Abstract
The purpose of the study was to evaluate the relationship between serum 25(OH)D and the clinical phenotype in 215 consecutive Italian Caucasian women with sporadic primary hyperparathyroidism (PHPT) not taking vitamin D supplements. The study was performed at a single Italian tertiary center. PHPT-related manifestations, serum 25(OH)D, and other parameters of calcium metabolism and bone mineral density (BMD) by DXA were recorded. Serum 25(OH)D was negatively correlated with age (r = −0.18; P = 0.006), BMI (r = −0.20; P = 0.002), PTH (r = −0.21; P = 0.001), bone-specific alkaline phosphatase (BSAP) (r = −0.27; P < 0.001), and eGFR (r = −0.22; P = 0.01), and positively with serum creatinine and 1/3 distal radius BMD (R-BMD; r = 0.17; P = 0.015). In a multivariate regression analysis, serum 25(OH)D remained significantly correlated with age (r = −0.18; P = 0.005), BMI (r = −0.23; P = 0.049), serum PTH (r = −0.01; P = 0.023), BSAP (r = −0.01; P = 0.023) and eGFR (r = −0.09; P = 0.001), but not with R-BMD. Serum 25(OHD) was higher in patients with nephrolithiasis than in those without nephrolithiasis (18.5 ± 8.8 vs. 15.6 ± 8.0 ng/ml; P = 0.029), whereas no difference was found between fractured and unfractured patients (16.8 ± 9.3 vs. 16.0 ± 7.7; P = 0.663). There was a statistically significant inverse correlation between vitamin D status [defined by quartiles of measured values as well as commonly accepted cutoffs of serum 25(OH)D] and severity of the disease, as reflected by higher PTH and BSAP, but not by meeting the latest guidelines for parathyroidectomy. In conclusion, a low vitamin D status is associated with some features reflecting a more severe biochemical and clinical phenotype of PHPT in Italian women not taking vitamin D supplements.
Similar content being viewed by others
References
S.J. Silverberg, M.D. Walker, J.P. Bilezikian, Asymptomatic primary hyperparathyroidism. J. Clin. Densitom. 16(1), 14–21 (2013). doi:10.1016/j.jocd.2012.11.005
E. Nordenstrom, A. Sitges-Serra, J.J. Sancho, M. Thier, M. Almquist, Vitamin d status in patients operated for primary hyperparathyroidism: comparison of patients from Southern and Northern Europe. Int. J. Endocrinol. 2013, 164939 (2013). doi:10.1155/2013/164939
P.V. Pradeep, B. Jayashree, A. Mishra, S.K. Mishra, Systematic review of primary hyperparathyroidism in India: the past, present, and the future trends. Int. J. Endocrinol. 2011, 921814 (2011). doi:10.1155/2011/921814
J.M. Liu, N.E. Cusano, B.C. Silva, L. Zhao, X.Y. He, B. Tao, L.H. Sun, H.Y. Zhao, W.W. Fan, M.E. Romano, G. Ning, J.P. Bilezikian, Primary hyperparathyroidism: a tale of two cities revisited—New York and Shanghai. Bone. Res. 1(2), 162–169 (2013). doi:10.4248/BR201302005
S. Varshney, S.K. Bhadada, U.N. Saikia, N. Sachdeva, A. Behera, A.K. Arya, S. Sharma, A. Bhansali, A. Mithal, S.D. Rao, Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians. Eur. J. Endocrinol. 169(1), 109–116 (2013). doi:10.1530/EJE-13-0085
A.C. Ross, J.E. Manson, S.A. Abrams, J.F. Aloia, P.M. Brannon, S.K. Clinton, R.A. Durazo-Arvizu, J.C. Gallagher, R.L. Gallo, G. Jones, C.S. Kovacs, S.T. Mayne, C.J. Rosen, S.A. Shapses, The 2011 dietary reference intakes for calcium and vitamin D: what dietetics practitioners need to know. J. Am. Diet. Assoc. 111(4), 524–527 (2011). doi:10.1016/j.jada.2011.01.004
