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)

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 9; pp. 4449 - 4454
• Main Authors: Popovic, Vera, Mattsson, Anders F, Gaillard, Rolf C, Wilton, Patrick, Kołtowska-Häggström, Maria, Ranke, Michael B
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.09.2010; Copyright by The Endocrine Society
• Subjects: Adult; Aged; Biological and medical sciences; Case-Control Studies; Databases, Factual; Drug Industry; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Hormone Replacement Therapy; Human Growth Hormone - blood; Human Growth Hormone - deficiency; Human Growth Hormone - therapeutic use; Humans; Hypopituitarism - blood; Hypopituitarism - complications; Hypopituitarism - drug therapy; Hypopituitarism - epidemiology; Insulin-Like Growth Factor Binding Protein 2 - blood; Insulin-Like Growth Factor Binding Protein 3 - blood; Insulin-Like Growth Factor I - analysis; International Cooperation; Male; Medical sciences; Middle Aged; Neoplasms - blood; Neoplasms - epidemiology; Neoplasms - etiology; Risk; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; World; Endocrinopathy; Hormone therapy; Risk; Malignancy; Insulin like growth factor binding protein; Database; Adult; Serum; Nutritional status; International; Human; Nutrition; Deficiency; Nutrition disorder; Metabolic diseases; Malignant tumor; Insulin like growth factor binding protein 3; Insulin like growth factor 1; Metabolism; Somatotropin; Insulin-like growth factor binding protein-3; Adenohypophyseal hormone; Risk factor; Endocrinology; Cancer
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2010-0287

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. IGF-I SD scores during GH replacement is not associated with the occurrence of malignancies; however, higher IGFBP-2 and/or IGFBP-3 SD scores may be associated.