Could there be a role of serum zonulin increase in the development of hypercalcemia in primary hyperparathyroidism

Purpose: To evaluate the serum level of zonulin, which is an intestinal permeability (IP) biomarker, in primary hyperparathyroidism (PHPT) and to investigate the relationship between zonulin, calcium, and parathormone (PTH) levels.

Methods: The study included 34 healthy control (HC) and 39 patients with PHPT. Serum calcium, phosphorus, magnesium, creatinine, albumin, and 24 h urine calcium levels were measured in all groups. Serum levels of zonulin were measured quantitatively by enzyme-linked immunosorbent assay (ELISA). Urinary ultrasonography (to assess the presence of nephrolithiasis) and dual energy X-ray absorptiometry (to assess the presence of osteoporosis) were used to evaluate complications related to PTHP.

Results: Serum zonulin levels were significantly higher in the PHPT group than the HC group (p < 0.001). Zonulin levels were significantly positively correlated with plasma PTH and serum calcium levels (r = 0.600, p < 0.001 and r = 0.610, p < 0.001; respectively). There was no correlation between serum zonulin levels and adenoma volume.

Conclusion: Serum zonulin level increases in patients with PHPT. Serum zonulin levels show a moderate/strong positive correlation with serum calcium and plasma PTH levels. This suggests that IP increase may play a role in the development of hypercalcemia in patients with PHPT.

Keywords: Hypercalcemia; Intestinal permeability; Primary hyperparathyroidism; Zonulin.