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胰岛素样生长因子1作为进行性中枢性性早熟的诊断标志物:一项前瞻性研究。

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

作者信息

Leite Ana Luísa, Azevedo Luís Filipe, Campos Rosa Arménia, Rangel Maria Adriana, Torres Clara, Santos Filipa Marques, Aires Sónia, Firmino-Machado João, Limbert Catarina

机构信息

Unit of Paediatric Endocrinology and Diabetes, Department of Paediatrics, Unidade Local de Saúde Gaia e Espinho, Vila Nova de Gaia, Portugal.

Clínica CUF, São João da Madeira, Portugal.

出版信息

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

Abstract

UNLABELLED

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.

摘要

未标注

中枢性性早熟(CPP)的诊断通常需要进行侵入性促性腺激素释放激素(GnRH)刺激试验。我们的目的是确定胰岛素样生长因子-1(IGF-1)及其标准差积分(IGF-1 SDS)是否为进行性CPP的可靠预测指标。这是一项前瞻性研究,纳入了82名8岁以下女孩。参与者被分为CPP组(n = 39)、非进行性CPP和快速进展型(NP-CPP和IT)组(n = 26)以及对照组(n = 17)。进行了人体测量、 Tanner分期、骨龄、盆腔超声检查以及血清IGF-1和IGF-1 SDS水平测定。GnRH刺激试验确诊CPP病例。CPP患者的平均IGF-1和IGF-1 SDS水平(分别为270.15 ng/mL;1.943 SDS)显著高于NP-CPP患者(174.12 ng/mL;0.788 SDS)和对照组(139.28 ng/mL;0.208 SDS)(p < 0.001)。多因素逻辑回归分析证实,IGF-1(比值比[OR]=1.025,95%可信区间[CI] 1.010 - 1.040)和IGF-1 SDS(OR = 8.721,95% CI 2.624 - 28.986)是CPP的显著预测指标。受试者工作特征(ROC)分析显示,IGF-1的曲线下面积(AUC)为0.837(95% CI 0.738 - 0.935),IGF-1 SDS的AUC为0.862(95% CI 0.771 - 0.953)。IGF-1的截断值为231 ng/mL(灵敏度71.8%,特异性97.7%),IGF-1 SDS的截断值为1.44(灵敏度79.5%,特异性90.7%),显示出良好的准确性(分别为82.2%和77.8%)。

结论

IGF-1 SDS和绝对IGF-1是区分CPP与非进行性性早熟的有前景的有效非侵入性诊断标志物。由于IGF-1 SDS值高于1.44时具有高特异性,可能显著增加CPP的检测后概率,从而有可能避免进行侵入性GnRH刺激试验。这些发现支持将IGF-1测量纳入有青春期早期体征女孩的初始诊断方法中。

已知信息

• 中枢性性早熟(CPP)通常需要进行侵入性GnRH刺激试验。• IGF-1水平在青春期升高,反映生长和青春期进展。

新发现

• 这项前瞻性研究表明,通过免疫发光法检测,IGF-1 SDS>1.44可作为进行性CPP的准确截断值。• IGF-1 SDS显示出高特异性和诊断准确性,支持其用于有青春期早期体征女孩的初始诊断方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e101/12187815/0c4a089ba33e/431_2025_6276_Fig1_HTML.jpg

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