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

Nine acromegalic patients selected to he well-controlled on subcutaneo us octreotide injections three times daily were transferred for more t han 1 year to intramuscular injections every month with a new microsph ere-encapsulated octreotide formulation (Sandostatin LAR(3), Sandoz, B asel, Switzerland). The dosage was titrated to between 20 and 60 mg/mo to approach optimum control in each patient. The study compares the e fficacy of subcutaneous octreotide three times daily versus intramuscu lar microsphere-encapsulated octreotide once monthly. For all patients , average serum growth hormone (GH), insulin-like growth factor bindin g 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 betwe en the two regimens. One patient was a relatively poor responder on bo th regimens, with average 8-hour serum GH concentrations of approximat ely 5 mu g/L and increased IGF-I. In two patients GH was suppressed be low 3 mu g/L, with IGF-I just above the normal range. The remaining si x 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 o btained during subcutaneous and intramuscular treatments. Total and fr ee IGF-II in serum were unchanged throughout. The new formulation was well tolerated and greatly preferred by the patients. There was occasi onal slight local tenderness at the injection site lasting up to a few days. Two patients developed asymptomatic biliary sludge. The previou sly described acute octreotide-induced stimulation of IGFBP-1 release appears to occur also during long-term treatment with elevation in fas ting levels. Another novel observation is the drastically reduced seru m free IGF-I in fasting samples, which may be an important new facet i n octreotide treatment. For both effects, continuous stable octreotide exposure seems to be more effective than intermittent exposure as occ urs with conventional subcutaneous octreotide injections three times p er day. (C) 1995 by W.B. Saunders Company