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Low Serum Levels of Free and Total Insulin-Like Growth Factor I (IGF-I) in Patients with Anorexia Nervosa Are Not Associated with Increased IGF-Binding Protein-3 Proteolysis¹

Department of Endocrinology (M) and Center for Eating Disorders, Odense University Hospital (R.K.S., J.H., M.H.-N., C.H.), DK-5000 Odense; and Medical Department M (Endocrinology and Diabetes), Medical Research Laboratory and Institute of Experimental Clinical Research, University Hospital of Aarhus (A.F., J.F., S.F.), DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: René Klinkby Støving, M.D., Department of Endocrinology (M), Odense University Hospital, DK-5000 Odense C, Denmark.

Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3 proteolysis. The present study was performed to examine the levels of free IGFs in AN and to clarify whether AN is associated with increased IGFBP-3 proteolytic activity. In 24 patients and 10 age-matched controls, the fasting serum concentrations of free IGF-I and -II were measured using ultrafiltration by centrifugation. In addition, GH, GH-binding protein, total IGFs, IGFBP-1 to -4, and IGFBP-3 proteolytic activity were measured. The IGFBPs were measured by both immunoassays and Western ligand blotting. Twelve of the patients were restudied 3 months after a minor increase in body mass index. In AN, the levels of GH-binding protein, free and total IGF-I, free IGF-II, and IGFBP-3 were significantly reduced; total IGF-II, IGFBP-2, and IGFBP-4 levels were unchanged; and IGFBP-1 was increased. No increased IGFBP-3 proteolytic activity could be detected in AN. In conclusion, the mechanisms responsible for the adaption of the GH-IGF-IGFBP axis in AN may be different from other catabolic conditions, because the low levels of free and total IGF-I in AN are not associated with increased IGFBP-3 proteolysis.

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