Indications for parathyroidectomy are indisputable in patients with primary HPT who exhibit clear and classic symptoms or marked hypercalcemia. The value of parathyroidectomy in asymptomatic patients with mild to moderate hypercalcemia has, however, been debated. Studies of the natural history of untreated primary HPT document that rapid increases in the serum calcium level, progression of symptoms or complications, or both is uncommon in patients with borderline hypercalcemia. Less clear is our knowledge about the long-term consequences of somewhat more marked hypercalcemia because no study has yet presented adequate follow-up of such patients for a prolonged period of time. It appears as if many patients with moderately elevated serum calcium levels (<3.0 mmol/L) have symptoms and silent complications of HPT if they are carefully studied. Although rapid progression of hypercalcemia is unusual, serum calcium levels, nevertheless, tend to increase progressively over years of observation in some patients.

This advancing hypercalcemia may be obscured by declining levels of active vitamin D, resulting from dietary deficiency, lack of sun exposure, and impairments of renal function. Because these factors lower serum calcium levels, progression of HPT may not be detected.7-55'56 The impact of such relative vitamin D deficiency may be difficult to determine and may simultaneously be part of the pathogenesis of primary HPT in elderly people.

The natural course of primary HPT is causally related to the genetic and functional abnormalities within the diseased parathyroid tissue. Variable tumor biology and clinical progression may, therefore, depend on heterogeneity of tumor genetics.57 Occasionally, patients' metabolic problems progress rapidly and are then reflected in excessively raised serum calcium values. These patients may have parathyroid tissues that harbor exceptional and critical mutations with oncogene activation or recruitment of growth factors. A PRAD1 oncogene rearrangement has been described in this context and has been associated with the largest parathyroid adenomas, whereas a menin gene abnormality has also been evident in sporadic, mild HPT.58 Rare patients with initially mild hypercalcemia but rapidly advancing disease may have parathyroid carcinoma.40 In addition, stepwise "clinical" progression may occur during observation in patients with primary HPT, possibly representing development of secondary mutations that cause accelerated growth of the tumor. Thus, a history of mild primary HPT has been reported in up to one third of patients with hypercalcemic crisis. Because it is not yet possible to predict whether progressive disease will occur in any patient, extended follow-up is crucial if surgery is deferred in primary HPT.59 60 Younger patients seem to be at greater risk for progressive disease.

The absence of marked progression of complications in most patients with mild primary HPT allows medical surveillance in older persons with borderline hypercalcemia (i.e., with increments of serum calcium to less than 2.75 to 2.85 mmol/L, or 11.0 to 11.4 mg/dL) and in those with associated illnesses. Medical surveillance is probably inappropriate in younger patients and in those with more marked hypercalcemia. Nonoperative management in any circumstance requires that the presence of symptoms or complications be carefully excluded and that precise monitoring of symptoms and metabolic function be done.4 A new consensus statement46 has substantiated a risk for disease progression if patients with HPT are monitored without surgery and therefore issued a general recommendation for parathyroidectomy in patients with serum calcium values raised 0.25 mmol/L above the normal reference.


1. Heath H III, Hodgson SF, Kennedy MA. Primary hyperparathyroidism: Incidence, morbidity, and economic impact in a community. N Engl J Med 1980;302:189.

2. Palmér M, Ljunghall S, Ákerstróm G, et al. Patients with primary hyperparathyroidism operated on over a 24-year period: Temporal trends of clinical and laboratory findings. J Chronic Dis 1987;40:121.

3. Potts JT. Management of asymptomatic hyperparathyroidism. J Clin Endocrinol Metab 1990:70:1489.

4. NIH Consensus Development Conference Panel. Diagnosis and management of asymptomatic primary hyperparathyroidism: Consensus development conference statement. Ann Intern Med 1991:114:593.

5. Nussbaum SR, Potts JT. Immunoassays for parathyroid hormone 1-84 in the diagnosis of hyperparathyroidism. J Bone Miner Res 1991; 6(Suppl 2):43.

6. Ljunghall S, Hellman P, Rastad J, et al. Primary hyperparathyroidism: Epidemiology, diagnosis and clinical picture. World J Surg 1991;15:681.

7. Ákerstróm G, Rudberg C, Grimelius L, et al. Histologic parathyroid abnormalities in an autopsy series. Hum Pathol 1986;17:520.

8. Ákerstróm G, Bergstróm R, Grimelius L, et al. Relation between changes in clinical and histopathological features of primary hyperparathyroidism. World J Surg 1986; 10:696.

9. Wallfelt C, Ljunghall S, Bergstróm R, et al. Clinical characteristics and surgical treatment of sporadic primary hyperparathyroidism. Surgery 1990;107:13.

