The Journal of Clinical Endocrinology and Metabolism Journal Article

Reduction in Pappalysin-2 Levels and Lower IGF-I Bioavailability in Female Adolescents With Anorexia Nervosa

March 26, 2024
 

Vicente Barrios, Álvaro Martín-Rivada, Santiago Guerra-Cantera, Ana Campillo-Calatayud, Ricardo A Camarneiro, Montserrat Graell, Julie A Chowen, Jesús Argente
The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 3, March 2024, Pages e920–e931
https://doi.org/10.1210/clinem/dgad713

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.

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