Calcium Reverses Octreotide Inhibition of Insulin and Glucagon Levels in Patients with Insulinoma and Glucagonoma

Abstract

Excessive secretion of peptides causes the clinical syndromes associated with functional gastro-intestinal tumours. The somatostatin analogue octreotide acetate inhibits peptide release from a variety of tumours. This study investigated the interactions of calcium and somatostatin analogues on peptide release in two patients, one with a glucagonoma (patient A) and one with an insulinoma (patient B). Peptide responses were evaluated before (fasting levels) and after provocative tests (a 4-hour calcium infusion, an intravenous tolbutamide infusion, a secretin bolus and a standard test meal) in the absence and presence of octreotide acetate treatment (100 micrograms subcutaneously every 8 h). Patients A and B had elevated fasting plasma levels of glucagon and insulin, respectively, which were reduced by octreotide therapy by 73 and 50%, respectively. The peak provoked levels and calculated values for peptide synthesis were lower after octreotide therapy. In both patients, tolbutamide provoked most peptide release, and calcium infusion was the least susceptible to the effects of octreotide therapy. Calcium appears to inhibit octreotide suppression of glucagon and insulin secretion in patients with glucagonoma and insulinoma, respectively. Calcium may stimulate peptide release from endocrine tumours by suppressing the inhibitory effects of endogenous somatostatin. Normalisation of serum calcium, either surgically or pharmacologically, may improve the effectiveness of somatostatin analogue therapy.