多发性内分泌腺瘤病2A型一例报告并文献复习

Multiple endocrine neoplasia type 2A： a case report and literature review

目的 报告1例多发性内分泌腺瘤病2A型（multiple endocrine neoplasia type 2A,MEN 2A）患者的资料,并进行相关文献复习,提高对该病的认识及诊治水平. 方法 回顾性分析2011年8月22日我院收治的1例MEN 2A患者的资料,女,38岁.因头痛、心悸、出汗,CT检查发现肾上腺肿物1个月入院.查体：血压200/100 mmHg（1 mmHg=0.133 kPa）,甲状腺两侧叶可触及多个质硬结节,腹部未触及肿物.去甲肾上腺素4.09 nmol/L,肾上腺素0.54 nmol/L,多巴胺0.53 nmol/L,甲状旁腺激素216.7 ng/L.腹部超声检查：左肾上腺区可见一直径约9.0 cm囊实性肿物,边界尚清,囊内有分隔,偏实性成分内无明显血流信号.腹部CT检查：左肾上腺区可见一直径约8.5 cm类圆形囊实性占位,左肾约2 cm×1 cm,强化明显,考虑左肾发育不全.131Ⅰ-间碘苄胍核素显像检查：左肾上腺区有异常放射性聚集,考虑为嗜铬细胞瘤.颈部超声检查：甲状腺两侧叶实性低回声肿物,血流丰富,甲状腺癌可能性大;甲状腺左叶下极背侧实性低回声肿物,甲状旁腺来源可能性大.颈部CT检查：甲状腺两侧叶可见多个均匀低密度实质性占位,增强扫描后病灶轻度不均匀强化,双侧未见淋巴结肿大.术前诊断：左肾上腺嗜铬细胞瘤,双侧甲状腺髓样癌,甲状旁腺增生,左肾发育不全.全麻下行腹腔镜下经腹腔途径左肾上腺切除术.术中分离肿瘤时,患者血压波动较大,收缩压波动范围80～230 mmHg.予对症处理后,完整切除肿瘤. 结果 手术时间130 min,出血量50 ml.术后病理检查：肿瘤直径约8.5 cm,有1个明确的包囊,剖面见肿瘤内液化坏死.镜下观察见左肾上腺细胞呈巢团状增生,细胞有中度异形性,免疫组化染色检查：CD34（-）,CK（-）,嗜铬粒蛋白A（＋）,Ki-67＜5％（＋）,神经元特异性烯醇化酶（＋）,S-100（＋）,突触素（＋）,波形蛋白（＋）,Melan-A灶状（＋）.病理诊断：嗜铬细胞瘤.术后第2天,患者血压降至110/70 mmHg.术后1周复查去甲肾上腺素水平降至正常.术后1个月,全麻下行甲状腺全切术＋颈淋巴结清扫术＋甲状旁腺切除术.术后病理诊断为甲状腺髓样癌,淋巴结可见癌转移（1/6）,甲状旁腺腺瘤样增生.术后给予甲状腺素替代及补钙治疗.基因分析：患者及其子女的RET原癌基因634密码子（外显子11）发生TGC→CGC突变.随访1年,患者血压正常,肿瘤未见复发. 结论 对于嗜铬细胞瘤伴甲状腺髓样癌及甲状旁腺增生/腺瘤的患者,应考虑有MEN2A的可能,基因检测可明确诊断,早期行手术治疗.

Objective To improve the diagnosis and treatment of multiple endocrine neoplasia type 2A （MEN 2A）.Methods We have retrospectively reviewed one case of MEN 2A,admitted in our hospital on August 22th,2011.A 38-year-old female admitted due to headache,palpitation,sweating with the CT image of left adrenal tumor for 1 month.Her blood pressure was 200/100 mmHg.Multiple firm thyroid nodules were felt,and there was no abnormal in the abdomen.Endocrine examination revealed high catecholamines：norepinephrine 4.09 nmol/L,epinephrine 0.54 nmol/L,and dopamine 0.53 nmol/L.Parathormone was 216.7 ng/L.Abdominal ultrasound showed a 9 cm cystic solid mass located in the left adrenal area.The border line of mass was clear.And the spetum was noticed in the cystic part.In the solid part,no blood flow was observed.CT scan revealed a large well defined mass lesion （8.5 cm） in left adrenal area with obvious enhanced,and left renal agenesis （2 cm×1 cm）.131Ⅰ-MIBG was positive for the pheochromocytoma.The cervical ultrasound showed multiple nodulars in the thyroid with rich blood supply,which was considered as thyroid carcinoma.And the CT examination also demonstrated the multiple low density solid mass in the thyroid with mild enhancement.No lymphadenopathy was observed in the neck.Preoperative diagnosis was the left adrenal pheochromocytoma,medullary thyroidcarcinoma,parathyroid hyperplasia,and left renal agenesis.The patient was undergone laparoscopic adrenalectomy with general anesthesia.There were fluctuations in the patient＇s blood pressure during operation.The systolic blood pressure （SBP） ranged from 80 to 230 mmHg.The neoplasm was completely resected.Results The operative time was 130 minutes,and blood loss was 50 ml.The tumor had a well-defined capsule （8.5 cm in diameter）.The cross section of the tumor showed liquefactive necrosis inside the mass.The microscopic observation revealed that chromaffin cells were found to be arranged as cell nests and showed moderate heteromorphism.Immunohistochemically,the tumor cells were positive for chromogranin A,neuron-specific enolase,S-100,synaptophysin,Vimentin,Melan-A.Ki-67 labeling was approximately 5%.The tumor cells were negative for CD34 and cytokeratins.Histopathologic examination demonstrated a pheochromocytoma.The following day,her blood pressure was 110/70 mmHg.One week later,the elevated serum nor-metanephrine levels dropped to the normal range.After one month,open thyroidectomy with neck lymph node dissection and parathyroidectomy were operated on the patient.Histopathologic examination demonstrated a medullary thyroid carcinoma and parathyroid hyperplasia.Medullary cancer metastases were found in one of six lymph nodes.After surgery,the patient was given adequate thyroid hormone and calcium supplementation.Genetic Analysis showed the RET mutation observed in the patient and her relatives at codon 634 （exon 11） was TGC→CGC.After a 1-year follow-up,the patient was alive with normal blood pressure and with no evidence of recurrent.Conclusions When pheochromocytoma is concomitant with thyroid carcinoma and parathyroid hyperplasia/adenoma,MEN 2A should be considered.Genetic analysis is the best way to approve the diagnosis.Operations,concerning the pheochromocytoma and medullary thyroid carcinoma,should be performed earlier.