The insulin-like growth factor-I receptor stimulating activity (IRSA) in health and disease.

Determination of true IGF-I bioactivity in serum and other biological fluids is still a substantial challenge. The IGF-IR Kinase Receptor Activation assay (IGF-IR KIRA assay) is a novel tool to asses IGF-IR stimulating activity (IRSA) and has opened a new era in studying the IGF system. In this paper we discuss many studies showing that measuring IRSA by the IGF-IR KIRA assay often provides fundamentally different information about the IGF system than the commonly used total IGF-I immunoassays.

Disagreement in normative IGF-I levels may lead to different clinical interpretations and GH dose adjustments in GH deficiency.

Introduction And Background: Normative data for the iSYS IGF-I assay have been published both in the VARIETE cohort and by Bidlingmaier et al.

Objective: To investigate whether normative data of the VARIETE cohort lead to differences in Z-scores for total IGF-I and clinical interpretation compared to normative data of Bidlingmaier et al.

Design: We used total IGF-I values previously measured by the IDS-iSYS assay in 102 GH-deficient subjects before starting GH treatment and after 12 months of GH treatment.

Serum Insulin Bioassay Reflects Insulin Sensitivity and Requirements in Type 1 Diabetes.

Context: Insulin resistance could increase insulin requirements in type 1 diabetes (T1D). Current insulin immunoassays do not detect insulin analogs. Kinase insulin receptor (IR) activation (KIRA) bioassays specific for human IR isoforms A (IR-A) and B (IR-B) permit assessment of all circulating insulin bioactivity.

Changes in circulating IGF1 receptor stimulating activity do not parallel changes in total IGF1 during GH treatment of GH-deficient adults.

Context: Previously we demonstrated that IGF1 receptor stimulating activity (IGF1RSA) offers advantages in diagnostic evaluation of adult GH deficiency (GHD). It is unknown whether IGF1RSA can be used to monitor GH therapy.

Objective: To investigate the value of circulating IGF1RSA for monitoring GH therapy.

IGF-IR Targeted Therapy: Past, Present and Future.

The IGF-I receptor (IGF-IR) has been studied as an anti-cancer target. However, monotherapy trials with IGF-IR targeted antibodies or with IGF-IR specific tyrosine kinase inhibitors have, overall, been very disappointing in the clinical setting. This review discusses potential reasons why IGF-I R targeted therapy fails to inhibit growth of human cancers.