PMON61 Evaluation of elevated IGF-1 in patients without clinical evidence of acromegaly

Abstract

Introduction Insulin-like growth factor-1 (IGF-1) acts downstream of growth hormone mediating many of its effects. It is the recommended screening test for acromegaly, in evaluating pituitary incidentalomas and possible hypopituitarism. Case-based observations suggest that 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. The 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. Results There were 2759 IGF-1 levels measured in 1963 people over the specified period. Out of these, 204 were in patients over 18 years of age and were >1.1 times the upper limit of the age-matched reference range. We excluded 48 with diagnosed acromegaly, 4 who had further workup for acromegaly planned, 9 on GH substitution for proven GH deficiency, 3 with Cushing's syndrome and 5 who were pregnant. A further 33 were excluded based on insufficient data available. A total of 102 cases (61M, 41F) were included in the analysis. Of these 102 people, 67 had pituitary MRI scans, 24 had a 75g oral glucose tolerance test, 28 had a subsequent repeat IGF-1 that had normalised and 13 had random GH <1ug/L. The characteristics of these 102 cases were compared to those of the matched control group (n=102) with normal IGF-1 assayed in the same period. There was no significant difference between the elevated and normal IGF-1 groups in age (mean 46.7 vs 47.0 years, P=0.90), sex (P>0.99), gonadal status (P=0.87) or pituitary status (P=0.15). Variables that were significantly different between cases and controls included dopamine agonist therapy (19/102 cases vs 6/102 controls, OR=3.66, 95% CI: 1.45-9.29, P=0.009) and chronic kidney disease (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 at a reference laboratory, a significantly elevated IGF-1 occurred in 204. In 102 (50%) of these patients, there was no known acromegaly, GH replacement or glucocorticoid excess, and no documented definitive acromegalic features. There were significant associations with dopamine agonist use and CKD. While assay-related issues and accuracy of the age-matched reference ranges probably represent the main influences on the prevalence of elevated IGF-1, we have identified two additional factors which should be considered. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.