Effects of octreotide on insulin-like growth factor I and metabolic indices in growth hormone-treated growth hormone-deficient patients.
Animals studies have demonstrated that in addition to inhibiting growth hormone (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral insulin-like growth factor I (IGF-I) generation. To test this hypothesis in humans we studied ten GH-deficient patients with frequent blood sampling during 38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each study period. At the start of each study a subcutaneous (sc) injection of GH (3 IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients received a continuous sc infusion of either octreotide (200 micrograms/24 h) or placebo (saline). The pharmacokinetics of GH were similar on the two occasions. The area under the curve +/- SEM of serum GH was 142.5 +/- 53.6 micrograms.l-1 x h-1 (octreotide) and 144.8 +/- 41.8 micrograms.l-1 x h-1 (placebo), (p = 0.73); Cmax (microgram/l) was 12.5 +/- 1.47 (octreotide) and 12.8 +/- 1.42 (placebo) (p = 0.83), and Tmax (h) was 6.1 +/- 0.97 (octreotide) and 5.2 +/- 0.65 (placebo) (p = 0.49). Growth hormone administration was associated with an increase in serum IGF-I (microgram/l), which was identical during the two studies, from 85.3 +/- 19.4 to 174.25 +/- 30.3 for octreotide and from 97.0 +/- 26.4 to 158.8 +/- 28.2 for placebo. Mean IGF-I levels (microgram/l) were 138.2 +/- 25.1 (octreotide) and 134.5 +/- 28.6 (placebo) (p = 0.78). Similarly, the increase in IGF binding protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (microgram/l) were 2303 +/- 323 (octreotide) and 2200 +/- 361 (placebo) (p = 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)
Laursen
T
T
Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, Denmark.
Jørgensen
J O
JO
Orskov
H
H
Møller
J
J
Harris
A G
AG
Christiansen
J S
JS
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000097:blood; D000704:Analysis of Variance; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015200:Fluoroimmunoassay; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006131:Growth Inhibitors / Q000097:blood; D006801:Humans; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011863:Radioimmunoassay; D016037:Single-Blind Method
D001786:Blood Glucose; D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D006131:Growth Inhibitors; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007773:Lactates; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon; D000409:Alanine; D015282:Octreotide