Journal of Endocrinological Investigation

, Volume 26, Issue 11, pp 1136–1142 | Cite as

Derangement of glucose metabolism in hyperparathyroidism

Review Article
First Online:
Accepted:

Abstract

The derangement of glucose metabolism is found frequently in all forms of hyperparathyroidism. Both in primary (PHPT) and secondary hyperparathyroidism (SHPT) PTH excess is thought to be involved in deteriorating insulin sensitivity and secretion though their different clinical and pathophysiological conditions. In PHPT these abnormalities are related to a high frequency of Type 2 diabetes mellitus and also impaired glucose tolerance according to recent clinical studies, without differences between symptomatic and asymptomatic clinical presentation. In chronic renal failure (CRF), the disorders of glucose metabolism due to SHPT do not bear an increased risk for diabetes whereas they seem to be involved in the progression of atherosclerotic vascular damage which connotes CRF. Moreover, clinical and experimental studies have shown that vitamin D deficiency associated with glucose metabolism abnormalities favors the development of the metabolic syndrome. The potential for metabolic and cardiovascular harm related to hyperparathyroidism, especially PHPT, is the most interesting issue for clinical endocrinologists. This short review of the clinical and pathophysiological data of literature on glucose homeostasis disorders in hyperparathyroidism focuses on its potential clinical and therapeutic impact, particularly in the management of PHPT.

Key-words

Hyperparathyroidism diabetes glucose intolerance insulin resistance cardiovascular diseases 
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References

