Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3)

Abstract

Assays for insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) have become essential tools in the diagnostic work-up of disorders of the somatotropic axis in children and adults. The aim of this study was to evaluate the automated IMMULITE IGF-I and IGFBP-3 assays and to establish reference limits--central 95% intervals, median, 0.1 and other centiles as clinically relevant--as a function of age from 797 females and 787 males, from the first week of life through the ninth decade. Pubertal children were classified by sex and by sexual maturation (Tanner stage). IGF-I and IGFBP-3 levels were also assayed in 20 pediatric patients each with growth hormone deficiency (GHD) and Turner syndrome (UTS), before and during 12 months of recombinant growth hormone (rhGH) therapy, as well as in 11 adult patients with GHD and seven with acromegaly before therapy. Both the IGF-I and IGFBP-3 assays were accurate, specific and sufficiently sensitive to measure IGF-I and IGFBP-3 in serum with good linearity and recovery. In the IGF-I assay, potential interference from IGFBPs was eliminated by blocking with excess IGF-II. Circulating IGF-I and IGFBP-3 concentrations, and their ratio IGF-I/IGFBP-3, were age-dependent, showing low levels immediately after birth, a typical pubertal peak for girls and boys, and a pronounced decline after puberty, reaching a plateau in early adulthood. In adults IGF-I and IGFBP-3 levels decreased smoothly but steadily with age. Children with GHD and UTS had low circulating IGF-I and IGFBP-3 levels which increased to normal reference limits under therapy with rhGH. Adult GHD patients showed IGF-I levels below the age-related median; untreated acromegalic patients mostly had IGF-I and IGFBP-3 levels above the age-related 97.5th centile. In conclusion, the automated IMMULITE IGF-I and IGFBP-3 assays are reliable tools in the diagnosis of pathologies of the GH/IGF axis and in the follow-up of their therapies.

Normal values of serum IGF-1 in adults: results from a Brazilian population

“…The maximum difference in the upper limit (97.5th percentile) was 7 µg/L (20 to 30 years) and the maximum difference in the lower limit (2.5th percentile) was 10 µg/L (21 to 25 years). Therefore, similar to previous studies (7)(8)(9)(10)(11)(12)(13)(14), the IGF-1 reference values are reported according to age group, without distinction between genders ( Table 2). The curves representing the 97.5th, 50th (median) and 2.5th percentiles of IGF-1 as a function of age are shown in figure 1.…”

“…Ten groups divided according to age [5-year intervals (7,8)] were pre-defined, with 100 subjects per group (6,17). Since the need of different reference values for men and women is not clear (6), each group was divided into two subgroups (50 men and 50 women).…”

“…Because IGF-1 values were not normally distributed in the study population, the reference range was defined as follows : 1) 2) logarithmic transformation of the values obtained, calculation of the mean ± 2 SD of these values, and exponentiation to obtain the limits corresponding to the original scale (7)(8)(9)(10)12). The Student t-test and Kruskal-Wallis test were used to determine differences between groups according to gender (10)(11)(12)14).…”

“…To our knowledge, there is no study evaluating IGF-1 reference ranges in the Brazilian population. For example, in the case of the assay tested in the present study the reference values are derived from a German population (8).…”

“…The values should be assay-specific (9,10), should be reported according to age (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), and should preferentially be population-specific (17). The sample from which these values are extracted should be of adequate size (7,9) and the subjects should be selected rigorously, excluding conditions known to interfere with the levels of this hormone (6).…”