Precocious puberty due to intracranial germ cell tumors: a case-control study
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Updated: Sep 2, 2025
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Published on: February 17, 2023
1Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
Intracranial germ cell tumors can cause precocious puberty (PP) through gonadotropin-releasing hormone (GnRH)-dependent or independent pathways. GnRH-independent PP often resolves with tumor treatment, unlike GnRH-dependent PP.
Area of Science:
- Pediatric Endocrinology
- Neuro-oncology
- Reproductive Medicine
Background:
- Intracranial germ cell tumors (GCTs) are a significant cause of central precocious puberty (PP) in children.
- PP can manifest through gonadotropin-releasing hormone (GnRH)-dependent or GnRH-independent mechanisms.
- Human chorionic gonadotropin (hCG) elevation is a key marker in GCTs and can drive PP.
Purpose of the Study:
- To differentiate between GnRH-dependent and GnRH-independent PP in children with intracranial GCTs.
- To analyze the relationship between tumor regression and hormonal changes in these patients.
- To identify factors predicting PP development in children with intracranial GCTs and elevated hCG.
Main Methods:
- Retrospective single-center study of 37 patients with intracranial GCTs and PP.
- Comparison with 25 age-matched prepubertal controls with elevated hCG.
- Classification of PP based on hCG, gonadotropin, and sex steroid levels and their dynamics.
Main Results:
- Five boys were classified as GnRH-dependent (G1), and 32 patients (31 boys, 1 girl) as GnRH-independent (G2).
- G2 patients showed simultaneous decreases in hCG and sex steroids with tumor regression.
- Boys with higher hCG levels were more prone to developing PP; significant differences in hCG and gender ratio were noted between G2 and controls.
Conclusions:
- GnRH-independent PP associated with intracranial GCTs typically resolves alongside tumor regression.
- The regression of GnRH-dependent PP in conjunction with tumor treatment remains inconclusive.
- Elevated hCG levels in boys with intracranial GCTs are strongly associated with precocious puberty development.
Abstract:
Children with intracranial germ cell tumors may present premature sexual development via either gonadotrophin-releasing hormone (GnRH)-dependent cause or GnRH-independent cause. We conducted a single-center retrospective study on 37 precocious puberty (PP) patients with intracranial germ cell tumors and 25 age-matched prepubertal patients with elevated human chorionic gonadotropin (hCG) levels. Classification of PP was derived from hCG, gonadotropin and sex steroid levels and their changes. Five boys were assigned to GnRH-dependent group (G1). Thirty-one boys and one girl were assigned to GnRH-independent group (G2) with a median hCG of 76.75 (8.29-2747) IU/L. Seven boys and 18 girls were conducted as controls, with a median hCG of 17.12 (2.91-1062) IU/L. Patients in G1 had constant pubertal LH and testosterone levels after tumor complete response. Patients in G2 had hCG levels that decreased simultaneously with testosterone/estradiol levels, prior to tumor regression. The differences in hCG levels and the gender ratio were significant between G2 and controls (P = 0.006 and P < 0.001, separately). Among intracranial germ cell tumor patients with positive hCG, boys with significantly higher hCG levels more easily developed PP. Our results suggest that GnRH-independent PP commonly regresses together with tumor regression. In comparison, results were inconclusive in tying tumor regression to the regression of GnRH-dependent PP.
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