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

V Guarnotta,S Radellini,G Pizzolanti,C Giordano,C Baiamonte,R Petrancosta

doi:10.1007/s40618-022-01757-y

V Guarnotta, S Radellini + Show 4 more

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https://doi.org/10.1007/s40618-022-01757-y

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Abstract

PurposeTo evaluate circulating soluble α-klotho (sαKL) levels in GHD children before and after 12 months of GH treatment (GHT).MethodsAuxological 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.ResultsAt 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).ConclusionsGender-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.

Highlights

Growth hormone deficiency (GHD) affects about 1 out of 4000 children [1]
After 12 months of GH treatment (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), homeostasis model assessment estimate of insulin resistance (Homa-IR) (p < 0.001) and soluble α-klotho (sαKL) (p < 0.001; females p = 0.004 and males p = 0.001) levels, with a concomitant decrease in body mass index (BMI) (SDS) (p = 0.002) and waist circumference (WC) (SDS) (p = 0.038) compared to baseline (Table 2)
We evaluated the effects of GHT on sαKL levels in a paediatric cohort of GHD children and healthy controls

Summary

Introduction

Growth hormone deficiency (GHD) affects about 1 out of 4000 children [1]. The diagnosis of GHD is based on many factors including clinical, auxological, and biochemical parameters. Children with normal GH secretion and GHD frequently show superimposable peak GH concentrations [9]. A minority of children with idiopathic GHD remain GH deficient after discontinuation of GHT [10–13], and about 20% of healthy children may test “deficient” if a single stimulation test is used [14]. For these reasons, two stimulation tests are recommended to assess the diagnosis of GHD [14]. Serum biomarkers (e.g., IGF-1, IGFBP-3) are not fully accurate in distinguishing between GH sufficient and deficient children [15]

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