伴促甲状腺激素瘤的多发性内分泌腺瘤病1型一例报道及文献复习

目的通过研究1例伴有促甲状腺激素瘤的多发性内分泌腺瘤病1型(MEN1)患者的临床诊治过程及结局以提高对本病的认识。方法分析1例伴有促甲状腺激素瘤的MEN1患者诊治过程中的临床表现、生化和激素、影像学、手术及术后病理结果。使用二代测序再以Sanger法验证分析MEN1及其他基因,并以PolyPhen2和PROVEAN在线检测其产物危害性。结果1例19岁的男性患者因高代谢症状和甲状腺激素(THs)升高诊断甲亢,TSH 2.78 mIU/L,TSH受体抗体(TRAb)阴性。并发现高血钙和低血磷、血浆甲状旁腺激素(PTH)升高以及右下甲状旁腺99mTc显影阳性,诊断甲状旁腺腺瘤,手术治疗后上述指标恢复正常。抗甲状腺药物治疗1年症状和激素无明显改变,MRI显示右下垂体大腺瘤,考虑TSH瘤;经鼻蝶入路切除肿瘤后1个月复查TSH和TH恢复正常,免疫组化TSH阳性。CT和MRI发现胰腺体尾部占位,无相关症状。基因分析发现MEN1杂合突变:c.415C>T,p.His139Tyr(H139Y),蛋白质预测为有害。文献复习目前仅有5例报道。结论MEN1中的TSH瘤少见,既需要在甲状腺功能亢进中鉴别出TSH瘤,同时要考虑TSH瘤合并于MEN1,以减少误诊误治。

Thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1:one case report and literature review

Objective To improve the understanding of thyrotropin-secreting adenoma in multiple endocrine neoplasia type 1(MEN1)through analyzing the clinical diagnosis and treatment process,as well as outcomes in one case of this disorder.Methods The clinical manifestations,biochemical and hormone levels,imaging presentations,medical and surgical treatments,and post-operational pathologic findings in the process of diagnosis and treatment of a patient with thyrotropin-secreting adenoma in MEN1 were analyzed.The next generation sequencing followed by Sanger method was used for analyzing MEN1 and related genes.The results were evaluated with online PolyPhen2 and PROVEAN for variation hazard.Results One 19-year old male patient was diagnosed with hyperthyroidism due to thyrotoxicosis and high level of thyroid hormones(THs)with measurable TSH(2.78 mIU/L)and negative thyrotropin receptor antibody(TRAb).Meanwhile,primary hyperparathyroidism was suggested by hypercalcemia,hypophosphatemia,and elevated intact parathyroid hormone(PTH)level,all the parameters were returned to normal after surgical resection of the mass which was below the left thyroid lobe indicated by ultrasound and 99mTc scan.Thyrotoxicosis remained in spite of one year treatment with antithyroid drug,thyrotropinoma was then suspected,and subsequent MRI scan found a macroadenoma at right pituitary.TSH and THs returned to normal 1 month after transsphenoidal removal of the adenoma.As expected,immunohistochemical staining revealed TSH positive.In addition,a pancreatic mass was found by both CT and MRI scan,which was considered as a silent neuroendocrine tumor.Gene analysis revealed a missense mutation of MEN1 as c.415C>T and p.His139Tyr(H139Y),which was predicted highly hazard.Only five cases of thyrotropinoma in MEN1 were previously reported.Conclusion Thyrotropinoma should be cautiously identified from hyperthyroidism to avoid misdiagnosis and mistreatment,and it should keep in mind that thyrotropinoma may be associated with MEN1 though it would be very rare.