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Hypomagnesemia may be associated with symptomatic disease in patients with primary hyperparathyroidism

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Abstract

Aim

Magnesium (Mg) homeostasis is closely related to calcium (Ca) metabolism. Hypercalcemia inhibits the reabsorption of Mg from the kidneys, leading to hypomagnesemia. Therefore, patients with primary hyperparathyroidism (PHPT) are predisposed to hypomagnesemia. However, there are few studies on the clinical significance of hypomagnesemia in PHPT. The aim of this study was to retrospectively evaluate the association of hypomagnesemia with the clinical outcomes of PHPT.

Materials and methods

A retrospective evaluation was made of the data of 538 consecutive patients (478 females, 60 males) diagnosed with PHPT in our center.

Results

The mean age of the study population was 56.5 ± 11.66 years. The mean serum Mg level was 2 ± 0.26 mg/dl. Asymptomatic disease was present in 241 (44%) patients. Symptomatic patients with osteoporosis, Ca level ≥11.2 mg/dl, and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 had lower levels of Mg (p < 0.05). Hypomagnesemia was detected in 129 of 538 patients (23.9%). The patients with hypomagnesemia had a higher rate of symptomatic disease (80% vs. 48%, p < 0.0001). The serum parathormone (PTH) level was found to be higher in patients with hypomagnesemia and the lumbar and femur T-scores and serum vitamin D levels were lower (p < 0.05). Patients with hypomagnesemia had higher rates of kidney stones (34% vs. 21%, p = 0.003) and osteoporosis (74% vs. 32%, p < 0.001). Multivariate logistic regression analysis revealed that hypomagnesemia had a significant effect on the development of symptomatic disease (OR:6.88, CI 95%: 5.20–11.27, p < 0.001).

Conclusions

The current study results demonstrate that hypomagnesemia may be associated with a higher risk of osteoporosis and kidney stones in PHPT patients. Routine evaluation of serum Mg may predict the clinical outcomes of PHPT.

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References

  1. B. Reiner, B. Christoph, Bone disorders. 1st ed. (Springer, Munich, Germany, 2017)

  2. J.P. Bilezikian, S.J. Silverberg, F. Bandeira, F. Cetani, M. Chandran, N.E. Cusano, P.R. Ebeling, A.M. Formenti, M. Frost, J. Gosnell et al. Management of primary hyperparathyroidism. J. Bone Min. Res. 37, 2391–2403 (2022). https://doi.org/10.1002/jbmr.4682

    Article  Google Scholar 

  3. M. Kızılgül, M. Çalışkan, S. Beysel, M. Özbek, E. Çakal, Effect of parathyroidectomy on epicardial fat thickness as a cardiovascular risk factor in patients with primary hyperparathyroidism. Turk. J. Med. Sci. 8, 1165–1169 (2019). https://doi.org/10.3906/sag-1902-40

    Article  CAS  Google Scholar 

  4. Y. Assadipour, H. Zhou, E.J. Kuo, P.I. Haigh, A.L. Adams, M.W. Yeh, End-organ effects of primary hyperparathyroidism: a population-based study. Surgery 165, 99–104 (2019). https://doi.org/10.1016/j.surg.2018.04.088

    Article  PubMed  Google Scholar 

  5. L. Paunier, Effect of magnesium on phosphorus and calcium metabolism. Monatsschr Kinderheilkd. 140, 17–20 (1992)

    Google Scholar 

  6. H.A. Bulger, F. Gausmann, Magnesium Metabolism in hyperparathyroidism. J. Clin. Invest 12, 1135–1142 (1933). https://doi.org/10.1172/JCI100564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. R.T. Alexander, J.G. Hoenderop, R.J. Bindels, Molecular determinants of magnesium homeostasis: insights from human disease. J. Am. Soc. Nephrol. 19, 1451–1458 (2008). https://doi.org/10.1681/ASN.2008010098

    Article  CAS  PubMed  Google Scholar 

  8. R.J.M. Bindels, G.J. Hoenderop, J. Biber. Tansport of calcium, magnesium, and phosphate. In: M.W. Taal, G.M. Chertow, P.A. Marsden, et al. (eds) Herausgeber. Brenner & Rector’s the Kidney. 9th edn. (Saunders, Philadelphia, 2012), pp. 226–251

