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Primary hyperparathyroidism: pathophysiology, differential diagnosis and management

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Diagnosis and Management of Endocrine-related Tumors

Part of the book series: Cancer Treatment and Research ((CTAR,volume 20))

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Abstract

The routine availability of serum calcium screening in both hospitals and the physician’s office has produced a dramatic increase in the apparent prevalence of primary hyperparathyroidism [1, 2]. This growth in recognition has stimulated a number of additional questions concerning the pathogenesis, criteria for diagnosis and management of such patients, particularly those with asymptomatic disease [3]. The physiologic abnormalities that characterize primary hyperparathyroidism as well as other disorders in which hypercalcemia is found can best be understood in relation to the multiple advances in our knowledge of the biochemistry and physiology of bone and the calcium-regulating hormones in the past two decades. The introduction to this discussion of hyperparathyroidism will concentrate, therefore, on aspects of normal calcium homeostasis and the biochemistry and physiology of the hormones which will be helpful in understanding the clinical disorders.

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References

  1. Heath H III, Hodgson SF, Kennedy MA: Primary hyperparathyroidism. Incidence, morbidity and potential economic impact in a community. N Engl J Med 302: 189–193, 1980.

    Article  PubMed  Google Scholar 

  2. Mundy GR., Cove DH, Fisken R: Primary hyperparathyroidism: changes in the pattern of clinical presentation. Lancet 1: 1317–1320, 1980.

    Article  PubMed  CAS  Google Scholar 

  3. Frame B, Potts JT Jr. (eds): Clinical Disorders of Bone and Mineral Metabolism. Amsterdam: Excerpta Medica, 1983, pp 129–168.

    Google Scholar 

  4. Copp DH: Comparative endocrinology of calcitonin. In: Handbook of Physiology, Sect. 7, Aurbach GD (ed). American Physiological Society, Washington, D.C. 7: 431, 1976.

    Google Scholar 

  5. Schneider AB, Sherwood LM: Calcium homeostasis, and the pathogenesis and management of hypercalcemic disorders. Metabolism 23: 975–1007, 1974.

    Article  PubMed  CAS  Google Scholar 

  6. De Luca HF, Schnoes HK: Metabolism and action of vitamin D. Annu Rev Biochem 45: 631–636, 1976.

    Article  Google Scholar 

  7. De Luca H, Schnoes HK: Vitamin D: Recent Advances. Annu Rev Biochem 52: 411–440, 1983.

    Article  Google Scholar 

  8. Lindgärd F, Zettervall O: Characterization of a calcium-binding IgC myeloma protein. Scand J Immunol 3: 277–285, 1974.

    Article  Google Scholar 

  9. Rodman JS, Sherwood LM: Disorders of mineral metabolism in malignancy. In: Metabolic Bone Disease Vol. II, Avioli LV, Krane SM (eds). New York: Academic Press, 1978, p 555–631.

    Google Scholar 

  10. Phang JM, Weiss IW: Maintenance of calcium homeostasis in human beings. In: Handbook of Physiology, sect. 7, Aurbach GD (ed). American Physiological Society, Washington, D.C., 7:157, 1976.

    Google Scholar 

  11. Talmage RV, Meyer RA Jr: Physiological role of parathyroid hormone. In: Handbook of Physiology, sect. 7, Aurbach GD (ed). American Physiological Society, Washington, D.C. 7:343, 1976.

    Google Scholar 

  12. Potts JT Jr, Kronenberg HM, Rosenblatt M: Parathyroid hormone: chemistry, biosynthesis and mode of action. Adv Protein Chem 35: 323–396, 1982.

    Article  PubMed  CAS  Google Scholar 

  13. Cohn DV, MacGregor RR: The biosynthesis, intracellular processing, and secretion of parathormone. Endocr Rev 2: 1–26, 1981.

    Article  PubMed  CAS  Google Scholar 

  14. Abe M, Sherwood LM: Regulation of parathyroid hormone secretion by adenyl cyclase. Biochem Biophys Res Commun 48: 396, 1972.

    Article  PubMed  CAS  Google Scholar 

  15. Brown EM, Gardner DG, Windeck RA, Aurbach GD: Relationship of intracellular cAMP accumulation to parathyroid hormone release from dispersed bovine parathyroid cells. Endocrinology 103: 2323–2333, 1978.

    Article  PubMed  CAS  Google Scholar 

  16. Hanley DA, Takatsuki K, Birnbaumer M, Schneider AB, Sherwood LM: In vitro perifusion for the study of parathyroid hormone secretion. Calcif Tissue Int 32: 19–27, 1980.

