Relationship between serum and urinary insulin-like growth factor-I through childhood and adolescence: Their use in the assessment of disordered growth

OBJECTIVE: Serum insulin-like growth factor-I (sIGF-I) measurement as an index of growth hormone status has become a common test in the investigation of disordered growth. IGF-I may also be measured in the urine. The aims of this study were to investigate the correlation between serum and urinary IGF- I in normal children and compare their use in the evaluation of growth disorders. DESIGN: Normal ranges for serum and urinary IGF-I were devised from a cross-sectional study of normal schoolchildren. These were then used to assess the sensitivity and specificity of serum and urinary IGF-I in the diagnosis of childhood GH deficiency. PATIENTS: A cohort of 333 (M = 156, F = 177) healthy schoolchildren aged 5-19 years were recruited and data previously collected from 22 growth hormone deficient (GHD) and 47 short normal (SN) children were compared with those of the normal children. MEASUREMENTS: Height, weight and pubertal status were assessed in all children. Serum IGF-I (sIGF-I) (n = 305) and total amount of urinary IGF-I excreted overnight (TuIGF-I) (n = 205) were measured by RIA using excess IGF- II to block the interference of IGFBPs. RESULTS: Serum IGF-I was log(e) transformed and overall levels (geometric mean ± 1 tolerance factor) were higher in females than males (F: 569 (329, 985)μg/l; M: 398 (227, 696) μg/l). Log(e)IGF-I correlated with age (F: r=+0.76, P<0.001, M: r=+0;71, P<0.001) and was significantly affected by both sex and Tanner stage of puberty (TS) (both P < 0.001). The distribution of TuIGF-I was normalized by performing a square root transformation (√TuIGF-I). √TuIGF-I was correlated with age (F: r=+0.36, P<0.001; M: r=+0.5, P<0.001) and was significantly affected by TS (P<0.001). In both sexes there was a highly significant correlation between log(e)IGF-I and √TuIGF-I (F: r=+0.39, P<0.001; M: r=+0.41, P<0.001). Using the third centile of our normal ranges as a cut off to identify GHD, sIGF-I had a sensitivity of 82% and specificity of 62%, whereas TuIGF-I had a sensitivity of 18% and specificity of 79%. CONCLUSIONS: This study demonstrates that although urinary IGF-I has no place in the diagnosis of growth disorders, in normal children there is a highly significant relationship between serum and urinary IGF-I with levels of each changing in a similar manner through childhood and adolescence. Thus, TuIGF- I could be used as a valid surrogate for sIGF-I in the physiological assessment of the relationship between IGF-I status and the normal growth process.