Novel inflammatory biomarkers in primary hyperparathyroidism M H E Christensen 1,2 , I S Fenne 1,2 , Y Nordbø 3 , J E Varhaug 3,4 , K O Nyga ˚ rd 1,5,6 , E A Lien 1,2 and G Mellgren 1,2,5 1 Department of Clinical Science, University of Bergen, Bergen, Norway, 2 Hormone Laboratory and 3 Department of Surgery, Haukeland University Hospital, 5021 Bergen, Norway, 4 Department of Surgical Science, University of Bergen, Bergen, Norway, 5 KG Jebsen Center for Diabetes Research, Bergen, Norway and 6 Department of Heart Disease, Haukeland University Hospital, Bergen, Norway Correspondence should be addressed to M H E Christensen Email monika.christensen@ k2.uib.no Abstract Objective: Primary hyperparathyroidism (PHPT) has been associated with low-grade inflammation and increased risk of cardiovascular disease (CVD). The aim of the study was to investigate systemic levels of pro-inflammatory proteins that previously have not been examined in patients with PHPT. The selection of the pro-inflammatory biomarkers included in this study, MMP9, S100A4, S100A8/A9 and the receptors sCD14 and RAGE, was based on a previous microarray screen of mRNAs in adipose tissue from PHPT patients. Design: A prospective study was conducted on a total of 57 patients with PHPT and a control group of 20 healthy blood donors. Methods: PHPT patients with normalisation of serum calcium levels after parathyroidectomy were followed for 6 months. Forty-two patients participated in the longitudinal study, in which blood samples were taken at inclusion, and 1, 3 and 6 months after surgery. Results: We observed increased serum levels of MMP9 (PZ0.029), S100A4 (P!0.001) and sCD14 (PZ0.002) in the 57 patients with PHPT compared to the control-group. During 6 months of follow up, S100A4 (PZ0.022) and sCD14 (0.002) decreased significantly, while serum levels of MMP9 increased (PZ0.025). Conclusions: The results demonstrate an increased inflammatory response in PHPT patients shown by elevated MMP9, S100A4 and sCD14 at inclusion. During the 6 months of follow-up, MMP9 increased further, possibly due to the tissue repair process after parathyroidectomy. S100A4 and sCD14 decreased after surgery demonstrating a partial reversal of the systemic inflammation. European Journal of Endocrinology (2015) 173, 9–17 Introduction Patients with primary hyperparathyroidism (PHPT) have increased levels of parathyroid hormone (PTH) resulting in enhanced levels of serum calcium (Ca) (1). The most thoroughly investigated clinical feature in patients with PHPT is decreased bone mineral density (2). Additionally, several risk factors for cardiovascular disease (CVD) are observed in these patients, including increased inflam- mation, hypertension, left ventricular hypertrophy and metabolic changes (3, 4, 5, 6). Increased mortality in patients with PHPT is described, largely due to cardiovascular death (7, 8, 9). Even though PHPT has changed to a more asymptomatic disease during the last decades, an increased disposition for CVD and mortality seems to persist, even at only slightly elevated levels of PTH (10). Serum PTH levels, rather than serum calcium, have been found to predict the longtime risk of both fatal and non-fatal CVD in untreated PHPT (11). Most patients with PHPT have either a single adenoma producing excessive amounts of PTH or glandular hyper- plasia. By removing the adenomas or hyperplastic glands, European Journal of Endocrinology Clinical Study M H E Christensen and others Inflammation in primary hyperparathyroidism 173 :1 9–17 www.eje-online.org Ñ 2015 European Society of Endocrinology DOI: 10.1530/EJE-14-1038 Printed in Great Britain Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 06/03/2020 05:09:14PM via free access