ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study investigated the effects of anorexia nervosa (AN) on the insulin-like growth factor (IGF) axis in female adolescents. It evaluated levels of various proteins and their role in the IGF axis, including pregnancy-associated plasma protein A2 (PAPP-A2) and stanniocalcins (STC-1 and STC-2). The reduced levels of PAPP-A2 may impair IGFBP cleavage, thereby reducing IGF-I bioavailability. IGF1 plays a crucial role in regulating growth, metabolism, and bone health.

This study assessed the impact of AN on IGF system function in 68 female adolescents diagnosed with AN and 62 healthy age-matched female controls. All participants had reached full pubertal maturity. Female adolescents with AN showed lower levels of both total and free IGF-I, a growth factor strongly influenced by nutritional status. A decrease in intact IGFBP-3 and an increase in intact IGFBP-4 were found in patients with AN, suggesting a change in IGF bioavailability and IGFBP cleavage. PAPP-A2, a metalloproteinase that cleaves IGFBPs to increase IGF bioavailability, was significantly reduced in AN patients. This reduction may contribute to lower IGF-I bioavailability, further exacerbating the effects of malnutrition. Furthermore, a significant correlation between reduced IGF-I and PAPP-A2 levels and reduced bone mineral density was found. In patients with secondary amenorrhea (a condition commonly seen in AN) lower IGF-I and IGFBP-3 levels were observed compared to those who retained menstrual cycles, indicating more severe endocrine disruptions in these individuals.

These findings highlight the dysregulation of IGF system in adolescents with AN, suggesting the need of monitoring the IGF system in the management of AN in adolescents. In particular, the assessment of PAPP-A2 levels could provide insight into how malnutrition affects bone metabolism and growth in patients with AN and could help develop targeted therapeutic strategies to limit these effects.

References: 1. Silén Y, Keski-Rahkonen A. Worldwide prevalence of DSM-5 eating disorders among young people. Curr Opin Psychiatry. 2022;35(6): 362-371.2. Muñoz MT, Argente J. Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances. Eur J Endocrinol. 2002;147(3):275-286.3. Støving RK, Chen JW, Brixen K, Flyvbjerg A, Hørder K, Frystyk J. Bioactive insulin-like growth factor (IGF) I and IGF-binding protein-1 in anorexia nervosa. J Clin Endocrinol Metab. 2007;92(6):2323-2329.