Grave's Disease Patients Research Articles

STAT3 single-nucleotide variants in autoimmune thyroid disease in the Pakhtun population of Khyber Pakhtunkhwa, Pakistan

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases (AluI) and AciI respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease (p = 0.002, OR = 0.28, 95 % CI = 0.11–0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control (p = 0.032, OR = 0.29, 95 % CI = 0.09–0.86). Similarly, the G and C alleles showed a significant (p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship.

ODP505 Polymorphisms of ITM2A rs1751094 on×Chromosome Is Associated with intractable Graves’ disease in Korean Children

Abstract Background Autoimmune thyroid diseases (AITDs) are female predominant and much attention has been focused on integral membrane protein 2A (ITM2A) on the X chromosome as Grave's disease (GD) susceptible locus. Methods We genotyped ITM2A rs1751094 single nucleotide polymorphism (SNP) in 166 patients (142 females and 24 males) diagnosed with AITD (67 HD and 99 GD cases). The mean age (±SD) of GD patients at enrollment was 14.4 ± 3.5 years and HD patients was 13.8 ± 3.5 years. In GD patients, 49 patients (49/99, 49.5%) had thyroid-associated ophthalmopathy (TAO). Among the 85 GD patients, 60 patients (60/85, 70.6%) were intractable GD. The data were analyzed by sex-stratified or combined with 198 healthy Korean individuals (97 females and 101 males). Results Target SNP fits the HWE. In patients with AITD (n = 166), the genotype and allele frequencies of rs1751094 AC (OR=2.5, corrected P (Pc) = 0. 000), C (OR=2. 0, Pc = 0. 000) were higher and those of AA/A (OR=0.3, Pc = 0. 000), A (OR=0.5, Pc = 0. 000) were lower than those in controls (n = 198) (Table 3). In female AITD patients (n = 143), those of rs1751094 CC (OR=2.4, Pc = 0. 031), C (OR=1.8, Pc = 0. 003) were higher and those of rs1751094 AA (OR=0.5, Pc = 0. 027), A (OR=0.6, Pc = 0. 003) were lower than those of female controls (n = 97). In patients with GD (n = 99), rs1751094 CC/C (OR=3.5, Pc = 0. 000) and C (OR=3.4, Pc = 0. 000) were higher those in controls (n = 198). In intractable GD Patients (n = 60), rs1751094 AC (OR=2.2, Pc = 0. 026) and C (OR=2.5, Pc = 0. 000) were higher than those in controls. In GD with TAO (n=49), rs1751094 CC/C (OR=2.9, Pc = 0. 003), C (OR=3.3, Pc = 0. 000) were higher than those in controls. In patients with HT (n = 67), the genotype frequencies of rs1751094 AC (OR=3. 0, Pc = 0. 000) was higher and those of AA/A (OR=0.4, Pc = 0. 002) were lower than those in controls (n = 198). Conclusions Polymorphisms in ITM2A rs1751094 on the X chromosome might be associated with AITD in Korean children. Presentation: No date and time listed

LBSAT290 Papillary Thyroid Cancer Discovered After Benign Afirma Gene Testing, A Case Report

