Serum IGF-I and IGFBP-3 concentrations do not accurately predict growth hormone deficiency in children with brain tumours

Abstract

Objective: The growth hormone (GH)-dependent growth factors insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be superior to provocative GH testing in diagnosing GH deficiency (GHD) in children. In adults with brain tumours (BT) and GHD, however, provocative GH testing more accurately reflects GHD than either IGF-I or IGFBP-3. We assessed growth factor levels in children with GHD due to BT with respect to brain tumour type, pubertal stage, growth velocity, bone age delay, and body mass index (BMI).

Design: Retrospective case review of all patients followed at our centre with GHD following treatment of BT.

Patients: 72 children (51 M, 21 F) with BT diagnosed with GHD by clinical and auxological criteria, including provocative GH testing, in whom pre-GH treatment IGF-I and IGFBP-3 levels were obtained.

Measurements: Auxological data, including height, weight, growth velocity, and pubertal stage; and biochemical data, including GH response to provocative GH testing and pre-GH treatment serum IGF-I and IGFBP-3 concentrations.

Results: IGF-I levels were normal (above -2 SD) in 19 of 70 children (27%), and IGFBP-3 levels were normal in 21 of 42 (50%). In children with GHD, pubertal stage correlated significantly with both IGF-I (r = 0.328, p < 0.006) and IGFBP-3 (r = 0.364, P < 0.02). Normal IGF-1 levels were found in 1/15 children with craniopharyngioma (Cranio) (7%), 10/30 with primitive neuroectodermal tumours (PNET) (33%), and 5/12 children with hypothalamic/chiasmatic glioma (HCG) (42%) (P < 0. 05). IGFBP-3 levels were normal in 4/13 Cranio patients (31%), 8/15 PNET patients (53%), and 6/8 HCG patients (75%) (P = ns). Tanner staging varied significantly among tumour types: mode = 1 for Cranio and PNET vs. mode = 3 for HCG (P < 0.03). BMI did not differ between patients with low vs. normal growth factor levels.

Conclusions: Low IGF-I levels were more predictive of growth hormone deficiency than low IGFBP-3 levels in our brain tumour patients, but both were poor predictors of growth hormone deficiency in children with hypothalamic-chiasmatic glioma and in pubertal children. Serum IGF-I and IGFBP-3 levels, therefore, do not always reflect growth hormone deficiency in children with brain tumours, particularly in those with hypothalamic-chiasmatic glioma or those already in puberty.