IGF-I assay methods and biologic variability: evaluation of acromegaly treatment response.

Serum insulin-like growth factor (IGF-I) is the primary biochemical measure of disease activity in patients with acromegaly, and the 2014 Endocrine Society guidelines recommended normal age-adjusted serum IGF-I as the biochemical target of treatment. However, quantification and interpretation of IGF-I levels are subject to limitations that may affect therapeutic decisions. Techniques for measuring IGF-I have evolved greatly over the past 40 years and continue to do so. Results can vary substantially for different assays, procedures, and laboratories. For any assay, the interpretation of IGF-I values requires robust reference ranges. Using currently available large normative databases, the upper limit of normal (ULN) for IGF-I in middle-aged and elderly individuals is lower than historical reference ranges. Thus, the goal of achieving IGF-I < 1× ULN is more demanding than in the past, and some patients with acromegaly who were classified as "normal" (IGF-I < 1× ULN) in previous studies would be reclassified as above the ULN based on newer normative data. In addition, substantial intra-individual, week-to-week variation in serum IGF-I levels (unrelated to assay performance) has been observed. With changes over time in the measurement of IGF-I and the advent of updated reference ranges derived from large normative databases, it is difficult to justify rigid adherence to the goal of maintaining IGF-I below the ULN for all patients with acromegaly. Instead, symptoms, comorbidities, and quality of life should be considered, along with growth hormone and IGF-I levels, when evaluating the need for further treatment.
Competing Interests: Conflict of interest: DRC is a consultant for Crinetics Pharmaceuticals and Amyolyt Pharmaceuticals. He has also served on advisory boards for Novo Nordisk. MB reports receiving research support, consultancy, and/or lecture fees from Camurus, Chiasma, Crinetics Pharmaceuticals, DiaSorin, Genexine, Genescience, IDS, Ionis Pharmaceuticals, Ipsen Pharma, Merck, Midatech Pharma, Novartis, Ono Pharma, OPKO Health, Pfizer, Recordati, Roche, Sandoz, and StrongBridge Biopharma.
(© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)