  9. G.A. Quamme, Renal magnesium handling: new insights in understanding old problems. Kidney Int. 52, 1180–1195 (1997). https://doi.org/10.1038/ki.1997.443

    Article  CAS  PubMed  Google Scholar 

  10. R.G. King, S.W. Stanbury, Magnesium metabolism in primary hyperparathyroidism. Clin. Sci. 39, 281 (1970). https://doi.org/10.1042/cs0390281

    Article  CAS  PubMed  Google Scholar 

  11. R.A. Sutton, Plasma magnesium concentration in primary hyperparathyroidism. Br. Med. J. 28, 529–533 (1970). https://doi.org/10.1136/bmj.1.5695.529

    Article  Google Scholar 

  12. D. Na, G. Tao, L. Shu-Ying, W. Qin-Yi, Q. Xiao-Li, L. Yong-Fang, O. Yang-Na, S. Zhi-Feng, Y. Yan-Yi, Association between hypomagnesemia and severity of primary hyperparathyroidism: a retrospective study. BMC Endocr. Disord. 20, 170 (2021). https://doi.org/10.1186/s12902-021-00838-y

    Article  CAS  Google Scholar 

  13. E.S. Siris, R. Adler, J. Bilezikian, M. Bolognese, B. Dawson-Hughes, M.J. Favus, S.T. Harris, S.M. Jan de Beur, S. Khosla, N.E. Lane et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos. Int 25, 1439 (2014). https://doi.org/10.1007/s00198-014-2655-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. A.S. Levey, L.A. Stevens, C.H. Schmid, Y.L. Zhang, A.F. Castro, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann. Intern Med. 150, 604–612 (2009). https://doi.org/10.7326/0003-4819-150-9-200905050-00006

    Article  PubMed  PubMed Central  Google Scholar 

  15. L.G. Yanevskaya, T. Karonova, I.V. Sleptsov, M.E. Boriskova, A.R. Bakhtiyarova, R.A. Chernikov, K.A. Pogosian, A.T. Andreeva, D.A. Lebedev, E.N. Grineva et al. Clinical phenotypes of primary hyperparathyroidism in hospitalized patients who underwent parathyroidectomy. Endocr. Connect 10, 248–255 (2021). https://doi.org/10.1530/EC-20-0515

    Article  PubMed  PubMed Central  Google Scholar 

  16. C. Cipriani, F. Biamonte, A.G. Costa, C. Zhang, P. Biondi, D. Diacinti, J. Pepe, S. Piemonte, A. Scillitani, S. Minisola et al. Prevalence of kidney stones and vertebral fractures in primary hyperparathyroidism using imaging technology. J. Clin. Endocrinol. Metab. 100, 1309–1315 (2015). https://doi.org/10.1210/jc.2014-3708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Y.D. Tay, M. Liu, L. Bandeira, M. Bucovsky, J.A. Lee, S.J. Silverberg, M.D. Walker, Occult urolithiasis in asymptomatic primary hyperparathyroidism. Endocr. Res. 43, 106–115 (2018). https://doi.org/10.1080/07435800.2018

    Article  PubMed  PubMed Central  Google Scholar 

  18. J.P. Bilezikian, Primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 103, 3993–4004 (2018). https://doi.org/10.1210/jc.2018-01225

    Article  PubMed  PubMed Central  Google Scholar 

  19. H. Ejlsmark-Svensson, L.S. Bislev, L. Rolighed, T. Sikjaer, L. Rejnmark, Predictors of renal function and calcifications in primary hyperparathyroidism: a nested case-control study. J. Clin. Endocrinol. Metab. 103, 3574–3583 (2018). https://doi.org/10.1210/jc.2018-00923

    Article  PubMed  Google Scholar 

  20. T. Vetter, M.J. Lohse, Magnesium and the parathyroid. Curr. Opin. Nephrol. Hypertens. 11, 403–410 (2002). https://doi.org/10.1097/00041552-200207000-00006

    Article  PubMed  Google Scholar 

  21. A.C. Schmulen, M. Lerman, C.Y. Pak, J. Zerwekh, S. Morawski, J.S. Fordtran, P. Vergne-Marini, Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease. Am. J. Physiol. 238, 349–352 (1980). https://doi.org/10.1152/ajpgi.1980.238.4.G349

