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Graves' Disease (graves' + disease)
Selected AbstractsAssociation between the TAP2 gene codon 665 polymorphism and Graves' DiseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Rong-Hsing Chen Abstract A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303,10.598 and 1.020,4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449,3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development. J. Clin. Lab. Anal. 20:93,97, 2006. © 2006 Wiley-Liss, Inc. [source] Elderly patient presenting with severe thyrotoxic hypercalcemiaGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2006Reiko Kikuchi An 81-year-old woman with Graves' disease and osteoporosis was referred to the hospital because of anorexia over one month and impaired consciousness. She also presented with low-grade fever and emaciation. Laboratory tests revealed marked hypercalcemia (corrected serum calcium level of 12.4 mg/dL), which was initially suspected to result from vitamin D toxicity, because she had been taking vitamin D3 (alphacalcidol of 0.5 µg/day) for the treatment of osteoporosis. However, discontinuation of vitamin D3 and fluid infusion did not ameliorate hypercalcemia one week later. After excluding hyperparathyroidism and malignancy-related hypercalcemia, hypercalcemia was considered to be attributable to the exacerbation of hyperthyroidism (free T4 of 6.69 ng/dL, free T3 of 13.27 pg/mL and thyroid stimulating hormone (TSH) <0.015 µIU/mL) with increased bone resorption. Finally, the increased dose of thiamazole (30 mg/day) normalized serum calcium level and thyroid function three months later. Laboratory tests suggested that normal bone formation in spite of increased bone resorption contributed to hypercalcemia in hyperthyroid state. [source] Carbimazole-induced agranulocytosis: does antineutrophil cytoplasmic antibody have a role?INTERNAL MEDICINE JOURNAL, Issue 4 2010G. Yip Abstract Carbimazole is a drug that is widely used for hyperthyroid disorders, such as Graves' disease. Agranulocytosis is a rare idiosyncratic adverse reaction to the drug which is potentially fatal. This report describes a patient with a history of successfully treated pyoderma gangrenosum, who developed agranulocytosis 3 weeks after commencement of carbimazole for Graves' disease. It may give credence to the theory that implicates antineutrophil cytoplasmic antibodies in the pathogenesis of agranulocytosis induced by antithyroid drugs. [source] Evaluation of management of Graves' disease in District General Hospital: achievement of consensus guidelinesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2005S. Dasgupta Summary The management of Graves' disease in a District General Hospital was audited. A local care pathway was designed, which was inclusive of diagnosis, treatment and follow-up. This was then compared with consensus guidelines proposed by the Royal College of Physicians. Forty-six patients with Graves' disease attended the endocrine clinic. The diagnosis was based on clinical and biochemical features of autoimmune thyrotoxicosis, a raised thyroid-stimulating hormone receptor antibody (TRAB) and a diffusely increased uptake in thyroid technetium scan. They were treated for 18 months with antithyroid medications, which was subsequently discontinued provided satisfactory euthyroid state was achieved. Patients were followed up to assess remission and relapse status. The audit suggested that care pathway was in keeping with the guidelines. A few excess TRAB tests were requested. The relapse rate was 42% in our series and one-third of them (33%) chose to continue medical therapy. [source] Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseasesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007Ala'eddin Jebreel Summary Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0,3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology. [source] Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic idiopathic hypoparathyroidism in Asian IndiansINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 4 2006D. Ray Summary Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in 80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37 females, mean ± SD age and duration of symptoms 32.5 ± 14.1 years and 6.7 ± 7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male : female ratio 91:102, mean ± SD age, 43.1 ± 11.6 years) to assess association of 1858T allele with the disease. Polymerase chain reaction,restriction fragment length polymorphism analysis was performed to genotype C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51,7.37). Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian Indians. The trend of higher prevalence of 1858T allele in patients with SIH needs to be studied further in other population with higher rate of the allele to support the autoimmune basis of the disease. [source] Lack of association between pro-inflammatory cytokine (IL-6, IL-8 and TNF-,) gene polymorphisms and Graves' diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2005R.-H. Chen Summary Graves' disease (GD) is a common, autoimmune disease involving the thyroid gland, and it has been previously suggested that pro-inflammatory cytokines are involved in the disease's pathogenesis. The aim of this study was to test whether the interleukin (IL)-6 gene promoter region, or tumour necrosis factor (TNF)-, or IL-8 gene 3,-untranslated region (3,-UTR) polymorphisms could provide useful genetic markers for an individual's susceptibility to GD. A normal control group of 60 healthy people and 95 patients featuring GD were examined. Polymerase chain reaction (PCR)-based restriction analysis was performed for the three gene polymorphisms using endonucleases BsrBI, NcoI and ApaLI, respectively. We found no significant difference between the frequencies of genotype and allelic variants for the IL-6 gene promoter (,572 G/C), the TNF-, gene promoter (,308 A/G) and the IL-8 gene 3,-UTR (2767 A/G) for GD patients and for normal controls. Cytokines are a large group of proteins that may elicit multiple effects upon immunological reactions. It still appears to be very worthwhile to continue to aggressively search for cytokine gene polymorphisms in order to predict the development of such disease. [source] Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012,1704) of the TSH receptor gene in Graves' diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2000Viktória Kaczur We determined the genetic variability of the 1st (CCC/ACC, P52T polymorphic variant) and 10th exons (bp 1012,1704) of the TSH receptor (TSHR) gene in Graves' disease. A total of 101 Graves' patients and 163 control subjects were screened. The A253 mutant allele was carried by nine patients with Graves' disease (8.91%) and 13 control subjects (7.98%) in heterozygous genotype. No significant difference in the frequency of the mutant allele was found between Graves' patients and control subjects. These results provide evidence that the A253 polymorphism has no genetic relevance in Graves' disease. Moreover, the DNA nucleotide sequence of 693 bp of the 10th exon (bp 1012,1704) of the TSHR gene was determined in 15 Graves' patients. Six patients were homozygous for the wild-type allele and nine were heterozygous for the mutant allele at the 253rd nucleotide of the first exon. No polymorphism was found in the DNA sequences obtained from leukocytes of Graves' patients, similarly to the sequences obtained from the nine control subjects. None of the nine patients carrying the A253 polymorphism in the 1st exon of the TSHR had polymorphism in the examined part of the 10th exon, including two additional patients whose thyroid tissue was directly analysed. In all likelihood, the polymorphisms of the examined regions of either the 1st or the 10th exon of the THSR gene do not contribute to the genetic susceptibility to Graves' disease. [source] Association between the TAP2 gene codon 665 polymorphism and Graves' DiseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Rong-Hsing Chen Abstract A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303,10.598 and 1.020,4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449,3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development. J. Clin. Lab. Anal. 20:93,97, 2006. © 2006 Wiley-Liss, Inc. [source] Acute ataxia, Graves' disease, and stiff person syndromeMOVEMENT DISORDERS, Issue 13 2007Su-Ynn Chia MD Abstract Stiff person syndrome (SPS) has been associated with autoimmune diseases, such as Type 1 diabetes mellitus and autoimmune thyroid disease (Hashimoto's thyroiditis), among others. The association of SPS with hyperthyroidism is extremely rare. We describe a patient with uncontrolled Graves' disease and undiagnosed SPS, who presented initially with acute ataxia simulating a cerebrovascular accident. Initiation of immunosuppressive therapy dramatically improved the patient's Graves' disease within 2 weeks but the neurological symptoms were not alleviated after a follow-up period of 3 years. © 2007 Movement Disorder Society [source] Autoimmune polyglandular syndrome Type 3 and growth hormone deficiencyPEDIATRIC DIABETES, Issue 6 2010JB Quintos Quintos JB, Grover M, Boney CM, Salas M. Autoimmune polyglandular syndrome type 3 and growth hormone deficiency. The simultaneous occurrence of prepubertal Graves' disease, type 1 Diabetes Mellitus (DM), and Growth hormone deficiency (GHD) is uncommon. GHD has been reported in Autoimmune Polyglandular Syndrome (APS) Type 1 and Type 2 but not in APS Type 3. We report a 3-yr-old boy who presented simultaneously with type 1 DM and Graves' disease. After he developed urticarial rash to Propylthiouracil and Methimazole with persistent thyrotoxicosis, he received 8 millicuries of 131I at 5 yr of age. We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. Both insulin-like growth factor (IGF) 1 (90 ng/mL; normal 113,261 ng/mL) and IGFBP3 (1.3 mcg/mL; normal 2.1,4.2 mcg/mL) levels were low and peak growth hormone level measured by RIA was 5.2 ng/mL after L-Dopa and insulin tolerance test. The rest of his pituitary functions and magnetic resonance imaging of the pituitary gland were normal. Growth hormone treatment (0.3 mg/kg/wk) was administered at 8 yr 9 months until near final adult height (FAH). Near FAH (172 cm) was close to midparental target height of 180 cm. GHD may be a component of all APS even though it is rare. Growth in treated children with Graves' disease should be followed closely as catch down growth below genetic height potential may be a harbinger of underlying GHD. [source] Prolonged honeymoon phase in an adolescent with diabetes and thyrotoxicosis provides support for the accelerator hypothesisPEDIATRIC DIABETES, Issue 4pt2 2008Nadeem Abdullah Abstract:, A 14-yr-old female presented with diabetes and Graves' disease. Eighteen months later, she was euthyroid on carbimazole, and her haemoglobin A1c (HbA1c) was normal (5.2%) on a small insulin dose (0.3,0.4 units/kg/day). An assessment of her pancreatic beta-cell reserve, determined by comparing HbA1c and insulin dose, suggested that this was greater than other patients with type 1 diabetes in our service 18 months postdiagnosis (n = 185). We suspect that excess thyroid hormone led to an insulin-resistant state and accelerated her presentation with hyperglycaemia. Insulin resistance fell once normal thyroid function was restored and helped to attenuate further beta-cell destruction when beta-cell mass was relatively well preserved. [source] Hepatitis B vaccine and risk of autoimmune thyroid disease: a Vaccine Safety Datalink study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 7 2007Onchee Yu MS Abstract Purpose Hepatitis B vaccine has been postulated as a possible cause of autoimmune disorders, including autoimmune thyroid diseases (ATD). Cases of Graves' disease and Hashimoto's thyroiditis, following hepatitis B vaccine have been reported to the Vaccine Adverse Events Reporting System (VAERS). To test the hypothesis that hepatitis B vaccine increases the risk of ATD, we conducted a case-control study, within the Vaccine Safety Datalink project. Methods We identified potential cases of Graves' disease and Hashimoto's thyroiditis, among persons aged 18,69 years from administrative data recorded by three health maintenance organizations (HMOs) and verified cases by medical record review. Controls were frequency-matched to cases by birth year, sex, and study site. Vaccine information was collected from administrative records, chart review, and telephone interviews with study subjects. We enrolled 355 Graves' disease cases, 418 Hashimoto's thyroiditis cases, and 1102 controls. We assessed the association between ever-receipt of hepatitis B vaccine, as well as receipt of hepatitis B vaccine less than 1 year, 1,5 years and at least 5 years prior to the index date, and the risk of ATD. Results Ever-receipt of hepatitis B vaccine was not associated with risk of Graves' disease (odds ratio (OR), 0.90; 95% confidence interval (CI), 0.62,1.32) or Hashimoto's thyroiditis (OR, 1.23; 95%CI, 0.87,1.73). There was also no association between the time interval since receipt of hepatitis B vaccination and either outcome. Conclusions We did not observe an increased risk of Graves' disease or Hashimoto's thyroiditis, following receipt of hepatitis B vaccine. Copyright © 2007 John Wiley & Sons, Ltd. [source] Thyroid storm prior to induction of anaesthesiaANAESTHESIA, Issue 10 2004E. A. Hirvonen Summary A 53- year-old woman without a previous history of thyroid disease was scheduled for mastectomy. On arrival in the operating theatre unpremedicated she appeared restless and tachycardic. Midazolam and fentanyl was administered intravenously. Concomitantly, sinus tachycardia developed and a flush reaction was observed in the skin of the thoracic region and neck. The blood pressure increased to 265/160 mmHg and the patient lost consciousness and became apnoeic. Unconsciousness and apnoea lasted for approximately 25 min and the operation was postponed. Further investigations