Skip to main content
SpringerLink
Log in

Das familiäre Nebenschilddrüsenkarzinom

Indikation zur prophylaktischen Parathyreoidektomie?

Prophylactic parathyroidectomy for familial parathyroid carcinoma

  • Leitthema
  • Published:
Der Chirurg Aims and scope Submit manuscript

Zusammenfassung

Im Gegensatz zum primären Hyperparathyreoidismus (pHPT) sind Nebenschilddrüsenkarzinome (NSD-Ca) sehr selten. Bei Patienten mit einem Hyperparathyreoidismus-Jaw-Tumor (HPT-JT-)Syndrom, welches durch Keimbahnmutationen in HRPT2 verursacht wird, muss in 10–15% der Patienten mit der Entstehung eines NSD-Ca gerechnet werden. In der vorliegenden Übersicht werden die klinischen und molekulargenetischen Angaben von knapp 100 Patienten aus der Literatur sowie 3 eigenen Patienten zusammengefasst. Leider treten die typischen Osteofibrome (Jaw-Tumor), welche eine frühzeitige Diagnose ermöglichen könnten, erst relativ spät sowie in nur ca. 30% der Patienten auf. In ca. 80% liegt eine Eindrüsenerkrankung vor. Eine generelle Empfehlung zur prophylaktischen Parathyreoidektomie kann derzeit nicht gegeben werden, ein engmaschiges Screening der Betroffenen ist indiziert. Wichtig ist, dass auch bei vermeintlich sporadischem NSD-Ca in bis zu 20% Keimbahnmutationen in HRPT2 nachgewiesen wurden, d.h., dass Patienten mit einem NSD-Ca auf eine entsprechende Mutation hin untersucht werden sollten.

Abstract

In contrast to primary hyperparathyroidism, parathyroid carcinoma is a rare disease. In patients with hyperparathyroidism jaw tumor (HPT-JT) syndrome, caused by germline mutations in HRPT2, the development of parathyroid carcinoma is estimated to be 10–15%. This review summarizes the clinical and molecular genetic data of about 100 patients in the literature and three of our own cases. Unfortunately, osteofibromas, which might enable timely diagnosis of HPT-JT syndrome, occur in only about 30% of patients; about 80% have uniglandular disease. Based on the current data, a general recommendation to perform prophylactic parathyroidectomy cannot be given. However, thorough screening of patients at risk is mandatory. Of note in patients thought to have sporadic parathyroid carcinoma, germline HRPT2 mutations are found in up to 20%. Hence, any patient with parathyroid carcinoma should undergo HRPT2 mutation analysis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Abb. 1
Abb. 2

Literatur

  1. Adami S, Marcocci C, Gatti D (2002) Epidemiology of primary hyperparathyroidism in Europe. J Bone Miner Res 17 Suppl 2: N18–23

    Google Scholar 

  2. Brandi ML, Falchetti A (2004) Genetics of primary hyperparathyroidism. Urol Int 72 Suppl 1:11–16

    Article  Google Scholar 

  3. Brandi ML, Gagel RF, Angeli A et al. (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671

    Article  PubMed  Google Scholar 

  4. Carling T, Szabo E, Bai M et al. (2000) Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor. J Clin Endocrinol Metab 85:2042–2047

    Article  PubMed  Google Scholar 

  5. Carling T, Udelsman R (2005) Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med 257:27–37.#

    Article  PubMed  Google Scholar 

  6. Carpten JD, Robbins CM, Villablanca A et al. (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32:676–680

    Article  PubMed  Google Scholar 

  7. Cavaco BM, Guerra L, Bradley KJ et al. (2004) Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene. J Clin Endocrinol Metab 89:1747–1752

    Article  PubMed  Google Scholar 

  8. Cetani F, Pardi E, Borsari S et al. (2004) Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 89:5583–5591

    Article  PubMed  Google Scholar 

  9. Cetani F, Pardi E, Giovannetti A et al. (2002) Genetic analysis of the MEN1 gene and HPRT2 locus in two Italian kindreds with familial isolated hyperparathyroidism. Clin Endocrinol (Oxf) 56:457–464

