Background: Customary blood protein markers for malnutrition are of limited value in the diagnosis of protein-energy malnutrition or anorexia nervosa in children and in the follow-up to refeeding in such children. Objectives: For these diseases, we compared the diagnostic value of sex hormone binding globulin (SHBG) with that of albumin, transferrin, transthyretin, and retinal binding protein and determined the relations between concentrations of insulin, insulinlike growth factor I, and SHBG. Design: SHBG was assayed in children with protein-energy malnutrition (29 children with kwashiorkor and 28 with marasmus), in 29 anorectic girls (before and after refeeding), and in age-and sex-matched control subjects. Results: Mean (± SE) serum SHBG concentrations were higher in the children with kwashiorkor (0.18 ± 0.07 mol/L) than in the children with marasmus (0.11 ± 0.05 mol/L, P < 0.0001) or the control subjects (0.11 ± 0.03 mol/L, P < 0.0005). In the children with anorexia nervosa before weight gain, serum SHBG concentrations were significantly higher (0.10 ± 0.04 mol/L) than in the age-matched control subjects (0.06 ± 0.03 mol/L, P < 0.001) and decreased significantly after 30 d of refeeding (0.04 ± 0.01 mol/L, P < 0.0001). This decrease was negatively correlated with insulin-like growth factor I but not with insulin. Mean serum SHBG concentrations were influenced neither by inflammation, as indicated when C-reactive protein was used as a marker (0.27 ± 0.27, 0.34 ± 0.42, and < 0.04 mol/L in the children with marasmus, kwashiorkor, and anorexia nervosa, respectively), nor by glomerular filtration, as indicated when cystatin-C was used as a marker (68.46 ± 23.08, 66.90 ± 43.08, and 49.23 ± 7.69 mol/L, respectively). Conclusions:The high SHBG concentration observed in anorexia nervosa and kwashiorkor seems to be of multifactorial origin. For these 2 diseases, SHBG is a reliable marker of nutritional status, is unrelated to either C-reactive protein or cystatin-C, and may be helpful in distinguishing kwashiorkor from marasmus and as a follow-up marker after refeeding. Am J Clin Nutr 2002;76:239-44. KEY WORDSSex hormone binding globulin, anorexia nervosa, kwashiorkor, marasmus, malnutrition, inflammation, renal failure, insulin-like growth factor I, insulin INTRODUCTIONThe term protein-energy malnutrition (PEM) is widely used to describe a group of diseases (2 extreme forms, kwashiorkor and marasmus, and many mixed forms) that often affect young children in most developing countries. Inflammation and changes in hormonal patterns are usually associated with kwashiorkor and marasmus. For a long time, kwashiorkor and marasmus have been considered to be the clinical translation of either inadequate protein intake or deficient energy intake (1). However, it has been observed that kwashiorkor and marasmus may coexist in the same infantile population having the same diet (2). More recently, kwashiorkor has been considered a metabolic misadaptation of the organism to malnutrition, explaining the development of edema. ...