Female patient: breast development (Tanner ≥ 2) before age 8 years
Refer to pediatric endocrinology
Initial Workup
Labs
- Basal LH, FSH, Estradiol (early morning)
- TSH — exclude hypothyroidism-induced PP
- DHEAS, 17-OHP — exclude adrenal etiology
- CAH, adrenal tumor
Bone Age
- Left hand & wrist X-ray
- Compare BA to CA
- Significant: BA ≥ CA + 2 years
Bone age advanced ≥ 2 years above chronological age?
no →
Observe / Monitor
- Consider isolated thelarche
- Tanner + height every 3–6 months
- Repeat bone age at 6–12 months
- Re-evaluate if progression accelerates
yes ↓
Leuprolide Stimulation Test
- Leuprolide acetate 20 mcg/kg subcutaneous (max 500 mcg)
- Measure serum LH at 1 hour post-injection
- Pubertal threshold: peak LH ≥ 5 IU/L
- LH:FSH ratio > 0.66 also supports pubertal response; some centers use threshold ≥ 3.3 IU/L
Peak LH ≥ 5 IU/L (pubertal response)?
no →
Not Central PP — consider
- McCune-Albright syndrome
- Ovarian cyst or tumor
- Isolated / premature thelarche
- Exogenous estrogen exposure
yes ↓
central precocious puberty confirmed
MRI Brain — with and without gadolinium
- Indicated for all girls with confirmed CPP
- Prioritize urgently: age < 6 years, neurological symptoms, or very rapid progression
- Evaluate for: hypothalamic hamartoma, glioma, suprasellar mass
Treatment with GnRH agonist indicated?
Treat if any
Age at onset < 6 years ·
BA > 2 years above CA ·
Growth velocity markedly ↑ ·
Predicted height below target ·
>1 Tanner stage in 6 months ·
Significant psychosocial distress
no →
Expectant Management
- Tanner + growth every 3–6 months
- Bone age annually
- Reassess treatment annually
- Treat if new criteria emerge
yes ↓
GnRH Agonist Therapy
Treatment Options
- Leuprolide acetate (Lupron Depot-Ped)
11.25 mg IM every 3 months
- Leuprolide acetate (Lupron Depot-Ped)
30 mg IM every 6 months
- Histrelin implant (Supprelin LA)
50 mg SC, replaced annually
On-Therapy Monitoring
- Visit q3–6 months: Tanner staging, growth velocity
- Estradiol + LH to confirm suppression
- Bone age annually
- Repeat stim test if breakthrough puberty suspected
Discontinuation
- Target stop age: ~10.5–11 years (to align with normal pubertal timing in girls)
- Or bone age ≥ 12 years · reassess annually · patient/family preference
- After discontinuation: puberty resumes 6–12 months later; menarche ~12–18 months post-discontinuation