Evolving therapeutic strategies for acromegaly.

Abstract

Acromegaly is an uncommon endocrine disorder characterized by pathologically elevated growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels. In more than 99% of cases acromegaly is caused by a GH-secreting pituitary adenoma. If untreated, life expectancy is reduced by an average of 10 years (1) and the increased mortality rate is due to cardiovascular, cerebrovascular, respiratory and malignant disease (2). The object of therapy is 2fold, restore normal life expectancy and reduce the morbidity associated with the disease. There are now several epidemiological reports which indicate that if GH levels can be reduced to less than 5 mU/l life expectancy is normalized (2). The achievement of a GH level less than 5 mU/l, however, does not imply removal of every single GH-secreting tumor cell, i.e. cure, but rather that “epidemiological safe” GH levels (“cure”) have been attained. Thus, it is not uncommon to see the combination of a pathologically elevated IGF-I level in the presence of a mean GH level less than 5 mU/l. The mortality and life expectancy data are almost all derived from GH studies although there is one oft-quoted report suggesting that IGF-I levels have to be normalized before life expectancy is normalized (3); however the latter report does not actually contain IGF-I data! Nonetheless a significant proportion of patients with a mean GH level less than 5 mU/l and a raised IGF-I level may be affected adversely by disease morbidity. Traditionally, primary therapy for acromegaly has been pituitary surgery followed by pituitary irradiation in those in whom the disease remained active post-operatively. The advent of modern medical therapy began with bromocriptine and now is represented by a more powerful dopamine agonist (DA) drug, cabergoline, somatostatin (SS) analogue depot preparations