Skip to main content

Advertisement

Log in

Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Cardiometabolic disorders have been associated with primary hyperparathyroidism (PHPT), while the relationship of cardiovascular risk score (CRS) and metabolic syndrome (MS) with different clinical presentation of PHPT remains undefined. Our aim was to evaluate CRS, MS and its components in PHPT looking for their correlation to different clinical forms. In 68 consecutive PHPT patients and 68 matched controls, CRS, MS and its components were assessed to perform an observational case–control study at an ambulatory referral center for Bone Metabolism Diseases. Patients were stratified in symptomatic and asymptomatic PHPT; these latter were divided in high-risk and low-risk subgroups for end-organ damage. An increased proportion of PHPT patients had intermediate-high CRS and MS (mean, 95 % Confidence Interval (CI) 51.5 %, 39.6–63.3 and 20.6 %, 11.0–30.2, respectively, p < 0.02 vs. controls). Intermediate-high CRS was prevalent both in symptomatic and low-risk asymptomatic PHPT while MS resulted prevalent in low-risk asymptomatic but not in symptomatic PHPT. Type 2 DM, IFG, mixed dyslipidemia, hypertriglyceridemia, HDL-hypocholesterolemia, and LDL-hypercholesterolemia predominated in low-risk asymptomatic, while only LDL-hypercholesterolemia prevailed also in symptomatic PHPT. In patients and controls without cardiometabolic risk factors, HOMA-IR index was significantly increased in PHPT vs. controls (p < 0.03) and associated to total calcium (R = 0.73; p < 0.001). By multivariate analysis low-risk asymptomatic PHPT predicted MS after adjusting for age, sex, and BMI. Our data show an increased frequency of intermediate-high CRS both in symptomatic and low-risk asymptomatic PHPT while MS prevails in low-risk asymptomatic PHPT, supporting the potential for cardiovascular morbidity and mortality also in this form.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. S.J. Silverberg, E.M. Lewiecki, L. Mosekilde, M. Peacock, M.R. Rubin, Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J. Clin. Endocrinol. Metab. 94, 351–365 (2009)

    Article  PubMed  CAS  Google Scholar 

  2. I.L. Nilsson, L. Yin, E. Lundgren, J. Rastad, A. Ekbom, Clinical presentation of primary hyperparathyroidism in Europe–nationwide cohort analysis on mortality from nonmalignant causes. J. Bone Miner. Res. 17(Suppl 2), N68–N74 (2002)

    PubMed  Google Scholar 

  3. N. Yu, P.T. Donnan, R.W. Flynn, M.J. Murphy, D. Smith, A. Rudman, G.P. Leese, Increased mortality and morbidity in mild primary hyperparathyroid patients. The parathyroid epidemiology and audit research study (PEARS). Clin. Endocrinol. 73, 30–34 (2010)

    Google Scholar 

  4. E. Osto, F. Fallo, M.R. Pelizzo, A. Maddalozzo, N. Sorgato, F. Corbetti, R. Montisci, G. Famoso, R. Bellu, T.F. Lüscher, S. Iliceto, F. Tona, Coronary microvascular dysfunction induced by primary hyperparathyroidism is restored after parathyroidectomy. Circulation 126, 1031–1039 (2012)

    Article  PubMed  Google Scholar 

  5. M.D. Walker, S.J. Silverberg, Cardiovascular aspects of primary hyperparathyroidism. J. Endocrinol. Invest. 31, 925–931 (2008)

    Article  PubMed  CAS  Google Scholar 

  6. F. Tassone, M. Procopio, L. Gianotti, G. Visconti, A. Pia, M. Terzolo, G. Borretta, Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidism. Diabet. Med. 26, 968–973 (2009)

    Article  PubMed  CAS  Google Scholar 

  7. E. Hagstrom, E. Lundgren, H. Lithell, L. Berglund, S. Ljunghall, P. Hellman, J. Rastad, Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years. Clin. Endocrinol. 56, 253–260 (2002)

    Article  Google Scholar 

  8. A. Bergenfelz, A. Bladström, M. Their, E. Nordenström, S. Valdemarsson, J. Westerdahl, Serum levels of uric acid and diabetes mellitus influence survival after surgery for primary hyperparathyroidism: a prospective cohort study. World J. Surg. 31, 1393–1400 (2007)

