A long‐term dose‐response study of somatostatin analogue (SMS 201–995, octreotide) in resistant acromegaly *

Ten acromegalic subjects were studied in a trial designed to ascertain the optimum dosage of the somatostatin analogue SMS 201–995 (octreotide) In active acromegaly. Twenty‐four‐hour growth hormone (GH) profiles were assessed monthly for 6 months and again after 1 year of continuous therapy. After basal assessment octreotide was administered subcutaneously at a dose of 100 μg three times a day throughout the first month. The dose was increased by 300 μg/day at monthly intervals to a maximum of 1500 μg/day, unless serum GH fell to within set criteria. Eight patients completed the trial. One patient withdrew because of intractable diarrhoea while another died of causes related to his acromegaly and we have no evidence that octreotide played any part in his death. Mean 24‐h GH fell from a basal level of 34·3 ± SEM 7·6 mU/I to 8·0 ± 1·3 mU/I (P > 0·05) after 6 months. At 1 month (300 μg/day) mean GH was 13·6 ± 2·2 mU/I and at 2 months (600 μg/day) 10·8 ± 2·2 mU/I (P > 0·05 vs 300 μg/day dose), and at 5 months (1500 μg/day) 11·3 ± 2·0 mU/i (all P > 0·05 vs basal). Analysis of group means revealed no significant difference between any dose schedules above 600 μg/day. After 1 year the mean GH of the group (n= 8) was 7·5 ± 1·3 mU/I (P > 0·05 vs basal). Three patients developed a deterioration and one an improvement in their glucose tolerance and three developed asymptomatic gallstones during the year of therapy. In conclusion, octreotide lowered GH levels in acromegaly over a 1‐year period. We found no evidence that routinely increasing the dose beyond 600 μg/day was helpful.