Skip to main content
SpringerLink
Log in

Familial Hyperparathyroidism: Multiple Endocrine Neoplasia Types II and I; Familial Hypocalciuric Hypercalcemia; Hyperparathyroidism-Jaw Tumor Syndrome

  • Chapter
  • First Online:
Medical and Surgical Treatment of Parathyroid Diseases

  • 1019 Accesses

Abstract

Familial hyperparathyroidism occurs in a handful of genetic syndromes including Multiple Endocrine Neoplasia (MEN) type 1 and 2A, Familial Hypocalciuric Hypercalcemia (FHH), and Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT). MEN 1 is characterized by a loss of function in the tumor suppressor gene, Menin, whereas MEN 2 is characterized by a gain of function mutation in the RET proto-oncogene. FHH is characterized by mutations that alter the calcium-sensing receptor in the kidney and parathyroid glands, resulting in mild hypercalcemia and elevated PTH levels. HPT-JT is characterized by hereditary predisposition to jaw tumors and benign and malignant tumors of the parathyroids. All four syndromes are autosomal dominant, with variable penetrance of degree of clinical hyperparathyroidism. Each of these disorders requires careful evaluation, diagnostic testing, genetic analysis, and potentially, surgical management.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pieterman CR, Schreinemakers JM, Koppeschaar HP, et al. Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of genetic screening on clinical outcome. Clin Endocrinol (Oxf). 2009;70(4):575–81. Clinical Investigation; Level 2; Grade B.

    Article  CAS  Google Scholar 

  2. Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276(5311):404–7. Basic Science; Level 2; Grade B.

    Article  CAS  PubMed  Google Scholar 

  3. Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013;38(8):394–402. Basic Science; Level 2; Grade B.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dreijerink KM et al. Breast-cancer predisposition in multiple endocrine neoplasia type 1. N Engl J Med. 2014;371(6):583–4. Clinical Review; Level 1; Grade C.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011. Clinical Review; Level 2; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  6. Eller-Vainicher C, Chiodini I, Battista C, et al. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res. 2009;24(8):1404–10. Clinical Review; Level 2; Grade A-B.

    Article  PubMed  Google Scholar 

  7. Marx SJ, Menczel J, Campbell G, et al. Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf). 1991;35:521–6. Clinical Investigation; Level 2; Grade C.

    Article  CAS  Google Scholar 

  8. Rizzoli R, Green 3rd J, Marx SJ. Primary hyperparathyroidism in familial multiple endocrine neoplasia type I. Long-term follow-up of serum calcium levels after parathyroidectomy. Am J Med. 1985;78(3):467–74. Population/Observational Study; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  9. Lairmore TC, Piersall L, DeBenedetti M, et al. Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg. 2004;239(5):645–47. Clinical Investigation; Level 2; Grade C.

    Article  Google Scholar 

  10. Sugg SL, Krzywda EA, Demeure MJ, et al. Detection of multiple gland primary hyperparathyroidism in the era of minimally invasive parathyroidectomy. Surgery. 2004;136:1303–9. Population/Observational Study; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  11. Wells Jr SA, Famdon JR, Dale JK, et al. Long term evaluation of patients with primary parathyroid hyperplasia managed by total parathyroidectomy and heterotopic autotransplantation. Ann Surg. 1980;192(4):451–8. Population/Observational Study; Level 3; Grade A-B.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Prinz RA, Gamvros OI, Sellu D, et al. Subtotal parathyroidectomy for primary chief cell hyperplasia in the multiple endocrine neoplasia type I syndrome. Ann Surg. 1981;193(1):26–9. Population/Observational Study; Level 3; Grade A-B.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Van Heerden JA, Kent 3rd RB, Sizemore GW, et al. Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes: surgical experience. Arch Surg. 1983;118(5):533–6. Population/Observational Study; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  14. Kraimps JL, Duh QY, Demeure M, et al. Hyperparathyroidism in multiple endocrine neoplasia syndrome. Surgery. 1992;112(6):1080–8. Population/Observational Study; Level 3; Grade A-B.

    CAS  PubMed  Google Scholar 

  15. Hellman P, Skogseid B, Juhlin C, et al. Findings and long term results of parathyroid surgery in multiple endocrine neoplasia type 1. World J Surg. 1992;16(4):718–22. Population/Observational Study; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  16. Hellman P, Skogseid B, Oberg K, et al. Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1. Surgery. 1998;124(6):993–9. Population/Observational Study; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  17. Dotzenrath C, Cupisti K, Goretzki PE, et al. Long-term biochemical results after operative treatment of primary hyperparathyroidism associated with multiple endocrine neoplasia types I and IIa: is a more or less extended operation essential? Eur J Surg. 2001;167(3):173–8. Population/Observational Study; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  18. Goudet P, Cougard P, Verges B, et al. Hyperparathyroidism in multiple endocrine neoplasia type I: surgical trends and results of a 256-patient series from Groupe D’etude des Neoplasies Endocriniennes Multiples Study Group. World J Surg. 2001;25(7):886–90. Population/Observational Study; Level 3; Grade A.