    Article  PubMed  CAS  Google Scholar 

  17. Takatsuki K, Hanley DA, Schneider AB, Sherwood LM: The effects of magnesium ion on parathyroid hormone secretion in vitro. Calcif Tissue Int 32: 201–206, 1980.

    Article  PubMed  CAS  Google Scholar 

  18. Davis BM, Pfefferbaum A, Krutzik S, Davis K: Lithium effect on parathyroid hormone. Am J Psychiat 138: 489–492, 1981.

    PubMed  CAS  Google Scholar 

  19. Canterbury JM, Lerman S, Claflin AJ, Henry H, Norman AW, Reiss E: Inhibition of parathyroid hormone secretion by 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol in the dog. J Clin Invest 61: 1375, 1978.

    Article  PubMed  CAS  Google Scholar 

  20. Chertow BS, Baker GR, Henry HL, Norman AW: Effects of vitamin D metabolites on bovine parathyroid hormone release in vitro. Am J Physiol 238: 384, 1980.

    Google Scholar 

  21. Golden P, Greenwalt A, Martin K, Bellorin-Font E, Mazey R, Klahr S, Slatopolsky E: Lack of a direct effect of 1,25-dihydroxycholecalciferol on parathyroid hormone secretion by normal bovine parathyroid glands. Endocrinology 107: 602, 1980

    Article  PubMed  CAS  Google Scholar 

  22. Wecksler WR, Henry HL, Norman AW: Studies on the mode of action of calciferol subcellular localization of 1,25-dihydroxy-vitamin D3 in chicken parathyroid glands. Arch Biochem Biophys 183:168, 1977.

    Article  PubMed  CAS  Google Scholar 

  23. Wecksler WR, Ross FP, Mason RS, Posen S, Norman AW: Biochemical properties of the 1α,25-dihydroxyvitamin D3 cytoplasmic receptor from human and chick parathyroid glands. Arch Biochem Biophys 201:95, 1980.

    Article  PubMed  CAS  Google Scholar 

  24. Kemper B, Habener JF, Rich A, Potts JT, Jr: Parathyroid secretory protein: Discovery of a major calcium-dependent protein. Science 184: 167–168, 1974.

    Article  PubMed  CAS  Google Scholar 

  25. Sherwood LM, Takatsuki K, Porat A, Shin KY, Jackimek A: Parathyroid secretory protein: Intracellular concentration and release by calcium. Clin Res 29: 579A, 1981.

    Google Scholar 

  26. Bhargava G, Russell J, Sherwood LM: Phosphorylation of parathyroid secretory protein. Proc Natl Acad Sci USA 80: 878–881, 1983

    Article  PubMed  CAS  Google Scholar 

  27. Martin KJ, Hruska KA, Freitag JJ, Klahr S, Slatopolsky E: The peripheral metabolism of parathyroid hormone. N Engl J Med 301: 1092–1098, 1979.

    Article  PubMed  CAS  Google Scholar 

  28. Raisz LG, Kream BE: Regulation of bone formation. N Engl J Med 309: 29–35, 1983.

    Article  PubMed  CAS  Google Scholar 

  29. DeLuca HF: The vitamin D system in the regulation of calcium and phosphorus metabolism. Nutr Rev 37: 161–193, 1979.

    Article  PubMed  CAS  Google Scholar 

  30. Norman AW, Roth J, Orci L: The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins). Endocr Rev 3: 331–366, 1982.

    Article  PubMed  CAS  Google Scholar 

  31. Sherwood LM: The relative importance of parathyroid hormone and calcitonin in calcium homeostasis. N Engl J Med 278: 663–669, 1968.

    Article  PubMed  CAS  Google Scholar 

  32. Mallette LE, Bilezikian JP, Heath DA, Aurbach GD: Primary hyperparathyroidism: clinical and biochemical features. Medicine (Baltimore) 53: 127–146, 1974.

    Article  PubMed  CAS  Google Scholar 

  33. Lloyd HM: Primary hyperparathyroidism: an analysis of the role of the parathyroid tumors. Medicine (Baltimore) 47: 53–71, 1968.

    Article  PubMed  CAS  Google Scholar 

  34. Rao SD, Frame B, Miller MJ, Kleerekoper M, Block MA, Parfitt AM: Hyperparathyroidism following head and neck irradiation. Arch Intern Med 140: 205–207,1980.

    Article  PubMed  CAS  Google Scholar 

  35. Katz A, Braunstein GD: Clinical, biochemical and pathologic features of radiation-associated hyperparathyroidism. Arch Intern Med 143: 79–82, 1983.

    Article  PubMed  CAS  Google Scholar 

  36. Fialkow PJ, Jackson CE, Block MA, Greenwald KA: Multicellular origin of parathyroid adenomas. N Engl J Med 297: 696–698, 1977.

    Article  PubMed  CAS  Google Scholar 

  37. Brown EM, Brennan MF, Hurwitz S, Windek R, Marx SJ, Spiegel AM, Koehler JO, Gardner DG, Aurbach GD: Dispersed cells prepared from human parathyroid glands: Distinct calcium sensitivity of adenomas vs primary hyperplasia. J Clin Endocrinol Metab 46: 267–276, 1978.

    Article  PubMed  CAS  Google Scholar 

  38. Birnbaumer ME, Schneider AB, Palmer D, Hanley DA, Sherwood LM: Secretion of parathyroid hormone by abnormal human parathyroid glands in vitro. J Clin Endocrinol Metab 45: 105–113, 1977.

    Article  PubMed  CAS  Google Scholar 

  39. Tibblins S, Palsson N, Rydberg J: Hyperparathyroidism in the elderly. Ann Surg 197: 135–138, 1983.

    Article  Google Scholar 

  40. Mowschenson PM, Rosenbergs S, Pallotta J, Silen W: Effect of hyperparathyroidism and hypercalcemia on lower esophageal sphincter pressure. Am J Surg 153: 36–39, 1982.

    Article  Google Scholar 

  41. Paloyan D, Simowowitz D, Paloyan E, Snyder TJ: Pancreatitis associated with primary hyperparathyroidism. Ann Surg 48: 366–368, 1982.

    CAS  Google Scholar 

  42. Gardner EC, Jr, Hersh T: Primary hyperparathyroidism and the gastrointestinal tract. South Med J 74: 197–199, 1981.

    Article  PubMed  Google Scholar 

  43. Parks J, Coe F, Favus M: Hyperparathyroidism and nephrolithiasis. Arch Intern Med 140:1479–1481, 1980.

    Article  PubMed  CAS  Google Scholar 

  44. Daniels J, Goodman AD: Hypertension and hyperparathyroidism Relation of serum phosphate level and blood pressure. Am J Med 75: 17–23, 1983.

    Article  PubMed  CAS  Google Scholar 

  45. Klimiuk PS, Davies M, Adams PH: Primary hyperparathyroidism and thiazide diuretics. Postgrad Med J 57: 80–83, 1981.

    Article  PubMed  CAS  Google Scholar 

  46. Stewart AF, Horst R, Deftos LJ, Cadman EE, Lang R, Broadus AE: Biochemical evaluation of patients with cancer-associated hypercalcemia: Evidence for humoral and non-humoral groups. N Engl J Med 303: 1377–1382, 1980.

    Article  PubMed  CAS  Google Scholar 

  47. Sherwood LM: The multiple causes of hypercalcemia in malignancy. N Engl J Med 303: 1412–1413, 1980.

    Article  PubMed  CAS  Google Scholar 

  48. Marx SJ, Spiegel AM, Levine MA, Rizzoli RE, Lasker RD, Santara AC, Downs RW Jr, Aurbach GD: Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia. N Engl J Med 307: 416–426, 1982.

    Article  PubMed  CAS  Google Scholar 

  49. Eisenberg H, Pallotta J, Sherwood LM: Selective arteriography, venography and venous hormone assay in diagnosis and localization of parathyroid lesions. Am J Med 56: 810–817, 1974.

    Article  PubMed  CAS  Google Scholar 

  50. Sommer B, Walter HF, Spelsberg F, Scherer U, Lissner J: Computed tomography for localizing enlarged parathyroid glands in primary hyperparathyroidism. J Comput Assist Tomog 6: 521–526, 1982.

    Article  CAS  Google Scholar 

  51. Stark DD, Moss AA, Gooding GA, Clark H: Parathyroid scanning by computed tomography. Radiology 148: 297–299, 1983.

    PubMed  CAS  Google Scholar 

  52. Reading CC, Charboneau JW, James EM, Karsell PR, Purnell DC, Grant CS, Van Heerden JA: High resolution parathyroid sonography. Am J Radiol 139: 539–546, 1982.

