ABSTRACT
CONTEXT: Anorexia nervosa (AN) can cause severe undernutrition associated with alterations in the IGF axis. Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) modulate IGF binding-protein (IGFBP) cleavage and IGF bioavailability, but their implications in AN are unknown. OBJECTIVE: We determined serum levels of PAPP-As and STCs in relationship with classical IGF axis parameters in female adolescents with AN and their association with nutritional status and secondary amenorrhea. METHODS: Parameters of the IGF axis were determined in fasting serum samples of 68 female adolescents with AN at diagnosis and 62 sex- and age-matched controls. Standardized body mass index (BMI) and bone mineral density (BMD) were calculated. RESULTS: Patients with AN had lower concentrations of total and free IGF-I, total IGFBP-3, acid-labile subunit (ALS), insulin, PAPP-A2, STC-1, and STC-2 and higher levels of IGF-II and IGFBP-2. Their free/total IGF-I ratio was decreased and the intact/total IGFBP-3 and -4 ratios increased. BMI was directly related to total IGF-I and intact IGFBP-3 and inversely with IGFBP-2 and intact IGFBP-4. Weight loss was directly correlated with intact IGFBP-4 and negatively with intact IGFBP-3, ALS, STC-2, and PAPP-A2 concentrations. BMD was directly related to intact IGFBP-3 and inversely with intact IGFBP-4 and PAPP-A2 levels. Patients with amenorrhea had lower levels of total IGF-I and IGFBP-3 than those with menses. CONCLUSION: The reduction of PAPP-A2 in patients with AN may be involved in a decline in IGFBP cleavage, which could underlie the decrease in IGF-I bioavailability that is influenced by nutritional status and amenorrhea.