    Article  CAS  PubMed  Google Scholar 

  19. Arnalsteen LC, Alesina PF, Quiereux JL, et al. Long-term results of less than total parathyroidectomy for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery. 2002;132(6):1119–24. Population/Observational Study; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  20. Schreinemakers JM, Pieterman CR, Scholten A, et al. The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg. 2011;35(9):1993–2005. Clinical Review; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  21. Tonelli F et al. Is total parathyroidectomy the treatment of choice for hyperparathyroidism in multiple endocrine neoplasia type 1? Ann Surg. 2007;246(6):1075–82. Population/Observational Study; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  22. Tonelli F, Marcucci T, Fratini G, et al. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy. Clinics (Sao Paulo). 2012;67 Suppl 1:155–60. Clinical Review; Level 3; Grade A-B.

    Article  Google Scholar 

  23. Lairmore TC, Govednik CM, Quinn CE, et al. A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery. 2014;156(6):1326–34. Clinical Investigation; Level 1; Grade B.

    Article  PubMed  Google Scholar 

  24. Cohen MS, Dilley WG, Wells Jr SA, et al. Long-term functionality of cryopreserved parathyroid autografts: a 13-year prospective analysis. Surgery. 2005;138(6):1033–40. Clinical Investigation; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  25. Wells Jr SA, Asa SL, Dralle H, et al. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. Clinical Review; Level 3; Grade A-B.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Maruyama S, Iwashita T, Imai T, et al. Germ line mutations of the ret proto-oncogene in Japanese patients with multiple endocrine neoplasia type 2A and type 2B. Jpn J Cancer Res. 1994;85(9):879–82. Clinical Investigation; Level 2; Grade B.

    Article  CAS  PubMed  Google Scholar 

  27. Raue F, Frank-Raue K, Grauer A. Multiple endocrine neoplasia type 2. Clinical features and screening. Endocrinol Metab Clin North Am. 1994;23(1):137–56. Clinical Review; Level 3; Grade A-B.

    CAS  PubMed  Google Scholar 

  28. Durante C, Romagnoli E, Maranghi M, et al. Hyperparathyroidism in multiple endocrine neoplasia type II A. Clin Cases Miner Bone Metab. 2006;3(2):162–6. Clinical Review; Level 3; Grade A-B.

    Google Scholar 

  29. Skinner MA, Moley JF, Dilley W, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353(11):1105–13. Clinical Investigation; Level 2; Grade B.

    Article  CAS  PubMed  Google Scholar 

  30. Machens A, Niccoli-Sire P, Hoegel J, et al. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med. 2003;349(16):1517–25. Clinical Investigation; Level 2; Grade B.

    Article  CAS  PubMed  Google Scholar 

  31. Gagel RF, Tashjian AH, Cummings T, et al. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med. 1988;318(8):478–84. Clinical Investigation; Level 2; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  32. O’Riordain DS, O’Brien T, Grant CS, et al. Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2. Surgery. 1993;114(6):1031–7. Population/Observational Study; Level 3; Grade A-B.

    PubMed  Google Scholar 

  33. Moley JF, Skinner M, Gillanders WE, et al. Management of parathyroid glands during preventive thyroidectomy in patients with multiple endocrine neoplasia type 2. Ann Surg. 2015;262(4):641–6. Clinical Investigation; Level 2; Grade A-B.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Szabó J, Heath B, Hill VM, et al. Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31. Am J Hum Genet. 1995;56(4):944–50. Basic Science; Level 2; Grade A-B.

    PubMed  PubMed Central  Google Scholar 

  35. Carpten JD, Robbins CM, Villablanca A, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. Dec 2002;32(4):676–80. Basic Science; Level 2; Grade A.

    Google Scholar 

  36. Marx SJ, Simonds WF, Agarwal SK, et al. Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res. 2002;17 Suppl 2:N37–43. Clinical Review; Level 3; Grade A-B.

    CAS  PubMed  Google Scholar 

  37. Masi G, Barzon L, Iacobone M, et al. Clinical, genetic and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer. 2008;15(4):1115–26. Basic Science; Level 2; Grade B.

    Article  CAS  PubMed  Google Scholar 

  38. Hannan FM, Nesbit MA, Christie PT, et al. Familial isolated primary hyperparathyroidism caused by mutations of the MEN1 gene. Nat Clin Pract Endocrinol Metab. 2008;4(1):53–8. Clinical Investigation; Level 4.

    Article  CAS  PubMed  Google Scholar 

  39. Thakker RV. Genetics of endocrine and metabolic disorders: parathyroid. Rev Endocr Metab Disord. 2004;5(1):37–51. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  40. Jackson CE. Hereditary hyperparathyroidms associated with recurrent pancreatitis. Ann Intern Med. 1958;49(4):829–36. Clinical Investigation; Level 4.

