Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia

D C Chrysis, T K Alexandrides, E Koromantzou, N Georgopoulos, P Vassilakos, W Kiess, J Kratsch, N G Beratis, B E Spiliotis
Clinical Endocrinology 2001, 54 (2): 253-9

OBJECTIVE: Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation.

DESIGN: We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation.

MEASUREMENTS: IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls.

RESULTS: N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children.

CONCLUSION: The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.

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