C. Marcocci, J. Bollerslev, A.A. Khan, D.M. Shoback, Medical management of primary hyperparathyroidism: proceedings of the fourth international workshop on the management of asymptomatic primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 99(10), 3607–3618 (2014). doi:10.1210/jc.2014-1417
T.D. Beyer, E.L. Chen, N. Nilubol, R.A. Prinz, C.C. Solorzano, Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufficiency. J. Surg. Res. 143(1), 145–150 (2007). doi:10.1016/j.jss.2007.06.009
D.S. Rao, M. Honasoge, G.W. Divine, E.R. Phillips, M.W. Lee, M.R. Ansari, G.B. Talpos, A.M. Parfitt, Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications. J. Clin. Endocrinol. Metab. 85(3), 1054–1058 (2000). doi:10.1210/jcem.85.3.6440
B. Moosgaard, P. Vestergaard, L. Heickendorff, F. Melsen, P. Christiansen, L. Mosekilde, Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism. Clin. Endocrinol. 63(5), 506–513 (2005). doi:10.1111/j.1365-2265.2005.02371.x
P. Boudou, F. Ibrahim, C. Cormier, E. Sarfati, J.C. Souberbielle, A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism. J. Endocrinol. Invest. 29(6), 511–515 (2006). doi:10.1007/BF03344140
S.J. Silverberg, E. Shane, D.W. Dempster, J.P. Bilezikian, The effects of vitamin D insufficiency in patients with primary hyperparathyroidism. Am. J. Med. 107(6), 561–567 (1999)
G. Jones, D.E. Prosser, M. Kaufmann, 25-hydroxyvitamin D-24-hydroxylase (CYP24A1): its important role in the degradation of vitamin D. Arch. Biochem. Biophys. 523(1), 9–18 (2012). doi:10.1016/j.abb.2011.11.003
K. Tashiro, T. Abe, N. Oue, W. Yasui, M. Ryoji, Characterization of vitamin D-mediated induction of the CYP 24 transcription. Mol. Cell. Endocrinol. 226(1–2), 27–32 (2004). doi:10.1016/j.mce.2004.07.012
M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney, M.H. Murad, C.M. Weaver, S. Endocrine, Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96(7), 1911–1930 (2011). doi:10.1210/jc.2011-0385
J.P. Bilezikian, M.L. Brandi, R. Eastell, S.J. Silverberg, R. Udelsman, C. Marcocci, J.T. Potts Jr, Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J. Clin. Endocrinol. Metab. 99(10), 3561–3569 (2014). doi:10.1210/jc.2014-1413
M.D. Walker, E. Cong, J.A. Lee, A. Kepley, C. Zhang, D.J. McMahon, S.J. Silverberg, Vitamin D in primary hyperparathyroidism: effects on clinical, biochemical, and densitometric presentation. J. Clin. Endocrinol. Metab. 100(9), 3443–3451 (2015). doi:10.1210/jc.2015-2022
F. Cetani, E. Pardi, S. Borsari, M. Tonacchera, E. Morabito, A. Pinchera, C. Marcocci, G. Dipollina, Two Italian kindreds with familial hypocalciuric hypercalcaemia caused by loss-of-function mutations in the calcium-sensing receptor (CaR) gene: functional characterization of a novel CaR missense mutation. Clin. Endocrinol. 58(2), 199–206 (2003)
A.S. Levey, J.P. Bosch, J.B. Lewis, T. Greene, N. Rogers, D. Roth, A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal Disease study group. Ann. Intern. Med. 130(6), 461–470 (1999)
