Kian Y. Ho, MD; Andrew J. Weissberger, MB BS; Peter Marbach, PhD; Leslie Lazarus, MB BS
Study Objective: To determine the efficacy of stepwise incremental doses, to compare twice- with thrice-daily administration of the same total daily dosage of the long-acting somatostatin analog SMS 201-995 (octreotide, Sandoz Australia, Sydney, Australia), and to evaluate the risk for cholelithiasis after long-term therapy for acromegaly.
Design: Nonrandomized, controlled trial.
Setting: Tertiary care center at a medical research institute.
Patients: Sequential sample of 19 patients with active acromegaly. Twenty-five age-matched normal subjects were also studied to establish the normal range for growth hormone (GH) and insulin-like growth factor 1 (IGF-I).
Interventions: Eight patients (group 1 ) were treated with 100, 250, and 500 μg twice daily of octreotide, then switched to 333 μg three times daily, whereas 11 patients (group 2) were treated with 100, 200, 300, and 500 μg three times daily. Each treatment stage lasted 6 to 12 weeks.
Measurements and Main Results: Octreotide, 100 μg administered twice or thrice daily, significantly reduced mean 12-hour and nadir GH (P < 0.01), IGF-1 (P < 0.05), and hand volume (P < 0.05). Dose increment to 500 μg in both groups did not further reddce mean 12-hour GH, nadir GH, or hand volume. Switching from 500 μg twice daily to 333 ?g thrice daily resulted in significant (P < 0.05) reduction of mean 12-hour GH, IGF-1, and hand volume. Normalization of mean 12-hour GH and IGF-1 occurred in 8 of 19 patients; 7 of the 8 patients had pretherapy mean 12-hour GH below 20 mIU/L. The pretherapy mean blood glucose was a significant negative predictor (r = -0.89) of the change in mean blood glucose during therapy. Gallstones were present in 9 of 18 patients after therapy.
Conclusion: Thrice-daily was more effective than twicedaily administration of octreotide, and dose increments above 100 μg thrice daily did not confer additional benefit. Biochemical remission was achieved in 40% of patients and was dependent on the GH concentration at initiation of treatment. Cholelithiasis is a risk of octreotide therapy. Octreotide is effective and can be considered as a first-line therapy in patients with acromegaly with mean pretherapy GH concentrations below 20 mIU/L. In patients with mean GH over 20 mIU/L, octreotide may be used as an adjuvant to surgery or radiotherapy.
Ho KY, Weissberger AJ, Marbach P, Lazarus L. Therapeutic Efficacy of the Somatostatin Analog SMS 201-995 (Octreotide) in Acromegaly: Effects of Dose and Frequency and Long-Term Safety. Ann Intern Med. ;112:173–181. doi: 10.7326/0003-4819-112-3-173
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Published: Ann Intern Med. 1990;112(3):173-181.
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