revealed an elevated serum free thyroxine level and suppressed serum thyrotropin diagnostic of hyperthyroidism. The serum TSH receptor antibody concentration was elevated, indicating that the patient was suffering from Graves' disease. We present a case of a previously unknown hyperthyroid patient, with breast cancer, presenting as a thyroid crisis on induction of anaesthesia. Although being quite a rare occurrence, unsuspected thyroid disease should be borne in mind when an agitated patient enters the operating theatre. [source] Does autoimmune thyroid disease affect parathyroid autotransplantation and survival?ANZ JOURNAL OF SURGERY, Issue 5 2009Houman Ebrahimi Abstract Background:, While the increased risk to parathyroid gland preservation has long been recognized during surgery for thyroid cancer, the effect of different benign pathological conditions on parathyroid preservation has not previously been reported. The aim of this study was to examine parathyroid viability in relation to autoimmune thyroid disease. Methods:, This is a retrospective cohort study including all patients having an initial total thyroidectomy (TT) performed by this unit during the period 2004,2005. Results:, A total of 628 patients underwent TT in the study period. For the Graves' disease cases, 45 (62.5%) required the autotransplantation of one or less parathyroid gland, whereas 27 (37.5%) required two or more glands to be autotransplanted. This was significantly higher than for the benign thyroid disease group in which the respective figures were 242 (77.6%) and 70 (22.4%) (P= 0.01). Of the lymphocytic thyroiditis cases, 61 (65.5%) required the autotransplantation of one or less gland, whereas 32 (34.4%) required the autotransplantation of two or more glands. This was also significantly higher (P= 0.03). Temporary hypocalcaemia was significantly higher when two or more glands were autotransplanted (23 out of 177, 13.2%) than one or less gland autotransplanted (18 out of 451, 4.0%, P < 0.01). However, the overall incidence of permanent hypoparathyroidism was 1.0%, and there was no significant difference between the groups. Conclusion:, TT performed for Graves' disease and lymphocytic thyroiditis results in the autotransplantation of more parathyroid glands, leading to a higher incidence of temporary hypocalcaemia post-operatively. Despite this, the incidence of permanent hypoparathyroidism remains low at 1%. [source] Association of the IL2RA/CD25 gene with juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 1 2009Anne Hinks Objective IL2RA/CD25, the gene for interleukin-2 receptor ,, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the association of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are associated with juvenile idiopathic arthritis (JIA). Methods Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an association with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n = 654) and controls (n = 3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n = 747) and controls (n = 1,161). Association analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results SNP rs2104286 within the IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele 0.76 [95% CI 0.66,0.88], P for trend = 0.0002). A second SNP (rs41295061) also showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63,1.0], P = 0.05). Association with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65,0.99], P for trend = 0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of association with JIA (OR 0.76 [95% CI 0.62,0.88], P = 4.9 × 10,5). Conclusion These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required. [source] A nonsense mutation in exon 2 of the DNase I gene is not present in UK subjects with systemic lupus erythematosus and Graves' disease: Comment on the article by Rood et alARTHRITIS & RHEUMATISM, Issue 11 2002Matthew J. Simmonds BSc No abstract is available for this article. [source] Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 7 2002Sampath Prahalad Objective To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. Methods Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. Results There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1,5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6,7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. Conclusion These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity. [source] Thiocyanate overload and thyroid diseaseBIOFACTORS, Issue 3-4 2003Murat Faik Erdo Abstract Thiocyanate [SCN,] is a complex anion which is a potent inhibitor of iodide transport. It is the detoxification product of cyanide and can easily be measured in body fluids. Consumption of naturally occurring goitrogens, certain environmental toxins and cigarette smoke can significantly increase SCN, concentrations to levels potentially capable of affecting the thyroid gland. Goiter endemics were reported to develop when the critical urinary iodine/ SCN, ratio decreases below 3 ,g iodine per mg SCN,. Iodine supplementation completely reverses the goitrogenic influence of SCN,. SCN, is also generated from cigarette smoking as a detoxifying product of cyanide. During the past two decades many reports dealt with the possible effects of cigarette smoking on thyroid hormone synthesis, thyroid gland size and thyroid autoimmunity including infiltrative ophtalmopathy of Graves' disease. In this mini-review, issues regarding thiocyanate overload and thyroid disease will be summarized. [source] Transient hyperthyroidism of hyperemesis gravidarumBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2002Jackie Y.L. Tan Objective To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. Design Prospective observational study. Setting Hospital inpatient gynaecological ward. Population Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. Methods Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. Main outcome measures Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). Results Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of >5% of their pre-pregnancy weight was lower compared with those of women who did not (P= 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. Conclusions In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism. [source] Prognosis of small thyroid cancer in patients with Graves' diseaseBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2006S. Kikuchi Background: To find the best ways to follow up patients with small thyroid cancer (STC; 1 cm or less in diameter) and concomitant Graves' disease, this study examined whether such patients had the same excellent prognosis as those with STC without Graves' disease. Methods: Between 1970 and 1996, 2199 patients were diagnosed as having STC by pathology after thyroidectomy. Of those, 509 patients (33 males and 476 females, mean age 43·5 years) underwent thyroidectomy for Graves' disease. Control patients with STC without Graves' disease were matched for age, sex, treatment year and tumour size (33 males and 476 females, mean age 44·0 years). Results: Patients with STC and Graves' disease had a longer disease-free survival than those with STC alone (99 and 93 per cent at 20 years' follow-up, respectively; P < 0·001). The Cox's proportional hazard analysis showed that concomitant Graves' disease and age at surgery are more significant factors for predicting disease-free survival than surgical procedures. Conclusion: Patients who undergo thyroidectomy for Graves' disease and are found to have STC have an excellent prognosis and longer disease-free survival than patients with STC alone. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] The +869T/C polymorphism in the transforming growth factor-,1 gene is associated with the severity and intractability of autoimmune thyroid diseaseCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008H. Yamada Summary The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor-,1 (TGF-,1) gene, which is associated with TGF-,1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF-,1 +869T/C polymorphism by polymerase chain reaction,restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50 years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50 years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF-,1 gene is associated with the severity and intractability of autoimmune thyroid disease. [source] Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progressionCLINICAL ENDOCRINOLOGY, Issue 1 2010Kadija Yesmin Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source] Optimizing remission rates using antithyroid drugs for Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2010Laszlo Hegedüs No abstract is available for this article. [source] Graves' disease in children and adolescents: Response to long-term treatmentACTA PAEDIATRICA, Issue 11 2005RAQUEL BARRIO Abstract Background: Optimal treatment of Graves' disease in paediatric patients is still a matter of controversy. Antithyroid drugs, radioiodine and thyroidectomy are the three therapeutic options available. Aim: To report our experience of long-term medical treatment and outcome of paediatric Graves' disease. Methods: A 5-y-long medical protocol was implemented in 20 children and adolescents with Graves' disease. All patients received antithyroid drugs as the first therapeutic option; patients who did not enter long-term remission received I131 and/or surgery as