Brain MRI Findings in CPP Cluster in Younger Children

Key Takeaways

• In a retrospective MRI cohort of 1,087 children with CPP or EFP at a single Chinese center, intracranial lesions were detected in 14.5% of girls and 19.6% of boys.
• All 26 pathogenic lesions were identified in children with CPP, and none were found in children with EFP.
• Among girls younger than 6 years, overall lesion detection was 33.7% and pathogenic lesion prevalence was 16.8%, versus 12.1% and 0.2% in older girls.
• Among boys younger than 7 years, overall lesion detection was 53.8% and pathogenic lesion prevalence was 42.9%, versus 16.9% and 0.6% in older boys.
• Incidental findings were not associated with different baseline phenotype or short-term GnRHa response, whereas pathogenic lesions were associated with earlier onset, greater LH activation, and in treated girls higher drug exposure plus faster early growth.

Magnetic resonance imaging abnormalities in children with central precocious puberty (CPP) or early and fast puberty (EFP) can range from incidental cysts to lesions involving the hypothalamic-pituitary axis, and their clinical meaning is often less clear than their detection. Whether those lesion categories track with a different pubertal phenotype or early gonadotropin-releasing hormone agonist (GnRHa) course remains uncertain in practice. Imaging categories were reviewed alongside baseline endocrine features and short-term treatment response.

At the Child Growth Center of the First Affiliated Hospital of Sun Yat-sen University, a January 2011 through June 2023 retrospective cohort examined MRI findings in children with central precocious puberty and early/fast puberty. The cohort included 1,087 children who underwent complete brain and/or sellar magnetic resonance imaging (MRI), including 908 girls and 179 boys, at a single Chinese center. EFP was defined as girls aged 8 to 10 years or boys aged 9 to 11 years with hypothalamic-pituitary-gonadal (HPG) axis activation and accelerated bone maturation. Imaging was grouped as no lesion, other or incidental lesions, and pathogenic lesions defined as hypothalamic hamartoma or low-grade glioma, and baseline clinical features, luteinizing hormone (LH), follicle-stimulating hormone (FSH), bone-age measures, and growth parameters were compared with a treated subgroup followed for at least 1 year.

Overall intracranial lesion prevalence did not differ significantly by sex (P=0.089). All pathogenic intracranial lesions in CPP were confined to CPP rather than EFP, and the pathogenic findings were hypothalamic hamartoma or low-grade glioma. Within this center’s experience, pathogenic yield was concentrated in the youngest children, whereas older CPP groups and children with EFP had much lower yield. The authors note their findings are consistent with a newly issued Endocrine Society guideline recommending against routine MRI screening in girls 6–8 years and boys 8–9 years old, adding independent cohort data in support of that recommendation.

Children with pathogenic lesions had earlier pubertal onset and higher baseline and stimulated LH levels than peers with no lesion or incidental findings, while bone age advancement and height standard deviation score (SDS) for bone age did not differ significantly across lesion groups. In treated girls, the pathogenic-lesion group had a median cumulative 6-month GnRHa dose of 852.0 μg/kg, along with higher dosing (P=0.025) and faster 6-month growth velocity (P=0.007). Post-treatment hormonal suppression and 1-year height SDS change were otherwise similar across groups, and incidental lesions did not differ meaningfully from no-lesion cases in baseline phenotype or short-term response.

The retrospective design, single-center setting, and 1-year treatment window limit generalizability, and several sex-specific subgroup comparisons were based on small numbers. Post-treatment data were not available for boys with pathogenic lesions, leaving therapeutic comparisons unresolved in that subgroup. Within the authors’ interpretation, pathogenic-lesion yield was concentrated in younger children with CPP, while older CPP groups and children with EFP showed low pathogenic prevalence at this center.

In this cohort, pathogenic MRI findings clustered in younger children with CPP and tracked with earlier onset and stronger HPG-axis activation. Incidental structural findings behaved much like no-lesion cases over short-term follow-up, without a clear shift in baseline pubertal features or early GnRHa response. The main clinical distinction in this Chinese center was not MRI abnormality alone, but whether the abnormality appeared pathogenic.

Clinician Questions

What MRI findings were considered incidental in children with CPP or EFP?

The study’s other-lesion category included Rathke’s cleft cysts, pineal cysts, non-suprasellar arachnoid cysts, pituitary microadenomas, and pituitary stalk thickening. In this cohort of children with CPP or EFP, those incidental findings were not associated with different baseline pubertal features or short-term GnRHa response compared with no-lesion cases.

Why were GnRHa outcomes not analyzed for boys with pathogenic lesions in CPP?

Post-treatment data were not available for boys with pathogenic lesions in CPP, so therapeutic outcome comparisons could not be performed for that subgroup. The available male post-treatment comparisons were limited to boys with no lesion versus boys with incidental lesions.

What was reported for pituitary stalk thickening in children with CPP or EFP in this cohort?

Children with CPP or EFP who had pituitary stalk thickening showed normal hypothalamic-pituitary function, negative serum alpha-fetoprotein and human chorionic gonadotropin, and no malignant features identified. Within this cohort, those findings did not appear to alter pubertal progression or short-term treatment response.