OCTREOTIDE TREATMENT OF ACROMEGALY - A RANDOMIZED, MULTICENTER STUDY

Objective: To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. Design: Double-blind, randomized trial. Setting: Fourteen university-affiliated medical centers. Patients: One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. Intervention: Subcutaneous octreotide, 100 mug, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 mug octreotide subcutaneously every 8 hours for 6 months. Results: After 2 weeks of treatment, a single 100-mug injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 mug/L to 9 +/- 2 mug/L (P < 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P < 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 mug/L by 300 mug of octreotide and from 29 +/- 5 mug/L to 9 +/- 2 mug/L by 750 mug of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500+/-400 U/L after 300 and 750 mug octreotide, respectively. Integrated mean GH levels were reduced to less than 5 mug/L in 53% (95% Cl, 39% to 67%) and 49% (Cl, 35% to 63%), and IGF-1 levels were normal in 68% (Cl, 54% to 82%) and 55% (Cl, 40% to 70%) of patients receiving low- and high-dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (Cl, 5% to 33%) and 37% (Cl, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. Conclusion: Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit.