Biochemical following-up of treated acromegaly. Limitations of the current determinations of IGF-I and perspective

A cromegaly is a rare disease caused by excess growth hormone (GH) secretion leading to an insulin-like growth factor-1 (IGF-I) which is the major mediator of GH action. Biochemical diagnosis of GH excess is accomplished by the combined measurement of baseline serum IGF-I concentration and the response of GH on an oral glucose tolerance test (OGTT). Several drawbacks regarding the interpretation of biochemical tests that include measurement of GH have been widely described in the literature, including different protocols for obtaining serum samples, great differences in the results obtained by different immunoassays, different cut-off points used to differentiate the normal status of the hypersecretion of GH. Clinical guidelines related to the diagnosis and management of patients with acromegaly state that "normal" IGF-I concentrations, (within an established age- and sex-reference range), excludes the diagnosis of active acromegaly, and mean disease control in patients who have received treatment. But many factors may exert influence over IGF-I measurement or interpretation and limit its value as a biological marker of disease activity. Major drawbacks of IGF-I measurements derive both from its own physiology, to the divergences in results obtained from different biochemical methods used for their quantification, to the heterogeneous ways of expressing the results obtained and to the lack of uniformity of the cut-offs to define treatment effectiveness. All these issues make it difficult to compare the results obtained by different authors. We will focus on the issues regarding the measurement and interpretation of IGF-I concentrations in the management of acromegaly patients.