Fibroblast Growth Factor-21 May Mediate Growth Hormone Resistance in Anorexia Nervosa

Context: Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. Fibroblast growth factor (FGF)-21, a hormone produced in the liver and adipocytes, is induced in the liver by fasting and peroxisome proliferator-activated receptor-alpha agonists. In a transgenic mouse model, FGF-21 reduces IGF-I levels by inhibiting signal transducer and activator of transcription-5, a mediator of the intracellular effects of GH. Objective: The objective of the study was to investigate the relationship between FGF-21, GH, and IGF-I in AN. Design: This was a cross-sectional study. Setting: The study was conducted at a clinical research center. Patients: Patients included 23 girls: 11 with AN (16.5 +/- 0.6 yr) and 12 normal-weight controls (15.7 +/- 0.5 yr). Interventions: There were no interventions. Main Outcome Measures: We measured fasting FGF-21, glucose, insulin, IGF-I, and total area under the curve for GH (GH-AUC) and leptin during 12-h overnight frequent sampling. Results: FGF-21 levels were significantly higher in AN compared with controls, and there was a positive correlation between FGF-21 and GH-AUC (P = 0.03) after controlling for percent body fat and insulin resistance. In subjects with elevated FGF-21 levels, there was a strong inverse association between FGF-21 and IGF-I (R = -0.88, P = 0.004). FGF-21 strongly correlated with total area under the curve for leptin (R = 0.67, P = 0.02). Conclusions: FGF-21 levels are higher in AN independent of the effects of percent body fat and insulin resistance. The positive association between FGF-21 and GH-AUC and the inverse association between elevated FGF-21 levels and IGF-I suggests that above the normal range, FGF-21 may mediate a state of GH resistance in AN. (J Clin Endocrinol Metab 95: 369-374, 2010)