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Insulin-like growth factor 1 as a diagnostic marker of progressive central precocious puberty: a prospective study
Ana Luísa Leite1,2,3,4, Luís Filipe Azevedo5,6, Rosa Arménia Campos7,8
1Unit of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Unidade Local de Saúde Gaia e Espinho, Vila Nova de Gaia, Portugal. ana.leite@ulsge.min-saude.pt.
Insights
Insulin-like Growth Factor 1 (IGF-1) and its standard deviation score (SDS) can reliably predict central precocious puberty (CPP) in girls. Elevated IGF-1 SDS levels may help avoid invasive testing for early pubertal signs.
Area of Science:
- Pediatric Endocrinology
- Reproductive Medicine
- Biomarker Discovery
Background:
- Central precocious puberty (CPP) diagnosis typically involves invasive gonadotropin-releasing hormone (GnRH) stimulation tests.
- Insulin-like Growth Factor 1 (IGF-1) levels naturally increase during puberty and are indicators of growth and pubertal progression.
Purpose of the Study:
- To evaluate the reliability of IGF-1 and IGF-1 standard deviation scores (SDS) as predictors of progressive CPP in girls.
- To explore the potential of noninvasive IGF-1 measurements in diagnosing CPP and reducing the need for invasive tests.
Main Methods:
- A prospective study involving 82 girls under 8 years old, categorized into CPP, non-progressive CPP (NP-CPP) with transient (IT) groups, and a control group.
- Measurements included anthropometrics, Tanner staging, bone age, pelvic ultrasound, and serum IGF-1 and IGF-1 SDS levels.
- GnRH stimulation tests were used to confirm CPP diagnoses.
Main Results:
- Mean IGF-1 and IGF-1 SDS levels were significantly higher in the CPP group compared to NP-CPP and control groups (p < 0.001).
- Multivariate logistic regression identified IGF-1 (OR=1.025) and IGF-1 SDS (OR=8.721) as significant predictors of CPP.
- ROC analysis showed high accuracy for IGF-1 (AUC=0.837) and IGF-1 SDS (AUC=0.862), with specific cut-off values demonstrating good sensitivity and specificity.
Conclusions:
- IGF-1 and IGF-1 SDS are effective noninvasive markers for distinguishing CPP from nonprogressive precocious puberty.
- An IGF-1 SDS cut-off of 1.44 shows high specificity and diagnostic accuracy, potentially avoiding the need for invasive GnRH stimulation tests.
- Integrating IGF-1 measurements into the initial diagnostic workup for girls with early pubertal signs is supported by these findings.
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.
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