What is central precocious puberty and how is it treated?

Central Precocious Puberty: Information for Well-Educated Non-Medical Persons

Central precocious puberty (CPP) is defined as the premature activation of the hypothalamic-pituitary-gonadal axis causing pubertal development before age 8 in girls or age 9 in boys, and is primarily treated with gonadotropin-releasing hormone (GnRH) analogs to preserve adult height potential and prevent psychosocial difficulties. 1

What is Central Precocious Puberty?

Central precocious puberty occurs when the brain's normal puberty control center (hypothalamus) activates too early, causing:

• Early development of secondary sexual characteristics
• Acceleration of growth velocity
• Rapid bone maturation
• Potential reduction in final adult height 1, 2

CPP can be:

• Idiopathic (no identifiable cause) - more common in girls
• Secondary to underlying conditions:
  • Central nervous system abnormalities (tumors, hamartomas, injuries)
  • Genetic causes (mutations in KISS1, KISS1R, MKRN3, and DLK1 genes)
  • Previous exposure to sex hormones
  • Environmental factors 3

Diagnosis

The diagnostic process for CPP involves multiple components:

1. Clinical Assessment:

   • Evaluation of pubertal development using Tanner staging
   • Growth acceleration
   • Bone age advancement (typically via X-ray of the hand/wrist) 1

2. Laboratory Testing:

   • Measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex steroid levels
   • GnRH stimulation test (gold standard) to confirm central activation 1, 4

3. Imaging Studies:

   • MRI of the brain/sella: The preferred imaging modality, especially important for:
     • Girls under age 6
     • Boys under age 9
     • Any child with neurological symptoms 5, 1
   • Pelvic ultrasound in girls to assess ovarian volume and uterine size 1

4. Genetic Testing:

   • Particularly important in familial cases 3

Treatment

Primary Treatment: GnRH Analogs

GnRH analogs are the mainstay of treatment for CPP. These medications work by:

• Desensitizing pituitary gonadotrophs
• Reducing LH release
• Halting ovarian/testicular stimulation 1, 2

Treatment Goals

1. Preserve final adult height potential

   • Earlier treatment initiation (especially in younger patients) better preserves height potential 1

2. Delay development of secondary sexual characteristics

   • Allows physical development to occur at an age more appropriate with peers 1, 6

3. Prevent psychosocial difficulties

   • Reduces emotional and social challenges associated with early puberty 1

Treatment Duration and Monitoring

• Treatment typically continues until the normal age of puberty 1
• Monitoring includes:
  • Regular assessment of growth velocity
  • Bone age evaluation
  • Pubertal development assessment 1

Long-Term Outcomes

Research on long-term outcomes after GnRH analog treatment shows:

• Good menstrual and reproductive function
• Possibly higher prevalence of polycystic ovary syndrome than in the general population
• Recovery of the hypothalamic-pituitary-gonadal axis after treatment 1, 2

Important Considerations

• Not all children with CPP require medical intervention; treatment decisions should be based on:

  • Predicted adult height impact
  • Rate of pubertal progression
  • Psychosocial considerations 2

• Treatment should begin immediately once the decision to treat is made to maximize height preservation 1

• MRI is crucial for evaluation, particularly in:

  • Young girls (under 6 years)
  • Boys with CPP (higher risk of CNS abnormalities)
  • Children with neurological symptoms 5, 1

• Newer, longer-acting GnRH analog formulations are now available, offering more convenient treatment options 4

Recent Advances

• Ultrasensitive LH assays have reduced the need for stimulation testing in some cases 4
• Better understanding of genetic factors governing puberty onset 3, 4
• Reassuring long-term outcomes regarding obesity, cardiovascular risk factors, and fertility 4