Graves病患者中与性别相关的临床特点分析

Objective To investigate the gender-related differences in patients with Graves'disease (GD).Methods Seven hundred and eighty-seven consecutive patients with GD treated with anti-thyroid drug in out-patient clinic of department of endocrinology of Chinese PLA general hospital from Oct.2009 to May 2010 were included in the study.The diagnosis of GD WSB made according to common clinical and laboratory criteria.Results (1)In Graves'disease,a marked female preponderance Was found.The female/male ratio was 3.35:1.Female patients with GD presented at a younger age,compared with males[(33.20±13.07 vs 36.75±13.89)year,P=0.002],and the peak incidences of the disease occurred in female and male were 20-29 years and 40-49 years of age respectively.(2)Male patients presented a higher prevalence of weight loss,thyrotoxic cardiopathy,periodic paralysis,and non-invasive ophthalmopathy whereas tachycardia was more common in females.(3)The females presented larger diffuse goiters with higher serum TT4,FT4,and thyrotropin receptor antibody(TRAb)levels.Cases with TRAb>30 U/L were more common in females,whereas those with TRAb 10-30 U/L were frequently seen in males.(4)There was no gender-related difference in the family history of GD.(5)Remission atleast 6 months after anti-thyroid drug therapy in 211 patients,there was a relapse rate of 64.3%(137/211)without gender difference.Conclusion GD appeared at a younger age and with larger diffuse goiters in females,together with more marked elevation of serum TT4,FT4 and TRAb levels.Altogether,these findings depict different patterns for GD in males and females.     

Graves病患者中与性别相关的临床特点分析

Objective To investigate the gender-related differences in patients with Graves'disease (GD).Methods Seven hundred and eighty-seven consecutive patients with GD treated with anti-thyroid drug in out-patient clinic of department of endocrinology of Chinese PLA general hospital from Oct.2009 to May 2010 were included in the study.The diagnosis of GD WSB made according to common clinical and laboratory criteria.Results (1)In Graves'disease,a marked female preponderance Was found.The female/male ratio was 3.35:1.Female patients with GD presented at a younger age,compared with males[(33.20±13.07 vs 36.75±13.89)year,P=0.002],and the peak incidences of the disease occurred in female and male were 20-29 years and 40-49 years of age respectively.(2)Male patients presented a higher prevalence of weight loss,thyrotoxic cardiopathy,periodic paralysis,and non-invasive ophthalmopathy whereas tachycardia was more common in females.(3)The females presented larger diffuse goiters with higher serum TT4,FT4,and thyrotropin receptor antibody(TRAb)levels.Cases with TRAb>30 U/L were more common in females,whereas those with TRAb 10-30 U/L were frequently seen in males.(4)There was no gender-related difference in the family history of GD.(5)Remission atleast 6 months after anti-thyroid drug therapy in 211 patients,there was a relapse rate of 64.3%(137/211)without gender difference.Conclusion GD appeared at a younger age and with larger diffuse goiters in females,together with more marked elevation of serum TT4,FT4 and TRAb levels.Altogether,these findings depict different patterns for GD in males and females.     

性别差异对Graves病动物模型建立的影响

目的 在雌性或雄性BALB/c小鼠制备Graves病动物模型,观察其促甲状腺素受体抗体(TRAb)滴度,TT4水平以及甲状腺组织的增生情况,探讨性别差异对成模的影响.方法 用表达TSH受体A亚单位的重组腺病毒免疫雌性或雄性BALB/c小鼠诱导Graves病,每3周免疫1次,共3次,末次免疫后4周取血,检测TRAb、TT4,剥离甲状腺行组织学检查.结果 雌性和雄性实验组小鼠TRAb阳性率均达到100%,两组之间抗体滴度无显著性差异.雌性及雄性实验组分别有75.0%,41.7%的小鼠发生甲亢,雌性实验组TT4水平明显高于雄性实验组并有统计学差异(P＜0.01),各组甲亢小鼠甲状腺组织出现明显增生.结论 利用表达TSH受体A亚单位的重组腺病毒免疫雌性、雄性BALB/c小鼠诱导Graves病动物模型,尽管两性TRAb抗体水平相似,但其甲亢发生率及程度存在一定的性别偏倚,提示雌性小鼠更易于模型的诱导.

Abstract：

Objective To investigate the effect of mice gender on the TSH receptor antibody(TRAb)titers, the levels of TT4,and the degree of thyroid hyperplasia by establishing an animal model of Graves′ disease in male and female BALB/c mice. Methods Male and female BALB/c mice were immunized with recombinant adenovirus expressing TSHRA subunit(Ad-TSHR289)to induce Graves′ disease. Animals were injected 3 times at intervals of 3 weeks. All mice were sacrificed 4 weeks after the last injection to obtain blood for measurement of TSHR antibody titers and TT4evels, and thyroid glands for histological examination. Results TRAb positive rates were 100% both in female or male mice. No significant difference was observed in titers of TRAb between them. The incidence of hyperthyroidism in female mice was higher than that in male mice, being 75.0% and 41.7% respectively. There was statistical difference in levels of TT4between females and males(P＜0.01). Mice with high TT4exihibited marked thyroid hyperplasia. Conclusion Despite TSHR antibodies were similar between female and male mice, the incidence and degree of hyperthyroidism showed sex bias in Graves′s animal model. The results indicated that it was easier to induce model in females than in males by immunizing BALB/c mice with Ad-TSHR289.     

促甲状腺激素受体抗体检测的临床意义

50年前人们发现了促甲状腺激素受体抗体(TRAb),随着对促甲状腺激素受体(TSHR)结构和功能认识的不断更新,加之TSHR信号转导和与TRAb相互作用的逐步阐明,人们对TRAb及其临床应用的认识得到了进一步提高.TRAb的检测在Graves病(GD)及Graves眼病的诊断中有重要作用,并有效预测GD经抗甲状腺药物或放射性碘治疗后复发.其亦可应用于近期服碘的孕妇和乳母,因为甲状腺扫描对她们来说是禁忌的.另外,TRAb有助于胎儿、新生儿甲状腺功能亢进及其他类型的甲状腺毒症的诊断和鉴别诊断.目前,已有文献报道TRAb阳性的GD患者发生甲状腺肿瘤及不良预后之间的可能联系,但尚需更多的前瞻性研究来证实.

Abstract：

It has been 50 years since the discovery of thyrotropin receptor autoantibody (TRAb). Advances in the knowledge of thyrotropin receptor ( TSHR) structure and function, combined with the elucidation of TSHR signaling and TSHR-autoantibody interaction have greatly facilitated our understanding of TRAb and their clinical applications. Measurement of TRAb activity plays an important role in the diagnosis of Graves' disease ( GD) and Graves' opthalmopathy. It has also been well recognized that TRAb is an effective predictor of GD relapse or remission after antithyroid drug and radioactive iodine treatment. TRAb test is of particular help in pregnant women and lactating mothers with recent iodine load, where radioactive iodine or technetium tests are contraindicated. In addition, it is useful in the diagnosis and differential diagnosis of fetal and neonatal hyperthyroidism as well as some rare forms of thyrotoxicosis in clinical practice. Accumulating evidence also indicates the possible correlation between thyroid cancer occurring in GD patients with positive TRAb and adverse outcomes. However, further innovation and standardization of TRAb tests are required to help pave the way for clinical applications.     

Giardiasis in patients with dyspeptic symptoms

AIM: To investigate the prevalence of giardiasis in patients with dyspeptic symptoms. METHODS: Clinical records of consecutive patients who attended Gastroenterology Department at Aga Khan University Hospital from January 2000 to June 2003 and had esophagogastroduodenoscopy (EGD) with duodenal biopsies and international classification of diseases 9th revision with clinical modifications (ICD-9-CM) coded with giardiasis were studied. RESULTS: Two hundred and twenty patients fulfilled the above criteria. There were 44% (96/220) patients who were giardiasis positive, 72% (69/96) of them were males and 28% (27/96) of them were females. There were 65% (81/124) males and 35% (43/124) females who were giardiasis negative. The mean age of patients with giardiasis was 28±17 years, while that of giardiasis negative patients was 40±18 years (P<0.001). In patients with giardiasis, abdominal pain was present in 71% (68/96) of patients (P = 0.02) and diarrhea in 29% (28/96) (P = 0.005); duodenitis in 25% (24/96) on EGD (P = 0.006) and in 68% (65/96) on histopathology (P = 0.002). CONCLUSION: Giardiasis occurs significantly in young people with abdominal pain, while endoscopic duodenitis is seen in only 25% of giardiasis positive cases, which supports routine duodenal biopsy.     

Sex differences and effects of oestrogen in rat gastric mucosal defence

AIM To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence.METHODS Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model. Subsequently, sex differences in the distribution of oestrogen receptors and calcitonin gene related peptide in the gastric mucosa of animals exposed to oestrogen in the above experiments was evaluated using immunohistochemistry.RESULTS The absolute blood flow in the GI-tract was generally higher in males, but only significantly different in the corpus part of the stomach (1.12 ± 0.12 m L/min·g in males and 0.51 ± 0.03 m L/min·g in females) (P = 0.002). After removal of the loosely adherent mucus layer the thickness of the firmly adherent mucus layer in males and females was 79 ± 1 μm and 80 ± 3 μm respectively. After 60 min the mucus thickness increased to 113 ± 3 μm in males and 121 ± 3 μm in females with no statistically significant difference seen between the sexes. Following oestrogen administration(0.1 followed by 1 μg/kg·min), mean blood flow in the gastric mucosa decreased by 31% [68 ± 13 perfusion units (PFU)] in males which was significantly different compared to baseline(P = 0.02). In females however, mean blood flow remained largely unchanged with a 4% (5 ± 33 PFU) reduction. The permeability of the gastric mucosa increased to a higher level in females than in males (P = 0.01) after taurocholate challenge. However, the calculated mean clearance increase did not significantly differ between the sexes [0.1 ± 0.04 to 1.1 ± 0.1 m L/min·100 g in males and 0.4 ± 0.3 to 2.1 ± 0.3 m L/min·100 g in females(P = 0.065)]. There were no significant differences between 17β-Estradiol treated males (mean ratio of positive staining ± SEM)(0.06 ± 0.07) and females(0.11 ± 0.11) in the staining of ERα (P = 0.24). Also, there were no significant differences between 17β-Estradiol treated males (0.18 ± 0.21) and females (0.06 ± 0.12) in the staining of ERβ (P = 0.11). Finally, there were no significant differences between 17β-Estradiol treated males (0.04 ± 0.05) and females (0.11 ± 0.10) in the staining of CGRP(P = 0.14).CONCLUSION Gastric mucosal blood flow is higher in male than in female rats and is reduced in male rats by oestrogen administration.     

High prevalence of osteoporosis in patients with gastric adenocarcinoma following gastrectomy

AIM: To evaluate the prevalence and predictive factors of osteoporosis in patients with gastric adenocarcinoma after gastrectomy. METHODS: The study included 133 patients diagnosed with gastric adenocarcinoma but who did not undergo prior diagnostic work-up for osteoporosis. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and vertebral deformity was assessed by plain X-rays. We evaluated the effects of age, sex, body mass index (BMI), anemia, back pain, vertebral deformity, tumor staging, reconstruction type, and past medical history to determine predictive factors of osteoporosis in these patients. RESULTS: The prevalence of osteoporosis in the lumbar spine was 38.3% (male, 28.9%; female, 54.0%), and 15.0% in the femoral neck (male, 10.8%; female, 22.0%). The vertebral deformity rate was 46.6% (male, 43.4%; female, 52.0%). Age, BMI and hemoglobin correlated with BMD (P < 0.01). In males, anemia and age > 64 years were independent predictive factors of osteoporosis in multivariate analysis. In females, back pain was an independent factor for osteoporosis. CONCLUSION: The results of this study revealed that prevalence of osteoporosis and vertebral bone deformity rate were high in gastric cancer patients, regardless of post-gastrectomy duration and operation type. Early diagnosis and a proper management plan must be established in these patients.     

Association of serum interleukin 17A with thrombotic events in patients with non-valvular atrial fibrillation

<正>Objective To observe the level of interleukin-17A(IL-17A) in patients with atrial fibrillation (AF),to assess its clinical value of thrombotic events in AF patients. Methods 67 controls (38 males and 29 females,average age 60. 37±9. 51 years),65 patients with paroxysmal AF (35 males and 30 females,average age     

Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer

AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body...     

Effect of ezetimibe on the prevalence of cholelithiasis

AIM:To investigate the prevalence of cholelithiasis among patients treated with ezetimibe.METHODS:A retrospective,case-control study based on computerized medical records from patients of the Clalit Health Services,Sharon-Shomron region,from 2000 to 2009.Patients 20-85 years of age,who had been treated with ezetimibe and statins or statins only for at least 6 mo,and who had an abdominal ultrasound were included in the study.Collected data included age,gender,ezetimibe treatment duration,presence of hypothyroidism or diabetes,and existence of cholelithiasis as determined by ultrasound.Excluded were subjects after gallbladder resection,with hemolysis,myeloproliferative or inflammatory bowel diseases,and those treated with ursodeoxycholic acid and fibrates.Patients treated with statins and ezetimibe(study group) were compared to patients treated with statins only(control group).RESULTS:The study group included 25 patients and the control group 168.All patients in the study were treated with statins.The study group included 13 males(52%) and 12 females(48%),the control group 76 males(45%) and 92(55%) females(P = 0.544).The groups did not differ in age(mean age:68 ± 8 years,range 53-85 years vs mean age:71 ± 8 years,range 51-85 years;P = 0.153) or in the rate of diabetic and hypothyroid patients [11(44%) vs 57(33%),P = 0.347 in the study group and 5(20%) vs 23(14%),P = 0.449 in the control group,respectively].Patients in the study group were treated with ezetimibe for an average of 798 ± 379 d.Cholelithiasis was found in 4(16%) patients in the study group and in 33(20%) patients in the control group(P = 0.666).CONCLUSION:Ezetimibe does not appear to influence the prevalence of gallstones.     

甲状腺上动脉峰值血流速度在自身免疫性甲状腺毒症鉴别中的应用

目的探讨甲状腺上动脉峰值血流速度(STA-PSV)对自身免疫性甲状腺毒症病因鉴别诊断的临床应用价值。方法收集2015年1月至2018年10月北京大学人民医院内分泌科新诊断的未用抗甲状腺药物治疗的自身免疫性甲状腺毒症患者301例,其中Grave病(GD)患者241例,自身免疫性甲状腺炎(AIT)患者60例,比较两组患者STA-PSV、甲状腺功能、促甲状腺激素受体抗体(TRAb)等相关指标。通过多元线性回归分析影响STA-PSV的相关因素。通过受试者工作特征(ROC)曲线下面积(AUC)评价STA-PSV对GD的鉴别能力。结果GD组STA-PSV明显高于AIT组[61.00(41.00,86.50)cm/s比34.50(25.25,46.00)cm/s,P<0.001],ROC曲线分析,AUC为0.790(95%CI 0.734~0.845,P<0.001),当STA-PSV切点值≥49.5 cm/s时,诊断GD的敏感性为64.3%,特异性为83.3%。在所有甲状腺毒症患者中,以STA-PSV(对数转换后)为因变量,以游离甲状腺素(FT4)和TRAb为自变量进行多因素回归分析,结果显示STA-PSV与FT4(β=0.371,95%CI 0.005~0.010,P<0.001)和TRAb(β=0.138,95%CI 0.001~0.014,P=0.035)独立相关。结论STA-PSV对GD和AIT具有一定的鉴别诊断意义,且与甲状腺素水平和TRAb相关。     

影响甲亢患者药物治疗预后的因素分析

96例Graves病(GD)甲亢患者抗甲状腺药物(ATD)治疗一年半观察疗效.测定血清促甲 状腺激素受体抗体(TRAb)水平、血清总碘含量和外周血单个核细胞表面CD80 mRNA表达.多因素条件logistic回归分析各危险因素,结果 显示GD患者TRAb水平增高、GD阳性家族史、CD80表达量增高、血清 总碘含量增高、发病年龄早可能是导致ATD治疗后复发的危险因素.     

The significance of thyroid blood flow at the inferior thyroid artery as a predictor for early Graves' disease relapse

OBJECTIVE: We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse. MEASUREMENT: Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated. PATIENTS: ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17). RESULTS: In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF). CONCLUSION: ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.     

Graves病患者血清氨基端-脑钠肽前体水平的变化

目的 研究Graves病(GD)甲亢患者血清氨基端.脑钠肽前体(NT-proBNP)的变化特点及临床意义.方法 入选GD患者269例,其中初发患者90例.测定血清甲状腺激素、促甲状腺素受体抗体(TRAb)和NT-proBNP水平.结果 血清NT-pmBNP与FT3(r=0.260,P<0.01)、FT4(r=0.297,P<0.01)和心率正相关(r=0.251,P<0.05);与超敏TSH(sTSH)负相关(r=-0.157,P<0.01).校正年龄、性别和体重指数(BMI)后,血清NT-pmBNP仍与FT3、FT4和TRAb正相关(均P<0.01).校正血清FT3,FT4、sTSH、TRAb、年龄、性别、BMI后,初发组和治疗组的血清NT-proBNP差异仍有统计学意义(P<0.01),血清FT4对NT-pwBNP有显著影响(P<0.01),NT-proBNP水平的升高在甲亢已经控制的患者中同样存在.结论 GD患者血清NT-pwBNP水平随着FT4的升高而明显上升,不受性别、年龄和BMI的影响.监测血清NT-pmBNP有助于了解GD患者的血管僵硬度和容量变化,为早期防治甲亢引起的心血管疾病提供依据.     

Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism

Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mineral density. However, of patients with Graves' disease (GD) maintained on antithyroid drug (ATD) treatment, some exhibit persistent suppression of TSH long after normalization of their serum free T3 (FT3) and free T4 (FT4) levels. The aim of this study was to examine whether bone metabolism is still enhanced in TSH-suppressed premenopausal GD patients with normal FT3 and FT4 levels after ATD therapy (n = 19) compared with that in TSH-normal premenopausal GD patients (n = 30), and to evaluate the relationship between serum TSH receptor antibody (TRAb), an indicator of disease activity of GD, and various biochemical markers of bone metabolism. No difference was found between the two groups in serum Ca, phosphorus, or intact PTH, or in urinary Ca excretion. Serum bone alkaline phosphatase (B-ALP), bone formation markers, and urinary excretions of pyridinoline (U-PYD) and deoxypyridinoline (U-DPD), which are bone resorption markers, were significantly higher in the TSH-suppression group than in the TSH-normal group (B-ALP, P < 0.05; U-PYD, P < 0.001; U-DPD, P < 0.001). For the group of all GD patients enrolled in this study, TSH, but neither FT3 nor FT4, exhibited a significant negative correlation with B-ALP (r = -0.300; P < 0.05), U-PYD (r = -0.389; P < 0.05), and U-DPD (r = -0.446; P < 0.05), whereas TRAb exhibited a highly positive and significant correlation with B-ALP (r = 0.566; P < 0.0001), U-PYD (r = 0.491; P < 0.001), and U-DPD (r = 0.549; P < 0.0001). Even in GD patients with normal TSH, serum TRAb was positively correlated with B-ALP (r = 0.638; P < 0.001), U-PYD (r = 0.638; P < 0.001), and U-DPD (r = 0.641; P < 0.001). In conclusion, it is important to achieve normal TSH levels during ATD therapy to normalize bone turnover. TRAb was not only a useful marker for GD activity, but was also a very sensitive marker for bone metabolism in GD patients during ATD treatment.     

促甲状腺激素受体抗体的检测及应用进展

促甲状腺激素(thyroid stimulating hormone,TSH)受体抗体(TSH receptor antibody,TRAb)在自身免疫性甲状腺病患者体内特异性存在,其中甲状腺刺激性抗体(thyroid stimulating anti-body,TSAb)/TSI受体刺激性免疫球蛋白(TSI)被认为是Graves病(Graves'disease,GD)的致病因素。TRAb的检测技术不断更新,新一代针对特异性TSI的检测方法正逐步应用于临床。TRAb尤其是TSI不仅对GD和Graves眼病的诊断、治疗及预后评估有重要的意义,对妊娠期甲状腺功能亢进症的治疗以及新生儿甲状腺功能异常的风险评估也具有重要价值。     

The incidence of gestational hyperthyroidism and postpartum thyroiditis in treated patients with Graves' disease.

Graves' disease (GD) is one of the most common thyroid diseases that cause hyperthyroidism. Gestational transient thyrotoxicosis (GTT) is nonautoimmune hyperthyroidism that occurs in women with a normal pregnancy. Postpartum transient thyroiditis (PTT) is a destructive thyroiditis induced by autoimmune mechanism in the postpartum period. Hyperthyroidism due to GD usually tends to improve during the course of gestation and exacerbate after delivery. When the patient with treated GD presents with thyrotoxicosis in the early pregnancy or in the postpartum period, differential diagnosis of exacerbation of GD with GTT or PTT is important because the latter disorders are fundamentally transient. To evaluate the incidence of GTT and PTT in a GD population, we investigated the thyroid functions, thyrotropin receptor antibodies (TRAb), and human chorionic gonadotropin (hCG) during pregnancy and for 1 year after delivery for 39 pregnancies in 34 women with GD. The incidence of GTT was 26% (10/39) of pregnancies. The peak value of hCG in the GTT group ([23.7 +/- 14.5] x 10(4) IU/mL, n = 9) was significantly higher than that in the non-GTT group ([13.3 +/- 4.7] x 10(4) IU/mL, n = 19). The incidence of PTT was 44% (17/39) of deliveries. The free triiodothyronine (FT(3))/free thyroxine (FT(4)) ratio of the exacerbation group of GD (3.1 +/- 1.0, n = 10) at the time of thyrotoxicosis after delivery was significantly higher than that of the PTT group (2.5 +/- 0.4, n = 16). The peak TRAb value of the exacerbation group of GD (72.5 +/- 121.7 IU/L, n = 10) at the time of thyrotoxicosis after delivery was also significantly higher than that of the PTT group (1.4 +/- 0.8 IU/L, n = 16). In conclusion, the high peak value of hCG is valuable for suspecting GTT, and the high FT(3)/FT(4) ratio is valuable for suspecting recurrence in the patients with GD. In both situations, changes of TRAb were also valuable in differentiating the recurrence of GD from GTT or PTT.     

Disseminated thyroid autonomy or Graves' disease: reevaluation by a second generation TSH receptor antibody assay.

The clinical diagnosis of disseminated autonomy (DISA) can only be established by exclusion of Graves' disease (GD). Both hyperthyroid conditions share the same scintigraphic appearance and can only be distinguished from each other clinically either by the presence or absence of endocrine ophthalmopathy (EO) or thyrotropin (TSH) binding inhibiting immunoglobulins (TBIIs). The purpose of this study was the reevaluation of thyroid autonomies originally classified as DISAs by a second-generation radioreceptor antibody assay (RAA) (DYNOtest TRAKhuman) (B.R.A.H.M.S. Diagnostika, Berlin, Germany). The analysis included 32 patients (female: n = 25, male: n = 7; mean age: 46 +/- 18 years) who were initially diagnosed with DISA. All patients were TSH receptor (TSHR) antibody (TRAb) negative by a conventional radioimmunoassay (RIA) (TSH-REZAK RIA) (Medipan Diagnostica, Selchow, Germany) during their first evaluation. The presence of EO was excluded by clinical signs in all patients. Surgery had been performed prior to our evaluation in 5 patients and after our survey in 1 patient. Four patients had been treated previously with 131I. Ten patients were treated with thionamides during our evaluation, and 13 had not been treated before. One hundred three patients who had either healthy thyroids, nontoxic goiters, or focal autonomies served as controls and were evaluated both by the TSH-REZAK assay and the DYNOtest TRAKhuman assay. Seven of thirty-two (22%) patients originally classified as DISA were TRAb positive in the second-generation assay. In this group, 5 of 7 patients had a total thyroid volume (TTV) <30 mL (positive predictive value [PPW] for TRAb positivity 71%), and 5 of 7 patients had a diffuse goiter (PPW for TRAb-positivity 71%). Six of seven patients were anti-thyroperoxidase (TPO) positive (PPW for TRAb positivity 85%). A hypoechoid pattern on ultrasound was present by visual analysis in 3 of 7 patients (PPW for TRAb positivity 43%). A 100% PPW for TRAb positivity could be obtained if a goiter <30 ml was combined with anti-TPO positivity, but this combination was present in only 4 of 7 (57%) patients. With the second-generation assay, one false positive test result was observed in the control group. Surgery was performed in 6 patients who were TRAb negative in both assays. In all these cases, the histologic findings were compatible with autonomous transformation of the thyroid. Our study demonstrates that a significant number (22%) of patients formerly classified as DISA may actually have GD. However, DISA still exists as a clinical entity, and its pathophysiological link to multifocal and unifocal autonomy should be further investigated.     

PROLONGED TREATMENT OF HYPERTHYROIDISM WITH SODIUM TYROPANOATE, AN ORAL CHOLECYSTOGRAPHIC AGENT: A RE-EVALUATION OF ITS CLINICAL UTILITY

To re-evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1.5 g daily) alone for 14 weeks, and six patients (TP + MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an 'escape' occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment. In the TP + MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4-14 weeks (7.3 +/- 5.0 weeks on the average), TP was withdrawn and replaced by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)