Primary hyperparathyroidism

Epidemiology and clinical consequences


The earliest clinical descriptions of primary hyperparathyroidism pointed to an inexorably progressive disorder. Now, in asymptomatic individuals who do not meet any surgical guidelines, primary hyperparathyroidism, in general, does not appear to be progressive. Asymptomatic patients appear to remain asymptomatic over many years of observation. In those with major clinical manifestations, nephrolithiasis is, by far, the most common. In these patients, surgery is clearly indicated. Bone densitometry is an indispensable component of the evaluation as well as in monitoring in that there is evidence for bone involvement by this technology in most patients. This contrasts with the skeletal X-ray, which is invariably negative. Nevertheless, only the unusual patients will show a bone mass measurement that either at the cortical or cancellous skeleton that is more than two standard deviations below age-and sex-matched control subjects. Such individuals should, however, also be recommended for parathyroid surgery. Bone density, the serum calcium concentration, and/or urinary calcium excretion per se can show evidence for progression in as many as 25% with asymptomatic primary hyperparathyroidism. For this reason, all patients who are not going to have surgery for primary hyperparathyroidism should be monitored with biannual (serum calcium concentration) or annual testing (urinary calcium excretion and bone densitometry).


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  1. 1.
    Heath H III, Hodgson SF, Kennedy M. 1980 Primary hyperparathyroidism: incidence, morbidity and potential economic impact in a community. N Engl J Med 302:189–193.PubMedCrossRefGoogle Scholar
  2. 2.
    Cope O. 1966 The story of hyperparathyroidism at the Massachusetts General Hospital. N Engl J Med 21(1):174–182.Google Scholar
  3. 3.
    Keating FR Jr, Cook EN. 1945 Recognition of primary hyperparathyroidism: analysis of 24 cases. J Am Med Assoc 129:994–1002.Google Scholar
  4. 4.
    Melton LJ III. 1991 Epidemiology of primary hyperparathyroidism. J Bone Mine Res 6(Suppl 2):S25-S30.Google Scholar
  5. 5.
    Stenstrom G, Heedman P. 1974 Clinical findings in patients with hypercalcemia: a final investigation based on biochemical screening. Acta Med Scand 195:473–477.PubMedCrossRefGoogle Scholar
  6. 6.
    Rastad J, Lundgren E, Ljunghall S. 2001 Clinical presentation of primary hyperparathyroidism. In: The Parathyroids, 2nd ed. Bilezikian JP, Marcus R, Levine MA, eds. Academic, San Diego, CA, 361–374.Google Scholar
  7. 7.
    Palmer M, JacobssonG, Akerstrom G, Ljunghall S.1988 Prevalence of hypercalcemia in a health survey: a 14-year follow-up study of serum calcium values. Eur J Clin Invest 18:39–46.PubMedGoogle Scholar
  8. 8.
    Christensson T, Hellstrom K, Wengle B, Alveryd A, Wikland B. 1976 Prevalence of hypercalcemia in a health screening in Stockholm. Acta Med Scand 200:131–137.PubMedCrossRefGoogle Scholar
  9. 9.
    Akerstrom G, Rudberg C, Grimelius L, Bergstrom R, Johansson H, Ljunghall S, et al. 1986 Histologic parathyroid abnormalities in an autopsy series. Hum Pathol 17:520–527.PubMedCrossRefGoogle Scholar
  10. 10.
    Lundgren E, Rastad J, Thurfjell E, Akerstrom G, Ljunghall S. 1997 Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Surgery 121:287–294.PubMedCrossRefGoogle Scholar
  11. 11.
    Lundgren, E. 1999 Primary hyperparathyroidism of postmenopausal females. Prospective case-control analysis on prevalence, clinical characteristics and treatment. Comprehensive Summary Uppsula Faculty Medicine 820:1–51.Google Scholar
  12. 12.
    Lindstedt G, Nystrom E, Lundberg P-A, Johansson E, Eggertsen R. 1992 Screening of an elderly population in primary care for primary hyperparathyroidism. Scand J Primary Health Care 10:192–197.Google Scholar
  13. 13.
    Sorva A, Valvanne J, Tilvis RS. 1992 Serum ionized calcium and the prevalence of primary hyperparathyroidism in age cohorts of 75, 80 and 85 years. J Intern Med 231:309–312.PubMedGoogle Scholar
  14. 14.
