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.

The aim of this study was to establish reference ranges for children (neonates to young adults), for serum lutropin (LH), follitropin (FSH), estradiol (E2), progesterone, prolactin, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), cortisol and ferritin, using the nonisotopic, automated chemiluminescence immunoassay system, Immulite (DPC). Serum samples from 762 children (369 female; age 1 day to 19 years) were examined. Of these, 381 were classified as pubertal. Due to non-normal distribution, the 2.5th, 50th and 97.5th percentiles (central 95% interval) were calculated for each group. Statistical differences between the reference ranges were analyzed with respect to age, sex and the stage of sexual maturation. The median concentrations of E2, prolactin, progesterone, DHEAS, cortisol and ferritin were higher during the first 2 weeks post-partum than thereafter. The largest difference was seen with prolactin, which showed up to 27-fold higher values during this period. In contrast, before the onset of puberty, hardly any sex difference was observed and all analyte concentrations remained relatively constant, apart from SHBG which increased steadily after the neonatal period. The increase of gonadal activity in females with the onset of sexual maturation included an increase in LH and FSH, which was accompanied by a strong increase in E2, progesterone and prolactin. Cortisol increased to a lesser extent during puberty. In males, the increase in the median concentrations of the hormones was smaller, except for DHEAS. The concentration of ferritin was high in the neonatal period but did not change during sexual maturation. Our findings agree with earlier studies. The calculated reference intervals can be used to assess the development of children, particularly for measurements performed by the Immulite and Immulite 2000 chemiluminescence assay systems.

Disorders in thyroid function can impair normal development in children. Therefore it was our aim to establish reference intervals for serum triiodothyronine (T3), free T3 (fT3), thyroxine (T4), free T4 (fT4), thyroxine binding globulin (TBG) and thyrotropin (TSH) which are applicable from birth to adulthood by using the non-isotopic automated chemiluminescence immunoassay system, Immulite (DPC Los Angeles, USA). Serum samples from 762 euthyroid newborns, children and adolescents (369 female, 393 male; age 1 day to 19 years) were examined; of these, 381 were classified as pubertal. Due to non-normal distribution, the 2.5th, 50th and 97.5th percentiles (the central 95% interval) were calculated for each group. The median concentrations of T4, fT4 and TSH were up to 3.2-fold higher during the first 2 weeks, while T4 increased during the first month of life. The concentrations in all age groups showed no sex differences. From 1 year onwards, the concentration of all parameters tended to decrease until adult age, with the exception of TBG which increased by >60% (p<0.02) and reached a maximum at approximately 5 years of age. The findings underscore the fact that thyroid hormones are not associated with sexual development, except for TBG, which decreased slightly (p<0.04) between Tanner stages 1 and 5. However, the reference intervals established here demonstrate that marked changes occur in concentrations of thyroid hormones after the neonatal period. Our findings complement these of earlier studies. The developed reference intervals can be used to assess the thyroid status of patients, particularly if the measurements are done on the Immulite/Immulite 2000 system.

The cytokines RANTES and MlP-1α are 8-kD peptides which belong to the C-C subfamily of chemokines. They are both potent chemotactic factors for basophils and eosinophils. Apart from lymphocytes, the RANTES peptides was recently shown to be released from human platelets stimulated with thrombin [Kameyoshi et al: J Exp Med 1992;176:587–592]. Employing postembedding immunocytochemistry, we could detect RANTES and for the first time also MlP-1α within the α-granules of human platelets. To date, MlP-1α was not reported to occur in platelets. In slightly activated platelets, as found in stored platelet concentrates (PC), label for RANTES and MlP-1α could also be observed within cisterns of the open canalicular system and on the plasma membrane, indicating a release of both peptides. These findings were confirmed by in vitro studies in PC, by investigation of RANTES and MlP-1α release into the suspending medium. Over a period of 8 days, RANTES was steadily released in relatively high amounts, whereas MlP-1α was measured in rather small amounts in the suspending medium. As RANTES and MlP-1α, besides their chemotactic activity on eosinophils and basophils, are able to mediate the release of histamine, it is tempting to speculate about a participation of platelets in inflammatory reactions in which eosinophils and basophils are involved.

Pediatric reference ranges for osteocalcin measured by a new, fully automated, chemiluminescent immunometric assay on the Immulite immunoanalyzer are presented. Samples from 627 children, ranging from newborns to 18 years of age, were measured. Osteocalcin values are generally higher in children than in adults, highest levels being reached during the puberty growth spurt at about 12 years in girls and 14 years in boys, thereafter rapidly declining towards adult levels.