Plasma Levels of Insulin-Like Binding Protein-2 in Prepubertal Short Children and Its Diagnostic Value in the Evaluation of Growth Hormone Deficiency

Abstract

Aim: This study was designed to investigate whether determination of plasma insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) levels could be of benefit in the evaluation of childhood growth hormone (GH) deficiency (GHD). Method: A retrospective analysis was performed on 91 prepubertal children referred for investigation of short stature. Maximal GH levels in plasma after provocative stimuli were between 1.0 and 93.0 mU/l, 6 subjects exhibiting peak values of <5 mU/l. Initially a GH peak of 20 mU/l was used as a cutoff limit to define GHD and idiopathic short stature (ISS) patients. The results of GH provocative tests were compared to age- and gender-based standard deviation scores (SDS) of plasma IGFBP-2, IGF-I, IGFBP-3 and the molar ratios of the latter two to IGFBP-2. The respective normative range values for these parameters were determined in plasma samples from 353 healthy children (i.e. 171 girls, 182 boys). Results: Circulating IGFBP-2 levels did not correlate with height SDS, height velocity SDS or the peak GH levels after provocative stimuli. A weak negative relationship was found between IGFBP-2 and IGF-I. Plasma levels of IGFBP-2 in GHD patients were higher than those of ISS children, who had normal levels. Although at the optimal cutoff point of –0.71 SDS 91.5% of the GHD patients were identified correctly, a substantial proportion (71.9%) of the ISS subjects also had IGFBP-2 levels above this limit. The use of various combinations of IGFBP-2, IGF-I, IGFBP-3 and the derived ratios only slightly improved the diagnostic efficiency as compared to the results of the individual tests. Neither IGFBP-2 nor the IGFBP-3/IGFBP-2 and IGF-I/IGFBP-2 ratios were found to be related to the short- (1 year) or long-term (3 years) growth response to GH therapy. Conclusion: It is concluded that none of the tests investigated, either alone or in various combinations, are reliable in either predicting the peak GH level after provocative stimuli in prepubertal short children or in predicting their growth response to GH.

Idiopathic short stature: Definition, epidemiology, and diagnostic evaluation

“…Other IGF binding proteins such as ALS or IGFBP-2 do not have an established role in diagnosing GHD [187]. In those found to have very low or undetectable IGF-I levels but only modest short stature, measurement of ALS may be required to identify those children with ALS defects [82,89].…”

Characterization of the IGF system in 15 patients with Alström syndrome

“…Moreover, GH regulates IGFBP‐2 and IGF‐I in an opposite manner 22,23 . Also, the IGBP‐2 levels in GHD patients could be significantly elevated in the face of subnormal concentrations of IGF‐I and IGFBP‐3 25 . Therefore, the increase of both IGFBP‐2 and the molar ratio of IGFBP‐2/IGF‐I in adult ALMS further supports a condition of GH deficiency.…”

“…Although patients with chronic renal failure have been reported to have an increase of circulating IGFBP‐2 (and IGFBP‐3) due to a lowered rate of renal filtration, 23 we did not observe any correlation with BUN or creatinine in this cohort. Under various pathological conditions, including GHD, circulating levels of IGFBP‐2 appear to be inversely related to plasma IGFBP‐3 24,25 . Moreover, GH regulates IGFBP‐2 and IGF‐I in an opposite manner 22,23 .…”

Insulin-Like Growth Factors as Diagnostic Tools in Growth Hormone Deficiency during Childhood and Adolescence: The KIGS Experience

“…In contrast to IGF-I, the diagnostic value of IGFBP-3 is generally better in younger children. Few data are currently available regarding the diagnostic significance of ALS and IGFBP-2 [9, 11, 12]. ALS levels evidently parallel those of IGF-I and IGFBP-3, while elevated IGFBP-2 levels are rather characteristic in GHD.…”