Familial Cancer

, Volume 12, Issue 3, pp 577–580

A complex endocrine conundrum

  • G. Bano
  • V. Siedel
  • N. Beharry
  • P. Wilson
  • T. Cranston
  • S. Hodgson
Short Communication
  • 272 Downloads

Abstract

We describe a case of recurrent primary hyperparathyroidism, manifested as 3 metachronous parathyroid adenomata, in a 50 year-old woman who also had Hashimoto hypothyroidism, gastric gastrointestinal stromal tumour (GIST), cysts in liver and kidneys, 5 intestinal polyps (one of these a villous adenoma), diverticulitis and telangiectasia of lips. She did not have medullary thyroid carcinoma (MTC). Genetic analysis of the CDC73 gene [for Hyperparathyroidism—jaw tumor (HPT-JT)], MEN1 for Multiple Endocrine Neoplasia Type1, CDKN1B for MEN4, SDHB and SDHD for Paraganglioma/Pheochromocytoma susceptibility, VHL for von Hippel-Lindau Syndrome, BMPR1A and SMAD4 for Juvenile Polyposis Syndrome (JPS) (sequencing and MLPA), karyotype and array CGH (44 K) were all normal. She was found to be homozygous for a synonomous germline variant in exon 14 (p. Ser836Ser) of the RET oncogene. This RET variant is of unclear clinical significance, and has been previously reported both in normal individuals and in individuals with MTC. It is unlikely that homozygosity for the RET variant has been casual in the multiple pathologies that our patient has developed.

Keywords

Hyperparathyroidism GIST MTC RET proto oncogene 

References

  1. 1.
    Ruiz A, Antiñolo G, Fernández RM, Eng C, Marcos I, Borrego S (2001) Germline sequence variant S836S in the RET proto-oncogene is associated with low level predisposition to sporadic medullary thyroid carcinoma in the Spanish population. Clin Endocrinol 55:399–402CrossRefGoogle Scholar
  2. 2.
    Machens A, Spitschak A, Lorenz K, Pützer BM, Dralle H (2011) Germline RET sequence variation I852M and occult medullary thyroid cancer: harmless polymorphism or causative mutation? Clin Endocrinol 75:801–805CrossRefGoogle Scholar
  3. 3.
    Machens A, Frank-Raue K, Lorenz K, Rondot S, Raue F, Dralle H (2012) Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer. Clin Endocrinol 76:691–697CrossRefGoogle Scholar
  4. 4.
    Baumgartner-Parzer SM, Lang R, Wagner L, Heinze G, Niederle B, Kaserer K, Waldhäusl W, Vierhapper H (2005) Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma? J Clin Endocrinol Metabol 90:6232–6236CrossRefGoogle Scholar
  5. 5.
    Costa P, Domingues R, Sobrinho LG, Bugalho MJ (2005) RET polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population. Endocrine 27:239–243PubMedCrossRefGoogle Scholar
  6. 6.
    Siqueira DR, Romitti M, da Rocha AP, Ceolin L, Meotti C, Estivalet A, Puñales MK, Maia AL (2010) The RET polymorphic allele S836S is associated with early metastatic disease in patients with hereditary or sporadic medullary thyroid carcinoma. Endocr Relat Cancer 17:953–963PubMedCrossRefGoogle Scholar
  7. 7.
    Pai R, Arun Nehru G, Samuel P, Paul MJ, Thomas N, Premkumar JA, Hephzibah J, Shanthyl N, Oommen R, Nair A, Seshadri MS, Rajaratnam S (2011) Mutational analysis of RET proto-oncogene among patients with medullary thyroid carcinoma and ‘at risk’ carriers from India. Clinical Endocrinol 75:571–572CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • G. Bano
    • 1
    • 6
  • V. Siedel
    • 2
  • N. Beharry
    • 3
  • P. Wilson
    • 4
  • T. Cranston
    • 5
  • S. Hodgson
    • 2
  1. 1.Cellular and Molecular MedicineSt. George’s University of LondonLondonUK
  2. 2.Department of Clinical GeneticsSt. George’s Healthcare NHS TrustLondonUK
  3. 3.Department of RadiologySt. George’s Healthcare NHS TrustLondonUK
  4. 4.Department of Cellular PathologySt. George’s Healthcare NHS TrustLondonUK
  5. 5.Oxford Medical Genetics LaboratoriesOxford University Hospitals NHS Trust, The Churchill HospitalOxfordUK
  6. 6.Thomas Addison UnitSt. George’s HospitalLondonUK

Personalised recommendations