    Article  Google Scholar 

  22. I. Hornum, I. Transbol, Partial escape of magnesium from the renal action of parathyroid hormone in hyperparathyroidism. Acta Med. Scand. 193, 325–330 (1973). https://doi.org/10.1111/j.0954-6820.1973.tb10585.x

    Article  CAS  PubMed  Google Scholar 

  23. S.H. Bassett, Van, Alstine HE. Mineral exchanges of man; effects of extirpation of parathyroid tumour on balances of electrolytes. J. Nutr. 9, 345–362 (1935). https://doi.org/10.1093/jn/9.3.323

    Article  CAS  Google Scholar 

  24. F.W. Heaton, L.N. Pyrah, Magnesium metabolism in patients with parathyroid disorders. Clin. Sci. 24, 475–485 (1963)

    Google Scholar 

  25. J. Wu, Z. Yang, J. Wei, C. Zeng, Y. Wang, T. Yang, Association between serum magnesium and the prevalence of kidney stones: a cross-sectional study. Biol. Trace Elem. Res. 195, 20–26 (2020). https://doi.org/10.1007/s12011-019-01830-3

    Article  CAS  PubMed  Google Scholar 

  26. S. Jawalekar, V.T. Surve, A.K. Bhutey, Twenty four hours urine and serum biochemical parameters in patients with urolithiasis. Nepal Med. Coll. J. 12, 5–7 (2010)

    CAS  PubMed  Google Scholar 

  27. Y. Ogawa, T. Hatano, Risk factors in urinary calcium oxalate stone formation and their relation to urinary calcium oxalate supersaturation. Int. J. Urol. 3, 356–360 (1996). https://doi.org/10.1111/j.1442-2042.1996.tb00553.x

    Article  CAS  PubMed  Google Scholar 

  28. N. Wu, W.F. Thon, H. Krah, R. Schlick, U. Jonas, Effects of magnesium citrate and phytin on reducing urinary calcium excretion in rats. World J. Urol. 12, 323–328 (1994). https://doi.org/10.1111/j.1442-2042.1996.tb00553.x

    Article  CAS  PubMed  Google Scholar 

  29. F. Saponaro, C. Marcocci, M. Apicella, L. Mazoni, S. Borsari, E. Pardi, M. Di Giulio, F. Carlucci, M. Scalese, J.P. Bilezikian et al. Hypomagnesuria is associated with nephrolithiasis in patients with asymptomatic primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 105, dgaa233 (2020). https://doi.org/10.1210/clinem/dgaa233

    Article  PubMed  Google Scholar 

  30. G. Johansson, B.G. Danielson, S. Ljunghall, Magnesium homeostasis in mild-to-moderate primary hyperparathyroidism. Acta Chir. Scand. 146, 85–91 (1980)

    CAS  PubMed  Google Scholar 

  31. V. Aina, G. Lusvardi, B. Annaz, I.R. Gibson, F.E. Imrie, G. Malavasi, L. Menabue, G. Cerrato, G. Martra, Magnesium- and strontium-co-substituted hydroxyapatite: the effects of doped-ions on the structure and chemico-physical properties. J. Mater. Sci. Mater. Med 23, 2867–2879 (2012). https://doi.org/10.1007/s10856-012-4767-3

    Article  CAS  PubMed  Google Scholar 

  32. I. Zofková, P. Nemcikova, P. Matucha, Trace elements and bone health. Clin. Chem. Lab. Med 51, 1555–1561 (2013). https://doi.org/10.1515/cclm-2012-0868

    Article  CAS  PubMed  Google Scholar 

  33. R.K. Rude, H.E. Gruber, Magnesium deficiency and osteoporosis: animal and human observations. J. Nutr. Biochem. 15, 710–716 (2004). https://doi.org/10.1016/j.jnutbio.2004.08.001

    Article  CAS  PubMed  Google Scholar 

  34. J. Zheng, X. Mao, J. Ling, Q. He, J. Quan, H. Jiang, Association between serum level of magnesium and postmenopausal osteoporosis: a meta-analysis. Biol. Trace Elem. Res. 159, 8–14 (2014). https://doi.org/10.1007/s12011-014-9961-3

    Article  CAS  PubMed  Google Scholar 

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Düğer, H., Uçan, B., Çalışkan, M. et al. Hypomagnesemia may be associated with symptomatic disease in patients with primary hyperparathyroidism. Endocrine 83, 466–472 (2024). https://doi.org/10.1007/s12020-023-03577-3

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