Gender-specific soluble α-klotho levels as marker of GH deficiency in children: a case-control study

Purpose To evaluate circulating soluble alpha-klotho (s alpha KL) levels in GHD children before and after 12 months of GH treatment (GHT). Methods Auxological and basal metabolic parameters, oral glucose tolerance test for glucose and insulin levels, insulin sensitivity indices and klotho levels were evaluated before and after 12 months of follow-up in 58 GHD children and 56 healthy controls. Results At baseline, GHD children showed significantly lower growth velocity standard deviation score (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001), GH peak and area under the curve (AUC) after arginine test (ARG) (both p < 0.001) and glucagon stimulation test (GST) (p < 0.001 and 0.048, respectively), IGF-1 (p < 0.001), with higher BMI (SDS) (p < 0.001), WC (SDS) (p = 0.003) and s alpha KL (p < 0.001) than controls. After 12 months of GHT, GHD children showed a significant increase in height (SDS) (p < 0.001), growth velocity (SDS) (p < 0.001), bone/chronological age ratio (p < 0.001) IGF-1 (p < 0.001), fasting insulin (p < 0.001), Homa-IR (p < 0.001) and s alpha KL (p < 0.001) with a concomitant decrease in BMI (SDS) (p = 0.002) and WC (SDS) (p = 0.038) than baseline. At ROC curve analysis, we identified a s alpha KL cut-off to discriminate controls and GHD children of 1764.4 pg/mL in females and 1339.4 pg/mL in males. At multivariate analysis, the independent variables significantly associated with s alpha KL levels after 12 months of GHT were the oral disposition index (p = 0.004, beta = 0.327) and IGF-1 (p = 0.019, beta = 0.313). Conclusions Gender-related s alpha KL may be used as a marker of GHD combined to GH and IGF-1. Insulin and IGF-1 are independently associated with s alpha KL values after 12 months of GHT.