Background: Pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC-1, STC-2) are novel regulators of the GH-IGF axis, modulating IGF bioavailability through control of cleavage of IGFBPs and release of IGF from the ternary complex. Changes in the peripheral IGF system, including low IGF concentrations independently of GH secretion, have been reported in scenarios of malnutrition such as anorexia nervosa (AN). The role of pappalysins and stanniocalcins in the pathophysiology of this disorder is not fully established.
Objective: Our objective was to determine the changes in the serum levels of the peripheral GH-IGF axis components in a cohort of female adolescents with AN.
Patients and Methods: One hundred and six female adolescents with AN, age 14.93 ± 1.80 years, BMI: -2.13 ± 0.65 SDS, weight loss at diagnosis: 9.06 ± 5.70 kg, and 106 healthy females (age: 14.61 ± 1.42 years, BMI: 0.05 ± 0.85 SDS) were included. At diagnosis, total IGF-I, free IGF-I, IGF-II, IGFBP-2, total and intact IGFBP-3, total and intact IGFBP-4, IGFBP-5, ALS, insulin, PAPP-A, STC-1 and STC-2 were measured by ELISA and PAPP-A2 by CLIA in fasting serum samples.
Results: Patients with AN showed lower concentrations of total and free IGF-I, total IGFBP-3 (P < 0.001), ALS, insulin (P < 0.01), PAPP-A2, STC-1 and STC-2 (P < 0.001) than the controls. Conversely, AN patients presented higher serum levels of IGF-II and IGFBP-2 (P < 0.001). The free/total IGF-I ratio was decreased (P < 0.05), whereas the intact/total IGFBP-3 and -4 ratios (P < 0.001) were increased in patients with AN. No changes were observed in total IGFBP-4, IGFBP-5 or PAPP-A levels.
In patients with AN, standardized BMI was positively correlated with total IGF-I (P < 0.001), total IGFBP-3 (P < 0.001) and STC-2 (P < 0.01), and negatively with IGFBP-2 (P < 0.001) and the intact/total IGFBP-4 ratio (P < 0.01). Additionally, weight loss was negatively correlated with STC-2 (P < 0.01) and PAPP-A2 (P < 0.05) levels.
Conclusions: The decrease in circulating pappalysin and stanniocalcin levels in patients with anorexia nervosa, would explain, at least in part, the reduction in IGF-I bioavailability, with these changes being influenced by both the nutritional status and changes in body composition.
22 Sep 2021 - 26 Sep 2021