    Google Scholar 

  10. Chandrasekharappa SC, Guru SC, Manickam P et al. (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407

    Article  PubMed  Google Scholar 

  11. Chen JD, Morrison C, Zhang C, Kahnoski K, Carpten JD, Teh BT (2003) Hyperparathyroidism-jaw tumour syndrome. J Intern Med 253:634–642

    Article  PubMed  Google Scholar 

  12. Chen Q, Kaji H, Nomura R, Sowa H et al. (2003) Trial to predict malignancy of affected parathyroid glands in primary hyperparathyroidism. Endocr J 50:527–534

    Article  PubMed  Google Scholar 

  13. Dinnen JS, Greenwoood RH, Jones JH, Walker DA, Williams ED (1977) Parathyroid carcinoma in familial hyperparathyroidism. J Clin Pathol 30:966–975

    PubMed  Google Scholar 

  14. Dionisi S, Minisola S, Pepe J, De Geronimo S, Paglia F, Memeo L, Fitzpatrick LA (2002) Concurrent parathyroid adenomas and carcinoma in the setting of multiple endocrine neoplasia type 1: presentation as hypercalcemic crisis. Mayo Clin Proc 77:866–869

    PubMed  Google Scholar 

  15. Donis-Keller H, Dou S, Chi D et al. (1993) Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Hum Mol Genet 2:851–856

    PubMed  Google Scholar 

  16. Dralle H, Sekulla C, Haerting J et al. (2004) Risk factors of paralysis and functional outcome after recurrent laryngeal nerve monitoring in thyroid surgery. Surgery 136:1310–1322

    Article  PubMed  Google Scholar 

  17. Eng C, Clayton D, Schuffenecker I et al. (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276:1575–1579

    Article  PubMed  Google Scholar 

  18. Fujikawa M, Okamura K, Sato K, Mizokami T, Tamaki K, Yanagida T, Fujishima M (1998) Familial isolated hyperparathyroidism due to multiple adenomas associated with ossifying jaw fibroma and multiple uterine adenomyomatous polyps. Eur J Endocrinol 138:557–561

    Article  PubMed  Google Scholar 

  19. Fuleihan Gel H (2002) Familial benign hypocalciuric hypercalcemia. J Bone Miner Res 17 Suppl 2: N51–56

    Google Scholar 

  20. Gertner ME, Kebebew E (2004) Multiple endocrine neoplasia type 2. Curr Treat Options Oncol 5:315–325

    PubMed  Google Scholar 

  21. Gibril F, Schumann M, Pace A, Jensen RT (2004) Multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome: a prospective study of 107 cases and comparison with 1009 cases from the literature. Medicine (Baltimore) 83:43–83

    Google Scholar 

  22. Gimm O (2001) Multiple endocrine neoplasia type 2: clinical aspects. Front Horm Res 28:103–130

    PubMed  Google Scholar 

  23. Hamill J, Maoate K, Beasley SW, Corbett R, Evans J (2002) Familial parathyroid carcinoma in a child. J Paediatr Child Health 38:314–317

    Article  PubMed  Google Scholar 

  24. Haven CJ, Wong FK, van Dam EW et al. (2000) A genotypic and histopathological study of a large Dutch kindred with hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 85:1449–1454

    Article  PubMed  Google Scholar 

  25. Heath DA (2000) Familial hypocalciuric hypercalcemia. Rev Endocr Metab Disord 1:291–296

    Article  PubMed  Google Scholar 

  26. Hendy GN (2000) Molecular mechanisms of primary hyperparathyroidism. Rev Endocr Metab Disord 1:297–305

    Article  PubMed  Google Scholar 

  27. Hobbs MR, Pole AR, Pidwirny GN et al. (1999) Hyperparathyroidism-jaw tumor syndrome: the HRPT2 locus is within a 0.7-cM region on chromosome 1q. Am J Hum Genet 64:518–525

    Article  PubMed  Google Scholar 

  28. Howell VM, Haven CJ, Kahnoski K et al. (2003) HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 40:657–663

    Article  PubMed  Google Scholar 

  29. Howell VM, Zori RT, Stalker HJ et al. (2004) A molecular diagnosis of hyperparathyroidism-jaw tumor syndrome in an adolescent with recurrent kidney stones. J Pediatr 145:567