    CAS  Google Scholar 

  53. Stanbury WE: Vitamin D and hyperparathyroidism: Lumleian Lecture 1981. J R Coll Phys (London) 15: 205–217, 1981.

    CAS  Google Scholar 

  54. Slatopolsky E, Rutherford WE, Hoffsten FH, Elkan IO, Butcher HR, Bricker NS: Nonsuppressible secondary hyperparathyroidism in chronic progressive renal disease. Kidney Int 1: 38, 1972.

    Article  PubMed  CAS  Google Scholar 

  55. David DS, Sakai S, Brenne BL, Riggio RA, Cheigh J, Stenzel KH, Rubin AL, Sherwood LM: Hypercalcemia after renal transplantation: Long-term follow-up data. N Engl J Med 289: 398, 1973.

    Article  PubMed  CAS  Google Scholar 

  56. Marx SJ, Attie MF, Spiegel AM, Levine MA, Lasker RD, Fox M: An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds. N Engl J Med 306: 257–264, 1982.

    Article  PubMed  CAS  Google Scholar 

  57. Marx SJ, Spiegel AM, Brown EM, Aurbach GD: Family studies in patients with primary parathyroid hyperplasia. Am J Med 62: 698–706, 1977.

    Article  PubMed  CAS  Google Scholar 

  58. Scholz DA, Purnell DC: Asymptomatic primary hyperparathyroidism. Ten year prospective study. Mayo Clinic Proc 56: 473–478, 1981.

    CAS  Google Scholar 

  59. Bilezikian JP: The medical management of primary hyperparathyroidism. Ann Intern Med 96: 198–202, 1982.

    PubMed  CAS  Google Scholar 

  60. Russell CF, Edis AJ: Surgery for primary hyperparthyroidism: experience with 500 consecutive cases and evaluation of the role of surgery in the asymptomatic patient. Br J Surg 69: 244–247, 1982.

    Article  PubMed  CAS  Google Scholar 

  61. LJunghal S, Akerström G, Rudberg C, Selking O, Johansson H, Wide L.: Treatment with Cimetidine in patients with primary hyperparathyroidism. Acta Endocrinol 99: 546–550, 1982.

    Google Scholar 

  62. LJunghal S, Rudberg C, Akerström G, Wide L: Effects of beta adrenergic blockade on serum parathyroid hormone in normal subjects and patients with primary hyperparathyroidism. Acta Med Scand 211: 27–30, 1982.

    Article  Google Scholar 

  63. Broadus AE, Magee JS, Mallette LE, Horst RL, Lang R, Jensen PS, Gertner JM, Baron R: A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. J Clin Endocrinol Metab 56: 953–961, 1983.

    Article  PubMed  CAS  Google Scholar 

  64. Mundy GR, Wilkinsen R, Heath DA: Comparative study of available medical therapy for hypercalcemia of malignancy. Am J Med 74: 421–432, 1983.

    Article  PubMed  CAS  Google Scholar 

  65. Wang CA, Castleman B, Cope O: Surgical management of hyperparathyroidism due to primary hyperplasia. Ann Surg 195: 384–392, 1982.

    Article  PubMed  CAS  Google Scholar 

  66. Brennan MF, Marx SJ, Doppman J, Costa J, Saxe A, Spiegel A, Krudy A, Aurbach G: Results of reoperation for persistent and recurrent hyperparathyroidism. Ann Surg 194: 671–676, 1981.

    Article  PubMed  CAS  Google Scholar 

  67. Wells SA Jr, Ellis GJ, Gunnels JC, Schneider AB, Sherwood LM: Parathyroid autotransplantation in primary parathyroid hyperplasia. N Engl J Med 295: 57–63, 1976.

    Article  PubMed  Google Scholar 

  68. Saxe AW, Brennan MF: Reoperative parathyroid surgery for primary hyperparathyroidism caused by multiple gland disease: total parathyroidectomy and autotransplantation with cryopreserved tissue. Surgery 91: 616–621, 1982.

    PubMed  CAS  Google Scholar 

  69. Anderberg B, Gillquist J, Larsson L, Lundstrom B: Complications to subtotal parathyroidectomy. Acta Chir Scand 147: 109–13, 1981.

    PubMed  CAS  Google Scholar 

  70. Doppman JL: The treatment of hyperparthyoidism by transcatheter techniques. Cardiovasc Intervent Radiol 3: 268–276, 1980.