10. Tominaga Y, Grimelius L, Johansson H, et al. Histological and clinical features of non-familial primary parathyroid hyperplasia. Pathol Res Pract 1992:188:115.

11. Christensson T, Hellstróm K, Wengle B, et al. Prevalence of hypercal-caemia in a health screening in Stockholm. Acta Med Scand 1976;200:131.

12. Groth TL, Ljunghall S, DeVerdier CH. Optimal screening for patients with hyperparathyroidism with use of serum calcium observations: A decision-theoretical analysis. Scand J Clin Lab 1983;43:699.

13. Palmér M, Jakobsson S, Ákerstróm G, et al. Prevalence of hypercalcemia in a health survey: A 14-year follow-up of serum calcium levels. Eur J Clin Invest 1988:18:39.

14. Ljunghall S, Jakobsson S, Joborn C, et al. Longitudinal studies of mild primary hyperparathyroidism. J Bone Miner Res 1991 ;6:S 111.

15. Lundgren E, Rastad J, Thurfjell E, et al. Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Surgery 1997;294:287.

16. Jorde R, B0naa KH, Sundsfjord J. Primary hyperparathyroidism detected in a health screening. The Troms0 Study. J Clin Epidemiol 2000;53:1164.

17. Bilezikian JP, Potts JT Jr. Asymptomatic primary hyperparathyroidism: New issues and new questions—Bridging the past with the future. J Bone Miner Res 2002;17(Suppl 2):N57.

18. Wermers RA, Khosla S, Atkinson EJ, et al. The rise and fall of primary hyperparathyroidism: A population-based study in Rochester, Minnesota, 1965-1992. Ann Intern Med 1997:126:433.

19. Melton LJ. Epidemiology of primary hyperparathyroidism. J Bone Miner Res 1991;6:S25.

20. Ljunghall S, Rastad J, Ákerstróm G. Primary hyperparathyroidism: Prevalence, pathophysiology, pertinent findings and prognosis. In: Heersche JNM, Kanis JA (eds), Bone and Mineral Research 8. New York, Elsevier Science, 1994, p 1.

21. Christensson TAT. Primary hyperparathyroidism-pathogenesis, incidence and natural history. In: Rothmund M, Wells SA Jr (eds), Parathyroid Surgery: Progress in Surgery. Basel, Switzerland, Karger, 1986, p 1.

22. Christensson TAT, Hellström K, Wengle B. Blood pressure in subjects with hypercalcaemia and primary hyperparathyroidism detected in a health screening programme. Eur J Clin Invest 1977;7:109.

23. Palmer M, Adami H-O, Bergström R, et al. Survival and renal function in persons with untreated hypercalcaemia: A population-based cohort study with 14 years of follow-up. Lancet 1987;1:59.

24. Joborn C, Hetta J, Lind L, et al. Self-rated psychiatric symptoms in patients with primary hyperparathyroidism. Surgery 1989:105:72.

25. Joborn C, Hetta J, Johansson H, et al. Psychiatric morbidity in primary hyperparathyroidism. World J Surg 1988;12:476.

26. Lundgren E, Lind L, Palmar M, et al. Increased cardiovascular mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years. Surgery 2001:130:978.

27. Hedbäck G, Odin A. Death risk factor analysis in primary hyperparathyroidism. Eur J Clin Invest 1998;28:1011.

28. Soreide JA, van Heerden JA, Grant CS, et al. Survival after surgical treatment for primary hyperparathyroidism. Surgery 1997:122:1117.

29. Wermers RA, Khosla S, Atkinson EJ, et al. Survival after the diagnosis of hyperparathyroidism: A population-based study. Am J Med 1998:104:115.

30. Purnell DC, Smith LH, Scholz DA, et al. Primary hyperparathyroidism: A prospective clinical study. Am J Med 1971;50:670.

31. Scholz DA, Purnell DC. Asymptomatic primary hyperparathyroidism. Mayo Clin Proc 1981;56:473.

32. Röhl PE, Wilkinsson M, Clifton-Blight P, et al. Hyperparathyroidism: Experiences with treated and untreated patients. Med J Aust 1981; 1:519.

33. Adams PH. Conservative management of primary hyperparathyroidism. J R Coll Phys Lond 1982;16:184.

34. Van't Hoff W, Ballardie FW, Bicknell EJ. Primary hyperparathyroidism: The case for medical management. Br Med J (Clin Res Ed) 1983:287:1605.

35. Paterson CR, Burns J, Mowat E. Long-term follow-up of untreated primary hyperparathyroidism. Br Med J (Clin Res Ed) 1984:289:1261.

