ORIGINAL ARTICLE Involvement of a-klotho, fibroblast growth factor-, vitamin-D- and calcium-sensing receptor in 53 patients with primary hyperparathyroidism Joerg Latus • Renate Lehmann • Meike Roesel • Peter Fritz • Niko Braun • Christoph Ulmer • Wolfgang Steurer • Dagmar Biegger • German Ott • Juergen Dippon • M. Dominik Alscher • Martin Kimmel Received: 9 November 2012 / Accepted: 8 January 2013 Ó Springer Science+Business Media New York 2013 Abstract The presentation of patients with primary hyperparathyroidism is often atypical and ranges from normocalcemic, primary hyperparathyroidism to severe, symptomatic hypercalcemia. G-protein-coupled, calcium- sensing receptor (CaSR), vitamin D receptor (VDR), and fibroblast growth factor receptor (FGFR)/klotho complexes seem to be involved in the development of pHPT. Para- thyroid glands from 53 patients with pHPT and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional detailed morphological and immunohistochemical analyses of parathyroid glands were performed after dividing each slide in a 3 9 3 array. From morphology, the number of lipocytes was signifi- cantly lower in parathyroid tissue glands in the pHPT group (p \ 0.001). Protein expressions of klotho, CaSR, and VDR were significantly reduced in the pHPT compared with the control group (p = 0.004, p = 0.007, p \ 0.001). No differences were seen between the two groups (p = 0.35) regarding expression of FGFR. Correlations between expression showed significant positively correla- tions between klotho and CaSR and FGFR and VDR. No correlations between klotho expression and serum calcium levels could be detected (R =-0.13, p = 0.66), but there were positive correlations between expressions of CaSR/ serum phosphate and klotho/serum phosphate. Impaired protein expression of CaSR and VDR seem to be involved in the development of pHPT. The role of the FGFR/klotho- axis remains still unclear. Correlations between protein expression of CaSR and serum phosphate and klotho and serum phosphate levels could be detected. Whether these findings give new insights into the pathogenesis of the disease is yet unknown and has to be elucidated. Keywords Primary hyperparathyroidism Á Klotho Á VDR Á CaSR Á FGFR Introduction Primary hyperparathyroidism (pHPT) is mostly diagnosed in asymptomatic patients presenting with hypercalcemia found by routine biochemical screening. Sometimes, ‘‘asymp- tomatic’’ patients, when carefully questioned, report non- specific symptoms, such as weakness, fatigue, mild depression, anorexia, and mild cognitive or neuromuscular dysfunction [1–3]. In patients with pHPT, single adenomas account for up to 89 % of cases of primary hyperparathy- roidism and double adenomas are detected in an additional 5%[4–6]. Recently, experimental findings have advanced All authors read and approved the final manuscript J. Latus (&) Á R. Lehmann Á M. Roesel Á N. Braun Á M. D. Alscher Á M. Kimmel Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, 70376 Stuttgart, Germany e-mail: Joerg.latus@googlemail.com; Joerg.latus@rbk.de P. Fritz Á G. Ott Department of Diagnostic Medicine, Division of Pathology, Robert Bosch Hospital, Stuttgart, Germany C. Ulmer Á W. Steurer Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany D. Biegger Margarete Fischer–Bosch Institute of Clinical Pharmacology, Stuttgart, Germany J. Dippon Department of Mathematics, University of Stuttgart, Stuttgart, Germany 123 Endocrine DOI 10.1007/s12020-013-9881-6