Serum IGF-I levels in the diagnosis and monitoring of acromegaly

Abstract

Insulin-Like Growth Factor-I (IGF-I) is a reliable marker of disease activity and growth hormone (GH) status in acromegaly, but its clinical utility has been hampered over the years by various issues including a lack of robust reference range data and variability in assay sensitivity and specificity. In acromegaly IGF-I correlates well with GH activity and nadir GH on oral glucose tolerance test (OGTT) and is the most sensitive and specific test in diagnosis, where serum IGF-I is persistently seen to be elevated to a range that is distinct from that in healthy individuals. However it should not be relied on exclusively for diagnosis or used as the sole indication of disease severity and GH burden. Successful medical or surgical treatment of acromegaly is usually associated with normalisation of serum IGF-I but there is discordance between GH and IGF-I in some patients. Patients with a normal IGF-I but an abnormal GH suppression to OGTT are at risk of relapse and therefore it should not be used alone to establish disease remission. In contrast to the diagnosis of acromegaly, there is also considerable overlap in serum IGF-I with normality after primary treatment of disease, even in the presence of persisting GH excess. Gender, age and prior radiotherapy alters the relationship between GH and IGF-I and reliance on one marker of disease activity such as IGF-I is particularly precarious in certain disease states. However an elevated serum IGF-I has been shown to be associated with excess mortality and normalising IGF-I normalises mortality making it a useful marker. The tightening up of the assays means that establishing absolute concentrations as well as standard deviation scores are essential to allow cross-study comparisons. This becomes especially important in the use of Pegvisomant, where IGF-I becomes the sole biochemical marker of disease activity.