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Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese.

Zhao JQ, Chen ZG, Qi XP - Hered Cancer Clin Pract (2015)

Bottom Line: One of 20 symptomatic patients with MTC bone metastases after surgery received vandetanib therapy for 20 months and responded well.None of the patients required steroid replacement therapy.CSA can be utilized to preserve adrenocortical function in patients with pheochromocytomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022 China.

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.

No MeSH data available.


Related in: MedlinePlus

Genealogy of seven MEN2A families (F1-F7), one FMTC family (F8) and one MEN2B family (F9).
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Fig1: Genealogy of seven MEN2A families (F1-F7), one FMTC family (F8) and one MEN2B family (F9).

Mentions: The 33 MEN2 patients consisted of 9 index-cases (7 males and 2 females), 11 clinical patients (5 males and 6 females) and 13 asymptomatic carriers (4 males and 9 females). The mean age at the time of diagnosis was 38.6 ± 10.7 years (range, 23–58 years), 38.8 ± 16.6 years (range, 20–65 years), and 30.0 ± 18.5 years (range, 9–78 years), respectively. 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]). Of the 33 MEN2 patients, 32 (97%) were diagnosed with MTC (31) or C-cell hyperplasia (1) and 8 (33.3%) were diagnosed with PHEO (Table 1 and Figure 1). None of the 33 MEN2 patients had consistently evidence of any co-occurring related MEN2 clinical symptoms (pruritic cutaneous lichen amyloidosis or Hirschsprung’s disease), or HPT (serum PTH, Calcium or PTH/calcium rates, and serum phosphate levels ranged in all normal), except one MEN2B patient (F9-II3) had a broad spectrum of pathognomonic nonendocrine abnormalities: a Marfanoid body habitus, tongue mucosal neuromas, lips hypertrophy and CNT.Table 1


Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese.

Zhao JQ, Chen ZG, Qi XP - Hered Cancer Clin Pract (2015)

Genealogy of seven MEN2A families (F1-F7), one FMTC family (F8) and one MEN2B family (F9).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4307225&req=5

Fig1: Genealogy of seven MEN2A families (F1-F7), one FMTC family (F8) and one MEN2B family (F9).
Mentions: The 33 MEN2 patients consisted of 9 index-cases (7 males and 2 females), 11 clinical patients (5 males and 6 females) and 13 asymptomatic carriers (4 males and 9 females). The mean age at the time of diagnosis was 38.6 ± 10.7 years (range, 23–58 years), 38.8 ± 16.6 years (range, 20–65 years), and 30.0 ± 18.5 years (range, 9–78 years), respectively. 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]). Of the 33 MEN2 patients, 32 (97%) were diagnosed with MTC (31) or C-cell hyperplasia (1) and 8 (33.3%) were diagnosed with PHEO (Table 1 and Figure 1). None of the 33 MEN2 patients had consistently evidence of any co-occurring related MEN2 clinical symptoms (pruritic cutaneous lichen amyloidosis or Hirschsprung’s disease), or HPT (serum PTH, Calcium or PTH/calcium rates, and serum phosphate levels ranged in all normal), except one MEN2B patient (F9-II3) had a broad spectrum of pathognomonic nonendocrine abnormalities: a Marfanoid body habitus, tongue mucosal neuromas, lips hypertrophy and CNT.Table 1

Bottom Line: One of 20 symptomatic patients with MTC bone metastases after surgery received vandetanib therapy for 20 months and responded well.None of the patients required steroid replacement therapy.CSA can be utilized to preserve adrenocortical function in patients with pheochromocytomas.

View Article: PubMed Central - PubMed

Affiliation: Department of Head and Neck Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province 310022 China.

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.

No MeSH data available.


Related in: MedlinePlus