Overview/Definition
Definition:
• Precocious puberty is onset of secondary sexual characteristics before age 8 years in girls and 9 years in boys
Classified as central (GnRH-dependent) involving hypothalamic-pituitary-gonadal axis activation or peripheral (GnRH-independent) from other sources of sex hormones
Affects 1:5000-10000 children.
Epidemiology:
• Overall prevalence 1:5000-10000 children with female predominance (10-20:1 for central precocious puberty)
Age-specific prevalence increasing due to improved nutrition, obesity
Central precocious puberty more common in girls (90-95%), peripheral more common in boys
Earlier onset correlates with greater psychological impact.
Age Distribution:
• Girls: Central precocious puberty typically 6-8 years onset
Boys: Central precocious puberty typically 5-9 years onset, often pathological cause
Peak referral age 6-7 years girls, 7-8 years boys
Rapid progression variant: 6-12 months from thelarche to menarche.
Clinical Significance:
• Important topic for DNB Pediatrics and NEET SS examinations covering classification, diagnostic workup, treatment indications, psychological impact
Understanding GnRH analog therapy mechanisms, dosing, monitoring crucial
Knowledge of long-term outcomes and final height predictions essential.
Age-Specific Considerations
Newborn:
• Neonates (0-28 days): Mini-puberty normal physiological phenomenon with transient gonadotropin elevation
McCune-Albright syndrome may present with café-au-lait spots
Congenital adrenal hyperplasia screening important
True precocious puberty extremely rare in neonates.
Infant:
• Infants (1-24 months): Isolated thelarche or pubarche may occur
McCune-Albright syndrome more apparent
Ovarian cysts in girls normal physiological finding
Central nervous system lesions rare but possible
Careful monitoring for progression needed.
Child:
• Children (2-12 years): Peak presentation age group
Central precocious puberty most common in girls
Boys require more extensive evaluation for pathological causes
Psychological impact significant
School performance and peer relationships affected
Growth acceleration and bone age advancement prominent.
Adolescent:
• Adolescents (12-18 years): Rapid progression forms may present
Late recognition of earlier onset
Psychological adjustment issues
Final height concerns if untreated
Treatment decisions balance benefits vs
risks
Transition to adult care considerations.
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Clinical Presentation
Symptoms:
• Girls: Breast development (thelarche) earliest sign, followed by pubic hair (pubarche), body odor, acne, growth spurt
Menarche typically 1-2 years after thelarche
Boys: Testicular enlargement (>4 ml or >2.5 cm length) earliest sign, followed by penile growth, pubic hair, voice changes.
Physical Signs:
• General: Advanced height and weight percentiles, increased growth velocity >6 cm/year
Tanner staging: Assess breast development, genital development, pubic hair distribution
Neurological: Signs of CNS lesions (headache, visual field defects)
Dermatological: Acne, body odor, axillary hair.
Severity Assessment:
• Mild: Isolated breast or testicular development, normal growth velocity
Moderate: Multiple secondary sexual characteristics, accelerated growth, bone age advanced 1-2 years
Severe: Complete pubertal development, menarche in girls, bone age advanced >2 years, behavioral changes.
Differential Diagnosis:
• Normal variants: Premature thelarche, premature pubarche, normal variation in timing
Peripheral causes: McCune-Albright syndrome, ovarian/testicular tumors, adrenal disorders
Central causes: CNS tumors, infections, trauma, irradiation
Exogenous: Hormone exposure, medications.
Diagnostic Approach
History Taking:
• Onset and progression: Timeline of physical changes, growth patterns
Family history: Age of parental puberty, family members with early/late puberty
Medical history: Head trauma, CNS infections, irradiation, medications
Behavioral changes: Mood, aggression, sexualized behavior.
Investigations:
• Hormonal evaluation: LH, FSH (basal and GnRH-stimulated), estradiol/testosterone, DHEA-S, 17-OHP
Imaging: Bone age X-ray, pelvic ultrasound (girls), brain MRI if indicated
Additional: Thyroid function tests, IGF-1, tumor markers (AFP, β-hCG) if peripheral puberty suspected.
Normal Values:
• Prepubertal LH: <0.3 IU/L, FSH: <4 IU/L
GnRH stimulation test: LH peak >5 IU/L suggests central puberty
Bone age: Compare to chronological age using Greulich-Pyle atlas
Normal testicular volume: <4 ml prepubertal, >4 ml pubertal onset.
Interpretation:
• Central vs
peripheral: GnRH stimulation test differentiates, LH-predominant response indicates central
Bone age advancement: >2 years suggests significant hormonal exposure
Brain imaging: Indicated if boys <9 years, girls <6 years with central precocious puberty.
Management/Treatment
Acute Management:
• Initial evaluation: Complete physical examination, Tanner staging, growth measurements
Hormonal assessment: GnRH stimulation test if indicated
Psychological assessment: Emotional adjustment, behavioral changes
Family counseling: Education about condition and treatment options.
Chronic Management:
• GnRH analog therapy: Indicated for central precocious puberty with psychological distress, predicted short final height, rapid progression
Treatment duration: Until chronologically appropriate age (typically 11-12 years girls, 12-13 years boys)
Monitoring: Clinical response, growth, bone age.
