IMPROVEMENT OF DIAGNOSTIC-CRITERIA IN GROWTH-HORMONE INSENSITIVITY SYNDROME - SOLUTIONS AND PITFALLS

A survey to identify children and adolescents with primary growth horm one insensitivity syndrome (GHIS) yielded 38 patients who were positiv ely identified using a scoring system that included five criteria: hei ght, basal growth hormone (GH), GH binding protein, basal insulin-like growth factor I (IGF-I) and the increase of IGF-I after 4 days of GH administration (IGF generation test). Because of an overlap of the acc epted and excluded groups with respect to points scored, an attempt wa s made to improve the scoring system. The new criteria were: height be low -3 SDS, basal GH 4 mU/l or above, GH binding below 10%, basal IGF- I and basal IGF binding protein-3 (IGFBP-3) below the 0.1 centile for age, an increase of IGF-I in the IGF generation test less than 15 mu g /l, and the increase of IGFBP-3 less than 0.4 mg/l. With this scoring system, a clear separation between the accepted and the excluded group s was obtained. IGFBP-3 was included to give the GH-dependent paramete rs of the IGF system more weight and because the accuracy of IGFBP-3 i n the IGF generation tests was greater than the accuracy of IGF-I, whe n the group of patients with GHIS was compared with a group of patient s with GH deficiency. Unexpectedly, the IGF generation test was unable to segregate both cohorts completely. In the GHIS-positive group, a s ignificant correlation was found between basal IGF-I or IGFBP-3 levels corrected for age (SDS) and height SDS (r = 0.49, p < 0.002 and r = 0 .61, p < 0.0001, respectively). There was also a significant correlati on between the changes of IGF-I or IGFBP-3 in the IGF generation test and height SDS. That is, the patients with a slight response to GH wer e those with the least growth retardation, suggesting the existence of partial GH insensitivity.