Description

• Defined as the appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys
• Normal puberty occurs between age 8 and 14 years in girls and 9 and 14 years in boys (1,2).
• There are three types:
  • Gonadotropin-dependent precocious puberty (GDPP) or central precocious puberty; manifests secondary sexual characteristics in harmony such as bilateral breasts or testicular enlargement
  • Gonadotropin-independent precocious puberty (GIPP) or peripheral precocious puberty. Does not manifest secondary sexual characteristics in harmony. It presents a clinical picture of incomplete puberty.
  • Incomplete precocious puberty such as premature adrenarche and premature thelarche

Epidemiology

• More prevalent in African American children compared to white children
• Attention to racial differences is advised because African American girls normally develop secondary sexual characteristics at an earlier age than white girls.
• It is 10 times more common in girls than in boys.
• 80–90% of affected girls have idiopathic central precocious puberty (1,3).

Incidence
Estimated incidence of 0.01–0.05% per year in the United States (1)

Prevalence
In a population-based Danish study from 1993 to 2001, it was found that 0.2% of Danish girls and <0.05% of Danish boys were affected by some type of precocious puberty (3).

Etiology and Pathophysiology

• GDPP (4)
  • Caused either by a central dysregulation of the hypothalamic-pituitary-gonadal axis resulting in overproduction of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or by ectopic hormone production such as hCG by a neoplasm
  • Characterized by pubertal levels of FSH and LH
  • Affected individuals have advanced bone age and short stature due to premature epiphyseal closure.
  • Different causes include the following:
    • Idiopathic central precocious puberty is the most common type.
    • CNS lesions such as glioma, astrocytoma, hypothalamic hamartoma, and arachnoid cysts
    • Congenital CNS anomaly such as hydrocephalus
    • Infection such as encephalitis and meningitis
    • Trauma
    • CNS irradiation
    • Primary hypothyroidism
    • Gain-of-function mutation of the GPR54 protein, which is part of an essential signaling complex for the initiation of puberty
• GIPP (1)
  • Caused by excess secretion of androgens or estrogens produced from the gonads or adrenal glands or from exogenous sources
  • FSH and LH levels are in the prepubertal range.
  • Causes include the following:
    • Girls
      • Ovarian tumors such as Leydig cell tumors or granulosa cell tumors
      • Ovarian cyst
    • Boys
      • Germ cell tumors secreting hCG
      • Leydig cell tumors
      • Familial male-limited precocious puberty or testotoxicosis caused by an activation mutation of the LH-receptor gene
    • Both boys and girls
      • Adrenal androgen production due to adrenocorticotropic hormone (ACTH) stimulation: congenital adrenal hyperplasia, 21-hydroxylase deficiency, 11-β-hydroxylase deficiency
      • McCune-Albright syndrome: a triad of precocious puberty, café au lait skin pigmentation, and fibrous dysplasia of the bone
      • Excess exogenous estrogen exposure from creams, sprays, or ointments
• Incomplete precocious puberty (1)
  • A variant of normal puberty
  • Presents with early development of secondary sexual characteristics
• Premature thelarche
  • Can occur in two peaks: during the first 2 years of life and between ages 6 and 8 years
  • More common in black and Hispanic children
  • 14–20% of children affected can develop true precocious puberty.
  • Characterized by
    • Development of isolated unilateral or bilateral breasts
    • Absence of other sexual characteristics
    • Normal linear growth and normal bone age
    • Sex hormone levels are in the prepubertal range.
• Premature adrenarche
  • Characterized by the appearance of pubic and/or axillary hair, acne, and adult body odor before the age of 8 years in girls and 9 years in boys
  • Normal linear growth and bone age
  • Common in girls and individuals with insulin resistance and obesity
  • 20% of girls affected can develop polycystic ovarian syndrome as adults.
  • Most cases are idiopathic but may be caused by congenital adrenal hyperplasia, 21-hydroxylase deficiency, Cushing disease, dehydroepiandrosterone sulfate (DHEA-S) deficiency, autonomous endogenous or exogenous excess.

General Prevention

Precocious puberty is not preventable, but early detection is helpful, so the following steps are recommended:

• Careful growth chart review
• Thorough physical exam for early signs of puberty
• Anticipatory guidance in late childhood should include normal pubertal development.