Alström syndrome with a novel mutation of ALMS1 and Graves’hyperthyroidism:A case report and review of the literature

BACKGROUND Alström syndrome(AS,OMIM ID 203800)is a rare disease involving multiple organs in children and is mostly reported in non-Chinese patients.In the Chinese population,there are few reports on the clinical manifestations and pathogenesis of AS.This is the first report on the association between AS and Graves’hyperthyroidism.CASE SUMMARY An 8-year-old Chinese girl was diagnosed with AS.Two years later,Graves’hyperthyroidism developed with progressive liver dysfunction.The patient’s clinical data were collected;DNA from peripheral blood of the proband,parents and sibling was collected for gene mutation detection using the second-generation sequencing method and gene panel for diabetes.The association between the patient’s genotype and clinical phenotype was analyzed.She carried the pathogenic compound heterozygous mutation of ALMS1(c.2296_2299del4 and c.11460C>A).These stop-gain mutations likely caused truncation of the ALMS1 protein.CONCLUSION The manifestation of hyperthyroidism may suggest rapid progression of AS.

Influence of serum levels of TSH receptor antibody in pregnant women with Graves disease on neonatal hyperthyroidism

Objective:To investigate the clinical significance of serum thyroid stimulating hormone(TSH) receptor antibody(TRAb) levels in pregnant women with Graves'disease,on neonatal hyperthyroidism. Methods:The clinical data of 68 pregnant women with Graves' disease and their newborns were retrospectively analyzed.Testing indicators included thyroid function tests and TRAb levels during pregnancy,at delivery,and within 2 weeks after birth.The serum TRAb and T_3,T_4,Free T_3,Free T_4,TSH levels were detected by radio receptor assay(RRA) and electrical chemiluminescence immunoassay(ECLIA),respectively. Results:The results showed that serum TRAb levels of the third trimester of pregnancy was positively correlated with that of the umbilical vein(n = 68,r= 0.8494,P<0.01),and that of the newborns(n = 68, r=0.8286,P<0.01).The incidence of neonatal hyperthyroidism was 11.8%(8/68).The serum TRAb levels in the 8 neonates with hyperthyroidism within 2 weeks after birth were 3 times higher than those in the normal neonates.Of these 8 neonates,2 had 15 times higher serum TRAb levels than those of normal neonates within 2 weeks after birth.The thyroid function and TRAb levels of these 2 neonates were still abnormal 6 months later. Conclusions:The risk of hyperthyroidism in newborn whose mother's TRAb levels were high in the third trimester of pregnancy was increased.This study suggests a significant correlation between TRAb levels in pregnant women with Graves' disease and the severity of neonatal hyperthyroidism.

Diagnosing Graves’ Disease and Non-Graves Hyperthyroidism Using TSH Receptor Antibody Test versus Non-TSH Receptor Antibody Test Methods of Diagnosis

Background: Differentiating Graves hyperthyroidism from the other causes of hyperthyroidism, using serum TRAb testing is essential step for diagnosis. Objectives: To study importance of TRAb in the diagnosis of Graves’ disease, distinguishing it from thyroiditis, and comparing it with clinical features and other tests such as TPOAb, US thyroid and thyroid scintiscan. Methods: A cross-sectional study was conducted on 120 patients attending endocrine clinicErbil city. Patients were studied on clinical feature basis and investigated with serum TRAb, TPOAb, TSH, Free T4, and Ultrasound examination of thyroid gland. Fisher exact test and Chi Square test of independence, Correlation coefficient and t-test of independence were used. Results: Fifty-two patients were found to have Graves’ disease;There was significant correlation between TRAb positivity and diagnosis of Graves’ disease p 0.05. Conclusion: A positive correlation was found between TRAb titer and positivity and no significant relation between TPOAb levels between Graves’ disease patients compared with thyroiditis patients, respectively.

