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Four-Gland Exploration Versus Focused Parathyroidectomy for Hyperparathyroidism Jaw Tumor Syndrome

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Book cover Difficult Decisions in Endocrine Surgery

Part of the book series: Difficult Decisions in Surgery: An Evidence-Based Approach ((DDSURGERY))

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Abstract

Primary hyperparathyroidism, a common endocrine disorder, is associated with familial disease in about 10% of cases. These syndromes include multiple endocrine neoplasia types 1, 2A and 4 (MEN1, MEN2A, MEN4), familial isolated hyperparathyroidism (FIHP), and the hyperparathyroidism jaw tumor (HPT-JT) syndrome. HPT-JT syndrome, an autosomal dominant disease with incomplete penetrance, results from a germline inactivating mutation in the HRPT2 gene. HPT-JT manifests with about 20% of patients having multiple enlarged parathyroid glands and/or parathyroid carcinoma. Furthermore, 28% of patients will have a recurrence during follow-up. Since these patients have a high rate of multiple enlarged parathyroid glands, parathyroid carcinoma, and recurrence, it is controversial as to what is the optimal initial surgical approach for parathyroidectomy. Clinical evidence for the optimal initial surgical approach for HPT-JT syndrome is limited to case series and retrospective small cohort studies. Furthermore, there is scant data on the clinical utility of localization studies to select the optimal operative approach. Only one study reported the results of localization studies and showed a lack of benefit due to high rates of multigland disease that would have been missed if a focused parathyroidectomy approach was used. Given the high rates of multigland disease, parathyroid carcinoma, risk of recurrence, and the possibility of missing additional enlarged glands not seen on preoperative localizing studies, bilateral neck exploration with identification of all four glands and removal of enlarged glands would be the best surgical approach given our current knowledge.

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References

  1. Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 2002;32(4):676–80. PMID: 12434154.

    Article  PubMed  CAS  Google Scholar 

  2. Bradley KJ, Hobbs MR, Buley ID, Carpten JD, Cavaco BM, Fares JE, et al. Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J Intern Med. 2005;257(1):18–26. PMID: 15606373.

    Article  PubMed  CAS  Google Scholar 

  3. Korpi-Hyovalti E, Cranston T, Ryhanen E, Arola J, Aittomaki K, Sane T, et al. CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma. J Clin Endocrinol Metab. 2014;99(9):3044–8. PMID: 24823466. PMCID: 4207936.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D, Hess D, et al. The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol. 2005;25(12):5052–60. PMID: 15923622. PMCID: 1140601.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Masi G, Barzon L, Iacobone M, Viel G, Porzionato A, Macchi V, et al. Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Carcinoma. 2008;15(4):1115–26. PMID: 18755853.

    Article  CAS  Google Scholar 

  6. Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349(18):1722–9. PMID: 14585940.

    Article  PubMed  CAS  Google Scholar 

  7. Howell VM, Haven CJ, Kahnoski K, Khoo SK, Petillo D, Chen J, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet. 2003;40(9):657–63. PMID: 12960210. PMCID: 1735580.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Simonds WF, Robbins CM, Agarwal SK, Hendy GN, Carpten JD, Marx SJ. Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab. 2004;89(1):96–102. PMID: 14715834.

    Article  PubMed  CAS  Google Scholar 

  9. Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, 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. PMID: 15531515.

    Article  PubMed  CAS  Google Scholar 

  10. Villablanca A, Calender A, Forsberg L, Hoog A, Cheng JD, Petillo D, et al. Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet. 2004;41(3):e32. PMID: 14985403. PMCID: 1735713.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Cavaco BM, Guerra L, Bradley KJ, Carvalho D, Harding B, Oliveira A, et al. Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene. J Clin Endocrinol Metab. 2004;89(4):1747–52. PMID: 15070940.

    Article  PubMed  CAS  Google Scholar 

  12. Howell VM, Zori RT, Stalker HJ, Williams C, Jesse N, Nelson AE, et al. A molecular diagnosis of hyperparathyroidism-jaw tumor syndrome in an adolescent with recurrent kidney stones. J Pediatr. 2004;145(4):567. PMID: 15480389.

    Article  PubMed  Google Scholar 

  13. Gimm O, Lorenz K, Nguyen Thanh P, Schneyer U, Bloching M, Howell VM, et al. Das familiare Nebenschilddrusenkarzinom Indikation zur prophylaktischen Parathyreoidektomie? [Prophylactic parathyroidectomy for familial parathyroid carcinoma]. Chirurg. 2006;77(1):15–24. PMID: 16418876.