36. Corlew DS, Bryda SL, Bradley EL, et al. Observations on the course of untreated primary hyperparathyroidism. Surgery 1985:98:1064.

37. Heath DA, Heath EM. Conservative management of primary hyperparathyroidism. J Bone Miner Res 1991 ;6:S 117.

38. Rubinoff H, McCarthy N, Hiatt RA. Hypercalcemia: Long-term follow-up with matched controls. J Chronic Dis 1983:36:859.

39. Posen S, Clifton-Bligh P, Reeve TS, et al. Is parathyroidectomy of benefit in primary hyperparathyroidism? Q J Med 1985:215:241.

40. Corsello SM, Folli G, Crucitti F, et al. Acute complications in the course of "mild" hyperparathyroidism. J Endocrinol Invest 1991:14:971.

41. Rao DS, Wilson RJ, Kleerekoper M, et al. Lack of biochemical progression or continuation of accelerated bone loss in mild asymptomatic primary hyperparathyroidism: Evidence for biphasic disease course. J Clin Endocrinol Metab 1988:67:1294.

42. Parfitt AM, Rao DS, Kleerekoper M. Asymptomatic primary hyperparathyroidism discovered by multichannel biochemical screening: Clinical course and considerations bearing on the need for surgical intervention. J Bone Miner Res 1991;6:S97.

43. Rudnicki M, Transb0l I. Increasing parathyroid hormone concentrations in untreated primary hyperparathyroidism. J Intern Med 1992:232:421.

44. Silverberg SJ, Shane E, Jacobs T, et al. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 1999:341:1249.

45. Lafferty FW, Hubay CA. Primary hyperparathyroidism. A review of the long-term surgical and nonsurgical morbidities as a basis for a rational approach to treatment. Arch Intern Med 1989:149:789.

46. Bilezikian JP, Potts JT Jr, El-Hajj Fuleihan G, et al. Summary statement from a Workshop on Asymptomatic Primary Hyperparathyroidism: A perspective for the 21st century. J Clin Endocrinol Metab 2002:87:5353.

47. Mitlak BH, Daly M, Potts JT Jr, et al. Asymptomatic primary hyperparathyroidism. J Bone Miner Res 1991;6:S 103.

48. Davies M. Current therapy. Primary hyperparathyroidism: Aggressive or conservative treatment? Clin Endocrinol (Oxf) 1992:36:325.

49. Nagant de Deuxchaisnes C, Devogelaer JP, Huaux JP. Long-term followup of untreated primary hyperparathyroidism. Br Med J (Clin Res Ed) 1985:290:64.

50. Vestergaard P, Mollerup CL, Geds0 Fr0kjaer V, et al. Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ 2000:321:598.

51. Vestergaard P, Mosekilde L. Fractures in patients with primary hyperparathyroidism: Nationwide follow-up study of 1201 patients. World J Surg 2003 ;27:343.

52. Heath H III. Clinical spectrum of primary hyperparathyroidism: Evolution with changes in medical practice and technology. J Bone Miner Res 1991;6:S63.

53. Hedback G, Tisell L-E, Bengtsson B-A, et al. Premature death in patients operated on for primary hyperparathyroidism. World J Surg 1990;14:829.

54. Hedback G, Oden A, Tisell L-E. The influence of surgery on the risk of death in patients with primary hyperparathyroidism. World J Surg 1991; 15:399.

55. Turner G, Brown RC, Silver A, et al. Renal insufficiency and secondary hyperparathyroidism in elderly patients. Ann Clin Biochem 1991;28:321.

56. Siperstein AE, Shen W, Chan AK, et al. Normocalcemic hyperparathyroidism: Biochemical and symptom profiles before and after surgery. Arch Surg 1992;127:1157.

57. Arnold A. Genetic basis of endocrine disease 5. Molecular genetics of parathyroid gland neoplasia. J Clin Endocrinol Metab 1993;77:1108.

58. Carling T, Correa P, Hessman O, et al. Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism. J Clin Endocrinol Metab 1998;83:2960.

59. Sarfati E, Desportes L, Gossot D, et al. Acute primary hyperparathyroidism. Br J Surg 1989;76:979.

60. Bondeson A-G, Bondeson L, Thompson NW. Clinicopathological peculiarities in parathyroid disease with hypercalcaemic crisis. Eur J Surg 1993:159:613.

Get The Body Of Your Dreams

Get The Body Of Your Dreams

Everybody wants to lose weight. This is one fact that is supported by the countless weight loss programs on the market along with the numerous weight loss products, ranging from snack bars, powdered juices, shakes and even slimming soaps and lotions.

Get My Free Ebook

Post a comment