Lithium carbonate plus ¹³¹I in the treatment of Graves’ hyperthyroidism

Aims: Effectiveness of radioiodine for Graves’ hyperthyroidism (GD) depends on its intrathyroidal persistence, which could be enhanced by lithium by blocking the release of organic iodine and thyroid hormone from the thyroid gland. The present aim focused on the effect of the addition of lithium carbonate to 131I therapy in patients with GD. Methods: 100 consecutive patients with GD were randomly assigned to two groups: group (A) patients treated with 131I and group (B) patients treated with 131I plus lithium carbonate. Patients in B group were treated with a dose of 0.5 g per day (2 × 0.25 g) of lithium carbonate for half a month before and after the administration of 131I. Thyroid weight was estimated by ultrasonography and careful palpation of the thyroid. Radiation absorbed dose rate in the front of the neck was measured on days 1530 and 45 after the administration of 131I. Serum concentrations of thyroidstimulation hormone (TSH), fee tri-iodothyrosine (T3) and free thyroxine (T4) were tested on days 30, 45, 90, 180 before and after treatment. Results: After RIT, radiation absorbed dose rate in the front of neck gradually decreased as time went on (p 0.05), free T3 and free T4 values in both groups rose significantly one month after treatment (all p 0.05). Cure rate of hyperthyroidism was achieved in 36 of the 50 patients (72%) treated with 131I alone and in 38 of the 50 patients (76%) treated with 131I plus lithium. Conclusion: We suggest that for patients withdrawing of ATD and those with short effective half-time, as well as those intolerant or invalid, the short term addition of lithium to 131I allows for a better control of thyrotoxia and the completeness of treatment.

Selective Pituitary Resistance to Thyroid Hormone: Clinical Hyperthyroidism with High TSH on Levothyroxine Administration in I-131 Ablated “Graves Disease”

Resistance to Thyroid Hormone (RTH) is a rare form of hormone resistance secondary to changes in the genes encoding thyroid hormone receptors. The two subtypes, Pituitary RTH (PRTH) and Generalized RTH (GRTH), cause clinically distinguishable patient presentations. In PRTH, typically only the pituitary gland is resistant to thyroid hormone (TH) while the rest of the body maintains sensitivity. Selective pituitary resistance to thyroid hormone results in dysregulation of thyroid hormone homeostasis with clinical presentation as either euthyroid or hyperthyroidism. PRTH is characterized by elevated thyroid hormone levels with an elevated or inappropriately normal TSH concentration. Herein we describe a case report of a 70-year-old woman who complained of weight loss of over 35 lbs., palpitations, jitters, hair loss, diarrhea, fatigue, muscle weakness, etc. over 6 months, thus, indicating the presence of iatrogenic hyperthyroidism while receiving levothyroxine 175 ug daily prescribed by her primary care provider because of a reported history of “Graves disease” treated by radioactive iodine ablation of the thyroid several years ago. The daily dose of levothyroxine had been increased gradually at an interval of 3 months over a year because of persistent elevation of serum TSH level. Laboratory tests revealed markedly elevated Free T4, Free T3 and TSH levels, along with low concentrations of all lipid fractions, serum creatinine and urea nitrogen levels, indicating TSH induced hyperthyroidism or PRTH. Further testing documented a mutation of thyroid hormone receptor beta gene 2 confirming presence of PRTH. We believe that the initial diagnosis of Graves Disease was erroneous and I-131 ablation further confounded and missed the diagnosis of PRTH. Thus, the purpose of this report is to report a patient with PRTH and describe potential pitfalls in diagnosis and management of this rare disorder.

Alternating Hyperthyroidism and Hypothyroidism in Graves’ Disease: A Case Report and Literature Review

Background: Alternating thyroid function between hypo- and hyperthyroidism is a very rare phenomenon attributed to the switch between the types of thyroid stimulating hormone receptor autoantibodies;thyroid stimulating antibody and thyroid stimulating hormone blocking antibody. Case Presentation: We report an 18 years old male who presented with hyperthyroidism attributed to Graves’ disease. He was treated with antithyroid medication. During follow up, his thyroid function was switching between hyper- and hypothyroidism which was difficult to treat with antithyroid medication. His laboratory investigations revealed high thyroid stimulating immunoglobulin and TSH binding inhibitory immunoglobulin. Due to the difficultly of managing him with antithyroid medication, he was offered a definitive management for his Graves’ disease. Conclusion: This case demonstrates a rare challenging presentation of Graves’ disease. Patients presenting with fluctuation in thyroid function between hyper-and hypothyroidism need a definitive management for Graves’ disease.

Peripheral blood NKT cell number and function in patients with Graves disease and their correlation with hyperthyroidism

Objective:To assess the peripheral blood NKT cell number and function in patients with Graves disease and study their correlation with hyperthyroidism.Methods: The patients who were diagnosed with Graves disease in our hospital between May 2014 and September 2016 were selected as GD group, and 55 healthy volunteers who received physical examination in our hospital during the same period were selected as control group. Peripheral blood was collected to determine the number of CD3+CD56+NKT cells, and serum was collected to detect the contents of cytokines and thyroid function indexes.Results: Peripheral blood CD3+CD56+NKT cell number in Graves disease group was significantly lower than that in control group;serum IL-2, IFN-γ, TNF-α, IL-10 and TGF-β contents in GD group were significantly lower than those in control group and positively correlated with peripheral blood CD3+CD56+NKT cell number while IL-4, IL-5, IL-17, FT3, FT4, TPOAb, TgAb and TRAb contents were significantly higher than those in control group and negatively correlated with peripheral blood CD3+CD56+NKT cell number.Conclusion:The abnormal reduction of peripheral blood NKT cell number in patients with Graves disease can affect the balance of Th1/Th2 and Th17/Treg and increase the TRAb secretion to cause hyperthyroidism.

夏枯草制剂治疗Graves病的有效性与安全性的系统评价

目的系统评价口服夏枯草制剂联合西医治疗Graves病的疗效及安全性,以期为Graves病的临床诊治提供循证医学证据。方法文章全面系统检索中文学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库(WanfangData)、维普中文期刊全文数据库(VIP)四大中文数据库和PubMed、Embase、CochraneLibrary三大英文数据库,检索时间均从建库至2022年08月。采用Cochrane系统偏倚风险评估工具对纳入研究进行质量评估,并用RevMan 5.4.1软件对结局指标进行Meta分析。结果最终纳入8项随机对照试验,共784例患者。试验组均为口服夏枯草制剂联合西医治疗,对照组均为西医治疗。Meta分析结果表明,口服夏枯草制剂联合西医治疗在甲状腺功能及自身抗体的改善、缩小甲状腺腺体等方面的临床治疗总有效率高于对照组(RR=1.13,95%CI[1.10,1.26],P<0.00001),并且能够显著改善甲状腺肿的临床症状(MD=-0.39,95%CI[-0.67,-0.11],P=0.006),降低血清FT3水平(MD=-1.76,95%CI[-3.10,-0.43],P=0.01)及血清FT4水平(MD=-3.89,95%CI[-6.79,-1.00],P=0.008),提高血清促甲状腺激素(TSH)水平(MD=0.45,95%CI[0.05,0.86],P=0.03),改善甲状腺肿大情况(MD=-0.39,95%CI[-0.67,-0.11],P=0.006),缩小甲状腺左叶前后径(MD=-0.31,95%CI[-0.57,-0.06],P=0.02)、左叶左右径(MD=-0.24,95%CI[-0.32,-0.16],P<0.00001)、右叶前后径(MD=-0.30,95%CI[-0.47,-0.13],P=0.0004)、右叶左右径(MD=-0.21,95%CI[-0.33,-0.10],P=0.0004)。结论夏枯草制剂联合西医治疗对比单用西医治疗Graves病在整体疗效、改善甲状腺肿的临床症状、甲状腺激素水平,缩小甲状腺腺体有明显的优势,且较安全,但仍需后续大样本、高质量文献的支持。

Graves眼病患者糖皮质激素治疗前后血清细胞因子的变化

目的对活动期Graves眼病(Graves'ophthalmopathy,GO)患者糖皮质激素治疗前后的血清细胞因子进行检测,探讨其水平变化与治疗的相关性。方法选取活动期GO患者28例[临床活动性评分(clinical activity score,CAS)≥3分],入组患者均经过糖皮质激素周脉冲治疗,激素总剂量为4.5 g。检测治疗前后患者血清34项细胞因子浓度,同时收集所有研究对象的性别、年龄、肝肾功能、治疗前后的甲状腺功能及抗体等临床指标。结果活动期GO患者经过糖皮质激素治疗后血清细胞因子包括白细胞介素(interleukin,IL)(IL-1α、IL-1β、IL-1Rα、IL-2Rα、IL-6、IL-8、IL-18、IL-12p40及IL-16)浓度显著下调,细胞因子皮肤T细胞吸引趋化因子(cutaneous T cell attraction chemokines,CTACK)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、巨噬细胞游走抑制因子(macrophage migration inhibitory factor,MIF)、基质细胞衍生因子-1α(stromal cell-derived factor 1α,SDF-1α)、血浆碱性成纤维细胞生长因子(basic fibrobast growth factor,basic-FGF)、粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及干扰素-γ(interferon-γ,IFN-γ)浓度显著下调,而IL-9显著上调,治疗前后两组差异有统计学意义(P<0.05)。结论糖皮质激素治疗活动期GO患者后血清IL-1α、IL-1β、IL-1Rα、IL-2Rα、IL-6、IL-8、IL-18、IL-12p40及IL-16浓度显著下调,细胞因子CTACK、MCP-1、MIF、SDF-1α、basic-FGF、G-CSF、TNF-α及IFN-γ的浓度显著下调,提示这些细胞因子与糖皮质激素治疗GO的疗效有相关性。

基于数据挖掘分析倪青主任病证结合治疗Graves病遣方用药经验

目的探讨倪青主任病证结合治疗Graves病(Graves disease,GD)的遣方用药经验。方法收集就诊于倪青主任门诊的GD患者235例,结合患者临床症状和特异性理化检测指标将病情分为重度、中度、轻度和病情相对平稳的类型;中药处方235张,构建数据库,应用相关软件,分析病情与方剂及中药的关系。结果235例患者中重度7例,中度19例,轻度52例,病情平稳者157例;235张处方共涉及方剂40种,中药201味。频次统计提示重度使用最多为滋阴潜阳甲亢方;中度常用四逆散;轻度以参芪地黄汤为主;病情平稳最多用藿朴夏苓汤。201味中药中,使用频次高于10次的中药共59味,重度常用中药为夜交藤、生地黄、玄参、田基黄、栀子、牡蛎等;中度常用药为枳壳、厚朴、柴胡、香附等;轻度常用茯苓、太子参、炙甘草、生黄芪、白术、山萸肉等;病情平稳常用茯苓、泽泻、厚朴、猪苓、半夏、藿香、佩兰等。关联规则提示,支持度>10%,置信度>10%,作用度>1 h,病情与中药一项关联中与重度一起出现的为玄参、生地黄、夜交藤;中度为青皮;轻度为太子参。两项关联中与重度一起出现的为玄参、夜交藤;中度为青皮、陈皮;轻度为女贞子、旱莲草;病情平稳为牛蒡子、桔梗;仙茅、仙灵脾;荆芥、防风。三项关联中与中度一起出现的为漏芦、路路通、丝瓜络;轻度为太子参、生黄芪、生地黄;病情平稳为生薏米、苍术、田基黄;大腹皮、砂仁、莱菔子;香附、枳壳、赤芍;泽兰、泽泻、川牛膝。结论倪青主任病证结合治疗GD临床经验丰富,依据不同病情分度,分别采用滋阴潜阳、疏肝理气、益气养阴、健脾化痰、疏风利咽、利湿活血之法遣方用药。

血清CYR61、IL-17、Klotho蛋白对Graves眼病病情的评估价值

目的 探讨血清高半胱氨酸蛋白61(CYR61)、白细胞介素-17(IL-17)、单向跨膜蛋白(Klotho)对Graves眼病(GO)病情的评估价值。方法 收集2020年1月至2023年10月于郑州大学第一附属医院眼五科诊治的103例患者的临床资料为研究对象,根据临床活动性评分(CAS)评估患者病情,将其分为活动期组42例及非活动期组61例,比较两组患者一般资料、临床基础指标[肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)及TSH受体抗体(TRAb)、CYR61、IL-17、Klotho蛋白水平及CAS评分],并通过多因素回归分析和ROC曲线分析GO眼病活动期的相关影响因素以及预测价值。结果 活动组Klotho、TSH、FT3、FT4、TRAb、TNF-α、IFN-γ、CYR61水平及CAS评分相较于非活动组更高,差异有统计学意义(t=7.953,4.364,5.232,6.100,4.364,7.344,4.890,6.541,6.995,13.283,P<0.05);经多因素回归分析得出TSH、FT3、FT4、TRAb、TNF-α、IFN-γ、IL-17、Klotho、CYR61合并CAS评分为影响GO眼病活动期的独立危险因素(OR=1.730,1.667,1.689,1.692,1.742,1.791,1.863,1.887,1.828,1.842,P<0.05);CYR61、IL-17、Klotho联合预测GO活动期的预测价值均高于三者单一检测,曲线下面积(AUC)分别为0.943,0.827,0.817,0.866(P<0.05)。结论 血清CYR61、IL-17、Klotho蛋白与GO活动期密切相关,三者联合联合检测对GO病情预测效能较好,评估价值确切。

放射性碘治疗对Graves病患者甲状腺功能及T淋巴细胞的影响

目的探究放射性碘治疗对Graves病患者甲状腺功能及T淋巴细胞功能的影响。方法选取濮阳市安阳地区医院2023年1月至2024年6月确诊的137例Graves病患者为研究对象,根据治疗方式的不同将其分为观察组76例(采用131Ⅰ治疗)和对照组61例(采用甲巯咪唑药物治疗)。比较两组的临床疗效、甲状腺功能、T淋巴细胞变化,并分析甲状腺功能与T淋巴细胞变化之间的相关性。结果观察组治疗总有效率为89.47%(68/76),高于对照组的73.77%(45/61)(χ^(2)=5.775,P=0.016)。两组患者治疗1个月、3个月后FT_(3)和FT_(4)较治疗前下降,TSH较治疗前增加(均P<0.05);治疗1个月后,观察组FT_(4)低于对照组(t=5.455,P<0.001);治疗3个月后,观察组FT_(3)和FT_(4)低于对照组(t=7.794、2.775,均P<0.05),TSH高于对照组(t=2.965,P=0.004)。两组患者治疗1、3个月后CD3+T淋巴细胞比例较治疗前增加,CD4^(+)T淋巴细胞比例治疗1个月后减少,治疗3个月后增加(均P<0.05);观察组治疗3个月后CD3^(+)T淋巴细胞比例相较于对照组更高,CD4^(+)T淋巴细胞比例低于对照组(t=3.780、2.775,均P<0.05)。CD4^(+)T淋巴细胞比例与FT_(3)、FT_(4)和TSH水平呈正相关(r=0.453、0.495、0.594,均P<0.05),CD4^(+)/CD8^(+)比值与FT_(3)、FT_(4)和TSH水平呈正相关(r=0.512、0.592、0.474,均P<0.05)。结论Graves病131Ⅰ治疗效果优于甲巯咪唑,且能改善甲状腺功能,提升患者的免疫功能。Graves病患者的131Ⅰ治疗应关注甲状腺功能和免疫功能相关指标。

Graves病合并自身免疫性肝病1例并文献复习

甲状腺功能亢进症导致肝损伤的原因有甲状腺激素增多引起的损伤、抗甲状腺药物治疗引起的药物性肝损伤(DILI)及可能合并的其他肝脏疾病等[1,2]。Graves病(Graves'disease,GD)是一种全身性自身免疫性疾病,也是甲状腺功能亢进症最常见的表现形式。2010年一项研究报道,另一种自身免疫性疾病,如类风湿关节炎、恶性贫血、系统性红斑狼疮等在GD患者的发生率为9.7%,在桥本甲状腺炎的发病率为14.3%[3]。近年来,部分文献报道了GD合并自身免疫性肝病,尤其是自身免疫性肝炎(autoimmune hepatitis,AIH),但合并原发性胆汁性胆管炎(primary biliary cholangitis,PBC)或合并重叠综合征(overlap syndrome,OS)的情况还比较少见。本文报道了1例GD患者在治疗期间反复出现肝功能异常,经肝活检组织病理学检查证实其合并PBC-AIH OS,经积极治疗后病情明显缓解。

磁共振T2-mapping评估Graves眼病活动性的价值

目的探讨磁共振T_(2)-mapping在Graves眼病(GO)活动性评估方面的价值。方法收集2019年7月-2021年1月于重庆医科大学附属第一医院内分泌科就诊的GO患者64例,使用计算机对其进行简单随机分组,其中49例作为观察研究对象,另外15例进行诊断试验评价。按照临床活动性评分(CAS)将49例GO患者分为活动组(CAS≥3分,48只患眼)与非活动组(CAS<3分,50只患眼)。同期招募31名健康志愿者作为正常对照组,共62只眼。所有人均行3.0T眼眶磁共振T_(2)-mapping成像。在T_(2)-mapping冠状位图像上测量上直肌、下直肌、内直肌、外直肌眼球后5个层面的T_(2)弛豫时间(T_(2)RT),每块眼外肌分别取眼球后5个层面的T_(2)RT最大值来代表该眼外肌的T_(2)RT,最后取4块眼外肌T_(2)RT中的最大值,以眼外肌最大T_(2)RT表示。比较活动组、非活动组与正常对照组间上述5个指标(上直肌T_(2)RT、下直肌T_(2)RT、内直肌T_(2)RT、外直肌T_(2)RT、眼外肌最大T_(2)RT)的差异;采用受试者工作特征(ROC)曲线分析上述5个指标对GO活动性评估的诊断价值,得出诊断阈值,然后利用另外15例GO患者进行诊断试验评价,确定诊断效能较高的指标及其诊断活动性的阈值。结果活动组所有眼外肌的T_(2)RT均明显高于非活动组及正常对照组,差异有统计学意义(P<0.001)。ROC曲线分析显示,上直肌、下直肌、内直肌、外直肌、眼外肌的最大T_(2)RT判断活动性的截断值分别为80.200 ms、97.045 ms、94.355 ms、85.750 ms、101.385 ms。利用另外15例GO患者进行诊断试验评价,综合评估敏感度、特异度、阳性预测值、阴性预测值较高的指标为下直肌T_(2)RT、眼外肌最大T_(2)RT,其判断活动性的截断值分别为97.045 ms、101.385 ms;敏感度分别为91.7%、93.8%;特异度均为80.0%。结论磁共振T_(2)-mapping序列对评估GO的活动性具有良好价值。临床上可选择测量下直肌T_(2)RT或眼外肌最大T_(2)RT协助评估GO的活动性。

TPOAb阴性的产后甲状腺炎合并产后Graves病一例并文献复习

目的:总结甲状腺过氧化物酶抗体(TPOAb)阴性的产后甲状腺炎(PPT)合并产后Graves病(PPGD)的特点,提高对该病的认识。方法:收集2021年广西医科大学第一附属医院诊治的1例产后甲状腺炎合并产后Graves病(GD)患者的临床资料并回顾相关文献。结果:患者产后4个月余出现高代谢表现,无GD特征性体征,实验室检查显示游离的三碘甲状腺原氨酸(FT3)、游离的甲状腺素(FT4)明显升高,促甲状腺激素(TSH)降低,促甲状腺素受体抗体(TRAb)阳性,TPOAb阴性,ATD治疗后高代谢症状迅速改善,治疗3个月内甲状腺功能检查骤降甚至出现甲状腺功能减退,超声检查提示PPT合并GD可能性大,行甲状腺细针穿刺确诊为产后甲状腺炎合并PPGD。结论:产后1年内出现的甲状腺毒症,应首先考虑PPT,同时也要考虑PPGD所致的可能;必要时可行甲状腺细针穿刺活检,避免误诊、漏诊。

黄药子治疗Graves病有效性和安全性的研究进展

甲状腺功能亢进症以弥漫性毒性甲状腺肿(Graves disease,GD)最多见,传统的抗甲状腺药物往往难以取得满意的功效,复发率高、疗程长是最为突出的缺点。中药黄药子具有“消瘿”的功效,近年被广泛用于治疗GD,但长期使用可能会导致肝功能和肾功能损害。故黄药子治疗GD的有效性和安全性需更多研究。

3 T MRI定量测量眼眶结构在Graves眼病分期中的诊断价值

目的应用3 T眼眶MRI技术评估Graves眼病(Graves ophthalmopathy,GO)患者泪腺参数与临床活动性评分(clinical activity score,CAS)的相关性。材料与方法前瞻性纳入2020年2月至2023年6月安徽医科大学附属阜阳医院和安徽医科大学第一附属医院确诊的GO患者40例80只眼作为GO组,选取与GO组性别与年龄段匹配的健康人群40例80眼作为对照组。根据CAS评分将GO患者分为活动期GO组、非活动期GO组。分别对三组进行MRI常规图像及读出分段平面回波弥散加权成像(readout segmentation of long variable echo-trains diffusion weighted imaging,RESOLVE DWI)图像采集,横断位T2加权成像脂肪抑脂(T2-weighted imaging fat suppression,T2WI-FS)获得眼球突出度、泪腺突出度,横断位及冠状位T2WI-FS测量获得泪腺最大截面时的长径、短径、面积,记录横断位泪腺表观扩散系数(apparent dispersion coefficient,ADC)平均值。使用SPSS 24.0软件进行统计学分析,P<0.05为差异有统计学意义。定量资料组间比较采用两独立样本t检验,性别、吸烟史、饮酒史、CAS评分的组间差异采用卡方检验。采用受试者工作特征(receiver operating characteristic,ROC)曲线及其曲线下面积(area under the curve,AUC)评价GO活动性的诊断效能。采用Spearman’s相关分析泪腺各定量参数与CAS评分的相关性。结果(1)活动期GO组眼球突出度、横断位泪腺各参数,包含泪腺突出度、长径、短径、面积及ADC平均值,均较非活动期GO组、对照组增大,非活动期GO组较对照组升高(P均<0.05)。(2)ROC曲线结果显示,眼球突出度、横断位泪腺面积对GO患者的诊断效能最高(AUC为0.906、0.905),泪腺突出度、横断位泪腺ADC平均值对GO患者也有一定的诊断价值(0.793、0.702)。RESOLVE DWI ADC值预测GO活动性的最佳截断点为1.181×10^(-3)mm^(2)/s,其敏感度高达95.00%,特异度76.30%。(3)眼球突出度(r=0.734,P<0.05)、泪腺突出度(r=0.719,P<0.05)、泪腺ADC值(r=0.742,P<0.05)与CAS呈高度相关。结论横断位泪腺突出度、泪腺DWI ADC平均值可作为GO诊断及分期的重要参考指标。

Graves病患者应用甲巯咪唑导致反应性浆细胞增多症1例报告及文献复习

目的:探讨Graves病(GD)患者应用甲巯咪唑(MMI)治疗后出现粒细胞缺乏症和反应性浆细胞增多症(RP)的临床表现和实验室检查结果,为临床医生鉴别诊断RP和多发性骨髓瘤(MM)提供依据。方法:分析1例GD粒细胞缺乏症并发RP患者的临床表现、实验室检查和诊治过程,并进行文献复习。结果:患者有GD和腹腔感染病史,入院查血常规白细胞计数明显降低且伴有中性粒细胞缺乏,涂片复检见可疑浆细胞。骨髓细胞学检查,骨髓浆细胞百分率为33%,外周血浆细胞百分率为4%;血清免疫球蛋白多克隆性增生;血清免疫固定电泳阴性;流式细胞学分析,浆细胞免疫表型正常。结合病史和实验室检验结果,基本排除MM可能,符合RP的诊断。考虑中性粒细胞缺乏与用药有关,暂停MMI,给予粒细胞集落刺激因子升高白细胞数,控制腹腔感染后进行GD专科治疗。患者预后良好,6个月后随访复查血常规正常。结论:GD患者出现粒细胞缺乏症并发RP在临床上较为罕见,血清免疫固定电泳、血细胞形态学和细胞免疫表型分析有助于明确诊断。积极治疗RP原发疾病后,患者预后良好。

中重度活动性Graves眼病药物治疗新进展

Graves眼病(GO)为Graves病的甲状腺外表现,是由细胞免疫介导的复杂的自身免疫性疾病,眼眶成纤维细胞和眼眶脂肪细胞是免疫反应的靶细胞,促甲状腺激素受体和胰岛素样生长因子-1是关键的自身靶抗原。除吸烟、放射性碘治疗后等危险因素外,高胆固醇血症被发现为GO新的危险因素。糖皮质激素至今在中重度活动性GO的治疗中有不可撼动的地位,但部分患者经治疗后并没有反应,或出现了复发。生物靶向制剂、细胞因子抑制剂以及具有抗炎作用的他汀类药物等已逐步研究并应用于GO的临床治疗。文章对GO主要发病机制及目前中重度活动性GO药物治疗的新进展进行综述。

剪切波弹性成像评估甲巯咪唑治疗初诊Graves病疗效的应用价值

目的 探讨超声剪切波弹性成像(shear wave elastography, SWE)技术评估甲巯咪唑治疗初诊Graves病疗效的临床应用价值。方法 收集60例经滨州医学院附属医院初诊确诊为Graves病的患者,给予服用甲巯咪唑进行治疗,检测治疗前及治疗2月后患者血清甲状腺功能指标包括血清促甲状腺激素(thyrotropin, TSH)、血清游离三碘甲状腺原氨酸(free triiodothyronine, FT3)和血清游离甲状腺素(free thyroxine, FT4),以及甲状腺自身免疫性炎症指标促甲状腺激素受体抗体(TRAb)。同时应用SWE技术分别测量患者治疗前及治疗2月后甲状腺组织的杨氏模量最大值、最小值和平均值,应用配对t检验对治疗前后的结果进行分析比较。结果 比较治疗前及治疗2月后结果显示,所测血清甲状腺功能指标(TSH、FT3、FT4)显著改善(P<0.01),TRAb显著好转(P<0.05);应用SWE技术测得患者甲状腺组织的各项杨氏模量值也有显著变化(P<0.01)。结论 SWE技术测得甲状腺组织杨氏模量值的变化与患者甲状腺功能指标变化的临床意义一致,说明SWE实时、定量且客观获取的患者甲状腺组织的硬度变化信息,可为临床医师准确评估Graves病治疗效果及调整用药剂量提供重要的量化参考依据,具有较高的临床应用价值。