    Article  PubMed  CAS  Google Scholar 

  71. Sherwood LM: Idopathic hypercalciuria: A ‘mixed bag’ of stones. J Lab Clin Med 90: 951–952, 1977.

    PubMed  CAS  Google Scholar 

  72. Bell NH, Stern PH, Pantzer E, Sinha TK, DeLuca HF: Evidence that increased circulating lα,25 dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest 64: 218–225, 1979.

    Article  PubMed  CAS  Google Scholar 

  73. Shai F, Baker RK, Addrizzo JR, Wallach S: Hypercalcemia in mycobacterial infection. J Clin Endocrinol 34: 251–256, 1972.

    Article  CAS  Google Scholar 

  74. Braman SS, Goldman AL, Scharz MI: Steroid-responsive hypercalcemia in disseminated boned tuberculosis. Arch Intern Med 132: 269–271, 1973.

    Article  PubMed  CAS  Google Scholar 

  75. Lee JC, Catanzaro A, Parthemore JG, Roach B, Deftos LJ: Hypercalcemia in disseminated coccidioidomycosis. N Engl J Med 297: 431–433, 1977.

    Article  PubMed  CAS  Google Scholar 

  76. Silver J, Shvil Y, Fainavu M: Vitamin D transport in an infant with vitamin D toxicity. Br Med J 2: 93–94, 1978.

    Article  PubMed  CAS  Google Scholar 

  77. Strewler GJ, Williams RD, Nissenson RH: Human renal carcinoma cells produce hypercalcemia in the nude mouse and a novel protein recognized by parathyroid hormone receptors. J Clin Invest 71: 769–774, 1983.

    Article  PubMed  CAS  Google Scholar 

  78. Parfitt AM, Dent CE: Hyperthyroidism and hypercalcaemia. Q J Med 39: 171–187,1970.

    PubMed  CAS  Google Scholar 

  79. Walser M, Robinson BHB, Duckett JW: The hypercalcemia of adrenal insufficiency. J Clin Invest 42: 456–465, 1963.

    Article  PubMed  CAS  Google Scholar 

  80. Popovtzer MM, Subryan VL, Alfrey AC, Reeve EB, Schrier RW: The acute effect of chlorothiazide on serum-ionized calcium: Evidence for a parathyroid hormone-dependent mechanism. J Clin Invest 55: 1295–1302,1975.

    Article  PubMed  CAS  Google Scholar 

  81. Lerman S, Canterbury JM, Reiss E: Parathyroid hormone and the hypercalcemia of immobilization. J Clin Endocrinol Metab 45: 425–428, 1977.

    Article  PubMed  CAS  Google Scholar 

  82. Frame B, Jackson CE, Reynolds WA, Ymphrey JE: Hypercalcemia and skeletal effects in chronic hypervitaminosis A. Ann Intern Med 80: 44–48, 1974.

    PubMed  CAS  Google Scholar 

  83. de Torrente A, Berl T, Cohn PD, Kawamoto E, Hertz P, Schrier RW: Hypercalcemia of acute renal failure. Am J Med 61: 119–123, 1976.

    Article  PubMed  Google Scholar 

  84. Koffer A, Friedler RM, Massry SG: Acute renal failure due to nontraumatic rhabdomyolysis. Ann Intern Med 85: 23–28, 1976.

    Google Scholar 

  85. Shane E, Baquiran DC, Bilezikian JP: Effects of dichloromethylene diphosphonate on serum and urinary calcium in primary hyperparathyroidism. Ann Intern Med 95: 23–27, 1981.

    PubMed  CAS  Google Scholar 

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Authors
  1. Justin Silver
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  2. Louis M. Sherwood
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Editors and Affiliations

  1. Division of Endocrinology, The Milton S. Hershey Medical Center, The Pennsylvania State University, 17033, P.O. Box 850, Hershey, PA, USA

    Richard J. Santen M.D. (Professor of Medicine, Chief) & Andrea Manni M.D. (Associate Professor of Medicine) (Professor of Medicine, Chief) &  (Associate Professor of Medicine)

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© 1984 Martinus Nijhoff Publishers, Boston

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Silver, J., Sherwood, L.M. (1984). Primary hyperparathyroidism: pathophysiology, differential diagnosis and management. In: Santen, R.J., Manni, A. (eds) Diagnosis and Management of Endocrine-related Tumors. Cancer Treatment and Research, vol 20. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2849-0_8

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  • DOI: https://doi.org/10.1007/978-1-4613-2849-0_8

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