Abstract

Repeated daily injections of the somatostatin analogue, octreotide (SMS201-995, Sandostatin) are an effective treatment for acromegaly, but lead to gall stone formation in about 50% of cases during longterm treatment. This is probably because of impaired gall bladder contraction. This study examined whether the timing of intermittent injections in relation to meals, or alternatively, continuous 24 hour subcutaneous octreotide infusion (CSOI) might avert adverse effects on gall bladder contraction. In six patients with active acromegaly, gall bladder volume, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in the fasting state and after consumption of a fatty meal. Measurements were made on five separate days: (a) without treatment, (b) 45 minutes after 100 micrograms octreotide given subcutaneously, (c) four hours after 100 micrograms octreotide given subcutaneously, (d) eight hours after 100 micrograms octreotide given subcutaneously, and (e) during CSOI of 300 micrograms/24 h for two weeks. Without treatment, postprandial gall bladder contraction was 86.2 (2.1%). Fasting gall bladder volume increased after octreotide injection and was almost doubled during CSOI. Octreotide injections impaired postprandial gall bladder contraction as well as CCK and PP release for at least four hours. Eight hours after injection and during CSOI, postprandial gall bladder contraction was partly restored (43.4% and 50.8% respectively). Postprandial CCK release was normal at eight hours after injection but very low during CSOI. PP release was suppressed by each mode of octreotide treatment. This study indicates that octreotide injections impair postprandial gall bladder contraction for at least four hours. Eight hours after injection and during CSOI, gall bladder contraction is partly restored.