TREATMENT OF INVASIVE GROWTH-HORMONE PITUITARY-ADENOMAS WITH LONG-ACTING SOMATOSTATIN ANALOG SMS-201-995 BEFORE TRANSSPHENOIDAL SURGERY

The purpose of this study was to determine whether the long-acting som atostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)- secreting adenomas and improves the results of subsequent transsphenoi dal surgery. Ten previously untreated active acromegalic patients (nin e women and one man) with invasive tumors were treated with SMS 201-99 5 (100 mu g subcutaneously every 8 hours) for 6 weeks prior to transsp henoidal surgery. The clinical activity, mean GH secretion, insulin-li ke growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment.The SM S 201-995 improved the symptoms of acromegaly in all patients. Mean le vels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 mu g/liter an d from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which th ere were only slight further decreases. Six (60%) of the 10 patients e xperienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6. 5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer admin istration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 mu g/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the liter ature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive v alue with respect to the surgical outcome.