    Article  PubMed  CAS  Google Scholar 

  14. Moon SD, Park JH, Kim EM, Kim JH, Han JH, Yoo SJ, et al. 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. 2005;90(2):878–83. PMID: 15613436.

    Article  PubMed  CAS  Google Scholar 

  15. Mizusawa N, Uchino S, Iwata T, Tsuyuguchi M, Suzuki Y, Mizukoshi T, et al. Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol. 2006;65(1):9–16. PMID: 16817812.

    Article  CAS  Google Scholar 

  16. Aldred MJ, Talacko AA, Savarirayan R, Murdolo V, Mills AE, Radden BG, et al. Dental findings in a family with hyperparathyroidism-jaw tumor syndrome and a novel HRPT2 gene mutation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(2):212–8. PMID: 16448924.

    Article  PubMed  Google Scholar 

  17. Bradley KJ, Cavaco BM, Bowl MR, Harding B, Cranston T, Fratter C, et al. Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol. 2006;64(3):299–306. PMID: 16487440.

    Article  CAS  Google Scholar 

  18. Juhlin C, Larsson C, Yakoleva T, Leibiger I, Leibiger B, Alimov A, et al. Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Carcinoma. 2006;13(2):509–23. PMID: 16728578.

    Article  CAS  Google Scholar 

  19. Guarnieri V, Scillitani A, Muscarella LA, Battista C, Bonfitto N, Bisceglia M, et al. Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for carcinoma surveillance. J Clin Endocrinol Metab. 2006;91(8):2827–32. PMID: 16720667.

    Article  PubMed  CAS  Google Scholar 

  20. Kelly TG, Shattuck TM, Reyes-Mugica M, Stewart AF, Simonds WF, Udelsman R, et al. Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res. 2006;21(10):1666–71. PMID: 16995822.

    Article  CAS  PubMed  Google Scholar 

  21. Yamashita Y, Akiyama T, Mizusawa N, Yoshimoto K, Goto M. A case of hyperparathyroidism-jaw tumour syndrome found in the treatment of an ossifying fibroma in the maxillary bone. Int J Oral Maxillofac Surg. 2007;36(4):365–9. PMID: 17052894.

    Article  CAS  PubMed  Google Scholar 

  22. Cetani F, Pardi E, Ambrogini E, Viacava P, Borsari S, Lemmi M, et al. Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation. Endocr Relat Carcinoma. 2007;14(2):493–9. PMID: 17639062.

    Article  CAS  Google Scholar 

  23. Cetani F, Ambrogini E, Viacava P, Pardi E, Fanelli G, Naccarato AG, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol. 2007;156(5):547–54. PMID: 17468190.

    Article  CAS  PubMed  Google Scholar 

  24. Raue F, Haag C, Frank-Raue K. Hyperparathyreoidismus-Kiefertumor-Syndrom. Eine hereditare Form des primaren Hyperparathyreoidismus mit Nebenschilddrusenkarzinom [Hyperparathyroidism-jaw tumor syndrome. A hereditary form of primary hyperparathyroidism with parathyroid carcinoma]. Dtsch Med Wochenschr. 2007;132(27):1459–62. PMID: 17583828.

    Article  CAS  PubMed  Google Scholar 

  25. Cetani F, Pardi E, Ambrogini E, Banti C, Viacava P, Borsari S, et al. Hyperparathyroidism 2 gene (HRPT2, CDC73) and parafibromin studies in two patients with primary hyperparathyroidism and uncertain pathological assessment. J Endocrinol Investig. 2008;31(10):900–4. PMID: 19092296.

    Article  CAS  Google Scholar 

  26. Sarquis MS, Silveira LG, Pimenta FJ, Dias EP, Teh BT, Friedman E, 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. PMID: 18436011.

    Article  PubMed  Google Scholar 

  27. Guarnieri V, Bisceglia M, Bonfitto N, Cetani F, Marcocci C, Minisola S, et al. Re: Familial hyperparathyroidism: surgical outcome after 30 years of follow-up in three families with germline HRPT2 mutations. Surgery. 2008;144(5):839–40. PMID: 19081034.

    Article  PubMed  Google Scholar 

  28. Howell VM, Gill A, Clarkson A, Nelson AE, Dunne R, Delbridge LW, et al. Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab. 2009;94(2):434–41. PMID: 19017757.

    Article  PubMed  CAS  Google Scholar 

  29. Iacobone M, Masi G, Barzon L, Porzionato A, Macchi V, Ciarleglio FA, et al. Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred. Langenbeck’s Arch Surg. 2009;394(5):817–25. PMID: 19529956.

