Biochemical markers of growth hormone (GH) sensitivity in children with idiopathic short stature: individual capacity of IGF-I generation after high-dose GH treatment determines the growth response to GH

Summary objective and patients To assess multiple dose–response relationships between three GH doses (1·5, 3·0 and 6·0 IU/m2) and nine different biochemical markers of GH sensitivity in a well‐defined group of 17 children with idiopathic short stature (ISS). design and measurements Serum levels of IGF‐I, IGF‐II and IGFBP‐3, and peripheral markers leptin, C‐terminal propeptide of type I collagen (PICP) and N‐terminal propeptide of type III collagen (PIIINP), alkaline phosphatase (AP) and osteocalcin (OC) were measured at the start and after 2 and 12 weeks of periods of no treatment, GH 1·5 IU/m2 and GH 3·0 IU/m2. Twelve‐week washout periods were applied between the 12‐week GH‐treatment periods. High‐dose GH treatment was given during the second year of study and all serum markers were measured at start, after 2 and 12 weeks and 1 year of GH 6·0 IU/m2. In 18 non‐GH‐treated children with ISS the same parameters were measured yearly. The bone resorption marker urinary deoxypyridinoline (DPD) was measured during 12‐h day and night periods at start and after 2 weeks GH 1·5, 3·0 and 6·0 IU/m2. results All markers were GH dependent, but the timing of maximal response varied among different markers. Height SDS at start, age at start and IGF‐II at baseline were inversely related to the first‐year growth response (r = −0·73, P = 0·001; r = −0·53, P = 0·03; and r = −0·53, P = 0·03, respectively). Some statistically significant correlations between biochemical responses on low GH doses (1·5 or 3·0 IU/m2) and second‐year growth response were found, but these showed no consistent pattern. However, all changes in IGF‐I SDS after GH 6·0 IU/m2 measured either after 2 or 12 weeks or 1 year correlated significantly with the second‐year growth response (r = 0·55, P = 0·02; r = 0·81, P = 0·001; and r = 0·86, P