Normal levels of serum IGF-I: determinants and validity of current reference ranges

Abstract

Insulin like growth factor I (IGF-I) represents the key marker for the evaluation of Growth hormone (GH) status. As a large number of determinants including age, gender, genetic factors, nutrition, and disease states influence IGF-I serum levels, accurate normative data are essential to translate patient data into diagnostic meaning or even use IGF-I levels for adequate monitoring of patients with an over- or under-active GH axis. Even though reference ranges have been developed in large cohorts of healthy subjects, the dependency of these data on a given assay technology argues for assay specific normative data for IGF-I.

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

“…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).…”

“…In adult GH deficiency, serum IGF-1 selects patients who need to be submitted to provoca-tive tests (4), defines severe GH deficiency [low IGF-1 (5)], and determines GH dose adjustments during therapy (4,5). In addition, epidemiological studies have associated serum IGF-1 levels with the risk of cardiovascular disease and death and cancer (6).…”

“…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). It is also important to know which variations in IGF-1 levels can be attributed to the treatment implemented or to progression of the disease and are not only due to interassay variability (18).…”

Classification of Patients With GH Disorders May Vary According to the IGF-I Assay

“…In the VARIETE study, the largest intercentile intervals This lack of concordance between certain assays has already been reported (7-10): one possible explanation was that the populations used to establish normative data were different, or that the quality of these normative data was suboptimal (too few patients studied, particularly in certain age ranges; bias, failure to select healthy subjects, with regard to concurrent treatments or medical conditions interfering with IGF-I measurement, etc.) (5,6,11,12,19). This is why we used the same large healthy population to establish normative data for the six immunoassays used here.…”

“…We suspected that a potential reason for these discrepancies was the use of different reference values. Indeed, it is difficult to establish IGF-I normative data, as they depend on the choice of healthy reference population (6,11,12). While IGF-I values depend on many factors, such as gender, age, nutritional status, treatments (especially hormonal medications), diabetes and A c c e p t e d m a n u s c r i p t renal and hepatic failure, normative data used for the different IGF I kits were not obtained in the same, apparently healthy population.…”