Serum Insulin-Like Growth Factor I (IGF-I), IGF-Binding Proteins 2 and 3, and the Risk for Development of Malignancies in Adults with Growth Hormone (GH) Deficiency Treated with GH: Data from KIMS (Pfizer International Metabolic Database)

Abstract

The association between IGFs and cancer in adults with GH deficiency (GHD) receiving GH replacement requires investigation. The objective was to examine the association between IGF-I, IGF-binding protein 2 (IGFBP-2), and IGFBP-3 SD scores (SDSs) in GH-deficient adults receiving GH therapy and the occurrence of de novo malignancies. Serum IGF-I, IGFBP-2, and IGFBP-3 levels in GH-deficient patients who developed a malignancy since receiving GH were compared with patients with idiopathic GHD but without malignancy. Measurements were related to age-, sex-, and body mass index-specific SDS reference regions. The setting included the KIMS (the Pfizer International Metabolic Database). One hundred patients with de novo malignancy during GH therapy were compared with 325 patients with idiopathic GHD without malignancy. Serum samples were obtained as close as possible to the diagnosis of malignancy, or after approximately 2 yr of GH replacement in KIMS. Associations between relative risk (RR) of malignancy and IGF-I, IGFBP-2, and IGFBP-3 SDSs were assessed in multiple log-linear Poisson working regression models, controlling for age, sex, onset of GHD, and GH naivety at KIMS entry. No association between IGF-I SDSs and RR was observed (P = 0.48). Increasing IGFBP-2 and IGFBP-3 SDSs were associated with increasing RRs [18% per unit IGFBP-2 SDSs (95% confidence interval, 7-30%; P = 0.0006), 13% per unit IGFBP-3 SDS (2-26%; P = 0.01)]. IGF-I levels targeted to within normal age-related reference ranges during GH replacement were not associated with the occurrence of malignancies. Higher IGFBP-2 and/or IGFBP-3 SDSs may be associated with increased cancer risk.