The pathomechanism of
primary polydipsia is poorly understood. Recent animal data reported a connection between
fibroblast growth factor 21 (FGF-21) and elevated fluid intake independently of hormonal control by the
hormone arginine-vasopressin (AVP) and osmotic stimulation. We therefore compared circulating
FGF-21 levels in patients with
primary polydipsia to patients with AVP deficiency (
central diabetes insipidus) and healthy volunteers. In this prospective cohort study, we analyzed
FGF-21 levels of 20 patients with
primary polydipsia, 20 patients with
central diabetes insipidus and 20 healthy volunteers before and after stimulation with hypertonic saline infusion targeting a plasma
sodium level ≥150 mmol/L. The primary outcome was the difference in
FGF-21 levels between the three groups. Baseline characteristics were similar between the groups except for patients with
central diabetes insipidus being heavier. There was no difference in baseline
FGF-21 levels between patients with
primary polydipsia and healthy volunteers (122 pg/mL (52,277) vs 193 pg/mL (48,301), but higher levels in patients with
central diabetes insipidus were observed (306 pg/mL (114,484); P = 0.037). However, this was not confirmed in a multivariate linear regression analysis after adjusting for age, sex, BMI and smoking status. Osmotic stimulation did not affect FGF-21 levels in either group (difference to baseline:
primary polydipsia -23 pg/mL (-43, 22);
central diabetes insipidus 17 pg/mL (-76, 88); healthy volunteers -6 pg/mL (-68, 22); P = 0.45). To conclude, FGF-21 levels are not increased in patients with
primary polydipsia as compared to
central diabetes insipidus or healthy volunteers. FGF-21 therefore does not seem to be causal of elevated fluid intake in these patients.