    Article  PubMed  Google Scholar 

  9. M.J. Bolland, A.B. Grey, G.D. Gamble, I.R. Reid, Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J. Clin. Endocrinol. Metab. 90, 1525–1530 (2005)

    Article  PubMed  CAS  Google Scholar 

  10. E. Delfini, L. Petramala, C. Caliumi, D. Cotesta, G. De Toma, G. Cavallaro, G. Panzironi, D. Diacinti, S. Minisola, E. D’ Erasmo, G.F. Mazzuoli, C. Letizia, Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism. Metabolism 56, 30–36 (2007)

    Article  PubMed  CAS  Google Scholar 

  11. R. Luboshitzky, Y. Chertok-Schaham, I. Lavi, A. Ishay, Cardiovascular risk factors in primary hyperparathyroidism. J. Endocrinol. Invest. 32, 317–321 (2009)

    Article  PubMed  CAS  Google Scholar 

  12. D. Han, S. Trooskin, X. Wang, Prevalence of cardiovascular risk factors in male and female patients with primary hyperparathyroidism. J. Endocrinol. Invest. (2011). doi:10.3275/7861

    Google Scholar 

  13. E. Hagström, P. Hellman, T.E., E. Ingelsson, L. Berglund, J. Sundström, H. Melhus, C. Held, L. Lind, K. Michaëlsson, J. Arnlöv. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 119, 2765–2771 (2009)

  14. J.L. Anderson, R.C. Vanwoerkom, B.D. Horne, T.L. Bair, H.T. May, D.L. Lappé, J.B. Muhlestein, Parathyroid hormone, vitamin D, renal dysfunction, and cardiovascular disease: dependent or independent risk factors? Am. Heart J. 162, 331–339 (2011)

    Article  PubMed  Google Scholar 

  15. W.D. Fraser, Hyperparathyroidism. Lancet 374, 145–158 (2009)

    Article  PubMed  CAS  Google Scholar 

  16. J.P. Bilezikian, A.A. Khan, J.T. Potts Jr, Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop. J. Clin. Endocrinol. Metab. 94, 335–339 (2009)

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. F. Tassone, L. Gianotti, C. Baffoni, F. Cesario, G. Magro, M. Pellegrino, I. Emmolo, M. Maccario, G. Borretta, Prevalence and characteristics of metabolic syndrome in primary hyperparathyroidism. J. Endocrinol. Invest. (2011). doi:10.3275/8192

    PubMed  Google Scholar 

  18. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106, 3143–3421 (2002)

    Google Scholar 

  19. D.R. Matthews, J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, R.C. Turner, Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412–419 (1985)

    Article  PubMed  CAS  Google Scholar 

  20. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia, Report of a WHO/IDF consultation (2006) (http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf accessed in data 22/08/2012)

  21. G. Mansia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A.M. Heagerty, S.E. Kjeldsen, S. Laurent, K. Narkiewicz, L. Ruilope, A. Rynkiewicz, R.E. Schmieder, H.A. Struijker Boudier, A. Zanchetti, European Society of Hypertension; European Society of Cardiology. ESH-ESC Practice Guidelines for the Management of Arterial Hypertension : the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Blood. Press 16, 135–232 (2007)

    Google Scholar 

  22. J.B. Meigs, P.W.F. Wilson, D.M. Nathan, R.B. D’Agostino Sr, K. Williams, S.M. Haffner, Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring studies. Diabetes 52, 2160–2167 (2003)

    Article  PubMed  CAS  Google Scholar 

  23. T. Apridonidze, P.A. Essah, M.J. Iuorno, J.E. Nestler, Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 90, 1929–1935 (2005)

    Article  PubMed  CAS  Google Scholar 

  24. D.A. De Luis, G.D. Soto, R. Conde, O. Izaola, B. de la Fuente, Relation of leptin and adiponectin with cardiovascular risk factors, intact parathormone, and vitamin D levels in patients with primary hyperparathyroidism. J. Clin. Lab. Anal. 26, 398–402 (2012). doi:10.1002/jcla.21541

    Article  PubMed  Google Scholar 

  25. P. Luigi, F.M. Chiara, Z. Laura, M. Cristiano, C. Giuseppina, C. Luciano, P. Giuseppe, C. Sabrina, S. Susanna, C. Antonio, C. Giuseppe, T. Giorgio, L. de Claudio, Arterial hypertension, metabolic syndrome and subclinical cardiovascular organ damage in patients with asymptomatic primary hyperparathyroidism before and after parathyroidectomy: preliminary results. Int. J. Endocrinol. (2012). doi:10.1155/2012/408295

