Medical therapy for acromegaly.

ABSTRACT

Both somatostatin analogues, which bind to the somatostatin receptor subtypes 2 and 5, and dopamine agonists, which are specific for the D2 receptor, have been used to treat acromegaly. Each of these classes of drugs contains several compounds that vary in duration of action, efficacy, and side effect profile. Although somatostatin analogues reduce GH levels and alleviate symptoms in most patients and restore IGF-1 levels to normal in 60% to 65% of patients, tumor shrinkage is limited to 40% of patients. evidence in the literature supports the use of these medications as secondary therapy in patients with acromegaly who have had surgery and who continue to have elevated GH levels (above 2 ng/mL during an oral glucose tolerance test) with or without IGF-1 concentrations that are above the upper limit of normal for age. In addition, medical therapy indicated in patients who refuse surgery and in patients who are poor surgical candidates. The controversial question is whether medical therapy should be an option for primary treatment of the acromegalic patient. Currently, ther are no data from prospective randomized trials comparing the effects of surgery versus somatostatin analogues as first-line therapy for for newly diagnosed acromegalic patients. Limited data from nonrandomized studies demonstrate that somatostatin analogues are effective long-term in suppressing GH and reducing IGF-1 into the normal range in approximately two-thirds of patients who have never undergone previous treatment. It is still the consensus that patients with GH-secreting microadenomas should undergo surgical resection, because the likelihood of complete cure by an experience neurosurgeon is high, at least 70% or greater. Successful surgical treatment has the advantage of completely removing the tumor in contrast to medical therapy, which rarely produces shrinkage greater than 50% despite the fact that IGF-1 and GH levels may be normal. In patients with macroadenomas of a size and location that suggest that the chance of complete resection is 40% or less, primary treatment with a somatostatin analogue should be considered as one option in the initial management of the patient. Another option in such an individual would be surgical debulking followed by medical therapy, because it is theoretically possible that biochemical cure with medical therapy after surgical debulking might be achieved with lower doses. The cost-effectiveness of these approaches has not yet been determined. Once the decision has been made to begin medical therapy, a choice must be made between dopamine agonists and somatostatin analogues. Most evidence suggests that somatostatin analogues are more effective than dopamine agonists and therefore would be the therapy of choice. In select patients, dopamine agonists, particularly the long-acting agonist cabergoline, may be preferred initially if the patient is unwilling to take injections or if the GH elevations are relatively modest (< 10 ng/mL). Biochemical cure should be assessed by measurement of GH (which can be performed 2 hours after an octreotide injection) and IGF-1 concentrations. The goal of treatment include reduction of of GH below 2 ng/mL and reduction of IGF-1 into the normal range. In patients who do not reach these goals, the dose or frequency of injection of the somatostatin analogue or both should be increased. If such measures are unsuccessful, a dopamine agonist may be added to the medical regimen because some studies suggest that combination therapy may be more effective in select cases than octreotide therapy alone. If such measures are still unsuccessful, other options should be considered, including surgery, pituitary radiation, and medical treatment with investigational drugs.