EFFECTS OF INTRAMUSCULAR MICROSPHERE-ENCAPSULATED OCTREOTIDE ON SERUM GROWTH-HORMONE, INSULIN-LIKE GROWTH-FACTORS (IGFS), FREE IGFS, AND IGF-BINDING PROTEINS IN ACROMEGALIC PATIENTS

Nine acromegalic patients selected to he well-controlled on subcutaneous octreotide injections three times daily were transferred for more than 1 year to intramuscular injections every month with a new microsphere-encapsulated octreotide formulation (Sandostatin LAR(3), Sandoz, Basel, Switzerland). The dosage was titrated to between 20 and 60 mg/mo to approach optimum control in each patient. The study compares the efficacy of subcutaneous octreotide three times daily versus intramuscular microsphere-encapsulated octreotide once monthly. For all patients, average serum growth hormone (GH), insulin-like growth factor binding protein-3 (IGFBP-3), and total insulin-like growth factor-l (IGF-I) were as follows (subcutaneous v washout v intramuscular after 9 months' treatment): 2.5 +/- 0.5 versus 13.0 +/- 3.3 versus 2.2 +/- 0.8 mu g/L (GH), 3,240 +/- 312 versus 3,880 +/- 547 versus 3,190 +/- 226 mu g/L (IGFBP-3), and 200 +/- 30 versus 364 +/- 32 versus 207 +/- 36 mu g/L (IGF-I; mean +/- SEM), ie, no significant differences were found between the two regimens. One patient was a relatively poor responder on both regimens, with average 8-hour serum GH concentrations of approximately 5 mu g/L and increased IGF-I. In two patients GH was suppressed below 3 mu g/L, with IGF-I just above the normal range. The remaining six patients had GH below 2 mu g/L and IGF-I within the normal range for age. Concomitant values for IGFBP-1 were 4.9 +/- 0.9 versus 1.6 +/- 0.3 versus 7.9 +/- 1.9 mu g/L (P =.043 for subcutaneous v intramuscular), and for free IGF-I, 1,150 +/- 262 versus 2,290 +/- 265 versus 660 +/- 153 ng/L (P = .009 for subcutaneous v intramuscular). For all five parameters mentioned above, washout values were different from those obtained during subcutaneous and intramuscular treatments. Total and free IGF-II in serum were unchanged throughout. The new formulation was well tolerated and greatly preferred by the patients. There was occasional slight local tenderness at the injection site lasting up to a few days. Two patients developed asymptomatic biliary sludge. The previously described acute octreotide-induced stimulation of IGFBP-1 release appears to occur also during long-term treatment with elevation in fasting levels. Another novel observation is the drastically reduced serum free IGF-I in fasting samples, which may be an important new facet in octreotide treatment. For both effects, continuous stable octreotide exposure seems to be more effective than intermittent exposure as occurs with conventional subcutaneous octreotide injections three times per day. (C) 1995 by W.B. Saunders Company