GnRH Stimulation Test Protocol for Precocious Puberty in an 8-Year-Old Female
For an 8-year-old girl with suspected precocious puberty, obtain a single blood sample for LH measurement at 3 hours after subcutaneous administration of 20 mcg/kg leuprolide acetate—this single timepoint has 100% sensitivity for diagnosing central precocious puberty. 1
Pre-Test Evaluation Required
Before performing the GnRH stimulation test, complete the following baseline assessments:
- Measure baseline gonadotropins (FSH, LH) and estradiol levels to determine if central (gonadotropin-dependent) or peripheral (gonadotropin-independent) precocious puberty is present 2
- Obtain bone age X-ray to assess skeletal maturation and predict impact on final height 2
- Perform pelvic ultrasound to assess ovarian volume, uterine size and stimulation, and rule out ovarian tumors or cysts 3, 2
- Document height, weight, growth velocity, and Tanner staging to assess pubertal development progression 2
GnRH Analog Stimulation Test Protocol
Since native GnRH is no longer available, GnRH analogs (specifically leuprolide acetate) are now the standard for stimulation testing 1:
- Administer 20 mcg/kg of subcutaneous leuprolide acetate 1
- Draw a single blood sample for LH measurement at 3 hours post-injection 1
- A peak LH >5 mIU/mL at 3 hours confirms central precocious puberty with 100% sensitivity (95% CI: 94-100%) 1
Alternative Sampling Timepoints
While the 3-hour sample is optimal for diagnosis, other protocols exist:
- 40-minute post-injection sample has 98% sensitivity and 100% specificity when using LH cut-off of 5 IU/L 4
- 90-minute post-injection sample can be used, though it may have lower specificity compared to the 3-hour timepoint 5
- The 1-hour sample captures only 88% of responders, making it inadequate as a single timepoint 1
Important Caveats
Do not confuse isolated pubic or axillary hair (adrenarche) with true precocious puberty—the first physical sign of HPG axis activation in girls is breast development (thelarche), not pubic hair 3, 6. Adrenarche does not indicate activation of the hypothalamic-pituitary-gonadal axis 6.
When to Order Brain MRI
- Brain MRI is indicated for confirmed central precocious puberty, especially in girls under 6 years of age who have the highest risk (>30%) of CNS abnormalities 2, 7
- For girls aged 6-8 years (like this patient), the likelihood of identifying a CNS lesion is lower (2-7%), but MRI should still be considered based on clinical presentation 2
- MRI is mandatory if neurological symptoms are present (severe headaches, visual changes, seizures) 2
- The American College of Radiology recommends MRI of the sella and hypothalamic-pituitary axis with gadolinium contrast as the preferred imaging modality 2
Referral Pathway
Refer to a pediatric endocrinologist after obtaining baseline LH, FSH, and estradiol levels if the patient has Tanner stage 2 breast development before age 8 years 3. The endocrinologist will determine whether the GnRH stimulation test is necessary based on baseline values, as elevated basal LH may be sufficient for diagnosis in some cases 3.