    Wermers RA, Khosla S, Atkinson EJ, Hodgson SF, O'Fallon WM, Melton LJ III. 1997 The rise and fall of primary hyperparathyroidism: a population-based study in Rochester. Minnesota, 1965–1992. Ann Intern Med 126:433–440.PubMedGoogle Scholar
  15. 15.
    Cohen J, Gierlowski TC, Schneider AB. 1990 A prospective study of hyperparathyroidism in individuals exposed to radiation in childhood. JAMA 264:581–584.PubMedCrossRefGoogle Scholar
  16. 16.
    Bondeson AG, Bondeson L, Thompson NW. 1989 Hyperparathyroidism after treatment with radioactive iodine: not only a coincidence? Surgery 106:1025–1027.PubMedGoogle Scholar
  17. 17.
    Gao P, Scheibel S, D'Amour P, John MR, Rao SD, Schmidt-Gayk H, et al. 2001. Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84 implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16:605–614.PubMedCrossRefGoogle Scholar
  18. 18.
    Silverberg SJ, Brown IN, Bilezikian JP, Deftos LJ. 2000 A new highly sensitive assay for parathyroid hormone in primary hyperparathyroidism. J Bone Miner Res 15(Suppl I):S167.Google Scholar
  19. 19.
    Cohen A, LoGerfo P, Gao P, Brown IB, Trokan S, Cantor T, et al. 2001 PTH(1–84) and N-truncated PTH fragment in the serum and parathyroid glands of patients with primary hyperparathyroidism. J Bone Miner Res 16(Suppl I):S156.Google Scholar
  20. 20.
    Silverberg SJ, Bilezikian JP. 2001 Primary hyperparathyroidism. In: Principles and Practice of Endocrinology and Metabolism. Becker KL, ed. Lippincott Williams & Wilkins, Philadelphia, 564–573.Google Scholar
  21. 21.
    Bilezikian JP. 1996 Nephrolithiasis in primary hyperparathyroidism. In: Kidney Stones: Medical and Surgical Treatment. Coe FL, Favus MJ, Pak CYC, Parks JH, Preminger GM, eds. Lippincott-Raven Philadelphia, 783–802.Google Scholar
  22. 22.
    Bilezikian JP, Silverberg SJ, Shane E, Parisien M, Dempster DW, 1991 Characterization and evaluation of asymptomatic primary hyperparathyroidism. J Bone Miner Res 6(Suppl I):585–589.Google Scholar
  23. 23.
    Silverberg SJ, Shane E, DeLaCruz L, et al. 1989 Skeletal disease in primary hyperparathyroidism. J Bone Miner Res 4:283–291.PubMedGoogle Scholar
  24. 24.
    Bilezikian JP, Silverberg SJ. 2000 Clinical spectrum of primary hyperparathyroidism. Rev Endocr Metab Disord 1:237–245.PubMedCrossRefGoogle Scholar
  25. 25.
    Silverberg SJ, Bilezikian JP. 2001 Primary hyperparathyroidism. In: Endocrinology, 4th ed. DeGroot LJ, Jameson JL, eds. WB Saunders, Philadelphia, 1075–1093.Google Scholar
  26. 26.
    Dauphine RT, Riggs BL, Scholz DA. 1975 Back pain and vertebral crush fractures: an unrecognized mode of presentation for primary hyperparathyroidism. Ann Intern Med 83:365–367.PubMedGoogle Scholar
  27. 27.
    Khosla S, Melton III LJ, Wermers RA, Crowson CS, O'Fallon WM, Riggs BL. 1999 Primary hyperparathyroidism and the risk of fracture: a population based study. J Bone Min Res 14:1700–1707.CrossRefGoogle Scholar
  28. 28.
    Wilson RJ, Rao DS, Ellis B, Kleerekoper M, Parfitt AM. 1988 Mild asymptomatic primary hyperparathyroidism is not a risk factor for vertebral fractures. Ann Intern Med 109:959–962.PubMedGoogle Scholar
  29. 29.
    Melton III LJ, Atkinson EJ, O'Fallon WM, Heath III H. 1992 Risk of age-related fractures in patients with primary hyperparathyroidism. Arch Intern Med 152:2269–2273.PubMedCrossRefGoogle Scholar
  30. 30.
    Kleerekoper M, Peterson E, Nelson D, et al. 1989 Identification of women at risk for developing postmenopausal osteoporosis with vertebral compression fractures: role of history and single photon absorptiometry. Bone Miner 7:171–186.PubMedCrossRefGoogle Scholar
  31. 31.