    PubMed  PubMed Central  Google Scholar 

  26. E. Hagstrom, E. Lundgren, J. Rastad, P. Hellman, Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening. Eur. J. Endocrinol. 155, 33–39 (2006)

    Article  PubMed  Google Scholar 

  27. K.M. Tordjman, M. Yaron, E. Izkhakov, E. Osher, G. Shenkerman, Y. Marcus-Perlman, N. Stern, Cardiovascular risk factors and arterial rigidity are similar in asymptomatic normocalcemic and hypercalcemic primary hyperparathyroidism. Eur. J. Endocrinol. 162, 925–933 (2010)

    Article  PubMed  CAS  Google Scholar 

  28. D.P. Macfarlane, N. Yu, P.T. Donnan, G.P. Leese, Should ‘mild primary hyperparathyroidism’ be reclassified as ‘insidious’: is it time to reconsider? Clin. Endocrinol. 75, 730–737 (2011). doi:10.1111/j.1365-2265.2011.04201.x

    Article  CAS  Google Scholar 

  29. J. Bollerslev, T. Rosen, C.L. Mollerup, J. Nordenström, M. Baranowski, C. Franco, Y. Pernow, G.A. Isaksen, K. Godang, T. Ueland, S. Jansson, Effect of surgery on cardiovascular risk factors in mild primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 94, 2255–2261 (2009)

    Article  PubMed  CAS  Google Scholar 

  30. A.A. Khaleeli, J.N. Johnson, W.H. Taylor, Prevalence of glucose intolerance in primary hyperparathyroidism and the benefit of parathyroidectomy. Diabetes Metab. Res. Rev. 23, 43–48 (2007)

    Article  PubMed  CAS  Google Scholar 

  31. M.R. Rubin, S.J. Silverberg, Glucose intolerance and primary hyperparathyroidism: an unresolved relationship. Endocrine 42, 231–233 (2012)

    Article  PubMed  CAS  Google Scholar 

  32. A. Kautzky-Willer, G. Pacini, B. Niederle, G. Schernthaner, R. Prager, Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery. Clin. Endocrinol. 37, 147–155 (1992)

    Article  CAS  Google Scholar 

  33. S. Kumar, A.O. Olukoga, C. Gordon, E.B. Mawer, M. France, J.P. Hosker, M. Davies, A.J. Boulton, Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism. Clin. Endocrinol. 40, 47–53 (1994)

    Article  CAS  Google Scholar 

  34. F. Tassone, M. Maccario, L. Gianotti, C. Baffoni, M. Pellegrino, S. Cassibba, F. Cesario, G. Magro, G. Borretta, Insulin sensitivity in normocalcaemic primary hyperparathyroidism. Endocrine (2013). doi:10.1007/s12020-013-0059-z

    PubMed  Google Scholar 

  35. I. Cakir, K. Unluhizarci, F. Tanriverdi, G. Elbuken, Z. Karaca, F. Kelestimur, Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism. Endocrine 42, 419–422 (2012)

    Article  PubMed  CAS  Google Scholar 

  36. T. Yamaguchi, I. Kanazawa, S. Takaoka, T. Sugimoto, Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus. Metabolism 60, 1334–1339 (2011)

    Article  PubMed  CAS  Google Scholar 

  37. P.J. Buizert, N.M. van Schoor, S. Simsek, P. Lips, A.C. Heijboer, M. den Heijer, D.J. Deeg, E.M. Eekhoff, PTH: a new target in arteriosclerosis? J Clin Endocrinol Metab (2013). doi:10.1210/jc.2013-1621

    PubMed  Google Scholar 

  38. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43, 618–625 (2013)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank gratefully Prof. Franco Camanni for his critical revision of this paper and radiologic technologists Mr Francesco Moricca and Damiano Allegro for their skillfulness in performing DXA test.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Procopio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Procopio, M., Barale, M., Bertaina, S. et al. Cardiovascular risk and metabolic syndrome in primary hyperparathyroidism and their correlation to different clinical forms. Endocrine 47, 581–589 (2014). https://doi.org/10.1007/s12020-013-0091-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-013-0091-z

Keywords

Navigation