E.M. Lewiecki, C.M. Gordon, S. Baim, M.B. Leonard, N.J. Bishop, M.L. Bianchi, H.J. Kalkwarf, C.B. Langman, H. Plotkin, F. Rauch, B.S. Zemel, N. Binkley, J.P. Bilezikian, D.L. Kendler, D.B. Hans, S. Silverman, International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions. Bone. 43(6), 1115–1121 (2008). doi:10.1016/j.bone.2008.08.106
E. Vignali, G. Viccica, D. Diacinti, F. Cetani, L. Cianferotti, E. Ambrogini, C. Banti, R. Del Fiacco, J.P. Bilezikian, A. Pinchera, C. Marcocci, Morphometric vertebral fractures in postmenopausal women with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 94(7), 2306–2312 (2009). doi:10.1210/jc.2008-2006
M. Peacock, Primary hyperparathyroidism and the kidney. The parathyroids. Basic and clinical concepts. (Elsevier Inc., London, 2015)
L. Rejnmark, P. Vestergaard, L. Mosekilde, Nephrolithiasis and renal calcifications in primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 96(8), 2377–2385 (2011). doi:10.1210/jc.2011-0569
M.A. Elkoushy, A.X. Yu, R. Tabah, R.J. Payne, A. Dragomir, S. Andonian, Determinants of urolithiasis before and after parathyroidectomy in patients with primary hyperparathyroidism. Urology. 84(1), 22–26 (2014). doi:10.1016/j.urology.2014.01.016
A. D’Angelo, M.G. Lodetti, S. Giannini, R. Castrignano, M. Al Awady, L. Malvasi, A. Fabris, G. Maschio, Hyperparathyroidism: cause or consequence of recurrent calcium nephrolithiasis? Miner. Electrolyte. Metab. 18(6), 359–364 (1992)
C.V. Odvina, K. Sakhaee, H.J. Heller, R.D. Peterson, J.R. Poindexter, P.K. Padalino, C.Y. Pak, Biochemical characterization of primary hyperparathyroidism with and without kidney stones. Urol. Res. 35(3), 123–128 (2007). doi:10.1007/s00240-007-0096-2
S.J. Silverberg, E. Shane, T.P. Jacobs, E.S. Siris, F. Gartenberg, D. Seldin, T.L. Clemens, J.P. Bilezikian, Nephrolithiasis and bone involvement in primary hyperparathyroidism. Am. J. Med. 89(3), 327–334 (1990)
F. Tassone, L. Gianotti, C. Baffoni, G. Visconti, M. Pellegrino, S. Cassibba, C.G. Croce, G. Magro, F. Cesario, R. Attanasio, G. Borretta, Vitamin D status in primary hyperparathyroidism: a Southern European perspective. Clin. Endocrinol. 79(6), 784–790 (2013). doi:10.1111/cen.12210
V. Carnevale, G. Manfredi, E. Romagnoli, S. De Geronimo, F. Paglia, J. Pepe, A. Scillitani, E. D’Erasmo, S. Minisola, Vitamin D status in female patients with primary hyperparathyroidism: does it play a role in skeletal damage? Clin. Endocrinol. 60(1), 81–86 (2004)
W. Saliba, I. Lavi, H.S. Rennert, G. Rennert, Vitamin D status in primary hyperparathyroidism. Eur. J. Intern. Med. 23(1), 88–92 (2012). doi:10.1016/j.ejim.2011.07.008
B. Moosgaard, P. Vestergaard, L. Heickendorff, F. Melsen, P. Christiansen, L. Mosekilde, Plasma 25-hydroxyvitamin D and not 1,25-dihydroxyvitamin D is associated with parathyroid adenoma secretion in primary hyperparathyroidism: a cross-sectional study. Eur. J. Endocrinol. 155(2), 237–244 (2006). doi:10.1530/eje.1.02197
H. Raef, S. Ingemansson, S. Sobhi, A. Sultan, M. Ahmed, M. Chaudhry, The effect of vitamin D status on the severity of bone disease and on the other features of primary hyperparathyroidism (pHPT) in a vitamin D deficient region. J. Endocrinol. Invest. 27(9), 807–812 (2004). doi:10.1007/BF03346273
