URINARY IGF AND IGF BINDING PROTEIN-3 IN CHILDREN WITH DISORDERED GROWTH

OBJECTIVE Both IGF-I and IGFBP-3 reflect spontaneous GH secretion in h ealthy individuals. We have evaluated the clinical usefulness of urina ry IGF-I and IGFBP-3 measurements in the diagnosis of children with di sordered growth. DESIGN Serum IGF-I and IGFBP-3 radioimmunoassays (RIA ) were developed, and modified for quantitation in urine. The relation ship between serum and urine levels, and the performance of these test s in the diagnosis of GH deficiency (GHD) were examined. PATIENTS Sixt y-nine children (age 9.5 +/- 3.6 years; 37 boys, 32 girls) provided a timed overnight urine collection and a serum sample collected on the s ame morning. Subjects were defined as GHD (n = 22) or short normal (SN ; n = 47) on the basis of medical history, clinical examination, auxol ogy and peak response to a GH stimulation test (<20 mU/I in GHD patien ts). MEASUREMENTS IGF-I and IGFBP-3 in serum and urine were measured b y RIA, urinary GH (uGH) by immunoradiometric assay (IRMA) after dialys is and urinary creatinine by the alkaline picrate method. Urine result s were expressed as total amount excreted (tulGFBP-3 tag), tulGF-I (ng ), tuGH (ng), tuCrt (mmol). RESULTS Urine IGF-I and IGFBP-3 excretion correlated significantly to serum levels of IGF-I and IGFBP-3 and also to tuGH excretion. There was a strong positive relationship between b oth urinary peptides and tuCrt, which suggested that renal filtration was the source of these peptides in urine. In addition, there were sig nificant correlations with age, bone age and height SD score, of simil ar magnitude to those for tuGH. In prepubertal children, serum IGF-I a nd IGFBP-3 were significantly lower in GHD compared with SN children, while in puberty only serum IGFBP-3 was significantly lower in GHD. Th ere was no difference, however, in tulGF-I or tulGFBP-3 between GHD an d SN children either prepubertally or in puberty with near complete ov erlap of the values between groups. CONCLUSIONS Measurements of tulGF- I and tulGFBP-3 have no place in the diagnosis of childhood GHD. Nonet heless, the significant correlations between serum and urinary IGF-I a nd IGFBP-3 levels and their correlation to uGH indicate that these pep tides could be used as non-invasive physiological markers of the GH-IG F axis.