Successful treatment of resistant acromegaly with a growth hormone receptor antagonist

Background/objective: Pegvisomant is a pegylated analogue of human GH and functions as a potent GH receptor antagonist. This novel mode of action gives it the potential to achieve biochemical control in patients with acromegaly whose disease activity cannot be satisfactorily controlled by conventional therapy. We have documented the clinical details of seven patients with residual active acromegaly after surgery and/or radiation therapy successfully treated with pegvisomant. Patients/methods: Seven patients (four male, mean age 47 years, range 34-67 years) who participated in two separate clinical trials of pegvisomant have completed 2 years (four patients) or 1 year (three patients) of treatment. All had active acromegaly (mean serum GH level >5 mU/l; serum IGF-I elevated for age) that could not be controlled with standard medical therapy (dopamine agonist and/or a somatostatin analogue) following appropriate primary treatment with surgery and/or radiotherapy. Results: On a median dose of 20 mg/day (range 15-40) pegvisomant, serum IGF-I fell from a mean of 920 +/- 351 ng/ml (S.D.) to 258 +/- 91 ng/ml and was normalised in all seven patients, These changes were associated with improvements in soft tissue enlargement and general well being. Treatment was well tolerated and no change in pituitary tumour size was evident on MRI scans performed every 6 months. Conclusions: Treatment with pegvisomant is safe and efficacy is maintained after 2 years. Serum IGF-I may be normalised in patients who are refractory to conventional therapy.