    Article  CAS  PubMed  Google Scholar 

  41. Pavlovic S, Valyi-Nagy T, Profirovic J, David O. Fine-needle aspiration of brown tumor of bone: cytologic features with radiologic and histologic correlation. Diagn Cytopathol. 2009;37(2):136–9. Clinical Investigation; Level 2; Grade A-B.

    Article  PubMed  Google Scholar 

  42. Teh BT, Farnebo F, Kristoffersson U, et al. Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of wild type allele in renal hamartomas. J Clin Endocrinol Metab. 1996;81(12):4204–11. Clinical Investigation; Level 2; Grade A-B.

    CAS  PubMed  Google Scholar 

  43. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med. 2000;343(25):1863–75. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  44. Sharretts JM, Simonds WF. Clinical and molecular genetics of parathyroid neoplasms. Best Pract Res Clin Endocrinol Metab. 2010;24(3):491–502. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shattuck TM, Välimäki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349(18):1722–9. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  46. Cetani F, Pardi E, Borsari S, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab. 2004;89(11):5583–91. Clinical Investigation; Level 2; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  47. Tan MH, Teh BT. Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome. Curr Mol Med. 2004;4(8):895–7. Clinical Investigation; Level 4.

    Article  CAS  PubMed  Google Scholar 

  48. Bradley KJ, Hobbs MR, Buley ID, et al. Uterine tumors are a phenotypic manifestation of hyperparathyroidism-jaw tumour syndrome. J Intern Med. 2005;257(1):18–26. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  49. Carling T, Udelsman R. Parathyroid tumors. Curr Treat Options Oncol. 2003;4(4):319–28. Clinical Review; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  50. Sarquis MS, Silveira LG, Pimenta FJ, et al. Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations. Surgery. 2008;143(5):630–40. Clinical Investigation; Level 2; Grade B.

    Article  PubMed  Google Scholar 

  51. Christensen SE, Nissen PH, Vestergaard P, Mosekilde L. Familial hypocalciuric hypercalcaemia: a review. Curr Opin Endocrinol Diabetes Obes. 2011;18(6):359–70. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  52. Heath 3rd H, Jackson CE, Otterud B, Leppert MF. Genetic linkage analysis in familial benign (hypocalciuric) hypercalcemia: evidence for locus heterogeneity. Am J Hum Genet. 1993;53(1):193–200. Basic Science; Level 2; Grade B.

    PubMed  PubMed Central  Google Scholar 

  53. Lloyd SE, Pannett AA, Dixon PH, Whyte MP, Thakker RV. Localization of familial benign hypercalcemia, Oklahoma variant (FBHOk), to chromosome 19q13. Am J Hum Genet. 1999;64(1):189–95. Basic Science; Level 2; Grade B.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Brown EM, Hebert SC. Calcium-receptor-regulated parathyroid and renal function. Bone. 1997;20(4):303–9. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  55. Brown EM. Clinical lessons from the calcium-sensing receptor. Nat Clin Pract Endocrinol Metab. 2007;3(2):122–33. Clinical Review; Level 3; Grade A-B.

    Article  CAS  PubMed  Google Scholar 

  56. Heath 3rd H. Familial benign (hypocalciuric) hypercalcaemia: a troublesome mimic of mild primary hyperparathyroidism. Endocrinol Metab Clin North Am. 1989;18(3):723–40. Clinical Investigation; Level 3; Grade A-B.

    PubMed  Google Scholar 

  57. Law Jr WM, Heath 3rd H. Familial benign hypercalcaemia (hypocalciuric hypercalcaemia): clinical and pathogenetic studies in 21 families. Ann Intern Med. 1985;102:511–9. Clinical Investigation; Level 3; Grade A-B.

    Article  PubMed  Google Scholar 

  58. Pasieka JL, Andersen MA, Hanley DA. Familial benign hypercalcaemia: hypercalciuria and hypocalciuria in affected members of a small kindred. Clin Endocrinol (Oxf). 1990;33(4):429–33. Clinical Investigation; Level 3; Grade A-B.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Gayan S. De Silva M.D. & Terry C. Lairmore M.D.

  2. Section of Endocrine and Oncologic Surgery, Department of Surgery, Washington University School of Medicine, Box 8109, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Jeffrey F. Moley M.D.

Authors
  1. Gayan S. De Silva M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Terry C. Lairmore M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeffrey F. Moley M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey F. Moley M.D. .

Editor information

Editors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Brendan C. Stack, Jr.

  2. Department of Geniatrics and Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Donald L. Bodenner

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

De Silva, G.S., Lairmore, T.C., Moley, J.F. (2017). Familial Hyperparathyroidism: Multiple Endocrine Neoplasia Types II and I; Familial Hypocalciuric Hypercalcemia; Hyperparathyroidism-Jaw Tumor Syndrome. In: Stack, Jr., B., Bodenner, D. (eds) Medical and Surgical Treatment of Parathyroid Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-26794-4_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26794-4_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26792-0

  • Online ISBN: 978-3-319-26794-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation