Agreement between circulating IGF-I, IGFBP-1 and IGFBP-3 levels measured by current assays versus unavailable assays previously used in epidemiological studies

Abstract

OBJECTIVE Levels of insulin-like growth factor (IGF) proteins are associated with risk of cancer and mortality. IGF assays produced by Diagnostics Systems Laboratories (DSL) were widely used in epidemiological studies, were not calibrated against recommended standards and are no longer commercially available. DESIGN In a split sample study among 1471 adults participating in the Cardiovascular Health Study, we compared values obtained using DSL assays with alternative assays for serum IGF-I (Immunodiagnostic Systems, IDS), IGFBP-1 (American Laboratory Products Company, ALPCO) and IGFBP-3 (IDS). RESULTS Results were compared using kernel density estimation plots, quartile analysis with weighted kappa statistics and linear regression models to assess the concordance of data from the different assays. Participants had mean age of 77 years. Results between alternative assays were strongly correlated (IGF-I, r=0.93 for DSL versus IDS; log-IGFBP-1, r= 0.90 for DSL versus ALPCO; IGFBP-3, r= 0.92 for DSL versus IDS). Cross tabulations showed that participants were usually in the same quartile categories regardless of the assay used (overall agreement, 74% for IGF-I, 64% for IGFBP-1, 71% for IGFBP-3). Weighted kappa also showed substantial agreement between assays (kw, 0.78 for IGF-I, 0.69 for IGFBP-1, 0.76 for IGFBP-3). Regression of levels obtained with DSL assays (denoted X) to alternative assays were, IGF-I: 0.52X +15.2 ng/ml, log-IGFBP-1: 1.01X – 1.73 ng/ml IGFBP-3: 0.87X + 791.1 ng/ml. Serum values of IGF-I, IGFBP-1 and IGFBP-3 measured using alternative assays are moderately correlated. CONCLUSIONS Care is needed in interpretation of data sets involving IGF analytes if assay methodologies are not uniform.

Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence: A Nested Case-Control Study

“…Another matching method would have been to use incidence density sampling where a patient could first be a control and then a case and thus be counted twice ( 44 ). Since discrepancies between studies in the IGF-field may in part be attributed to use of different test methods, the analytic assays selected for this study have been well validated ( 45 ) and all samples were run in duplicate. The antibody used for IGF-IR was also carefully selected ( 27 ) in order to minimize non-specific binding.…”

Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population

“…analyzing only those above the detection limit as well as replacing those below the detection limit with values of half the lower detection limit. Proportions with values below the detection limit have been observed in previous epidemiological studies investigating free IGF-1 52 and IGFBP-1 53 as independent variables, and similar approaches (assigning values of half the lower limit of detection) have been applied. Finally, participants were generally non-fasting (i.e.…”

Transient Isolated Idiopathic Growth Hormone Deficiency – a Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20-Years’ Real-World Experience with Retesting in One Center

“…Since 2017 new IGF-1 assays, standardized to WHO 1st International Standard 02/254, become available, that resulted in the need of conversion of the obtained results, according to the equation provided in Siemens Healthcare Diagnostics Customer Bulletin for IMMULITE® 2000 Immunoassay System, from May 2016 [44]. The agreement of IGF-1 measurements by different assays, especially for lower limits of reference values and with differences on raw values but not on SDS values, has been confirmed in dedicated studies [45,46]. All IGF-1 values were expressed as IGF-1 SDS for age and sex, according to the formula proposed by Blum & Schweitzer [47] and reference data for the laboratory method used [48].…”

“…The patients with other hormonal deficits (except for well controlled primary hypothyroidism), malnutrition, chronic diseases, neoplastic processes, diagnosed or suspected skeletal dysplasia, longterm or recurrent glucocorticoid administration and other therapies that might disturb growth or the function of somatotropic axis were excluded from the study; pubertal development was spontaneous and completed at therapy withdrawal in each case, however it could have been delayed. All girls included had normal female karyotype (46,XX). Magnetic resonance imaging (MRI) of hypothalamicpituitary region was performed in each case before treatment and all the patients with pituitary/hypothalamic structural defects (except for isolated decreased size of anterior pituitary) and/or with the history of brain injuries, neurosurgery or tumors were excluded from the study.…”