Abstract and Introduction
Abstract
Objectives: To (1) identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess, in a state-based reference laboratory over a 24-month period, and (2) to examine potential differences in comorbidities and relevant medications between people with an elevated IGF-1 compared to a matched control group.
Design: All IGF-1 measurements at Pathology Queensland between 1/12/2018–1/12/2020 were identified. The medical records of those with IGF-1 ≥1.1x the upper limit of the reference range were appraised to determine: (1) documentation of acromegalic features, (2) relevant comorbidities and medication use, and (3) further investigations to exclude pathological GH excess.
Patients and Measurements: There were 2759 IGF-1 samples measured in 1963 people ≥18 years, over the specified period. Of these, 204 had IGF-1 ≥1.1x 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 based on age, sex, gonadal status and pituitary anatomy on MRI.
Results: There were significant differences in the frequency of dopamine agonist use (19/102 cases vs. 6/102 controls, OR = 3.66, 95% confidence interval [CI]: 1.45–9.29, p = .009) and chronic kidney disease (CKD) (14/102 cases vs. 4/102 controls, OR = 3.90, 95% CI: 1.28–11.14, p = .024).
Conclusions: 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 endogenous glucocorticoid excess. Intraindividual biological variability, assay imprecision and physiological factors are known contributors to falsely elevated IGF-1, dopamine agonist therapy and CKD should also be considered.
Introduction
Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone synthesised mainly by the liver that acts downstream of growth hormone (GH) mediating many of its effects.[1] Acromegaly is a systemic disorder caused by excess GH almost always secondary to a pituitary somatotroph tumour.[2] Random serum sampling of GH is an inaccurate representation of total secretion due to hormonal pulsatility. Approximately 98% of circulating IGF-1 is bound to IGF-1 binding proteins (IGFBPs) which control bioavailability and half-life, making it a stable surrogate marker to screen for acromegaly as well as in evaluating possible hypopituitarism.[3] Given the prevalence of pituitary incidentalomas based on radiologic data is up to 22.5%,[4] IGF-1 testing is becoming increasingly more frequent. The prevalence of acromegaly ranges from 2.8 to 13.7 cases per 100,000 people.[5] At present, the widely accepted diagnostic workup for acromegaly includes a screening IGF-1 and, if elevated, an oral glucose tolerance test (OGTT) with GH nadir of >1 μg/L or >0.4 μg/L depending on assay methodology.[6,7] The 2014 Endocrine Society Guidelines suggest using a GH cut off <1 μg/L is sufficient to exclude the diagnosis.[2] There are published series however, of patients with clinical features and histological evidence of acromegaly with elevated IGF-1 but adequate GH suppression during OGTT before treatment, leading to the term 'micromegaly'.[8,9] Previous documented prevalence of micromegaly was in up to 31% of acromegalic patients, this is potentially under-reported given frequent exclusion of the condition based on OGTT results.[8] Case-based observations and previous studies suggest that elevated IGF-1 occurs in patients without clinical acromegaly.[7] Elevated IGF-1 in those without acromegaly has the potential to create unnecessary anxiety for patients, diagnostic uncertainty in clinical practice and can lead to financial costs for additional investigations. A retrospective case–control study was conducted to identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess in a single state-based reference laboratory (Pathology Queensland) over a 24-month period using the Diasorin Liaison XL chemiluminescence immunoassay. The secondary aim of this study was to examine potential differences in comorbidities and relevant medications between people with an elevated IGF-1 compared to a matched control group.
Clin Endocrinol. 2023;99(3):296-305. © 2023 Blackwell Publishing
