SAT-240 - Prevalence of Brain Abnormalities and Neuropsychiatric Symptoms in Children with Central Precocious Puberty: Stratification by Hypothalamic vs. Non-Hypothalamic Lesions

Background: Brain magnetic resonance imaging (MRI) is the primary tool for investigating anatomical lesions implicated in the etiology of central precocious puberty (CPP). Neuropsychiatric symptoms can be associated with CPP and prevalence varies by the type and location of brain lesions.

Objective: To determine the frequency of brain abnormalities and neuropsychiatric symptoms in children with CPP.

Methods: Retrospective review of brain MRI in 205 CPP children (177 girls [86.4%], 28 boys [13.6%]) followed in a pediatric endocrinology unit (1990–2024). Images were re-analyzed by an experienced radiologist, confirming initial reports. Lesions were classified as congenital/acquired, hypothalamic/non-hypothalamic, and CPP-related/incidental. Neuropsychiatric symptoms (neuropsychomotor developmental delay, attention and learning deficits, seizures, speech delay, depression, anxiety, socialization disorders and autism spectrum disorder) and clinical data were extracted from medical records.

Results: Normal brain MRI was found in 131/205 (64%) and abnormalities in 74 (36%), of which 50 (24.4%) were CPP-related lesions and 24 (11.7%) incidental lesions. Among CPP-related lesions, 28 (56%) were hypothalamic and 22 (44%) non-hypothalamic. Neuropsychiatric symptoms were found in 28.9% overall (57.1% boys vs 24.4% girls), 53.5% in hypothalamic and 77% in non-hypothalamic lesions; 16% had normal MRI. Hypothalamic abnormalities were associated with earlier symptom onset (median 2 y [0.6–6] vs. 6 y [5–7.6]; p=0.001), higher height Z-score (1.97 [0.7–3.94] vs. 0.7 [-1 to 1.69]; p=0.004), and more advanced bone age (6.8 y [4–12] vs. 9.5 y [7.8–13]; p=0.05) than non-hypothalamic lesions.
In girls, normal MRI was found in 70.6% (125/177); abnormalities in 29.4%, including 30 CPP-related (18 congenital: 11 hypothalamic hamartomas, 3 myelomeningoceles, 2 corpus callosum agenesis, 1 arachnoid cyst, 1 choroid plexus papilloma; 12 acquired: 7 hydrocephalus, 3 optic pathway gliomas, 2 post-insult) and 22 incidental (12.4%). Abnormalities in girls > 6 years were found in 13% (21/152); 6% of asymptomatic girls had CPP-causative lesions. In boys, normal MRI was found in 21.4% (6/28); 20 had CPP-related lesions (9 congenital hamartomas; 11 acquired: 1 pilocytic astrocytoma, 1 optic pathway glioma, 4 hydrocephalus, 2 pineal tumors, 1 dysgerminoma, 1 postnatal insult, 1 teratoma).

Conclusions: CPP brain abnormalities predominated in boys, mostly hypothalamic in both sexes (hamartoma most common). Hypothalamic lesions showed earlier onset, greater height acceleration, and more advanced bone age than non-hypothalamic. Neuropsychiatric symptoms were highly prevalent in CPP—more frequent with non-hypothalamic lesions, but also notable with normal MRI—highlighting location-dependent differences and need for comprehensive evaluation including neuropsychiatric assessment.

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