Insulin-like growth factor 1 as a diagnostic marker of progressive central precocious puberty: a prospective study

Eur J Pediatr. 2025 Jun 24;184(7):438. doi: 10.1007/s00431-025-06276-5.

Abstract

Central precocious puberty (CPP) diagnosis often requires invasive GnRH stimulation tests. Our purpose was to determine whether the IGF-1 and IGF-1 SDSs are reliable predictors of progressive CPP. This was a prospective study including 82 girls under 8 years of age. The participants were divided into CPP (n = 39), NP-CPP and IT (n = 26), and control groups (n = 17). Anthropometric measurements, Tanner staging, bone age, pelvic ultrasound, and serum IGF1 and IGF1-SDS level measurements were performed. GnRH stimulation tests confirmed CPP cases. The mean IGF1 and IGF1-SDS levels were significantly greater in CPP patients (270.15 ng/mL; 1.943 SDS) than in NP-CPP patients (174.12 ng/mL; 0.788 SDS) and controls (139.28 ng/mL; 0.208 SDS) (p < 0.001). Multivariate logistic regression analysis confirmed that IGF1 (OR = 1.025, 95% CI 1.010-1.040) and IGF1-SDS (OR = 8.721, 95% CI 2.624-28.986) were significant predictors of CPP. ROC analysis revealed an AUC of 0.837 for IGF1 (95% CI 0.738-0.935) and 0.862 for IGF1-SDS (95% CI 0.771-0.953). The cut-off values of 231 ng/mL for IGF1 (71.8% sensitivity, 97.7% specificity) and 1.44 for IGF1-SDS (79.5% sensitivity, 90.7% specificity) demonstrated good accuracy (82.2% and 77.8%, respectively).

Conclusion: IGF1-SDS, and absolute IGF1, are promising effective noninvasive diagnostic markers for distinguishing CPP from nonprogressive precocious puberty. Due to its high specificity IGF1 values above 1.44, SDS may significantly increase the post-test probability of CPP, potentially avoiding invasive GnRH stimulation tests. These findings support the integration of IGF1 measurements into the initial diagnostic approach for girls presenting with early pubertal signs.

What is known: • Central precocious puberty (CPP) often requires invasive GnRH stimulation tests. • IGF1 levels rise during puberty and reflect growth and pubertal progression.

What is new: • This prospective study suggests IGF1-SDS >1.44 as accurate cut-off for progressive CPP via the IMMULITE assay. • IGF1-SDS show high specificity and diagnostic accuracy, supporting its use in the initial diagnostic approach for girls presenting with early pubertal signs.

Keywords: Central precocious puberty; IGF1-SDS; Insulin-like growth factor 1.

MeSH terms

  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Insulin-Like Growth Factor I* / analysis
  • Insulin-Like Growth Factor I* / metabolism
  • Insulin-Like Peptides
  • Prospective Studies
  • Puberty, Precocious* / blood
  • Puberty, Precocious* / diagnosis
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Insulin-Like Growth Factor I
  • Biomarkers
  • IGF1 protein, human
  • Insulin-Like Peptides