Currently available medical therapies include dopamine agonist drugs and somatostatin analogs. Dopamine agonist drugs (bromocriptine, pergolide, cabergoline), provide symptomatic relief in approx 90% of patients, but reduction in serum IGF-1 to normal occurs in less than 20% (14). Somatostatin, the naturally occurring hypothalamic hormone that suppresses GH secretion, is effective only when given by continuous intravenous (iv) infusion. Analogs of somatostatin are effective when given by subcutaneous or intramuscular injection. Currently available analogs include octreotide, lanreotide and octreotide LAR (Sandostatin LAR®). This class of drugs reduces GH and IGF-1 concentrations to normal in 50% to 60% of patients and improves symptoms in more than
90% (15-27). Tables 2 and 3 summarize the results of short-acting (octreotide) and long-acting (lanreotide, octreotide LAR) somatostatin analogs in patients with acromegaly
Side effects of somatostatin analog drugs include transient abdominal discomfort, acholic stools, and diarrhea. These symptoms usually resolve within a few days to a week. Development of gall bladder sludge or gallstones occurs in approx 18% of patients (19).
A recent development in the medical treatment of acromegaly is a modification of the GH molecule, a 9-amino-acid substitution and pegylation to reduce immunogenicity, resulting in a GH antagonist. This antagonist, pegvisomant, prevents dimerization of the GH receptor and thus reduces IGF-1 generation. A consequence of reducing circulating IGF-1 concentrations is an increase in serum GH concentrations. Pegvisomant reduced serum IGF-1 concentrations in a dose-dependent fashion in a study of 112 patients with acromegaly, with suppression of IGF-1 to normal in 89% of patients treated with 20 mg/d (28). This medication is self- administered as a daily sc injection. A long-term study of pegvisomant of patients treated up to 18 mo (n=131) found that in the 90 patients treated for 12 mo or more, 97% achieved a normal serum IGF-1 concentration. Serum GH increased and achieved a plateau after 6 mo of treatment. In this study two patients developed abnormal liver enzymes and two patients had enlargement of the residual pituitary adenoma. The remaining patients had no change in pituitary size (29). This experimental medication is the most effective medical therapy for acromegaly and is currently under review by government regulatory agencies regarding approval for clinical use.
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