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Novel germline SDHD mutation: diagnosis and implications to the patient

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Abstract

A 54-year-old man presented with hypertensive crisis. He was found to have bilateral pheochromocytomas and left paraaortic sympathetic paraganglioma. Although he had no family history of paragangliomas or pheochromocytomas, he had been diagnosed with bilateral head and neck paragangliomas 10 years prior. The patient had symptoms of catecholamine excess exacerbated by vanilla ice-cream consumption. Biochemical testing revealed elevated plasma-free metanephrines and chromogranin A levels. Computed tomography showed bilateral carotid body tumors and four reteroperitoneal masses (two in the right adrenal, one in the left adrenal and one in the left paraaortic area). Metaiodobenzylguanidine-SPECT scans showed functional tumors in both the adrenal gland and left paraaortic area. Fluorine 18-fluorodeoxyglucose positron emission tomography did not show any visceral or skeletal metastasis. We carried out gene mutation analysis for succinate dehydrogenase complex subunit B, and succinate dehydrogenase complex subunit D. The patient was diagnosed with hereditary paraganglioma syndrome type 1 with a previously unreported subunit D mutation in exon 3 (c.198G > A, p.W66X). He was treated with phenoxybenzamine at 10 mg/day and with metoprolol at 12.5 mg/day. His blood pressures as well as symptoms of catecholamine excess were controlled. He then underwent bilateral adrenalectomy and reteroperitoneal dissection. His blood pressure normalized and he discontinued antihypertensive medications after surgery. He is currently on replacement therapy with hydrocortisone and fludrocortisone.

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Abbreviations

mm Hg:

Millimeters of mercury

CT:

Computed tomography

MIBG:

Metaiodobenzylguanidine

mCi:

Millicuries

MEN:

Multiple endocrine neoplasia

VHL:

Von Hippel-Lindau disease

FDG:

Fluorine 18 (18F)-fluorodeoxyglucose

PET:

Positron emission tomography

SDH:

Succinate dehydrogenase

PGL1:

Paraganglioma syndrome type 1

MRI:

Magnetic resonance imaging

References

  1. DeLellis RA, Lloyd RV, Heitz PU, Eng C (2004) Pathology and genetics of tumours of endocrine organs. In: Kleihues P, Sobin LE (eds) World health organization classification of tumours, vol 8. IARC Press, Lyon, pp 138–159

  2. Neumann HP, Bausch B, McWhinney SR et al (2002) Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346(19):1459–1466

    Article  PubMed  CAS  Google Scholar 

  3. Jimenez C, Cote G, Arnold A, Gagel RF (2006) Review: Should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 91(8):2851–2858

    Article  PubMed  CAS  Google Scholar 

  4. Hao HX, Khalimonchuk O, Schraders M et al (2009) SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 325(5944):1139–1142

    Article  PubMed  CAS  Google Scholar 

  5. Qin Y, Yao L, King EE et al (2010) Germline mutations in TMEM127 confer susceptibility to pheochromocytoma. Nat Genet 42(3):229–233

    Article  PubMed  CAS  Google Scholar 

  6. Favier J, Briere JJ, Strompf L et al (2005) Hereditary paraganglioma/pheochromocytoma and inherited succinate dehydrogenase deficiency. Horm Res 63(4):171–179

    Article  PubMed  CAS  Google Scholar 

  7. Burnichon N, Briere JJ, Libe R et al (2010) SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 19(15):3011–3020

    Article  PubMed  CAS  Google Scholar 

  8. King A, Selak MA, Gottlieb E (2006) Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25(34):4675–4682

    Article  PubMed  CAS  Google Scholar 

  9. Bayley JP, Devilee P, Taschner PE (2005) The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet 6:39

    Article  PubMed  Google Scholar 

  10. van Nederveen FH, Gaal J, Favier J et al (2009) An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol 10(8):764–771

    Article  PubMed  Google Scholar 

  11. Neumann HP, Pawlu C, Peczkowska M et al (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292(8):943–951

    Article  PubMed  CAS  Google Scholar 

  12. Ricketts CJ, Forman JR, Rattenberry E et al (2009) Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Hum Mutat 31(1):41–51

    Article  Google Scholar 

  13. Hensen EF, Jordanova ES, van Minderhout IJ et al (2004) Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene 23(23):4076–4083

    Article  PubMed  CAS  Google Scholar 

  14. Erlic Z, Neumann HP (2009) Familial pheochromocytoma. Hormones (Athens) 8(1):29–38

    Google Scholar 

  15. Lenders JW, Pacak K, Walther MM et al (2002) Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 287(11):1427–1434

    Article  PubMed  CAS  Google Scholar 

  16. Eisenhofer G, Pacak K, Huynh TT et al (2011) Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. Endocr Relat Cancer 18(1):97–111

    Article  PubMed  CAS  Google Scholar 

  17. Brink I, Hoegerle S, Klisch J, Bley TA (2005) Imaging of pheochromocytoma and paraganglioma. Fam Cancer 4(1):61–68

    Article  PubMed  CAS  Google Scholar 

  18. Timmers HJ, Kozupa A, Chen CC et al (2007) Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol 25(16):2262–2269

    Article  PubMed  Google Scholar 

  19. Ayala-Ramirez M, Callender GG, Kupferman ME et al (2010) Paraganglioma syndrome type 1 in a patient with Carney-Stratakis syndrome. Nat Rev Endocrinol 6(2):110–115

    Article  PubMed  Google Scholar 

  20. Ayala-Ramirez M, Feng L, Johnson MM et al (2010) Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab. doi:10.1210/jc.2010-1946

  21. Yip L, Lee JE, Shapiro SE et al (2004) Surgical management of hereditary pheochromocytoma. J Am Coll Surg 198(4):525–534 discussion 34-5

    Article  PubMed  Google Scholar 

  22. Peczkowska M, Erlic Z, Hoffmann MM et al (2008) Impact of screening kindreds for SDHD p.Cys11X as a common mutation associated with paraganglioma syndrome type 1. J Clin Endocrinol Metab 93(12):4818–4825

    Article  PubMed  CAS  Google Scholar 

  23. Havekes B, van der Klaauw AA, Weiss MM et al (2009) Pheochromocytomas and extra-adrenal paragangliomas detected by screening in patients with SDHD-associated head-and-neck paragangliomas. Endocr Relat Cancer 16(2):527–536

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Endocrine Neoplasia and Hormonal Disorders, Unit 1461, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Jeena Varghese, Montserrat Ayala-Ramirez & Camilo Jimenez

  2. Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Thereasa Rich

  3. Departments of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Eric Rohren

  4. Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Priya Rao

Authors
  1. Jeena Varghese
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  2. Montserrat Ayala-Ramirez
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  3. Thereasa Rich
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  4. Eric Rohren
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  5. Priya Rao
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  6. Camilo Jimenez
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Correspondence to Camilo Jimenez.

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Varghese, J., Ayala-Ramirez, M., Rich, T. et al. Novel germline SDHD mutation: diagnosis and implications to the patient. Familial Cancer 10, 365–371 (2011). https://doi.org/10.1007/s10689-011-9421-6

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  • DOI: https://doi.org/10.1007/s10689-011-9421-6

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