N. Ozbey, Y. Erbil, E. Ademoglu, S. Ozarmagan, U. Barbaros, A. Bozbora, Correlations between vitamin D status and biochemical/clinical and pathological parameters in primary hyperparathyroidism. World. J. Surg. 30(3), 321–326 (2006). doi:10.1007/s00268-005-0239-y
B. Moosgaard, S.E. Christensen, P. Vestergaard, L. Heickendorff, P. Christiansen, L. Mosekilde, Vitamin D metabolites and skeletal consequences in primary hyperparathyroidism. Clin. Endocrinol. 68(5), 707–715 (2008). doi:10.1111/j.1365-2265.2007.03109.x
E. Nordenstrom, J. Westerdahl, B. Lindergard, P. Lindblom, A. Bergenfelz, Multifactorial risk profile for bone fractures in primary hyperparathyroidism. World. J. Surg. 26(12), 1463–1467 (2002). doi:10.1007/s00268-002-6433-2
Y. Inoue, H. Kaji, I. Hisa, T. Tobimatsu, J. Naito, M.F. Iu, T. Sugimoto, K. Chihara, Vitamin D status affects osteopenia in postmenopausal patients with primary hyperparathyroidism. Endocr. J. 55(1), 57–65 (2008)
D.S. Rao, G. Agarwal, G.B. Talpos, E.R. Phillips, F. Bandeira, S.K. Mishra, A. Mithal, Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective. J. Bone. Miner. Res. 17(Suppl 2), N75–80 (2002)
P. Farahnak, G. Larfars, M. Sten-&&&&&&&Linder, I.L. Nilsson, Mild primary hyperparathyroidism: vitamin D deficiency and cardiovascular risk markers. J. Clin. Endocrinol. Metab. 96(7), 2112–2118 (2011). doi:10.1210/jc.2011-0238
A. Grey, J. Lucas, A. Horne, G. Gamble, J.S. Davidson, I.R. Reid, Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. J. Clin. Endocrinol. Metab. 90(4), 2122–2126 (2005). doi:10.1210/jc.2004-1772
M.L. Isidro, B. Ruano, Biochemical effects of calcifediol supplementation in mild, asymptomatic, hyperparathyroidism with concomitant vitamin D deficiency. Endocrine. 36(2), 305–310 (2009). doi:10.1007/s12020-009-9211-1
J.R. Tucci, Vitamin D therapy in patients with primary hyperparathyroidism and hypovitaminosis D. Eur. J. Endocrinol. 161(1), 189–193 (2009). doi:10.1530/EJE-08-0901
L. Rolighed, L. Rejnmark, T. Sikjaer, L. Heickendorff, P. Vestergaard, L. Mosekilde, P. Christiansen, Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. J. Clin. Endocrinol. Metab. 99(3), 1072–1080 (2014). doi:10.1210/jc.2013-3978
Acknowledgments
The authors thank Drs. Chiara Banti and Federica Saponaro for their work collecting some clinical data used in this study.
Authors’ contributions
Giuseppe Viccica contributed in design, acquisition of data, data analysis, and interpretation. Filomena Cetani contributed in acquisition of data and manuscript revision. Edda Vignali contributed in acquisition of data and manuscript revision. Mario Miccoli contributed in analysis of data and manuscript revision. Claudio Marcocci contributed in design, interpretation of data and manuscript drafting.
Funding
This study did not receive any specific grant or fellowship from any funding agency in the public, commercial or not-for-profit sector.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Viccica, G., Cetani, F., Vignali, E. et al. Impact of vitamin D deficiency on the clinical and biochemical phenotype in women with sporadic primary hyperparathyroidism. Endocrine 55, 256–265 (2017). https://doi.org/10.1007/s12020-016-0931-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12020-016-0931-8