    Article  Google Scholar 

  30. Mehta A, Patel D, Rosenberg A, Boufraqech M, Ellis RJ, Nilubol N, et al. Hyperparathyroidism-jaw tumor syndrome: Results of operative management. Surgery. 2014;156(6):1315–24. Discussion 24–5. PMID: 25444225. PMCID: 4255585.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nilubol N, Weinstein L, Simonds WF, Jensen RT, Phan GQ, Hughes MS, et al. Preoperative localizing studies for initial parathyroidectomy in MEN1 syndrome: is there any benefit? World J Surg. 2012;36(6):1368–74. PMID: 22350475.

    Article  PubMed  Google Scholar 

  32. Gimm O, Lorenz K, Nguyen Thanh P, et al. Das Familiäre Nebenschilddrüsenkarzinom. Indikation zur prophylaktischen Parathyreoidektomie? Chirurg. 2006;77:15–24. PMID: 16418876.

    Article  PubMed  CAS  Google Scholar 

  33. Rekik N, Ben Naceur B, Mnif M, Mnif F, Mnif H, Boudawara T, et al. Hyperparathyroidism-jaw tumor syndrome: a case report. Ann Endocrinol (Paris). 2010;71(2):121–6. PMID: 19942209. Epub 2009/11/28. eng.

    Article  CAS  Google Scholar 

  34. Panicker LM, Zhang JH, Dagur PK, Gastinger MJ, Simonds WF. Defective nucleolar localization and dominant interfering properties of a parafibromin L95P missense mutant causing the hyperparathyroidism-jaw tumor syndrome. Endocr Relat Carcinoma. 2010;17(2):513–24. PMID: 20304979. PMCID: 3098453. Epub 2010/03/23. eng.

    Google Scholar 

  35. Cavaco BM, Santos R, Felix A, Carvalho D, Lopes JM, Domingues R, et al. Identification of de novo germline mutations in the HRPT2 gene in two apparently sporadic cases with challenging parathyroid tumor diagnoses. Endocr Pathol. 2011;22(1):44–52. PMID: 21360064. Epub 2011/03/02. eng.

    Article  PubMed  CAS  Google Scholar 

  36. Pichardo-Lowden AR, Manni A, Saunders BD, Baker MJ. Familial hyperparathyroidism due to a germline mutation of the CDC73 gene: implications for management and age-appropriate testing of relatives at risk. Endocr Pract. 2011;17(4):602–9. PMID: 21324824. Epub 2011/02/18. eng.

    Article  PubMed  Google Scholar 

  37. Domingues R, Tomaz RA, Martins C, Nunes C, Bugalho MJ, Cavaco BM. Identification of the first germline HRPT2 whole-gene deletion in a patient with primary hyperparathyroidism. Clin Endocrinol. 2012;76(1):33–8. PMID: 21790700. Epub 2011/07/28. eng.

    Article  CAS  Google Scholar 

  38. Bricaire L, Odou MF, Cardot-Bauters C, Delemer B, North MO, Salenave S, et al. Frequent large germline HRPT2 deletions in a French National cohort of patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98(2):E403–8. PMID: 23293331. Epub 2013/01/08. eng.

    Article  PubMed  CAS  Google Scholar 

  39. Kong J, Wang O, Nie M, Shi J, Hu Y, Jiang Y, et al. Familial isolated primary hyperparathyroidism/hyperparathyroidism-jaw tumour syndrome caused by germline gross deletion or point mutations of CDC73 gene in Chinese. Clin Endocrinol. 2014;81(2):222–30. PMID: 24716902.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Dhaval Patel

  2. Department of Surgery, School of Medicine, Stanford University, Stanford, CA, USA

    Electron Kebebew

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  1. Dhaval Patel
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  2. Electron Kebebew
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Correspondence to Electron Kebebew .

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Editors and Affiliations

  1. Department of Surgery and MacLean Center for Clinical Medical Ethics, The University of Chicago, Chicago, IL, USA

    Peter Angelos

  2. Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA

    Raymon H. Grogan

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Patel, D., Kebebew, E. (2018). Four-Gland Exploration Versus Focused Parathyroidectomy for Hyperparathyroidism Jaw Tumor Syndrome. In: Angelos, P., Grogan, R. (eds) Difficult Decisions in Endocrine Surgery. Difficult Decisions in Surgery: An Evidence-Based Approach. Springer, Cham. https://doi.org/10.1007/978-3-319-92860-9_20

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  • DOI: https://doi.org/10.1007/978-3-319-92860-9_20

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