    Johnson BE, Lucasey B, Robinson RG, Lukert BP. 1989 Contributing diagnoses in osteoporosis. Arch Intern Med 149:1069–1072.PubMedCrossRefGoogle Scholar
  32. 32.
    Ljunghall S, Pahmer M, Akerstrom G, Wide L. 1983 Diabetes mellitus, glucose tolerance and insulin response to glucose in patients with primary hyperparathyroidism before and after parathyroidectomy. Eur J Clin Invest 13:373–377.PubMedCrossRefGoogle Scholar
  33. 33.
    Bannon MP, vanHeerden JA, Palumbo PJ, Ilstrup DM. 1988 The relationship between primary hyperparathyroidism and diabetes mellitus. Ann Surg 207:430–433.PubMedCrossRefGoogle Scholar
  34. 34.
    Silverberg SJ, Bilezikian JP. 2001 Clinical course of primary hyperparathyroidism. In: The Parathyroids. 2nd ed. Bilezikian JP, Marcus R, Levine MA, eds. Academic, San Diego, CA, 387–398.Google Scholar
  35. 35.
    Linos DA, vanHeerden JA, Abboud CF, Edis AJ. 1978 Primary hyperparathyroidism and peptic ulcer disease. Arch Surg 113:384–386.PubMedGoogle Scholar
  36. 36.
    Watson RG, vanHeerden JA, Grant CS, Klee GG. 1984 Postoperative hyperamylasemia, pancreatitis, and primary hyperparathyroidism. Surgery 96:1151–1157.PubMedGoogle Scholar
  37. 37.
    Sitges-Serra A, Alonso M, deLecea C, Gores PF, Sutherland DE. 1988 Pancreatitis and hyperparathyroidism. Br J Surg 75:158–160.PubMedCrossRefGoogle Scholar
  38. 38.
    Prinz RA, Aranha GV. 1985 The association of primary hyperparathyroidism and pancreatitis. Am Surg 51:325–329.PubMedGoogle Scholar
  39. 39.
    vanLanschot JJ, Bruining HA. 1984 Primary hyperparathyroidism and pancreatitis. Netherlands J Surg 36:38–41.Google Scholar
  40. 40.
    Paloyan D, Simonowitz D, Paloyan E, Snyder TJ. 1982 Pancreatitis associated with primary hyperparathyroidism. Am Surg 48:366–368.PubMedGoogle Scholar
  41. 41.
    Bess MA, Edis AJ, van Heerden JA. 1980 Hyperparathyroidism and pancreatitis. Chance or a causal association? JAMA 243:246–247.PubMedCrossRefGoogle Scholar
  42. 42.
    Turken SA, Cafferty M, Silverberg SJ, et al. 1989 Neuromuscular involvement in mild, asymptomatic primary hyperparathyroidism. Am J Med 87:553–557.PubMedCrossRefGoogle Scholar
  43. 43.
    Joborn C, Rastad J, Stalberg E, Akerstrom G, Ljunghall S. 1989 Muscle function in patients with primary hyperparathyroidism. Muscle Nerve 12:87–94.PubMedCrossRefGoogle Scholar
  44. 44.
    Wajngot A, Werner S, Granberg PO, Lindvall N. 1980 Occurrence of pituitary adenomas and other neoplastic diseases in primary hyperparathyroidism. Surg Gynecol Obstet 151:401–403.PubMedGoogle Scholar
  45. 45.
    Farr HW, Fahey TJ Jr, Nash AG, Farr CM. 1973 Primary hyperparathyroidism and cancer. Am J Surg 126:539–543.PubMedCrossRefGoogle Scholar
  46. 46.
    Attie JN, Vardhan R. 1993 Association of hyperparathyroidism with nonmedullary thyroid carcinoma: review of 31 cases. Head Neck 15:20–23.PubMedCrossRefGoogle Scholar
  47. 47.
    Kambouris AA, Ansari MR, Talpos GT. 1987 Primary hyperparathyroidism and associated neoplasms. Henry Ford Med J 35:207–210.Google Scholar
  48. 48.
    Wermers RA, Khosla S, Atkinson EJ, Grant CS, Hodgson SF, O'Fallon M, et al. 1998 Survival after the diagnosis of hyperparathyroidism. Am J Med 104:115–122.PubMedCrossRefGoogle Scholar
  49. 49.