    Article  PubMed  Google Scholar 

  30. Hundahl SA, Fleming ID, Fremgen AM, Menck HR (1999) Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985–1995: a National Cancer Data Base Report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 86:538–544

    Article  PubMed  Google Scholar 

  31. Iacobone M, Lumachi F, Favia G (2004) Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol 88:223–228

    Article  PubMed  Google Scholar 

  32. Jackson CE, Norum RA, Boyd SB, Talpos GB, Wilson SD, Taggart RT, Mallette LE (1990) Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. Surgery 108:1006–1012; discussion 1012–1003

    PubMed  Google Scholar 

  33. Jenkins PJ, Satta MA, Simmgen M et al. (1997) Metastatic parathyroid carcinoma in the MEN2A syndrome. Clin Endocrinol (Oxf) 47:747–751

    Google Scholar 

  34. Jorde R, Bonaa KH, Sundsfjord J (2000) Primary hyperparathyroidism detected in a health screening. The Tromso study. J Clin Epidemiol 53:1164–1169

    Article  PubMed  Google Scholar 

  35. Kakinuma A, Morimoto I, Nakano Y et al. (1994) Familial primary hyperparathyroidism complicated with Wilms‘ tumor. Intern Med 33:123–126

    PubMed  Google Scholar 

  36. Kassem M, Kruse TA, Wong FK, Larsson C, Teh BT (2000) Familial isolated hyperparathyroidism as a variant of multiple endocrine neoplasia type 1 in a large Danish pedigree. J Clin Endocrinol Metab 85:165–167

    Article  PubMed  Google Scholar 

  37. Kleinpeter KP, Lovato JF, Clark PB, Wooldridge T, Norman ES, Bergman S, Perrier ND (2005) Is parathyroid carcinoma indeed a lethal disease? Ann Surg Oncol 12:260–266

    Article  PubMed  Google Scholar 

  38. Koea JB, Shaw JH (1999) Parathyroid cancer: biology and management. Surg Oncol 8:155–165

    Article  PubMed  Google Scholar 

  39. Levin KE, Galante M, Clark OH (1987) Parathyroid carcinoma versus parathyroid adenoma in patients with profound hypercalcemia. Surgery 101:649–660

    PubMed  Google Scholar 

  40. Moon SD, Park JH, Kim EM et al. (2005) A Novel IVS2–1G>A mutation causes aberrant splicing of the HRPT2 gene in a family with hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 90:878–883

    Article  PubMed  Google Scholar 

  41. Mulligan LM, Kwok JBJ, Healey CS et al. (1993) Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363:458–460

    Article  PubMed  Google Scholar 

  42. Obara T, Fujimoto Y (1991) Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg 15:738–744

    Article  PubMed  Google Scholar 

  43. Poisson A, Zablewska B, Gaudray P (2003) Menin interacting proteins as clues toward the understanding of multiple endocrine neoplasia type 1. Cancer Lett 189:1-10

    Article  PubMed  Google Scholar 

  44. Rosen IB, Palmer JA (1981) Fibroosseous tumors of the facial skeleton in association with primary hyperparathyroidism: an endocrine syndrome or coincidence? Am J Surg 142:494–498

    Article  PubMed  Google Scholar 

  45. Rubello D, Casara D, Dwamena BA, Shapiro B (2001) Parathyroid carcinoma. A concise review. Minerva Endocrinol 26:59–64

    PubMed  Google Scholar 

  46. Sandelin K, Auer G, Bondeson L, Grimelius L, Farnebo LO (1992) Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg 16:724–731

    Article  PubMed  Google Scholar 

  47. Schuffenecker I, Virally-Monod M, Brohet R et al. (1998) Risk and penetrance of primary hyperparathyroidism in multiple endocrine neoplasia type 2A families with mutations at codon 634 of the RET proto-oncogene. Groupe D’etude des Tumeurs a Calcitonine. J Clin Endocrinol Metab 83:487–491

    Article  PubMed  Google Scholar 

  48. Shattuck TM, Valimaki S, Obara T et al. (2003) Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349:1722–1729

    Article  PubMed  Google Scholar 

  49. Silverberg SJ, Bilezikian JP (1996) Evaluation and management of primary hyperparathyroidism. J Clin Endocrinol Metab 81:2036–2040

