Additional metabolic effects of adding GH receptor antagonist to long-acting somatostatin analog in patients with active acromegaly.

OBJECTIVE: Somatostatin analogs, dopamine agonists and GH-receptor antagonist--pegvisomant are used in medical therapy of acromegaly. Since pegvisomant has not antitumor effect, the combination of pegvisomant and somatostatin analog could be an attractive option. Aim of study was to assess the effects of pegvisomant and octreotide LAR treatment on GH and IGF-1 levels, and glucose tolerance in acromegaly, and to assess efficacy and tolerability of rapid (after 7 days) pegvisomant dose titration.

MATERIAL AND METHODS: Six patients (4 men, 2 women) aged 47.5 years (median) with active acromegaly, after neurosurgery failed, resistant to maximal doses of octreotide, received daily 10-20 mg pegvisomant throughout 2 weeks. They were given octreotide LAR 30 mg monthly for at least 6 months before pegvisomant therapy. Clinical symptoms, GH, IGF-1, fasting glucose and insulin levels were measured on the 0, 8th and 15th day of pegvisomant therapy. On the 8th day pegvisomant dose was titrated based on serum IGF-1 level.

RESULTS: IGF-1 levels reduced from 739 at the beginning to 418 ng/ml (medians) on the 15th day of treatment and normalized in one patient. These changes were associated with improvement of glucose metabolism. One diabetic patient could even stop insulin therapy.

CONCLUSIONS: Pegvisomant is an attractive adjuvant therapy for controlling acromegaly. Pegvisomant improves insulin sensitivity as well as glucose tolerance. The GH receptor antagonist is good option for patients with active acromegaly coexistent with disturbances of glucose metabolism, especially with diabetes mellitus. Rapid pegvisomant dose increasing to efficient or maximal is well tolerated and effective.

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