FGF23 and primary hyperparathyroidism: is there a link?
Abstract
Introduction: Data regarding the role of fibroblast growth factor 23 (FGF23) in primary hyperparathyroidism (PHPT) are scarce and discordant. Our study aimed to evaluate the prognostic impact of FGF23 upon the clinical and biochemical evolution of PHPT.
Material and methods: Forty-two patients with ages between 30 and 80 years, diagnosed with PHPT caused by a sporadic, solitary parathyroid adenoma, and referred to surgery (minimally invasive parathyroidectomy) were prospectively included in the study. Serum levels of FGF23, PTH, 25(OH)D3, calcium (Ca), phosphate (P), total procollagen type 1 N-terminal propeptide, and C-terminal telopeptide of type I collagen were determined at baseline (preoperatory), one day after surgery, and in 13 patients also prospectively at three, six, and 12 months. Bone mineral density (BMD) was also evaluated before surgery in all patients and 12 months after surgery in the 13
followed up patients.
Results: In the 42 PHPT patients with D hypovitaminosis (mean 25(OH)D3 levels of 16.2 ± 1.5 ng/mL), preoperatory serum FGF23 concentration was within the normal range (75.55 ± 3.39 pg/mL) and remained unchanged one day post operation (81.69 ± 4.67 pg/mL, p = non-significant). The 13 patients followed prospectively for up to 12 months after surgery also showed unmodified FGF23 levels (80.9 ± 11.03 pg/mL, p = non-significant), despite PTH and Ca normalisation and vitamin D replenishment. Preoperatory FGF23 negatively correlated with PTH (r = –0.37, p = 0.038), but not with 25(OH)D3, Ca, P, bone mass, or metabolism markers.
Conclusions: In PHPT, correlations between FGF23 and PTH seem rather an epiphenomenon. Therefore, we think that FGF23 evaluation and dynamics are not informative regarding PHPT severity. (Endokrynol Pol 2020; 71 (4): 306–312)
Keywords: FGF23PTHvitamin Dparathyroid adenomabone
References
- Erben RG. Physiological Actions of Fibroblast Growth Factor-23. Front Endocrinol (Lausanne). 2018; 9: 267.
- Richter B, Faul C. FGF23 Actions on Target Tissues-With and Without Klotho. Front Endocrinol (Lausanne). 2018; 9: 189.
- Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev. 2012; 92(1): 131–155.
- Witteveen JE, van Lierop AH, Papapoulos SE, et al. Increased circulating levels of FGF23: an adaptive response in primary hyperparathyroidism? Eur J Endocrinol. 2012; 166(1): 55–60.
- Grabner A, Mazzaferro S, Cianciolo G, et al. Fibroblast Growth Factor 23: Mineral Metabolism and Beyond. Contrib Nephrol. 2017; 190: 83–95.
- Nilsson IL, Norenstedt S, Granath F, et al. FGF23, metabolic risk factors, and blood pressure in patients with primary hyperparathyroidism undergoing parathyroid adenomectomy. Surgery. 2016; 159(1): 211–217.
- Kobayashi K, Imanishi Y, Miyauchi A, et al. Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism. Eur J Endocrinol. 2006; 154(1): 93–99.
- Yamashita H, Yamashita T, Miyamoto M, et al. Fibroblast growth factor (FGF)-23 in patients with primary hyperparathyroidism. Eur J Endocrinol. 2004; 151(1): 55–60.
- Tebben PJ, Singh RJ, Clarke BL, et al. Fibroblast growth factor 23, parathyroid hormone, and 1alpha,25-dihydroxyvitamin D in surgically treated primary hyperparathyroidism. Mayo Clin Proc. 2004; 79(12): 1508–1513.
- Andrukhova O, Streicher C, Zeitz U, et al. Fgf23 and parathyroid hormone signaling interact in kidney and bone. Mol Cell Endocrinol. 2016; 436: 224–239.
- Carrillo-López N, Panizo S, Alonso-Montes C, et al. Direct inhibition of osteoblastic Wnt pathway by fibroblast growth factor 23 contributes to bone loss in chronic kidney disease. Kidney Int. 2016; 90(1): 77–89.
- Zimmermann P, Takala T, Pöyhönen L, et al. Ultrasonography of the thyroid gland in pregnancies complicated by autoimmune thyroid disease. J Clin Ultrasound. 1993; 21(2): 109–113.
- You SH, Suh SI, Ryoo IS, et al. Assessing the accuracy and reliability of ultrasonographic three-dimensional parathyroid volume measurement in a patient with secondary hyperparathyroidism: a comparison with the two-dimensional conventional method. Ultrasonography. 2017; 36(1): 17–24.
- Kawata T, Imanishi Y, Kobayashi K, et al. Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol. 2007; 18(10): 2683–2688.
- Erben RG. Update on FGF23 and Klotho signaling. Mol Cell Endocrinol. 2016; 432: 56–65.
- Smith ER, Cai MM, McMahon LP, et al. Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab. 2012; 97(9): 3357–3365.
- López I, Rodríguez-Ortiz ME, Almadén Y, et al. Direct and indirect effects of parathyroid hormone on circulating levels of fibroblast growth factor 23 in vivo. Kidney Int. 2011; 80(5): 475–482.
- Olauson H, Lindberg K, Amin R, et al. Parathyroid-specific deletion of Klotho unravels a novel calcineurin-dependent FGF23 signaling pathway that regulates PTH secretion. PLoS Genet. 2013; 9(12): e1003975.
- Walker MD, Bilezikian JP. Vitamin D and primary hyperparathyroidism: more insights into a complex relationship. Endocrine. 2017; 55(1): 3–5.
- Branisteanu D. Sunlight Exposure and Vitamin D Supplementation at the Institutionalized Elderly — Effects on Calcium and Bone Metabolism. Acta Endocrinol (Bucharest). 2007; 3(2): 169–178.
- Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010; 85(8): 752–7; quiz 757.
- de Jongh RT, van Schoor NM, Lips P. Changes in vitamin D endocrinology during aging in adults. Mol Cell Endocrinol. 2017; 453: 144–150.
- Latus J, Lehmann R, Roesel M, et al. Involvement of α-klotho, fibroblast growth factor-, vitamin-D- and calcium-sensing receptor in 53 patients with primary hyperparathyroidism. Endocrine. 2013; 44(1): 255–263.
- Björklund P, Krajisnik T, Akerström G, et al. Type I membrane klotho expression is decreased and inversely correlated to serum calcium in primary hyperparathyroidism. J Clin Endocrinol Metab. 2008; 93(10): 4152–4157.
- Nakajima K, Okazaki T, Okamoto T, et al. Genes up- or down-regulated by high calcium medium in parathyroid tissue explants from patients with primary hyperparathyroidism. Endocrine Journal. 2009; 57(2): 153–159.
- Gatu A, Velicescu C, Grigorovici A, et al. . The volume of solitary parathyroid adenoma is related to preoperative pth and 250h-d3, but not to calcium levels. Acta Endocrinol (Buchar). 2017; 13(4): 441–446.
- Silver J, Rodriguez M, Slatopolsky E. FGF23 and PTH — double agents at the heart of CKD. Nephrol Dial Transplant. 2012; 27(5): 1715–1720.
- Nagata Y, Imanishi Y, Ohara M, et al. Attenuated Dentin Matrix Protein 1 Enhances Fibroblast Growth Factor 23 in Calvaria in a Primary Hyperparathyroidism Model. Endocrinology. 2019; 160(5): 1348–1358.
- Podd D. Hypovitaminosis D: A common deficiency with pervasive consequences. JAAPA. 2015; 28(2): 20–26.
