Abstract
BackgroundMultiple 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.MethodsWe 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.ResultsThe 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.ConclusionsBased 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13053-015-0026-1) contains supplementary material, which is available to authorized users.
Highlights
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome
MEN2B-related medullary thyroid carcinoma (MTC) has a higher invasiveness than MEN2A or familial medullary thyroid cancer (FMTC), and often accompanies PHEO, mucosal and gastrointestinal ganglioneuromas, corneal nerve thickening (CNT), and Marfan’s body habitus [5]
All patients derived from 9 unrelated MEN 2 families and harbored 1 of 6 heterozygous missense mutations; 7 families had MEN2A (p.C634Y [n = 3], p.C634R [n = 2], p.C634F [n = 1], p.C618R [n = 1]), 1 family had FMTC (p.C618Y [n = 1]), and 1 family had MEN2B (p.M918T [n = 1])
Summary
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. And normative surgery is the only curative method for MEN 2-related medullary thyroid carcinoma (MTC). Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome, with an occurrence of approximately 1 in 30 000; MEN2 is due to germline mutations in the REarranged during Transfection (RET) proto-oncogene (OMIM: 164761) [1,2], which includes the following three subtypes: MEN2A (OMIM: 171400); familial medullary thyroid cancer (FMTC; OMIM: 155240); and MEN2B (OMIM: 162300) [3]. MEN2A mainly consists of MTC, adrenal pheochromocytoma (PHEO), and hyperparathyroidism (HPT). MEN2B-related MTC has a higher invasiveness than MEN2A or FMTC, and often accompanies PHEO, mucosal and gastrointestinal ganglioneuromas, corneal nerve thickening (CNT), and Marfan’s body habitus [5]. Distant metastases of MTC are the major cause of death [5,6,7]
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