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)

Context: The association between IGFs and cancer in adults with GH deficiency (GHD) receiving GH replacement requires investigation. Objective: 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. Design: 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. Setting: The setting included the KIMS (the Pfizer International Metabolic Database). Patients: One hundred patients with de novo malignancy during GH therapy were compared with 325 patients with idiopathic GHD without malignancy. Intervention(s): Serum samples were obtained as close as possible to the diagnosis of malignancy, or after approximately 2 yr of GH replacement in KIMS. Main Outcome Measures: 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. Results: 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)]. Conclusions: 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. (J Clin Endocrinol Metab 95: 4449-4454, 2010)