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

PURPOSE: To evaluate circulating soluble α-klotho (sαKL) 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 sαKL (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 sαKL (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 sαKL 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 sαKL levels after 12 months of GHT were the oral disposition index (p = 0.004, β = 0.327) and IGF-1 (p = 0.019, β = 0.313). CONCLUSIONS: Gender-related sαKL may be used as a marker of GHD combined to GH and IGF-1. Insulin and IGF-1 are independently associated with sαKL values after 12 months of GHT.