【作者】 胡平平；

【导师】 韩俊庆；

【作者基本信息】 山东大学 ， 肿瘤学， 2011， 硕士

【摘要】 [研究背景与研究目的]头颈部肿瘤在全球范围内是第5大常见肿瘤,在我国,约占全部肿瘤的20-30%0。由于头颈部解剖结构复杂,包含多个重要器官,手术困难大,且头颈部手术创伤较大,对患者器官功能影响明显,因此治疗创伤较小的放射治疗在头颈部肿瘤的治疗过程中占有重要的地位。它可以单独应用或与手术、化疗等其他治疗手段联合应用。对部分早期肿瘤,根治性放疗可取的与手术同样的效果,且较好的保留了器官功能,对局部晚期肿瘤,通过放疗、手术、化疗等结合的综合治疗手段,可以提高局部肿瘤的控制率和患者的生存率。甲状腺是人体最大的内分泌腺,位于下颈部,由于其解剖位置因素,在头颈部肿瘤的放射治疗过程中,甲状腺常被部分或全部包括在照射野内。放疗后可造成甲状腺不同程度的损伤.其中放疗后甲状腺功能减退是常见的并发症之一。甲状腺功能减退症(hypothyroidism简称甲减)是由于甲状腺激素合成和分泌减少或组织利用不足导致的全身代谢减低综合征。根据其程度不同,又分为临床甲减(TSH增高同时伴有甲状腺激素水平降低)、亚临床甲减(TSH增高但甲状腺激素水平在正常范围内)。本文旨在研究颈部放疗对患者甲状腺功能的影响。[研究对象和方法]1.研究对象：53例患者均来自2008年3月至2009年6月山东大学附属省立医院肿瘤科病人,均经组织病理学明确诊断为恶性肿瘤。全部病例放疗前均无甲状腺、垂体、下丘脑疾病及放疗史,无甲状腺切除史,放疗前甲状腺功能正常。年龄25-82岁,平均年龄50.4岁,其中≥60岁病人20例,<60岁病人33例。53例患者中,男性36例,女性17例。颈段食管癌14例,口咽癌3例,下咽癌17例,喉癌17例,颈部转移癌2例。根据2002年AJCC分期,Ⅰ期12例,Ⅱ期15例,Ⅲ期23例,Ⅳ期3例。放疗均在模拟定位机下透视定位行普通放疗,均采用6MV-X线照射,部分病人辅以电子线加量,每周5次,每次200cGy,颈部总剂量为5000-6600cGy,疗程5-6.6周。其中23例病人联合化疗,化疗方案均为5-Fu+DDP。2.研究方法：甲状腺功能检测采用直接化学发光法,分别于放疗前及放疗结束时、放疗后3个月、6个月、9个月,12个月,18个月测定患者空腹血清中TSH.T3.T4.FT3.FT4值。正常值范围：T3(1.3-3. lnmol/L)、T4 (66-181nmol/L)、FT3(3.1-6.8pmol/L)、FT4(12-22pmol/L)、TSH (0.27-4.2ulu/ml)。以TSH>4.2 ulu/ml作为诊断甲减的标准。3.统计学处理应用SPSS17.0医学统计软件建立完整数据库,数据以均数加减标准差的方式表达,用t检验法对个测量点血清甲状腺激素水平进行比较,用列联表确切概率法(Fisher’s Exact Test)对不同因素对发病情况的影响进行检验。[研究结果]随访期间10例病人发生甲减(18.9%),其中亚临床甲减6例,临床甲减4例。病人的最长随访时间为18个月,甲减发生的平均时间为放疗后11.7个月(范围从3个月-18个月),约70%的病人是在放疗后12个月内确诊的。统计学资料表明：非甲状腺切除的颈部手术史增加了放疗后甲减的发生率,16例病人放疗前曾行手术治疗,甲减的发生率为37.55%(6/16)；未行手术治疗的放疗病人甲减发生率为10.8%(4/37),P值0.032,有统计学差异；而性别、年龄联合化疗、吸烟与甲减的发生率无统计学差异,由于样本数量较小,未对不同肿瘤分期甲减的发病情况进行比较。[结论]头颈部肿瘤放射治疗后,可导致甲状腺功能减退。其诊断以实验室检测为依据。随着时间的延长,放疗后甲减的发生率可能增加,且部分亚临床甲减可能转变为临床甲减。颈部手术史是导致放疗后甲减发生的高危因素,而性别、年龄、联合化疗、吸烟与甲减的发生无明确关系。放疗后甲减的诊断中,TSH增高决定了甲减的发生,而T3、T4、FT3、FT4水平决定了甲减的程度。本文第一次对T3、T4、FT3、FT4在放疗后的变化情况进行了比较研究,其中FT4较其他指标发生显著性变化的时间更早,在临床甲减的诊断中可能具有更重要的作用。研究表明,放疗后甲减发生时间较晚,且发病隐匿,易与肿瘤的伴随症状混淆,因此定期监测甲状腺功能非常重要。对于监测的时间间隔没有定论,根据2011年NCCN头颈部肿瘤临床实践指南,对于放疗范围包括甲状腺的患者,应每6-12个月进行TSH的检测,以便及时发现甲状腺功能异常,并给与及时治疗、减少相关并发症的发生。更多还原

