Background: Analysis of insulin-like growth factor I in serum (S-IGF-I) is an integral component in the diagnosis of GH-related disorders and is going to be of interest in the diagnosis and follow-up of many disorders. The objective of the present study was to develop cross-sectional reference values for S-IGF-I measured by an automated chemiluminescence immunoassay (Nichols Advantage^®). Methods: The study included samples from 3,961 healthy subjects (2,201 males, 1,760 females) aged 1 month to 88 years. Six laboratories were involved in this study and the samples were analyzed by one of seven automated immunoassay systems run in these laboratories. For data analysis, polynomial age and sex-specific models were fitted after transformation of S-IGF-I values. Results: The results show the well-known age dependency of S-IGF-I levels. At ages <20, higher S-IGF-I levels were seen in girls with an estimated mean peak of 410 µg/l at age 14 and an estimated mean peak of 382 µg/l at age 16 in boys. Thereafter, a rapid decrease was seen to approximately 25 years of age, followed by a slow age-dependent decrease. In adulthood, S-IGF-I in males were slightly, but significantly higher than in females. It could be shown that the mean values of some reference sample subgroups differed significantly from the total mean. However, the multicenter approach used in this study reduces the impact of systematic population, sample handling and laboratory differences on the calculated reference mean. Conclusion: The present study establishes age- and sex-specific reference values for a fully automated immunoassay system based on a large population of healthy subjects. The established reference values may be used for this immunoassay system in different laboratories provided that the systematic difference between systems is low.

The age-dependent decline of the gonadal and somatotopic axis has been causally linked to frailty in the elderly by their effects on muscle mass and bone mineral density. However, for healthy men data on serum oestrogens and androgens, as well as IGF-1, as a common outcome measure covering the whole adult age range are scarce. We therefore studied healthy, nonobese male subjects between 20 and 80 years of age to asses their morning concentrations of total (T), free (FT), bioavailable testosterone (bT), oestradiol (E2), bioavailable oestradiol (bE2), oestrone (E1), sex-hormone binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1). Five hundred and seventy-two male healthy volunteers with a BMI < 30 kg/m2 recruited from regular blood donors and senior sports clubs participated in the study. Serum samples were obtained during morning hours and T, FT, E2, E1, SHBG, albumin and IGF-1 were measured by radio-immunoassay systems. In addition, bT and bE2 were calculated. A potential relationship between sex hormones and IGF-1 was tested by multiple regression analysis including age and BMI. Ageing was negatively related to serum levels of sex steroids and IGF-1 (both P < 0.0001) with a mean decrease (youngest vs. oldest) of 51% for T, 64% for FT, 78% for bT, 32% for E2, 62% for bE2, 29% for E1 and 51% for IGF-1 starting in early adulthood whereas SHBG increased after the 5th decade of life (ANOVA P < 0.001). The decline of sex hormones and IGF-1 remained relatively unchanged after adjustment for BMI. Multiple regression analysis revealed an age-and BMI- independent association between oestradiol and IGF-1. In contrast to the female situation sex hormones in healthy, nonobese men decline continuously with age. This process has already started in the third decade, and is paralleled by a decline of IGF-1 serum levels leading to a substantial proportion of elderly men with markedly lowered serum levels of bioavailable sex hormones and IGF-1 compared to the young adult male range. With the recent demonstration of beneficial effects of androgen replacement therapy in healthy males on general well being, muscle mass and bone mineral density the present data may underline the importance of more detailed studies on the biological significance of hormonal changes in men with age.

Hypermetabolism has no association with clinical data and thus is an extrahepatic manifestation of liver disease. Increased beta-adrenergic activity may explain approximately 25% of hypermetabolism.