    Article  PubMed  Google Scholar 

  50. Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, Marx SJ (2002) Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore) 81:1-26

    Google Scholar 

  51. Simonds WF, Robbins CM, Agarwal SK, Hendy GN, Carpten JD, Marx SJ (2004) Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 89:96–102

    Article  PubMed  Google Scholar 

  52. Streeten EA, Weinstein LS, Norton JA et al. (1992) Studies in a kindred with parathyroid carcinoma. J Clin Endocrinol Metab 75:362–366

    Article  PubMed  Google Scholar 

  53. Teh BT, Esapa CT, Houlston R et al. (1998) A family with isolated hyperparathyroidism segregating a missense MEN1 mutation and showing loss of the wild-type alleles in the parathyroid tumors. Am J Hum Genet 63:1544–1549

    Article  PubMed  Google Scholar 

  54. Teh BT, Farnebo F, Kristoffersson U et al. (1996) Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas. J Clin Endocrinol Metab 81:4204–4211

    Article  PubMed  Google Scholar 

  55. Teh BT, Farnebo F, Twigg S et al. (1998) Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families. J Clin Endocrinol Metab 83:2114–2120

    Article  PubMed  Google Scholar 

  56. Villablanca A, Calender A, Forsberg L et al. (2004) Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet 41: e32

    Article  PubMed  Google Scholar 

  57. Warner J, Epstein M, Sweet A et al. (2004) Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet 41:155–160

    Article  PubMed  Google Scholar 

  58. Wassif WS, Farnebo F, Teh BT et al. (1999) Genetic studies of a family with hereditary hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol (Oxf) 50:191–196

    Google Scholar 

  59. Wassif WS, Moniz CF, Friedman E et al. (1993) Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer. J Clin Endocrinol Metab 77:1485–1489

    Article  PubMed  Google Scholar 

  60. Weinstein LS, Simonds WF (2003) HRPT2, a marker of parathyroid cancer. N Engl J Med 349:1691–1692

    Article  PubMed  Google Scholar 

  61. Woodard GE, Lin L, Zhang JH, Agarwal SK, Marx SJ, Simonds WF (2005) Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene 24:1272–1276

    Article  PubMed  Google Scholar 

  62. Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA (1992) Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore) 71:197–205

    Google Scholar 

  63. Yamashita K, Suzuki S, Yumita W et al. (2001) A case of familial isolated hyperparathyroidism with ectopic parathyroid cancer. Endocr J 48:453–458

    PubMed  Google Scholar 

  64. Yoshimoto K, Endo H, Tsuyuguchi M et al. (1998) Familial isolated primary hyperparathyroidism with parathyroid carcinomas: clinical and molecular features. Clin Endocrinol (Oxf) 48:67–72

    Google Scholar 

Download references

Interessenkonflikt:

Es besteht kein Interessenkonflikt. Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Author information

Authors and Affiliations

  1. Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg

    O. Gimm, K. Lorenz, P. Nguyen Thanh & H. Dralle

  2. Endokrinologie Klinik für Innere Medizin II, Martin-Luther-Universität Halle-Wittenberg

    U. Schneyer

  3. Klinik für Hals- Nasen- Ohrenheilkunde, Gesichts- und Halschirurgie, Martin-Luther-Universität Halle-Wittenberg

    M. Bloching

  4. Institut für Pathologie, Martin-Luther-Universität Halle-Wittenberg

    U. Krause

  5. Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Australia

    V. M. Howell & D. J. Marsh

  6. Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan, USA

    B. T. Teh

  7. Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle

    O. Gimm

Authors
  1. O. Gimm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Lorenz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Nguyen Thanh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U. Schneyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Bloching
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. M. Howell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. J. Marsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B. T. Teh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. U. Krause
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H. Dralle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. Gimm.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gimm, O., Lorenz, K., Nguyen Thanh, P. et al. Das familiäre Nebenschilddrüsenkarzinom. Chirurg 77, 15–24 (2006). https://doi.org/10.1007/s00104-005-1110-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00104-005-1110-2

Schlüsselwörter

Keywords

Search

Navigation