  1. 1.
    Kumar S, Olukoga AO, Gordon C, et al. Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism. Clin Endocrinol (Oxf) 1994, 40: 47–53.CrossRefGoogle Scholar
  2. 2.
    De Fronzo RA, Smith D, Alvestrand A. Insulin action in uremia. Kidney Int 1983, 24: 102–24.Google Scholar
  3. 3.
    Silverberg SJ, Bilezikian JP, Bone HG, Talpos GB, Horwitz MJ, Stewart AF. Therapeutic controversy in primary hyperparathyroidism. J Clin Endocrinol Metab 1999, 84: 2275–85.PubMedCrossRefGoogle Scholar
  4. 4.
    Consensus Development Conference Panel. Diagnosis and management of asymptomatic primary hyperparathyroidism: Consensus Development Conference Statement. Ann Intern Med 1991, 114: 593–7.CrossRefGoogle Scholar
  5. 5.
    Bilezikian JP, Potts JT, Fuleihan GEH, et al. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 2002, 87: 5353–61.PubMedCrossRefGoogle Scholar
  6. 6.
    Valdermarsson S, Lindblom P, Bergenfelz A. Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 1998, 244: 241–9.CrossRefGoogle Scholar
  7. 7.
    Hagstrom E, Lundgren E, Lithell H, et al. Normalized dys-ipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years. Clin Endocrinol (Oxf) 2002, 56: 253–60.CrossRefGoogle Scholar
  8. 8.
    Procopio M, Magro G, Cesario F, et al. The oral glucose tolerance test reveals a high frequency of both impaired glucose tolerance and undiagnosed Type 2 diabetes mellitus in primary hyperparathyroidism. Diabet Med 2002, 19: 958–61.PubMedCrossRefGoogle Scholar
  9. 9.
    Piovesan A, Molineri N, Casasso F, et al. Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy. Clin Endocrinol (Oxf) 1999, 50: 321–8.CrossRefGoogle Scholar
  10. 10.
    Smith JC, Page MD, John R, et al. Augmentation of centra arterial pressure in mild primary hyperparathyroidism. J Clin Endocrinol Metab 2000, 85: 3515–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Nuzzo V, Tauchmanovà L, Fonderico F, et al. Increased inti-ma-media thickness of the carotid artery wall, normal blood pressure profile and normal left ventricular mass in subjects with primary hyperparathyroidism. Eur J Endocrinol 2002, 147: 453–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Nainby-Luxmoore JC, Langford HG, Nelson NC, et al. A case-comparison study of hypertension and hyperparathyroidism. J Clin Endocrinol Metab 1982, 55: 303–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Palmer M, Adami HO, Bergstrom R, et al. Mortality after surgery for primary hyperparathyroidism: a follow-up of 441 patients operated on from 1956 to 1979. Surgery 1987, 102: 1–7.PubMedGoogle Scholar
  14. 14.
    Palmer M, Adami HO, Bergstrom R, Jakobsson S, Akerstrom G, Ljunghall S. Survival and renal function in persons with untreated hypercalcemia: a population-based cohort study with 14 years of follow up. Lancet 1987, 1: 59–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Wermers RA, Khosla S, Atkinson EJ, et al. Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 1998, 104: 115–22.PubMedCrossRefGoogle Scholar
  16. 16.
    Ljunghall S, Palmer M, Akerstrom G, et al. Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy. Eur J Clin Invest 1983, 13: 373–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Taylor WH. The prevalence of diabetes mellitus in patients with primary hyperparathyroidism and among their relatives. Diabet Med 1991, 8: 683–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Taylor WH, Khaleeli AA. Prevalence of primary hyperparathyroidism in patients with diabetes mellitus. Diabet Med 1997, 14: 386–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Taylor WH, Khaleeli AA. Coincident diabetes mellitus and primary hyperparathyroidism. Diabetes Metab Res Rev 2001, 17: 175–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Werner S, Hjiern B, Sjoberg HE. Primary hyperparathyroidism. Analysis of findings in a series of 129 patients. Acta Chir Scand 1974, 140: 618–25.PubMedGoogle Scholar
  21. 21.
    Nilsson IL, Yin L, Lundgren E, Rastad J, Ekbom A. Clinica presentation of primary hyperparathyroidism in Europe-nationwide cohort analysis on mortality from non malignant causes. J Bone Miner Res 2002, 17 (Suppl 2): N68–74.PubMedGoogle Scholar
  22. 22.
    Micic D, Kendereski A, Popovic V, Manojlovic D, Micic J. nsulin sensitivity in patients with primary hyperparathyroidism before and after parathyroidectomy: sequentia euglycemic insulin clamp studies. Horm Metab Res 1991, 23: 288–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Matthews DR, Hosker JP, Rudensky AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing. Comparison with the euglycemic insulin clamp. Diabetes Care 1999, 22: 1462–70.PubMedCrossRefGoogle Scholar
  25. 25.
    Procopio M, Cesario F, Piovesan A, et al. Insulin resistance and metabolic syndrome in primary hyperparathyroidism. J Endocrinol Invest 2002, 25 (Suppl 6): 45 (Abstract).Google Scholar
  26. 26.
    DeFronzo RA, Lang R. Hypophosphatemia and glucose tolerance. Evidence for tissue insensitivity to insulin. N Engl J Med 1980, 303: 1259–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Chiu KC, Chuang L, Lee NP, et al. Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone evel. Metabolism 2000, 49: 1501–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Fliser D, Franek E, Fode P, et al. Subacute infusion of physiological doses of parathyroid hormone raises blood pressure in humans. Nephrol Dial Transplant 1997, 12: 933–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Wareham NJ, Byrne CD, Carr C, Day NE, Boucher BJ, Hales CN. Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism 1997, 46: 1171–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Brauman A, Gilboa Y, Hertzeanu I. The effect of acute hypercalcemia on the insulin response to OGTT. Horm Metab Res 1983, 15: 204–5.PubMedCrossRefGoogle Scholar
  31. 31.
    Andersson DEH, Rojdmark S, Hed R, Sundblad L. Hypercalcemic and calcium-antagonistic effects on insulin release and oral glucose tolerance in man. Acta Med Scand 1982, 211: 35–43.PubMedCrossRefGoogle Scholar
  32. 32.
