4 YEARS TREATMENT OF RESISTANT ACROMEGALY WITH OCTREOTIDE

This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refra ctory acromegaly. Eight patients (aged 21-62 years) with persistent gr owth hormone (GH) elevation (duration 1-15 years) despite previous the rapy were studied. Octreotide was given subcutaneously in increasing d oses for the first year to a maximum of 500 mu g three times daily. Th e dose then was reduced to 200 mu g three times daily for the next 3 y ears. At annual assessments, 24-h GH profiles, insulin-like growth fac tor I (IGF-I) and a side-effect profile including gall-bladder ultraso und were studied. Oral glucose tolerance tests (75 g) were performed b asally and after 6 months and 3 years of therapy. Haemoglobin A(1) (Hb A(1)) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subs equent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF -I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA(1) were not changed by therapy but 2-h glucose was elevated after 6 mont hs and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gall stones and in three these had disappeared following 1 year of bile sal t dissolution therapy. Octreotide continues to suppress serum GH and I GF-I long term without attenuation of effect. Gallstone formation is a major side effect. Two hours after glucose load the plasma glucose le vel was elevated but HbA(1) did not change long term. Further similar studies of long duration are required to establish the long-term safet y profile of the drug.