The endocrinologist is frequently faced with a patient with acromegaly who has undergone apparently successful pituitary surgery for removal of a GH-secreting tumor, but exhibits persistent elevations of GH and/or IGF-I levels in circulation. In developing an approach to managing such patients, it is important to consider currently available information about the disease and the consequences of prolonged GH hypersecretion, as well as the therapeutic efficacy of the various possible therapeutic modalities. The past two decades have witnessed dramatic changes in both our understanding of the pathogenesis and natural history of acromegaly and its diagnosis and management. The molecular pathogenesis of nearly half of all GH-secreting tumors is attributable to a single bp mutation in one of two locations in the a-subunit of the stimulatory guanosine triphosphate binding protein, G,(1, 21. These somatic mutations result in a constitutive activation of Gso, leading to increased cyclic AMP formation, activation of protein kinase-A and other downstream signal transduction components, eventually culminating in the stimulation of genes linked to mitogenesis. Thus, for at least this large subset of tumors, the long-standing question of hypothalamic ‘us. pituitary etiology appears to be resolved. Epidemiological surveys of patients with acromegaly, primarily in the United Kingdom (3) and Sweden (4), have provided new insights into the long-term morbidity and mortality of acromegaly. The life span of patients is significantly shortened, and the increased mortality is primarily attributable, not to the direct effects of the pituitary tumor mass, but rather to cardiovascular, respiratory, and cerebrovascular disease.

The diagnosis of acromegaly has been aided by the addition of serum IGF-I measurements, particularly in patients in whom circulating GH levels are only slightly elevated. The refinement in imaging techniques, including magnetic resonance imaging, positron emission tomography, and somatostatin receptor scintigraphy using octreotide analogs (51, has helped to identify small pituitary tumors previously considered undetectable. The availability of plasma GH-releasing hormone (GHRH) measurements has permitted the preoperative diagnosis of the rare patient with ectopic GHRH secretion as the etiology of acromegaly, thereby redirecting appropriate therapeutic approaches (6). The therapy of acromegaly has also undergone considerable change. The transsphenoidal surgical procedure has become widely established and is currently the procedure of choice for most patients. Irradiation, although administered