Low IGF-1 combined with a single clonidine stimulation test as a confirmatory tool for pediatric growth hormone deficiency.

BACKGROUND

Growth hormone deficiency (GHD) in children is a complex endocrine disorder that requires dynamic testing for accurate diagnosis due to the pulsatile nature of growth hormone (GH) secretion. The clonidine test is widely used as a standard diagnostic tool due to its favorable safety profile and effectiveness. Insulin-like growth factor-1 (IGF-1) has emerged as a potential adjunct marker; however, its diagnostic accuracy is limited when used alone. This study aims to evaluate the diagnostic effectiveness of combining low IGF-1 with a single clonidine stimulation test for diagnosing pediatric GHD.

METHODS

A retrospective cohort study was conducted at King Chulalongkorn Memorial Hospital, including 214 children with short stature (aged 2-16 years) evaluated between August 2019 and January 2025. GHD was confirmed in 63 patients using two GH stimulation tests (peak GH <7 ng/mL). Serum IGF-1 levels were expressed as standard deviation scores (SDS) and analyzed at cutoff points of ≤ -1, -1.5, -2, -2.5, and - 3 in combination with clonidine test results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

RESULTS

The combination of IGF-1 SDS ≤ -2.5 and a single clonidine test (peak GH < 7 ng/mL) demonstrated a sensitivity of 31.6% and a specificity of 98.6%. The positive predictive value (PPV) was 92.3%, and the negative predictive value (NPV) was 73.7%. Additionally, a cutoff of IGF-1 SDS ≤ -1.5 yielded a sensitivity of 60.5% and specificity of 95.9%.

CONCLUSION

An IGF-1 SDS cutoff of ≤ -2.5 combined with a single failed clonidine test demonstrated high specificity for GHD and may provide additional diagnostic confidence in selected patients, potentially reducing the reliance on a second stimulation test.