Medical therapy for acromegaly.

Medical therapy has taken on a more important role in the management of patients with acromegaly as the limitations of pituitary surgery and radiation have become apparent. Although surgical resection of growth hormone (GH)-secreting pituitary adenomas is still considered by many to be the treatment of choice, it is now clear that surgery fails to cure a significant number of patients, particularly patients with macroadenomas, which represent the majority of GH-secreting pituitary tumors. 76,84 Cure rates as high as 80% or 90% for GH-secreting microadenomas 0have been reported by experienced neurosurgeons. 40 The cure rate for macroadenomas is generally much lower, and in many reports is less than 50%. 25,32,95,96,101 Pituitary radiation has been used to treat acromegaly but generally takes years to be effective 5 and carries with it the risk of hypopituitarism in as many as 50% of patients. 28,103 Treatment of acromegaly may reverse many of the clinical manifestations of the disease, such as headache, oily skin, excessive perspiration, arthralgias, sleep apnea, and glucose intolerance, and may even improve facial features by reducing tissue edema. 74,75,85 Even in the asymptomatic patient, GH reduction is essential. Epidemiologic studies have found that acromegalic patients with active disease have a twofold greater mortality rate than the general population for cerebrovascular, cardiovascular, and respiratory diseases and malignancies. 3,12,116 Successful treatment is expected to reduce this excess morbidity and mortality. In a small study of 79 acromegalic patients, individuals with GH levels above 5.0 ng/mL after treatment had significantly greater mortality than the general population in comparison with patients with GH levels below 2.5 ng/mL who had no increase in mortality. 9 The criteria for cure of acromegaly have become more stringent in the past decade. 42,76,82,108 Although surgical series in the 1980s defined cure as a reduction in GH to levels below 10 ng/mL, later series used a value of 5 ng/mL when it became apparent that these patients still had active disease. Recently, the biochemical criteria for cure have been narrowed further and include suppression of GH to less than 2 ng/mL [as determined by conventional polyclonal radioimmunoassay (RIA)] after the ingestion of 75 or 100 g of glucose and reduction of insulin-like growth factor-1 (IGF-1) concentrations into the normal range. The upper limit of normal of 2 ng/mL for GH may actually be too high. Some evidence suggests that surgically treated patients with GH levels between 1 and 2 ng/mL after oral glucose have an increased chance of recurrence. 38 In assessing cure, the choice of GH assay method is extremely important. The upper limit of normal for the GH response during the oral glucose tolerance test has been derived from studies using a standard polyclonal RIA for GH. Although newer immunoradiometric assays are highly sensitive and detect lower amounts of GH, the interpretation of these GH levels is unclear owing to the lack of normative data. The major classes of drugs used to treat acromegaly are analogues of somatostatin and dopamine agonists. A compound with a novel mechanism of action, a GH antagonist, is currently in the early phases of development. 11 This article focuses on the pharmacokinetics, efficacy (GH, IGF-1, and tumor size reduction), and safety profile of the principal somatostatin analogues and dopamine agonists used in the United States and Europe for the treatment of acromegaly.