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 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months.
Results: After 2 weeks of treatment, a single 100-micrograms 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 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 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% (CI, 5% to 33%) and 37% (CI, 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.