Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency

Abstract

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

“…The increase in height SDS was similar in the defined IGFD group and in the GHD group. Interestingly, the therapy turned out to be the most effective in the IGFD-AGA subgroup, while the less effective in IGFD-SGA; however, the differences between all three groups was found to be insignificant [57]. It seems worth mentioning that IGFD-AGA was the only subgroup that did not fulfill the standard criteria of qualifying for growth promoting therapies, as these patients were neither GH-deficient nor GH-insensitive, nor SGA.…”

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

“…Interestingly, the therapy has turned out to be the most effective in IGFD-AGA subgroup (i.e. in the only subgroup which do not fulfill current criteria of qualifying to rhGH rherapy), while the less effective in IGFD-SGA, however the differences between all 3 groups presented to be insignificant [53]. Our observations have supported the possibility of growth response to rhGH therapy in children who in some other countries could be diagnosed with GHI and treated only with rhIGF-1.…”

Involvement of Sirtuin 1 in the Growth Hormone/Insulin-like Growth Factor 1 Signal Transduction and Its Impact on Growth Processes in Children

“…They clearly contribute to the metabolic effects of GH; however, their role in the growth of bones remains unclear [16][17][18]. Considering the cardinal importance of the GH-IGF-1 axis in linear human growth, the defects or modifications at various points of this axis may result in an impaired growth rate, leading to short stature [19,20].…”