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 micrograms sc every 8 h and the dose gradually titrated to a maximum of 1500 micrograms/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 micrograms dose. Mean GH levels decreased from 33 +/- 4 micrograms/l to 10 +/- 1 microgram/l (p < 0.001) while receiving the 300 micrograms/d dose. The percentage decrease in mean GH levels, however, was dose-independent reaching 50 +/- 5% of baseline with 300 micrograms/d, 55 +/- 5% with 600 micrograms/d, 57 +/- 6% with 900 micrograms/d, and 56 +/- 5% with 1500 micrograms/d. Maximal GH suppression, however, was achieved in 40%, 17%, 7%, and 16% of subjects by the 300 micrograms, 600 mg, 900 micrograms, and 1500 micrograms doses respectively. GH suppression was independent of duration of treatment. While there was a tendency for a greater degree of IGF-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Ezzat
S
S
Department of Medicine, University of Toronto, Canada.
Redelmeier
D A
DA
Gnehm
M
M
Harris
A G
AG
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000595:Amino Acid Sequence; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006728:Hormones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D011388:Prolactin / Q000097:blood; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed
D006728:Hormones; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone; D015282:Octreotide