the definitive treatment. Results: The mean age at diagnosis was 12.1±4 y. Only two patients were males, both presenting concomitant type 1 diabetes. Mean follow-up was 13.8 ± 5.5 y. Forty per cent of patients achieved long-term remission with low antithyroid drugs doses (mean treatment time: 5.4± 1.4 y). Six patients received I131 as definitive treatment and another six underwent surgery after completing medical treatment for 6.8 ± 4.1 and 5.1 ± 2 y, respectively. No patients requiring high antithyroid drugs doses to maintain euthy-roidism reached long-term remission and needed I131 and/or surgery. Conclusion: Implementation of a long-term antithyroid drug protocol achieved 40% long-term remissions in paediatric patients with Graves' disease. Need for maintained high doses of antithyroid drugs could be considered a predictive factor for no remission. When permanent remission was not obtained by medical treatment, I131 and/or surgery allowed healing in all cases. [source] Regulatory T cells in Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 4 2009Deshun Pan Summary Context, Graves' disease (GD) involves auto-immunity against thyroid cell antigens, but the reasons for induction of auto-immunity are uncertain. We wished to determine whether there was a deficiency of regulatory T cells in patients with active GD. Design, Venous blood samples were obtained from patients with GD before and after treatment, and controls, and peripheral blood mononuclear cells were prepared. Patients and measurements, Regulatory T cells were enumerated by Fluorescent Activated Cell sorting (FACS) in nineteen patients with untreated GD, 9 patients 6,8 weeks post RAI therapy, and 30 control subjects. Twenty-one patients with active GD prior to control of hyperthyroidism, 23 euthyroid controls without known autoimmune thyroid disease, and 10 patients who were euthyroid 6,12 months after RAI treatment were studied for expression of genes found in regulatory T cells by real-time Polymerase Chain reaction (PCR). Results, Percent distribution of CD4+, CD4+CD25+ and CD4+ CD25+int-hi CD127+lo regulatory T cells was similar in active GD patients and control subjects. The number of CD25+ and CD4+ CD25+int-hi CD127+lo cells was similar in GD patients and control subjects, but was lower in recently treated patients. Messenger RNA was prepared from PBMC, and reverse transcribed. Copy DNA abundance was evaluated by Real Time PCR using appropriate primers, for GAPDH (glyceraldehyde phosphate dehydrogenase) as a control housekeeping gene, and 5 genes related to function of regulatory T cells. Message RNA for Gadd45 alpha, Gadd45beta (growth arrest and damage inducible proteins), GITR (glucocorticoid inducible TNF receptor) and CD25 (IL-2R subunit) was more abundant in patients with active GD than in normal controls, and FoxP3 mRNA level was equal to that in controls. Message RNA levels in patients treated and euthyroid for 6 months were also greater than or equal to values in controls. Conclusion, This study provides evidence that there is no deficit in T regulatory cells during active GD, or during the months post therapy. [source] Too early to dismiss Yersinia enterocolitica infection in the aetiology of Graves' disease: evidence from a twin case,control studyCLINICAL ENDOCRINOLOGY, Issue 3 2008Thomas H. Brix Summary Background,Yersinia enterocolitica (YE) infection has long been implicated in the pathogenesis of Graves' disease (GD). The association between YE and GD could, however, also be due to common genetic or environmental factors affecting the development of both YE infection and GD. This potential confounding can be minimized by investigation of twin pairs discordant for GD. Aim, To examine whether YE infection is associated with GD. Design, We first conducted a classical case,control study of individuals with (61) and without (122) GD, and then a case,control study of twin pairs (36) discordant for GD. Methods, Immunoglobulin (Ig)A and IgG antibodies to virulence-associated Yersinia outer membrane proteins (YOPs) were measured. Main outcome measures, The prevalence of YOP IgA and IgG antibodies. Results, Subjects with GD had a higher prevalence of YOP IgA (49%vs. 34%, P = 0·054) and YPO IgG (51%vs. 35%, P = 0·043) than the external controls. The frequency of chronic YE infection, reflected by the presence of both IgA and IgG YOP antibodies, was also higher among cases than controls (49%vs. 33%, P = 0·042). Similar results were found in twin pairs discordant for GD. In the case,control analysis, individuals with GD had an increased odds ratio (OR) of YE infection: IgA 1·84 (95% CI 0·99,3·45) and IgG 1·90 (95% CI 1·02,3·55). In the co-twin analysis, the