    Palmer M, Adami H-O, Bergstrom R, Akerstroom G, Ljunghall S. 1987 Mortality after surgery for primary hyperparathyroidism: a follow-up of 441 patients operated on from 1956 to 1979. Surgery 102:1–7.PubMedGoogle Scholar
  50. 50.
    Hedback G, Tisell L-E, Bengtsson B-A, Hedman I, Oden A. 1990 Premature death in patients operated on for primary hyperparathyroidism. World J Surg 14:829–836.PubMedCrossRefGoogle Scholar
  51. 51.
    Palmer M, Adami H-O, Bergstrom R, Jakobsson S, Akerstrom G, Ljunghall S. 1987 Survival and renal function in persons with untreated hypercalcemia: a population-based cohort study with 14 years of follow-up. Lancet 1:59–62.PubMedCrossRefGoogle Scholar
  52. 52.
    Hedback G, Oden A. 1998 Increased risk of death from primary hyperparathyroidism—an update. Eur J Clin Invest 28:271–276.PubMedCrossRefGoogle Scholar
  53. 53.
    Hedback G, Oden A. 1998 Death risk factor analysis in primary hyperparathyroidism. Eur J Clin Invest 28:1011–1018.PubMedCrossRefGoogle Scholar
  54. 54.
    Ronni-Sivula H, Sivula A. 1985 Long-term effect of surgical treatment on the symptoms of primary hyperparathyroidism. Ann Clin Res 17:141–147.PubMedGoogle Scholar
  55. 55.
    Walgenbach S, Hommel G, Junginger T. 2000 Outcome after surgery for primary hyperparathyroidism: ten-year prospective follow-up study. World J Surg 24:564–569.PubMedCrossRefGoogle Scholar
  56. 56.
    Hedback G, Oden A. 1991 The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 15:399–407.PubMedCrossRefGoogle Scholar
  57. 57.
    Hedback G, Oden A, Tisell L-E. 1995 Parathyroid adenoma weight and the risk of death after treatment for primary hyperparathyroidism. Surgery 117:134–139.PubMedCrossRefGoogle Scholar
  58. 58.
    Hedback G, Oden A. 1999 Survival of patients operated on for primary hyperparathyroidism (letter). Surgery 125:240–241.PubMedGoogle Scholar
  59. 59.
    Bilezikian JP, Meng X, Shi Y, Silverberg SJ, 2000 Primary hyperparathyroidism in women: New York and Beijing (A Tale of Two Cities). Int J Fertil Women's Health 45:158–165.Google Scholar
  60. 60.
    Mithal A, Bandeira F, Meng X, Silverberg S, Shi Y, Mishra SK. et al. 2001 Primary hyperparathyroidism in India, Brazil and China. In: The Parathyroids. 2nd ed. Bilezikian JP, Marcus R, Levine MA, eds. Academic, San Diego, CA, 375–386.Google Scholar
  61. 61.
    Silverberg SJ Shane E, Dempster DW, Bilezikian JP. 1999 Vitamin D insufficiency in primary hyperparathyroidism. Am J Med 107:561–567.PubMedCrossRefGoogle Scholar
  62. 62.
    Scholz DA, Purnell DC. 1981 Asymptomatic primary hyperparathyroidism. Mayo Clinic Proc 56:473–478.Google Scholar
  63. 63.
    Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP, 1999 The natural history of treated and untreated asymptomatic primary hyperparathyroidism: a ten year prospective study. N Engl J Med 341:1249–1255.PubMedCrossRefGoogle Scholar
  64. 64.
    Parisien M, Dempster DW, Shane E, Bilezikian JP. 2001 Histomorphometric analysis of bone in primary hyperparathyroidism. In: The Parathyroids, 2nd ed. Bilezikian JP, Marcus, R, Levine M, eds. Academic, San Diego, CA, 423–436.Google Scholar
  65. 66.
    Guo CY, Thomas WER, Al-Dehaimi AW, Assiri AMA, Eastell R. 1996 Longitudinal changes in bone mineral density and bone turnover in women with primary hyperparathyroidism. J Clin Endocrinol Metab 81:3487–3491.PubMedCrossRefGoogle Scholar
  66. 67.
    Tanaka Y, Funahashi H, Imai T, Tominga Y, Takagi H. 1997 Parathyroid function and bone metabolic markers in primary and secondary hyperparathyroidism. Semin Surg Oncol 13:125–133.PubMedCrossRefGoogle Scholar
  67. 68.
