Secretin and Insulin Release in Acromegaly

It has been demonstrated that growth hormone influences the intestinal content of secretin and also that secretin plays an important role in the release of insulin. In this study serum levels of secretin were measured by radioimmunoassay in nine subjects with clinically active acromegaly following the stimulus of a 50 g oral glucose load. Blood glucose, serum insulin and serum growth hormone (hGH) levels were also measured. A comparison was made with a group of nine normal subjects and also with results obtained in seven of the acromegalics after cryogenic pituitary destruction. Secretin levels in the acromegalics were significantly greater (p < 0.01) than in the normals in the fasting state and from 30 to 120 min (p < 0.05) after glucose ingestion. High insulin levels and impaired glucose tolerance accompanied these findings but it was noted that two acromegalics with normal glucose tolerance did not show persistent elevation of secretin levels. After pituitary destruction the secretin response to glucose was reduced together with lower hGH levels and improved glucose tolerance. Prolonged elevation of serum secretin levels after oral glucose, similar to that noted in active acromegaly, was seen in a normal subject during an iv infusion of hGH. It has been proposed that insulin causes a feedback inhibition of the release of secretin. In acromegaly there is both insulin antagonism and compensatory hyperinsulinism. It is now suggested that once the increased release of insulin fails to compensate, as evidenced by impaired glucose tolerance, antagonism of insulin action may interfere with the feedback effect of insulin on secretin, resulting in the persistent release of secretin.