
• Other types of brain tumors.
• Neonatal infections.
• Cerebrovascular accident.
• Traumatic brain injury.
• Cerebral palsy.
• Hydrocephalus.
• Encephalopathies: brain damage or disease causing mental status changes, confusion, or behavioral alterations.
• Peripheral precocious puberty: autonomous secretion of sex steroids (estrogens or testosterone) independent of GnRH.
• Monogenic: caused by mutation in a single gene.
• Gain-of-function mutations in KISS1/KISS1R, a puberty-regulating gene: receptor becomes hyperactive, overresponding to kisspeptin, which controls sperm and egg production.
• Loss-of-function in MKRN3, a gene that inhibits puberty.
• Loss-of-function in DLK1, related to adipose tissue development.
• Loss-of-function in MECP2, encoding a protein critical for nervous system development.
• Syndromic: results from a genetic syndrome.
• Temple syndrome: chromosome 14 alteration causing muscular hypotonia, facial dysmorphism, obesity, or premature puberty.
• Rett syndrome: affects brain development.
• Williams-Beuren syndrome: microdeletion in chromosome 7 affecting elastin production.
• Prader-Willi syndrome: gene expression defects in chromosome 15 causing hypothalamic abnormalities.
• Idiopathic: unknown cause.
• Secondary: exposure to sex steroids.
• Combined or mixed precocious puberty: often evolves from peripheral to central precocious puberty, as steroid exposure may accelerate HPG axis activation.
• Congenital:
• McCune-Albright syndrome: GNAS gene mutation affecting bones, skin, and endocrine system.
• Congenital adrenal hyperplasia: limits hormone production, causing adrenal androgen excess.
• Generalized glucocorticoid resistance: compensatory increase in ACTH, stimulating androgen production.
• In males, testotoxicosis: activation of luteinizing hormone receptor stimulates testosterone production.

• Acquired:
• Ovarian follicular cysts.
• Tumors in ovaries, testes, or adrenal glands.
• In boys, HCG-secreting tumors.
• Exogenous exposure to sex steroids.
• Severe primary hypothyroidism.

Risk Factors

Risk of precocious puberty increases in the following situations:

• Sex: more common in girls.
• Obesity: body fat produces leptin, a hormone involved in pubertal development.
• Head radiotherapy.
• Presence of conditions that can trigger precocious puberty.
• Family history.
• Low birth weight.
• Internationally adopted children: higher risk than general population.

Complications

Significant complications include:

• Short stature: although patients may initially be taller than average in early childhood, early bone maturation often results in adult height below average.
• Emotional problems: coping with premature changes can lead to low self-esteem, anxiety, or depression.
• Social problems: children with precocious puberty may feel different, leading to social isolation or difficulty integrating with peers.
• Early sexual behavior: particularly in girls, onset of sexual activity may occur earlier, increasing the risk of unintended pregnancy.
• Higher susceptibility to substance use.

Prevention

In most cases, precocious puberty cannot be prevented. Risk can be reduced by maintaining a healthy weight, following a balanced diet, ensuring proper sleep hygiene, and limiting exposure to hormones through medications, supplements, or cosmetics.

Which Specialist Treats Precocious Puberty?

Precocious puberty is usually detected in pediatrics and managed by the endocrinology and nutrition specialty.