Aims: IGF-1 acts downstream of GH mediating many of its effects. It is the recommended screening test for acromegaly, in evaluating pituitary incidentalomas and possible hypopituitarism. Case-based observations suggest elevated IGF-1 may occur in patients without acromegaly. The aims were to 1) identify the frequency of elevated IGF-1 without evidence of GH excess, and 2) to examine potential differences in relevant medications and comorbidities between people with an elevated IGF-1 compared to a control group matched for age, sex, gonadal and pituitary status.
Methods: All people whose IGF-1 was measured at a single reference laboratory between Dec 1st 2018 – Dec 1st 2020 were identified. Electronic records of those with at least one IGF1 >1.1x the upper limit of the age-matched reference range were appraised to determine; 1) documentation of acromegalic features, 2) presence of relevant comorbidities and medication use, and 3) further investigation to exclude pathological GH excess. There were 2759 IGF-1 samples measured in 1963 people ≥18 years, over the specified period. Out of these, 204 had IGF-1 >1.1 times the upper limit of the age-matched reference range. 102 cases (61M, 41F) met inclusion criteria, and were matched to 102 controls with a normal IGF-1.
Results: There were significant differences in the frequency of dopamine agonist use (19/102 cases vs 6/102 controls, OR=3.66, 95%CI: 1.45-9.29, P=0.009) and chronic kidney disease (CKD) (14/102 cases vs 4/102 controls, OR=3.90, 95%CI: 1.28-11.14, P=0.024).
Conclusion: Out of 1963 patients having IGF-1 measured, 102 (5.2%) had an elevated IGF-1 where there was no known acromegaly, GH replacement or glucocorticoid excess. There were significant associations with dopamine agonist use and CKD. While assay imprecision, intra-individual biological variability and accuracy of reference ranges probably represent the main influences on the prevalence of elevated IGF-1, we have identified two additional factors which should be considered.