    Yasuda K, Hurukawa Y, Okuyama M, Kikuchi M, Yoshinaga K. Glucose tolerance and insulin secretion in patients with parathyroid disorders. Effect of serum calcium on insulin release. N Engl J Med 1975, 292: 501–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Mc Farlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 2001, 86: 713–8.Google Scholar
  34. 34.
    Bannon MP, van Heerden JA, Palumbo PJ, Ilstrup DM. The relationship between primary hyperparathyroidism and diabetes mellitus. Ann Surg 1988, 207: 430–3.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Richards ML, Thompson NW. Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy? Surgery 1999, 126: 1160–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Quin JD, Gumpert JR. Remission of non-insulin-dependent diabetes mellitus following resection of a parathyroid adenoma. Diabet Med 1997, 14: 80–1.PubMedCrossRefGoogle Scholar
  37. 37.
    Mak RHK. Insulin secretion in uremia: effect of parathyroid hormone and vitamin D metabolites. Kidney Int 1989, 36: 227–30.Google Scholar
  38. 38.
    Castellino P, Solino A, Luzi L, et al. Glucose and amino acid metabolism in chronic renal failure: effects of insulin and amino acids. Am J Physiol 1992, 262: 168–76.Google Scholar
  39. 39.
    Mak RHK, Bertinelli A, Turner C, Haycock B, Chantler C. The influence of hyperparathyroidism on glucose metabolism in uremia. J Clin Endocrinol Metab 1985, 60: 229–33.PubMedCrossRefGoogle Scholar
  40. 40.
    Graf H, Prager R, Kovarik J, Luger A, Schernthaner G, Pinggera WF. Glucose metabolism and insulin sensitivity in patients on chronic hemodialysis. Metabolism 1985, 34: 974–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Kautzky-Willer A, Pacini G, Barnas U, et al. Intravenous cal-citriol normalizes insulin sensitivity in uremic patients. Kidney Int 1995, 47: 200–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Baczynsky R, Massry SG, Magott M, EL-Belbessi S, Kohan R, Brautbar N. Effect of parathyroid hormone on energy metabolism of skeletal muscle. Kidney Int 1985, 28: 722–7.CrossRefGoogle Scholar
  43. 43.
    Mak RHK, De Fronzo RA. Glucose and insulin metabolism in uremia. Nephron 1992, 61: 377–82.PubMedCrossRefGoogle Scholar
  44. 44.
    Akmal M, Massry SG, Glodstein DA, Fanti P, Weisz A, De Fronzo RA. Role of the parathyroid hormone in the glucose intolerance of chronic renal failure. J Clin Invest 1985, 75: 1037–44.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Fadda GZ, Akmal M, Premdas FH, Lipson LG, Massry SG. nsulin release from pancreatic islets: effects of CRF and excess PTH. Kidney Int 1988, 33: 1066–72.PubMedCrossRefGoogle Scholar
  46. 46.
    Massry SG, Fadda GZ. Chronic renal failure is a state of cellular calcium toxicity. Am J Kidney Dis 1993, 21: 81–6.PubMedGoogle Scholar
  47. 47.
    Fadda GZ, Hajjar SM, Perna AF, Zhuo XJ, Lipson LG, Massry SG. On the mechanism of impaired insulin secretion in chronic renal failure. J Clin Invest 1991, 87: 255–61.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Bergesio F, Bandini S, Cresci B, et al. Hyperparathyroidism: is it really the major factor affecting glucose tolerance in uremia? Miner Electrolyte Metab 1996, 22: 187–91.PubMedGoogle Scholar
  49. 49.
    Lin S, Lin Y, Lu K, et al. Effects of intravenous calcitriol on lipid profiles and glucose tolerance in uremic patients with secondary hyperparathyroidism. Clin Sci (Lond) 1994, 87: 533–8.Google Scholar
  50. 50.
    Mak RHK. Intravenous 1.25 dihydroxycholecalciferol corrects glucose tolerance in hemodialysis patients. Kidney Int 1992, 41: 1049–54.PubMedCrossRefGoogle Scholar
  51. 51.
    Chan MK, Varghese Z, Moorhead JF. Lipid abnormalities in uremia, dialysis and transplantation. Kidney Int 1981, 19: 625–37.PubMedCrossRefGoogle Scholar
  52. 52.
    Hong S, Yang D. Insulin levels and fibrinolytic activity in patients with end-stage renal disease. Nephron 1994, 68: 329–33.PubMedCrossRefGoogle Scholar
  53. 53.
    Ganesch SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK. Association of elevated serum PO(4), CaxPO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001, 12: 2131–8.Google Scholar
  54. 54.
    Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001, 22: 477–501.PubMedCrossRefGoogle Scholar
  55. 55.
    Mc Kenna M. Differences in vitamin D status between countries in young adults and the elderly. Am J Med 1992, 93: 67–9.Google Scholar
  56. 56.
    Frankel BJ, Heldt AM, Grodsksy GM. Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 1980, 209: 823–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Cade C, Norman AW. Vitamin D3 improves impaired glucose tolerance and insulin secretion in the vitamin D-defi-cient rat in vivo. Endocrinology 1986, 119: 84–90.PubMedCrossRefGoogle Scholar
  58. 58.
    Gedik O, Akalin S. Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man. Diabetologia 1986, 29: 142–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJW. Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in East London Asians. Diabetologia 1995, 38: 1239–45.PubMedCrossRefGoogle Scholar
  60. 60.
    Storm TL, Sorensen OH, Lund B, et al. Vitamin D metabolism in insulin-dependent diabetes mellitus. Metab Bone Dis Relat Res 1983, 5: 107–10.PubMedCrossRefGoogle Scholar
  61. 61.
    Heat H, Lambert PW, Service FJ, et al. Calcium homeostasis in diabetes mellitus. J Clin Endocrinol Metab 1983, 49: 462–6.CrossRefGoogle Scholar
  62. 62.
    Boucher BJ. Inadequate vitamin D status: does it contribute to the disorders comprising syndrome ‘X’? Br J Nutr 1998, 79: 315–27.PubMedCrossRefGoogle Scholar
  63. 63.
    Kocian J. Diabetic osteopathy. Favorable effect of treatment of osteomalacia with vitamin D and calcium on high blood glucose levels. Vnitr Lek 1992, 38: 352–6.PubMedGoogle Scholar
  64. 64.
    Orwoll E, Riddle M, Prince M. Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus. Am J Clin Nutr 1994, 59: 1083–7.PubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2003

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Endocrinology and MetabolismOspedale MolinetteTorinoItaly
  2. 2.Division of EndocrinologyS. Croce e Carle HospitalCuneoItaly

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