Lifestyle Modifications:
• Age-appropriate activities: Avoid sexualized behaviors, maintain childhood activities
School support: Teacher education, peer interaction management
Nutrition: Healthy diet, weight management if obese
Exercise: Age-appropriate physical activities, monitor for excessive training.
Follow Up:
• Treatment monitoring: Every 3-4 months initially, then every 6 months
Growth assessment: Height, weight, growth velocity calculations
Hormone monitoring: Suppression of LH, FSH, sex steroids
Bone age: Annual assessment
Psychological support: Ongoing counseling as needed.
Age-Specific Dosing
Medications:
• Leuprolide acetate: 7.5-15 mg IM monthly (3.75 mg if weight <20 kg)
11.25-30 mg IM every 3 months
Goserelin acetate: 3.6 mg subcutaneous every 4 weeks
Triptorelin: 3.75 mg IM monthly
Histrelin implant: 50 mg subcutaneous annually.
Formulations:
• Long-acting preparations: Monthly or 3-monthly depot formulations preferred for compliance
Subcutaneous implants: Histrelin implant provides 12 months suppression
Nasal preparations: Daily nasal spray available but compliance issues
Injectable: Various depot formulations available.
Safety Considerations:
• Side effects: Hot flashes, mood changes, injection site reactions, initial testosterone/estrogen flare
Bone density: Monitor during prolonged therapy
Growth: May cause temporary growth deceleration
Contraindications: Pregnancy, undiagnosed abnormal vaginal bleeding.
Monitoring:
• Efficacy: Clinical suppression of pubertal progression, hormone suppression (LH <4 IU/L)
Safety: Growth velocity, bone density, injection site reactions
Laboratory: LH, FSH, sex steroids every 6 months
Imaging: Annual bone age, pelvic ultrasound if indicated.
Prevention & Follow-up
Prevention Strategies:
• Primary prevention: Limited options, mainly lifestyle factors (obesity prevention)
Secondary prevention: Early recognition and treatment to prevent psychological and physical complications
Avoidance of exogenous hormone exposure
Regular pediatric follow-up for early detection.
Vaccination Considerations:
• Standard immunization schedule maintained
HPV vaccination: Consider earlier administration given early sexual maturation potential
Meningococcal vaccine: Standard timing unless CNS involvement
No specific contraindications with GnRH analog therapy.
Follow Up Schedule:
• Treatment phase: Every 3-4 months initially, then every 6 months
Post-treatment: Every 6-12 months to monitor pubertal progression resumption
Long-term: Annual follow-up until final height achieved
Transition: Adult reproductive endocrinology if needed.
Monitoring Parameters:
• Growth: Height, weight, growth velocity, bone age progression
Hormonal: LH, FSH, sex steroid suppression
Psychological: Behavioral adjustment, school performance
Physical: Tanner staging regression/stability
Bone health: DEXA scan if prolonged therapy.
Complications
Acute Complications:
• Initial flare reaction: Temporary increase in sex hormones during first month of GnRH analog therapy
Injection site reactions: Pain, swelling, sterile abscess formation
Mood changes: Depression, anxiety, behavioral problems
Allergic reactions: Rare but possible with any formulation.
Chronic Complications:
• Untreated consequences: Short final height due to early epiphyseal closure, psychological maladjustment, early sexual activity risks
Treatment-related: Bone density reduction during therapy, growth deceleration
Late effects: Unknown long-term reproductive consequences.
Warning Signs:
• Treatment failure: Continued pubertal progression, inadequate hormone suppression
Severe mood changes: Depression, suicidal ideation, aggressive behavior
Injection complications: Persistent pain, signs of infection, allergic reactions
Growth concerns: Excessive deceleration of linear growth.
Emergency Referral:
• Immediate referral for: Severe mood changes, suicidal ideation, signs of CNS tumor
Pediatric endocrinology consultation: All cases of precocious puberty for evaluation and management
Psychology/psychiatry referral: Significant behavioral or emotional problems.
Parent Education Points
Counseling Points:
• Precocious puberty is medical condition, not behavioral problem
Treatment can help preserve final height and reduce psychological impact
Most children with central precocious puberty have excellent long-term outcomes
Importance of compliance with therapy for optimal results.
Home Care:
• Age-appropriate expectations: Maintain childhood activities despite physical maturation
Emotional support: Open communication, reassurance about normalcy
Hygiene: Body odor, acne management, menstrual hygiene if applicable
Privacy: Respect child need for privacy during physical changes.
Medication Administration:
• GnRH analog injections: Clinic administration typically required, proper storage if home administration
Side effect monitoring: Watch for mood changes, injection site reactions
Compliance: Importance of regular dosing schedule
Emergency contacts: When to call healthcare provider.
When To Seek Help:
• Contact healthcare provider for: Continued pubertal progression despite treatment, severe mood changes, injection site problems
Emergency care for: Signs of depression, behavioral changes concerning for safety, severe allergic reactions, signs of increased intracranial pressure.