Long-term effects of elevated gastrin levels on calcitonin secretion

Gastrin and pentagastrin stimulate thyroid C cells and elevate serum calcitonin levels. Gastrin levels may be elevated when histamine-2 receptor blockers (H2RB) and/or proton pump inhibitors (PPI) are used, or in patients with pernicious anemia (PA). This study was designed to investigate the long-term effects of elevated gastrin levels on serum calcitonin levels. We conducted a pentagastrin stimulation test to evaluate C cell reserves in patients who had been using PPI and/or H2RB for an extended period, as well as in patients with PA. We compared the results with a healthy control group of similar age and sex. A total of 40 controls (26 women, 24 men) and 25 patients (15 women, 10 men) using H2RB and/or PPI, and 37 patients (24 women, 13 men) with PA were enrolled. The groups were similar in terms of mean age and sex distribution. Mean fasting gastrin levels, and mean baseline and pentagastrin-stimulated calcitonin levels were significantly higher in the H2RB+PPI and PA groups than in controls. No significant differences were observed between the H2RB+PPI and PA groups. There was no correlation between gastrin and calcitonin levels. However, mean calcitonin levels were significantly higher in subjects with high baseline gastrin levels than in controls. The prevalence of autoimmune thyroid disease was 32% in the PA group. Patients with PA and thyroiditis had significantly higher baseline gastrin levels than patients with PA only (p<0.01). PA with autoimmune thyroid disease had also significantly higher baseline and pentagastrin-stimulated calcitonin levels than did PA patients without autoimmune thyroid disease. In conclusion, chronic elevated gastrin levels led to elevated calcitonin levels. Further histopathological studies showing C cell hyperplasia are needed to confirm the mechanism of this relationship.