twin with GD also had an increased OR of YE infection: IgA 5·5 (95% CI 1·21,24·81) and IgG 5·0 (95% CI 1·10,22·81). Conclusion, The finding of an association between GD and YE in the case,control study and within twin pairs discordant for GD supports the notion that YE infection plays an aetiological role in the occurrence of GD, or vice versa. Future studies should examine the temporal relationship of this association in more depth. [source] Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remissionCLINICAL ENDOCRINOLOGY, Issue 4 2007Anja K. Eckstein Summary Objective, To evaluate the relationship between severity of Graves' ophthalmopathy (GO) and relapse/remission rate of associated thyroid disease. Patients and methods, One hundred and fifty-eight patients with Graves' disease (GD) were seen within the first 6,12 months after the onset of GO and were followed for at least 18 months. During treatment, GO was classified as mild (n = 65) or severe course (n = 93) by severity and activity scores. All patients received standard anti-thyroid drug (ATD) treatment for 1 year, and in cases of relapse another cycle of ATD, thyroidectomy or radioiodine therapy. Results, Following ATD treatment, 27 patients (42%) with a mild course of GO went into thyroid disease remission, while only seven (8%) patients with a severe course of GO achieved remission (P < 0·0001). Eventually, 32 patients (49%) with a mild course needed definitive thyroid therapy and the remaining 9% preferred another cycle of ATD. However, among patients with a severe GO course, 84% needed definitive therapy (P < 0·0001) and 8% opted for another course of ATD treatment. The probability of relapse could also be predicted by TBII levels 12 months after initiation of ATD therapy, as 96·8% of patients with TBII levels above 7·5 IU/l relapsed (odds ratio 24·3). Conclusion, Patients with severe GO and high TBII are unlikely to go into remission. This allows early decision-making regarding definitive treatment of the thyroid in GD patients with severe GO or very high TBII levels. [source] Susceptibility genes in Graves' ophthalmopathy: searching for a needle in a haystack?CLINICAL ENDOCRINOLOGY, Issue 1 2007Tomasz Bednarczuk Summary The variety of clinical presentations of eye changes in patients with Graves' disease suggests that complex interactions between genetic, environmental, endogenous and local factors influence the development/severity of Graves' ophthalmopathy (GO). At present, the role of genetic factors in the development of GO remains unknown. Based on small case-control association studies with candidate genes, several susceptibility loci in GO have been proposed. These are human leucocyte antigen (HLA, 6p21·3), cytotoxic T-lymphocyte antigen-4 (CTLA-4, 2q33), tumour necrosis factor (TNF, 6p21·3), interferon-, (IFN-,, 12q14), intercellular adhesion molecule-1 (ICAM-1, 19p13), and thyroid stimulating hormone receptor gene (TSH-R, 14q31). Unfortunately, these results were either not confirmed or require replication in larger studies. There are many reasons for the lack of reproducibility of association studies in GO, including poor characterization of the studied groups and small sample sizes, which may result in both false positive and negative results. Thus, the genetic background of GO remains to be elucidated in future research. However, the possibility that GO may be a genetically heterogeneous disorder, or that the development of GO may be predominantly influenced by environmental factors such as cigarette smoking, can not be disregarded. [source] Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2004L. Harper Summary objective, Propylthiouracil treatment of Graves' disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA. design, The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross-sectional study in a consecutive series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects. measurements, ANCA was measured by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase-ANCA. results, The prevalence of ANCA, as measured by IIF, was increased in the Graves' disease cohort (19·9%) compared with euthyroid controls (4·6%; P < 0·001). The prevalence of MPO-ANCA (measured by ELISA) was also increased in Graves' disease (P = 0·019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0·0265), although risk of ANCA was also higher in Graves' patients treated with carbimazole than controls (RR 2·2, P < 0·0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis. conclusion, This study revealed a high prevalence of ANCA in treated patients with Graves' disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development. [source] | |||||||||||||||||||||||||