A PROSPECTIVE MULTICENTER OCTREOTIDE DOSE-RESPONSE STUDY IN THE TREATMENT OF ACROMEGALY

The somatostatin analog octreotide has proven to be an effective form of treatment for various hypersecretory states including acromegaly. This report describes the effects of escalating doses of octreotide on the growth hormone (GH) profiles, insulin-like growth factor-1 (IGF-1), prolactin (PRL), and adverse effects in 99 patients with acromegaly. Treatment with octreotide was initiated at 50 mu g sc every 8 h and the dose gradually titrated to a maximum of 1500 mu g/d if more than 75% of GH determinations in a 12-h day profile were above detection limits. This dose was maintained for the duration of 6 months. Seventy-three percent of patients did not reach the GH reduction criterion at the 300 mu g dose. Mean GH levels decreased from 33+/-4 mu g/l to 10+/-1 mu g/l (p<0.001) while receiving the 300 mu g/d dose. The percentage decrease in mean GH levels, however, was dose-independent reaching 50+/-5% of baseline with 300 mu g/d, 55+/-5% with 600 mu g/d, 57+/-6% with 900 mu g/d, and 56+/-5% with 1500 mu g/d. Maximal GH suppression, however, was achieved in 40%, 17%, 7%, and 16% of subjects by the 300 mu g, 600 mg, 900 mu g, and 1500 mu g doses respectively. GH suppression was independent of duration of treatment. While there was a tendency for a greater degree of 1GF-1 reduction with the higher doses, the rate of normalization (30-37%) was not influenced by the dose of octreotide administered. Elevated PRL levels also declined with the use of higher doses of octreotide. Gallstones or biliary sludge developed in 23% of subjects but this and other adverse events was not influenced by the dose administered. We conclude that octreotide is an effective therapeutic agent in the majority of patients with acromegaly. For nearly half of patients, a 300 mu g daily dose is sufficient for optimal GH suppression. A gradual titration of the dose may be necessary for some patients.