【Abstract】 [Background and objective]Carcinoma of head and neck is the 5th most common cancer in the world. The incidence of China is 20-30%.Due to the complex anatomy of the head and neck.which including a number of important organs, surgery encounter great difficulties.The surgical injury is huge, therefore radiotherapy take an important position during the treatment of head and neck cancer. The thyroid is the most developed endocrine gland of the body. Due to its anatomical location, it may be exposed to ionizing radiation in external radiotherapy involving head and neck.Radiotherapy can induce thyroid disorders, and hypothyroidism is a common one. Hypothyroidism is induced by the decreased thyroid hormone synthesis and secretion or by the inadequate use of organizations, which result the syndrome of the systemic metabolic decline. According to their different degrees, they are divided into clinical hypothyroidism and subclinical hypothyroidism.Clinical hypothyroidism is defined as a reduction in thyroid hormone, with a concomitant increase in TSH. Subclinical hypothyroidism refers to a state of elevated TSH with the presence of normal levels of thyroid hormone.The purpose of this study was to investigate the radiation-induced damage to the normal thyroid gland.[Methods and materials] From March 2008 to June 2009.53 patients with histopathological iagnosis of head and neck carcinoma from Shandong Provincial Hospital were enrolled in the study. All patients who had history of thyroid diseases、pituitary or hypothalamus diseases, who had previously radiated thyroid prior to treatment, who underwent a thyroidectomy for tumor control, and people with abnormal thyroid function were excluded from this analysis.The average age of the patients was 50.4(range 25—82).Of this group,20 cases were greater than or equal to 60-year-old and 33 cases less than 60 years.36 were men and 17 were women.14 patients had cancer in the Cervical esophageal carcinoma; 3 patients had cancer in the oropharynx;17 patients had cancer in the hypopharynx; 17 patients had cancer in the larynx, the remaining 2 patients had cancer in the cervical metastases. According to the 2002 AJCC staging,12 cases were in stagel;15 cases were in stageⅡ; 23 cases were in stage III and 3 cases were in stage IV.The total dose of radiotherapy was 50-66 grays (Gy) over 5-6.6weeks (2Gy/fraction,5fractions/week).23 patients received chemotherapy using 5-fluorouracil and cisplatin.The thyroid function was examined by the direct chemiluminescence.The serum levels of T3、T4、FT3、FT4 and TSH were obtained for each patient before radiotherapy, at the end of radiotherapy and at 3,6,9,12,18 months after radiotherapy. Reference ranges were 1.3-3.1nmol/L for T3、66-181nmol/L for T4、3.1-6.8pmol/L for FT3、12-22 pool/L for FT4. and 0.27-4.2ulu/ml for TSH. Hypothyroidism was defined as a value of thyroid stimulating hormone (TSH) greater than 4.2 ulu/ml, whether or not symptoms were present.Statistical analysis was carried out by SPSS 17.0, The results were expressed as means±standard deviations. The characteristics of each result were compared using the Student’s t-test, and used Fisher’s Exact Test to compare the relationship of different factors with the incidence of hypothyroidism,with P<0.05 indicating statistical significance。 [Results]Of the total 53 patients,10 became hypothyroid during the course of follow up. The incidence of hypothyroidism was 18.9%.Among them,6 cases developed subclinical hypothyroidism and 4 clinical hypothyroidism。The average time to detect hypothyroidism was11.7 months (range 3-18 months) after the completion of treatment. Approximately 70% of the cases of hypothyroidism were detected within 12 months. In my study,non-thyroidectomy neck surgery increased the incidence of radiation-induced hypothyroidism .The incidence was 37.55% among the patients who treated with radiation and neck surgery, while it was 10.8% among those treated with radiotherapy alone, with P<0.05. No statistically significant differences were found for such variables as gender, age, combined chemotherapy and smoking。Because of the small sample size, I did not compare compare the relationship of tumor stage with the incidence of developing hypothyroidism.[Conclusion]Radiotherapy for patients with carcinoma of head and neck caused radiation-induced hypothyroidism. The diagnosis was based on laboratory test。With time prolonging after radiotherapy, the incidence of hypothyroidism may increase and some subclinical hypothyroidism may develop into clinical hypothyroidism. Surgery is a risk factor for hypothyroidism, and such variables as gender, age, combined chemotherapy and smoking have no influence on the development of hypothyroidism. Hypothyroidism was defined by the elevated TSH, while the level of T3、T4、FT3 and FT4 determine the degree of hypothyroidism. This article compared the change of T3、T4、FT3 and FT4 after radiotherapy, and concluded that the change of FT4 is more early than other indicators, which will play an important role in the diagnosis of clinical hypothyroidism。Studies have shown that radiation-induced hypothyroidism is a late side effect. It is easy to be confused with tumor associated symptoms. Regular monitoring of thyroid function is very important. The time interval for monitoring has not been decided。According to the NCCN clinical practice guidelines of head and neck carcinomas thyroid function tests should be repeated at 6-12 month intervals after neck radiotherapy, so as to detect thyroid dysfunction in time, and to give timely treatment to reduce the incidence of complications.更多还原