Octreotide as Primary Therapy for Acromegaly1

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part of a multicenter study that took place between 1989–1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second phase, patients were randomized to treatment with either 100 or 250 μg octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient’s individual response, which included improvement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I (IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to either 100 or 250 μg octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 ± 5.2 to 6.0 ± 1.7 μg/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3–60 months). The mean final daily dose was 777 μg. In the patients receiving secondary treatment, mean GH fell from 30.2 ± 7.6 to 5.6 ± 1.1 μg/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 μg daily). Mean IGF-I concentrations fell from 5.2 ± 0.5 × 103 U/L (primary treatment group) and 4.7 ± 0.4 × 103 U/L (secondary treatment group) to a mean of 2.2 ± 0.3 × 103 U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 sd below the baseline mean GH were considered responders. There was no significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at base