title: Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. Early and normative surgery is the only curative method for MEN 2-related medullary thyroid carcinoma (MTC). In patients with adrenal pheochromocytoma, cortical-sparing adrenalectomy (CSA) can be utilized to preserve adrenocortical function.
  
  
  METHODS
  We present twenty-six of 33 MEN2 patients underwent prophylactic thyroidectomy with varying neck dissection and eight of 24 MEN2A patients with PHEO underwent adrenal-sparing surgery. Direct sequencing of entire RET exons was performed in all participants.
  
  
  RESULTS
  The RET mutations (p.C634Y [n = 10], p.C634R [n = 9], p.C634F [n = 2], p.C618Y [n = 8], p.C618R [n = 3], and p.M918T [n = 1]) were confirmed in 20 symptomatic patients and identified in 13 at-risk relatives (RET carriers). Twenty-six of 33 MEN2 patients underwent thyroidectomies with neck dissections; the mean age at the time of the first thyroid surgery and the tumor diameter of the 6 RET carriers was decreased compared with 20 symptomatic patients (P < 0.001 and P = 0.007, respectively), while the disease-free survival was increased (80% vs.10%, P = 0.0001). Seven RET carriers who were declined surgery. One of 20 symptomatic patients with MTC bone metastases after surgery received vandetanib therapy for 20 months and responded well. Additionally, 8 of 24 MEN2A patients who initially had unilateral pheochromocytomas underwent CSA, 1 developed contralateral pheochromo cytomas 10 years later, then also accepted and also agreed to a CSA. None of the patients required steroid replacement therapy.
  
  
  CONCLUSIONS
  Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. CSA can be utilized to preserve adrenocortical function in patients with pheochromocytomas.
authors: Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, 310022 Zhejiang Province China.
authors: Jian-Qiang
authors: JQ
authors: Zhao
authors: Department of Oncologic and Urologic Surgery, the 117th PLA Hospital, Wenzhou Medical University, 40 Jichang Road, Hangzhou, 310004 Zhejiang Province China.
authors: Zhen-Guang
authors: ZG
authors: Chen
authors: Department of Oncologic and Urologic Surgery, the 117th PLA Hospital, Wenzhou Medical University, 40 Jichang Road, Hangzhou, 310004 Zhejiang Province China.
authors: Xiao-Ping
authors: XP
authors: Qi
keywords: Cortical-sparing adrenalectomy; Multiple endocrine neoplasia type 2; Mutation screening; Prophylactic thyroidectomy; RET
references: Clin Cancer Res. 2013 Feb 1;19(3):524-9
references: 23231950
references: Arch Dermatol. 2011 Sep;147(9):1077-80
references: 21576551
references: J Clin Endocrinol Metab. 2013 Feb;98(2):E364-9
references: 23264394
references: Am J Clin Oncol. 2015 Oct;38(5):508-13
references: 24064755
references: J Clin Endocrinol Metab. 2001 Dec;86(12):5658-71
references: 11739416
references: Ann Surg Oncol. 2008 Sep;15(9):2506-8
references: 18618188
references: Nature. 1993 Jun 3;363(6428):458-60
references: 8099202
references: N Engl J Med. 2005 Sep 15;353(11):1105-13
references: 16162881
references: Ann Surg. 2011 Dec;254(6):1022-7
references: 22107743
references: PLoS One. 2011;6(5):e20353
references: 21655256
references: Cancer. 2006 Nov 1;107(9):2134-42
references: 17019736
references: Clin Cancer Res. 2012 Jul 15;18(14 ):3722-30
references: 22665903
references: Ann Surg. 1993 Jun;217(6):595-601; discussion 601-3
references: 8099474
references: Eur J Surg Oncol. 2013 Sep;39(9):1007-12
references: 23849459
references: Am J Hum Genet. 1997 Jan;60(1):233-7
references: 8981969
references: JAMA. 1996 Nov 20;276(19):1575-9
references: 8918855
references: Thyroid. 2012 Dec;22(12):1257-65
references: 23210566
references: Ann Surg. 2014 Apr;259(4):800-6
references: 23979292
references: J Clin Endocrinol Metab. 2012 Feb;97(2):426-35
references: 22162466
references: J Clin Endocrinol Metab. 2001 Mar;86(3):1104-9
references: 11238493
references: Lancet Oncol. 2014 May;15(6):648-55
references: 24745698
references: J Clin Oncol. 2001 Mar 1;19(5):1374-80
references: 11230481
references: Thyroid Res. 2013 Mar 14;6 Suppl 1:S9
references: 23514096
references: Hum Mol Genet. 1993 Jul;2(7):851-6
references: 8103403
references: Ann Surg. 2009 Aug;250(2):305-10
references: 19638924
references: Thyroid. 2009 Jun;19(6):565-612
references: 19469690
references: J Clin Endocrinol Metab. 2013 Feb;98(2):E336-45
references: 23284010
references: J Clin Endocrinol Metab. 2013 Jun;98 (6):2401-8
references: 23543666
references: Clin Endocrinol (Oxf). 2007 Oct;67(4):570-6
references: 17573899
references: J Clin Endocrinol Metab. 2013 Aug;98(8):3149-64
references: 23744408
references: Oncogene. 2001 Nov 22;20(53):7809-11
references: 11753660