Abstract Introduction Grave's disease is an autoimmune form of hyperthyroidism characterized by antibody stimulation of the thyrotropin receptor. Although there are conflicting study results, patients suffering from Grave's disease appear to have an increased incidence of thyroid cancer. Fine needle aspiration helps detect potential carcinoma, however, it is indeterminate in 15-30% of cases. In cases where fine needle aspiration of a thyroid nodule returns Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS), next-generation sequencing, including Afirma gene testing (created by Veracyte inc) provides guidance for therapy. However, like any screening test, the chance for false negatives still exists. We describe the case of a 41-year-old man suffering from Grave's disease with a solitary thyroid nodule which was found to be papillary thyroid carcinoma despite benign Afirma gene testing. Case description A 41-year-old male with no past medical history presented to his primary care provider with no active complaints but was found to have a blood pressure of 142/92 mmHg. He notably had a diffusely enlarged thyroid gland on examination. The patient was sent for thyroid function testing which demonstrated TSH: < 0. 01 uIU/ml and a free T4: 1.1 ng/dL. The patient was sent for a thyroid ultrasound which demonstrated a right-sided nodule measuring: 3.5 cm×2.4 cm×3.2 cm (TI-RADS 4). Radioactive idodine uptake scan revealed this was a cold nodule and the patient underwent fine-needle aspiration biopsy and Afirma gene testing. The patient's biopsy demonstrated AUS while Afirma gene testing was benign. After discussing treatment options for Grave's disease with his endocrinologist, the patient underwent total thyroidectomy. Post-surgical biopsy of the patient's thyroid demonstrated follicular variant papillary thyroid carcinoma with capsular invasion. The patient is currently being followed closely by endocrinology with regular TFT and thyroglobulin testing. Discussion Grave's disease is postulated to increase patients’ risk of developing papillary thyroid cancer. Many of the proposed hypotheses explaining this higher risk center around thyroid-stimulating antibodies promoting tumor invasion and angiogenesis. When these patients demonstrate suspicious thyroid nodules on imaging, they undergo fine-needle aspiration, however, these biopsies are indeterminate in 15-30% of cases. Afirma gene testing has been proposed as a sensitive test to rule out carcinoma in these indeterminate cases. We describe a case where, despite benign Afirma gene testing, the patient was found to have papillary thyroid cancer after thyroidectomy. We propose that Grave's disease patients with suspicious nodules with indeterminate biopsy and benign Afirma testing still be considered for total thyroidectomy given their increased risk of thyroid cancer. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Association of IL-1β, NLRP3, and COX-2 Gene Polymorphisms with Autoimmune Thyroid Disease Risk and Clinical Features in the Iranian Population.

Background Grave's disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune diseases of the thyroid gland in which genetic predisposition plays a major role in their development. Currently, the role of NLRP3 inflammasome and COX-2 has been documented in many autoimmune diseases. The purpose of the study is to delineate the impact of IL-1β (rs1143634), NLRP3 (rs3806265), and COX-2 (rs2745557) gene polymorphisms in the development of GD and HT. Methods A total of 256 newly diagnosed patients with autoimmune thyroid disease (135 patients with HT and 121 GD patients) as case groups and 145 controls were included in the study. Results Recessive and overdominant models showed a significant association between IL-1β rs1143634 SNP and HT development risk. The frequency of TT genotype and T allele of IL-1β rs1143634 SNP in the control group was significantly higher than the GD group. There was no significant association between NLRP3 rs3806265 polymorphism and HT and GD development. The frequency of GA genotype of COX-2 (rs2745557) in the control group was significantly higher than that in the HT group. There was no significant association between COX-2 rs2745557 genotypic and allelic distribution and GD development risk. The results revealed a significant relationship between some clinical features of HT and GD groups and SNPs studied. Conclusion The results manifest the significant impact of IL-1β rs1143634 and COX-2 (rs2745557) SNPs and HT development and IL-1β rs1143634 SNP on GD occurrence risk. Furthermore, a significant relationship was observed between some clinical features of HT and GD groups and studied SNPs.

Increased Risk of Polycystic Ovary Syndrome and It's Comorbidities in Women with Autoimmune Thyroid Disease.

Objective: To investigate the prevalence of polycystic ovary syndrome (PCOS) and its comorbidities in patients with autoimmune thyroid disease (AITD). Population: In this cohort study, patients newly diagnosed as having Hashimoto thyroiditis (HT) or Grave disease (GD) were recruited into the AITD group. Method: The logistic regression model was used to investigate the association between exposure, endpoint, later diseases and treatment. Main Outcome Measures: We assessed the cumulative incidence using the Kaplan–Meier method and verified the difference by the log-rank test. Results: The AITD group included 3599 GD patients and 1332 HT patients. PCOS risk in patients with AITD was higher than that in the control group (adjusted hazard ratio = 1.39; 95% confidence interval = 1.07–1.71). In patients with both AITD and PCOS, the odds ratios of diabetes, hyperlipidemia and coronary artery disease were 2.48, 2.05 and 2.63, respectively. Conclusions: The risks of PCOS and its comorbidities such as diabetes, dyslipidemia and cardiac artery disease are high in patients with AITD in Taiwan.

Mechanistic examination of methimazole-induced hepatotoxicity in patients with Grave's disease: a metabolomic approach.

Methimazole (MMI), the first-line anti-thyroid agent used in clinical practice is known to induce hepatotoxicity in patients with Grave's disease (GD), although its exact mechanism remains largely unclear. This cohort study aimed to examine the mechanism of MMI-induced hepatotoxicity using metabolomic approach. A total of 40 GD patients with MMI-induced hepatotoxicity (responders) and 80 GD patients without MMI-induced hepatotoxicity (non-responders) were included in this study and their plasma metabolomics was profiled with targeted gas chromatography-tandem mass spectrometry (GC-MS/MS). The plasma levels of 42 metabolites, including glucuronic acid, some amino acids, fatty acids, ethanolamine and octopamine were found to be significantly different between responders and non-responders. In agreement with our previous genotyping data, the genetic polymorphism of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6, which affects the glucuronidation activity and circulating glucuronic acid level was identified as one of the determinants of MMI-induced hepatotoxicity. Plasma level of ethanolamine has a significant correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The pathway analyses further revealed that monoamine oxidase (MAO) inhibition, reactive oxygen species (ROS) production, mitochondria dysfunction, and DNA disruption might contribute to MMI-induced hepatotoxicity. Interestingly, the metabolomic data further suggested the responders had a higher risk of developing osteoporosis and fatty liver disease in comparison to the non-responders. This mechanistic study sheds light on the pathogenesis of MMI-induced hepatotoxicity and prompts personalized prescription of MMI based on UGT1A1*6 genotype in the management of GD.

Association between genetic polymorphisms of SLCO1B1 and susceptibility to methimazole‐induced liver injury

Methimazole (MMI) has been used in the therapy of Grave's disease (GD) since 1954, and drug-induced liver injury (DILI) is one of the most deleterious side effects. Genetic polymorphisms of drug-metabolizing enzymes and drug transporters have been associated with drug-induced hepatotoxicity in many cases. The aim of this study was to investigate genetic susceptibility of the drug-metabolizing enzymes and drug transporters to the MMI-DILI. A total of 44 GD patients with MMI-DILI and 118 GD patients without MMI-DILI development were included in the study. Thirty-three single nucleotide polymorphisms (SNPs) in twenty candidate genes were genotyped. We found that rs12422149 of SLCO2B1, rs2032582_AT of ABCB1, rs2306283 of SLCO1B1 and rs4148323 of UGT1A1 exhibited a significant association with MMI-DILI; however, no significant difference existed after Bonferroni correction. Haplotype analysis showed that the frequency of SLCO1B1*1a (388A521T) was significantly higher in MMI-DILI cases than that in the control group (OR=2.21, 95% CI=1.11-4.39, P=0.023), while the frequency of SLCO1B1*1b (388G521T) was significantly higher in the control group (OR=0.52, 95% CI=0.29-0.93, P=0.028). These results suggested that genetic polymorphisms of SLCO1B1 were associated with susceptibility to MMI-DILI. The genetic polymorphism of SLCO1B1 may be important predisposing factors for MMI-induced hepatotoxicity.

Elevated serum concentrations of FGF23 and Klotho in patients with Graves disease and their significance

Objective To investigate the relationship between FGF23 and Klotho in GD patients. Methods From March 2016 to November 2016, forty-three newly diagnosed and untreated Grave disease patients (GD group) and 27 healthy subjects were selected.Meanwhile, Peripheral venous serum was collected to detect serum calcium, phosphorus and thyroid function in GD group.The levels of FGF23, Klotho protein and 1 in each group were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of FGF23, Klotho protein and 1, 25-dihydroxyvitamin D3 were detected by enzyme-linked immunosorbent assay (ELISA). The differences of FGF23, Klotho protein, 1, 25-dihydroxyvitamin D3, serum calcium and phosphorus between GD group and normal control group were compared, and the correlation between each index was analyzed.The relationship between FGF23 and Klotho protein and the pathogenesis of GD was explored. Results (1) Thyrotropin in thyroid function was significantly lower in GD group than that in normal group, and the difference was statistically significant (0.003(0.002, 0.004) mU/L vs.1.650(0.81, 2.14) mU/L, Z=- 7.587, P 0.05); (2) There was no correlation among Klotho and thyroid stimulating hormone receptor antibody, free thyroxin, 1, 25-dihydroxyvitamin D3, phosphorus and calcium (P>0.05). Conclusion The elevated expression of FGF23 in GD may be involved in the pathogenesis of GD, and the elevated expression of Klotho in GD may be due to the abnormal immune status in GD patients, which may play a protective role. Key words: Graves disease; Fibroblast growth factor-23; Klotho protein

Enhancement of CD4+ T cell response and survival via coexpressed OX40/OX40L in Graves' disease

OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4+ T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4+ T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4+ T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs. Confocal microscopy and coimmunoprecipitation analysis further revealed that OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of GD.

Technetium uptake predicts remission and relapse in Grave's disease patients on antithyroid drugs for at least 1 year in South Indian subjects.

Context:Most of the information on remission related factors in Grave's disease are derived from Western literature. It is likely that there may be additional prognostic factors and differences in the postdrug treatment course of Grave's disease in India.Aim:To study factors which predict remission/relapse in Grave's disease patients from South India. Also to establish if technetium (Tc) uptake has a role in predicting remission.Subjects and Methods:Records of 174 patients with clinical, biochemical, and scintigraphic criteria consistent with Grave's disease, seen in our Institution between January 2006 and 2014 were analyzed. Patient factors, drug-related factors, Tc-99m uptake and other clinical factors were compared between the remission and nonremission groups.Statistical Analysis Used:Mann–Whitney U-test and Chi-square tests were used when appropriate to compare the groups.Results:Fifty-seven (32.7%) patients attained remission after at least 1 year of thionamide therapy. Of these, 11 (19.2%) patients relapsed within 1 year. Age, gender, goiter, and presence of extrathyroidal manifestations were not associated with remission. Higher values of Tc uptake were positively associated with remission (P- 0.02). Time to achievement of normal thyroid function and composite dose: Time scores were significantly associated with remission (P - 0.05 and P - 0.01, respectively). Patients with lower FT4 at presentation had a higher chance of remission (P - 0.01). The relapse rates were lower than previously reported in the literature. A higher Tc uptake was found to be significantly associated with relapse also (P - 0.009).Conclusion:The prognostic factors associated with remission in Graves's disease in this South Indian study are not the same as that reported in Western literature. Tc scintigraphy may have an additional role in identifying people who are likely to undergo remission and thus predict the outcome of Grave's disease.

The sickness impact and the quality of life in Grave's disease patients after treatment with 131I

Objective To evaluate the sickness impact and the quality of life in patients who received 131I treatment for Grave's disease with one year of follow-up. Methods 376 patients with Grave's disease(GD) who voluntarily received 131I treatment were recruited. The follow-up archives were established. The Sickness Impact and the Quality of life in patient’s with GD were measured using the Sickness Impact Profile(SIP), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale(SAS) and Social Disability Screening Schedule (SDSS) and Quality of life scale(QLS, SF-36) before and after treatment with 131I for 6 months and 12 months. Results 57 out of 376 cases were lost. 319 cases finished follow-up studies. There was significant difference of SAS, SDS, SDSS, SIP and SF-36 and their agent score among three groups : before and 6months and 12months after 131I treatment in the 319 patients(F=8.561-1080.317, P 0.05). But there was significant difference between the score of SIP agent score of SD-I, HM, RP, SF-36 total score and it’s agent score of PF, GH, RE, MH at the end of 12 months compared to the score at the end of 6 months(P<0.05). At the end of 6 months and 12 months after treatment the subjects were divided five groups according to different clinical outcome. Not only at the end of 6 months, but also at the end of 12 months, there was significant difference of SAS, SDS, SDSS, SIP total score, and it’s agent score of SD-I, SD-II, SR, W, RP, SF-36 total score, and it’s agent score PF, RP, BP, GH, VT, SF, RE, MH among the five groups(F6=6.870-143.790, F12=13.956-837.184, P<0.001). There was no significant difference of HM among five groups(F6=1.733, P6=0.142; F12=2.015, P12=0.092). The score of SF-36 and its agent score PF, RP, VT, SF, RE, MH in three subgroup (healthy control, the patient group at end of 6 months and 12 months with normal thyroid function) was significant different, respectively(F=8.320-82.791, P<0.001). There was no significant different for agent score of BP and GH(F=2.990, 2.652, P=0.051, 0.072). Conclusion Quality of life of patients with GD is decrease. 131I treatment can improve it, but social-psycho function can not be improved satisfactorily. It is necessary for GD patients to pay attention to the quality of life and provide effective mental intervention to improve the recovery completely. Key words: Grave's disease; 131I; Mental health; Quality of life

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery

To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. 2b.

Eficacia del tratamiento con 131I en la enfermedad de Graves pediátrica

IntroductionRadioiodine is an important therapeutic option in young patients with Grave's disease (GD). In the United States it is a widespread therapy, but in Europe its use in paediatrics is still controversial. AimTo report our experience in radioiodine therapy of paediatric GD patients and analyse its effectiveness and safety. Patients and methodsWe retrospectively studied our paediatric population (<18 years of age) with GD, diagnosed from 1982 to 2012. A curative option was offered to patients who did not respond to anti-thyroid drug (AT) at puberty. We analysed, the patient characteristics, TSH, T4, T3 and thyroid antibodies levels, AT response, remission post I131, side effects, and hypothyroidism rates. ResultsA total of 50 patients were diagnosed with GD from 1982 to 2012. All patients received AT as initial treatment (mean duration: 35.3±25.9 months). Permanent remission was achieved in 46%. Thyroidectomy was performed in 5 patients, and 14 patients received I131 (mean dose: 10.9±1.09 mCi). Remission with I131 was obtained in 100%. The rate of permanent hypothyroidism was 90%. There was no progression of ophthalmopathy or side effects in any patients treated with I131. ConclusionRadioiodine treatment of paediatric GD patients is safe, leads to complete remission at the expense of hypothyroidism, and does not exacerbate ophthalmopathy. It can be considered in patients older than 5 years, who do no not respond to AT or with significant side effects with this medication.

The role of long term use of antithyroid drugs in Graves’ disease

Graves' disease is an autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies. Radioactive iodine (RAI) and antithyroid drugs (ATD) are the preferred initial treatment options in Graves' disease in many parts of the world. Long term treatment with methimazole in Grave's disease patients beyond the recommended period is shown to be safe and effective and emerging evidence suggests that continuous methimazole therapy may even be superior to RAI therapy in some aspects. Recent randomized trials comparing long-term methimazole to RAI in patients who relapse, have confirmed these findings Sri Lanka Journal of Diabetes, Endocrinology and Metabolism 2013; 3 : 41-44 DOI: http://dx.doi.org/10.4038/sjdem.v3i1.5503

Anti-thyroid peroxidase antibodies: Its effect on thyroid gland and breast tissue

Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions). TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement of antibodies to TPO that gives reliable information about autoimmune thyroid disease. Eighty percent of Grave's disease patients have high levels of antiTPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. There is always a controversy on the relationship between breast cancer and thyroid disorders. As these tissues, i.e., breast and thyroid, originate embryologically from the same type of cells, hypothyroid/hyperthyroid females are more prone to develop benign or malignant breast tumors. The studies on breast cancer patients indicate increased thyroid disorders in breast cancer patients, most commonly Hashimoto's thyroiditis accounts to increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer.

Identification of a novel staining pattern of bile duct epithelial cells in primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an inflammatory disease of the bile ducts with an unknown etiology. A number of autoantigens have been proposed, but an early diagnostic marker is still lacking. Our aim was to identify such an autoantigen. Immunostaining was performed on normal human bile duct with sera from patients with PSC and controls. To identify an autoantigen a cDNA library from normal human choledochus was constructed and immunoscreened with patient sera. Using in vitro transcription and translation and immunoprecipitation we examined the immunoreactivity against PDZ domain containing 1 (PDZK1) in 35 patients with PSC, 198 control patients, and 94 healthy controls. We observed a previously unpublished staining pattern in which cytoplasmatic granules and apical cell membranes of biliary epithelial cells were stained by PSC sera. Strong immunoreactivity to these structures was obtained with 12 out of 35 PSC sera (34%) but not with sera from healthy controls. By screening the cDNA library we identified PDZK1 as a candidate antigen. Immunoreactivity against PDZK1 was detected in 9% of PSC patients, 2% of inflammatory bowel disease (IBD) patients, 8% of autoimmune pancreatitis patients, 18% of Grave's disease patients, and 1% of healthy controls. Previously unpublished, specific, and strong autoantibodies against epithelial cells of the bile duct in PSC sera were identified. Furthermore, PDZK1 is suggested as a potential new autoantigen.

Radioiodine treatment for pediatric hyperthyroid Grave’s disease

Grave's disease (GD) is an autoimmune disease in which excessive amounts of thyroid hormones circulate in the blood. Treatment for pediatric GD includes (1) antithyroid drugs (ATD), (2) radioiodine, and (3) thyroidectomy. Yet, the optimal therapy remains controversial. We collected studies from all electronically available sources as well as from conferences held in China. All studies using radioiodine and/or ATD and/or thyroidectomy were included. Information was found on 1,874 pediatric GD patients treated with radioiodine, 1,279 patients treated with ATD and 1,362 patients treated surgically. The cure rate for radioiodine was 49.8%; the incidence of hypothyroidism, 37.8%; of relapse, 6.3%; of adverse effects, 1.55%; and of drop outs, 0.6%. These data show that radioiodine treatment is safe and effective in pediatric GD with significant lower incidence of relapse and adverse effects but significantly higher incidence of hypothyroidism as compared with both ATD and thyroidectomy. For the time being, radioiodine treatment for pediatric GD remains an excellent first-line therapy and a good second-line therapy for patients with ATD failure, severe complications, or poor compliance.

MICROSOMAL AND THYROGLOBULIN ANTIBODIES IN THYROID DISORDERS

Eighty patients with various thyroid disorders and 20 controls were investigated to determine antibodies against thyroglobulin and microsomal antigens by haemagglutination and immunofluorescent techniques. They were also tested for immunoglobulin profile by radial immunodiffusion methods. Patients with Hashimoto's disease, idiopathic hypothyroidism, and Grave's disease showed significant elevations of IgG. None of the patients with toxic nodular goitre or thyroid adenoma showed any thyroid antibodies while 69.2% patients with Grave's disease, 16% with euthyroid goitre, 58.3% with hypothyroidism and all the patients with Hashimoto's disease had microsomal antibodies by immunofluorescent test. Similarly, all the cases of Hashimoto's disease, 41.6% of those with hypothyroidism, 30% of Grave's disease patients and none of the patients with toxic nodule or thyroid adenoma had thyroglobulin antibodies by haemaglutination test. Evaluation for auto-antibodies may aid the clinician in the overall assessment of various thyroid disorders.

Expression polymerase chain reaction for the in vitro synthesis and epitope mapping of autoantigen application to the human thyrotropin receptor

The clinical applicability of a newly described polymerase chain reaction directed protein expression system was assessed for the in vitro synthesis and partial epitope mapping of large radiolabeled human thyrotropin receptor (hTSH-R) protein segments. PCR amplification of targeted regions within the hTSH-R cDNA followed by in vitro transcription and translation permitted rapid synthesis of protein segments ranging in size from 18 to 62 kDa. Initial epitope mapping was directed at a 52 amino acid segment unique to the hTSH-R compared to otherwise homologous glycoprotein hormone receptors. Sera from Grave's disease patients known to have autoantibodies against the hTSH-R were used to immunoprecipitate two protein fragments differing only by the presence of the unique region in the larger fragment (E5) but not in the smaller fragment (E4). Dense precipitation bands were obtained using Graves' sera to immunoprecipitate E5 whereas little or no specific immunoprecipitation of E4 occurred. Normal sera gave only weak immunoprecipitation bands of E5. The technique provides significant advantages over conventional cloning methods and should have general applicability in the study of other protein targets of autoimmune disease.