    Minisola S, Romagnoli E, Scarnecchia L, et al. 1994 Serum CITP in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery. Eur J Endocrinol 130:587–591.PubMedGoogle Scholar
  68. 69.
    Martin P, Bermann P, Sillet C. 1986 Partially reversible osteopenia after surgery for primary hyperparathyroidism. Arch Intern Med 146:689–691.PubMedCrossRefGoogle Scholar
  69. 70.
    Fuleihan GEH, Moore F Jr, LeBoff MS, Hurwitz S, Gundberg CM, Angell J, et al. 1999 Longitudinal changes in bone density in hyperparathyroidism. J Clin Densitom 2:153–162.CrossRefGoogle Scholar
  70. 71.
    Silverberg SJ, Locker FG, Bilezikian JP. 1996 Vertebral osteopenia: a new indication for surgery in primary hyperparathyroidism. J Clin Endocrinol Metab 81:4007–4012.PubMedCrossRefGoogle Scholar
  71. 72.
    Deaconson TF, Wilson SD, Lemann J. 1987 The effect of parathyroidectomy on the recurrence of nephrolithiasis. Surgery 215:241–251.Google Scholar
  72. 73.
    Kaplan RA, Snyder WH, Stewart A, et al. 1976 Metabolic effects of parathyroidectomy in asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab 42:415–426.PubMedGoogle Scholar
  73. 74.
    Brown GG, Preisman RC, Kleerekoper MD. 1987 Neurobehavioral symptoms in mild primary hyperparathyroidism: related to hypercalcemia but not improved by parathyroidectomy. Henry Ford Med J 35:211–215.Google Scholar
  74. 75.
    Cogan MG, Covey CM, Arieff AI, Wisniewski A, Clark OH. 1978 Central nervous system manifestations of hyperparathyroidism. Am J Med 65:963–970.PubMedCrossRefGoogle Scholar
  75. 76.
    Joborn C, Hetta J, Lind J, Rastad J, Akerstrom G, Ljunghall S. 1989 Self-rated psychiatric symptoms in patients operated on because of primary hyperparathyroidism and in patients with longstanding mild hypercalcemia. Surgery 105:72–78.PubMedGoogle Scholar
  76. 77.
    Solomon BL, Schaaf M, Smallridge RC. 1994 Psychologic symptoms before and after parathyroid surgery. Am J Med 96:101–106.PubMedCrossRefGoogle Scholar
  77. 78.
    Jones DB, Jones JH, Lloyd HJ, Lucas PA, Wilkins WE, Walker DA. 1983 Changes in blood pressure and renal function after parathyroidectomy in primary hyperparathyroidism. Postgrad Med J 59:350–353.PubMedGoogle Scholar
  78. 79.
    Bradley EL III, Wells JO. 1983 Primary hyperparathyroidism and hypertension. Am Surg 49:569–570.PubMedGoogle Scholar
  79. 80.
    Rapado A. 1986 Arterial hypertension and primary hyperparathyroidism. Am J Nephrol 6(Suppl I):49–50.PubMedCrossRefGoogle Scholar
  80. 81.
    Dominiczak AF, Lyall F, Morton JJ, et al. 1990 Blood pressure, left ventricular mass and intracellular calcium in primary hyperparathyroidism. Clin Sci 78:127–132.PubMedGoogle Scholar
  81. 82.
    Diamond TW, Botha JR, Wing J, Meyers AM, Kalk WJ. 1986 Parathyroid hypertension. A reversible disorder. Arch Intern Med 146:1709–1712.PubMedCrossRefGoogle Scholar
  82. 83.
    Broulik PD, Horky K, Pacovsky V. 1985 Blood pressure in patients with primary hyperparathyroidism before and after parathyroidectomy. Exp Clin Endocrinol 86:346–352.PubMedCrossRefGoogle Scholar
  83. 84.
    Ringe JD. 1984 Reversible hypertension in primary hyperparathyroidism pre- and postoperative blood pressur in 75 cases. Klin Wochenschr 62:465–469.PubMedCrossRefGoogle Scholar
  84. 85.
    Stefenelli T, Mayr H, Bergler-Klein J, Globits S, Woloszezuk W, Niederle B. 1993 Primary hyperparathyroidism: incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy. Am J Med, 95:197–202.PubMedCrossRefGoogle Scholar

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© Humana Press Inc. 2002

Authors and Affiliations

  1. 1.Department of Medicine College of Physicians and SurgeonsColumbia UniversityNew York

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