Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves disease

BACKGROUND: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.

Conversion to Graves disease from Hashimoto thyroiditis: a study of 24 patients

ABSTRACT Objective: The conversion of Hashimoto's thyroiditis (HT) to hyperthyroidism due to thyrotropin receptor antibodies is intriguing and considered rare. The contribution of TSH receptor blocking antibodies (TRAb), which may be stimulators (TSAb) or blockers (TBAb), is suspected. We describe clinical and biological variables in a series of patients switching from Hashimoto's thyroiditis to Grave's disease. Subjects and methods: Retrospective case study of 24 patients with Hashimoto's thyroiditis followed during 48 ± 36 months that developed later Graves' disease (GD). These variables were analysed in the hypo and hyperthyroid phase: age, sex, initial TSH, free triiodothyronine (fT3), free thyroxine (fT4), anti-TPO, TBII antibodies, parietal cell autoantibodies, time between hypo and hyperthyroidism, thyroid volume and levothyroxine doses (LT). Results: In HT, mean TSH was 9.4 ± 26.1 UI/L and levothyroxine treatment was 66.2 ± 30.8 µg/day. The switch to GD was observed 38 ± 45 months after HT diagnosis. As expected, we found significant differences on TSH, FT3, FT4 and TBAb levels. Three out of 14 patients had parietal cell autoantibodies. In two of these three cases there was an Helicobacter pylori infection. There were no significant differences between HT and GD groups with respect to thyroid volume. Conclusions: To our knowledge, large series documenting the conversion of HT to GD are scarce. Although rare, this phenomenon should not be misdiagnosed. Suspicion should be raised whenever thyroxine posology must be tapered down during the follow-up of HT patients. Further immunological and genetic studies are needed to explain this unusual autoimmune change.

Serum selenium and selenoprotein-P levels in autoimmune thyroid diseases patients in a select center: a transversal study

ABSTRACT Objective: Selenium (Se) supplementation has been used to help prevent the progression of Graves' ophthalmopathy (GO) and autoimmune thyroid diseases (AITD) patients. We investigated Se serum and selenoprotein P (SePP) levels in Graves' disease (GD) with and without GO, Hashimoto's thyroiditis (HT) patients and in 27 control individuals (C). Subjects and methods: We studied 54 female and 19 male patients: 19 with GD without GO, 21 GD with GO, 14 with HT and 19 with HT+LT4. Se values were measured using graphite furnace atomic absorption spectrophotometry. Serum SePP levels were measured by ELISA. Results: Median Se levels were similar among all groups; GD patients: 54.2 (46.5-61.1 μg/L), GO: 53.6 (43.5-60.0 μg/L), HT: 51.9 (44.6-58.5 μg/L), HT+LT4 54.4 (44-63.4) and C group patients: 56.0 (52.4-61.5 μg/L); P = 0.48. However, serum SePP was lower in GO patients: 0.30 (0.15-1.05 μg/mL) and in HT patients: 0.35 (0.2-1.17 μg/mL) compared to C group patients: 1.00 (0.564.21 μg/mL) as well as to GD patients: 1.19 (0.62-2.5 μg/mL) and HT+LT4 patients: 0.7 (0,25-1.95); P = 0.002. Linear regression analysis showed a significant relationship between SePP and TPOAb values (r = 0.445, R2 = 0.293; P < 0.0001). Multiple regression analysis found no independent variables related to Se or SePP. Conclusion: A serum Se concentration was lower than in some other countries, but not significantly among AITD patients. The low serum SePP levels in GO and HT patients seems to express inflammatory reactions with a subsequent increase in Se-dependent protein consumption remains unclear.

Prevalence of pancreatic autoantibodies in non-diabetic patients with autoimmune thyroid disease and its relation to insulin secretion and glucose tolerance

ABSTRACT Objective We evaluated the prevalence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase-protein antibodies (IA2A), their titers and their relation to first phase insulin response (FPIR) and glucose tolerance in autoimmune thyroid diseases (ATDs) patients. Subjects and methods Graves' disease (GD; n = 181) and Hashimoto's thyroiditis (HT; n = 143) patients in addition to healthy controls (n = 93) were studied. Secondly, FPIR and oral glucose tolerance tests (OGTT) were performed in 11 anti-pancreatic islet-cell (+) and in 20 anti-pancreatic-cell (-) patients. Results There was a non significant trend for higher prevalence of GADA positivity in GD vs HT (7.2% vs 2% p = 0.06), but the GADA titers were higher in HT. We also did not find a significant difference in IA2 prevalence (0.7% vs 0.0%) between these two groups or compared to the control group. In the subsequent analysis, low FPIR was found in 10% of these patients but without statistical difference for OGTT between pancreatic antibody-positive and -negative patients. Conclusion A trend for greater prevalence of GADA was observed for GD patients than for HT or control. However, the titers of these autoantibodies were higher in HT patients, but there was no significant relation to insulin secretion and glucose tolerance at that moment and stage of autoimmune diseases.

Where does her mood come from? An organic approach to a once functional patient / De onde vem seu humor? Uma abordagem orgânica para um paciente previamente funcional

Objective: To report the rare development of manic symptoms in a patient with schizophrenia and discuss its differential diagnosis. Case description: Diagnostic criteria were based on the International Classification of Diseases, 10th edition (ICD-10). A 63-year-old female (diagnosed with schizophrenia since she was 28) was brought to the emergency room with symptoms consistent with manic episode and physical examination suggestive of thyrotoxicosis. Graves' disease was confirmed by subsequent laboratory tests. She was treated successfully with radioiodine ablation, leading to full remission of manic symptoms. Comments: Schizophrenia is a chronic disease that affects about 1% of the population worldwide. The main symptoms of the disorder are altered affection, delusions, and hallucinations. Graves' disease is an autoimmune condition in which antibodies increase the production and release of thyroid hormones. There are reports about the development of mood symptoms in patients with Graves' disease that remit with adequate treatment. .

Objetivo: Relatar um caso raro de desenvolvimento de sintomas maníacos em uma paciente com esquizofrenia e discutir o diagnóstico diferencial desses sintomas. Descrição do caso: Foram utilizados como base os critérios diagnósticos da Classificação Internacional de Doenças, 10ª edição (CID-10). Paciente de 63 anos do sexo feminino e com diagnóstico de esquizofrenia desde os 28 anos foi levada a emergência com sintomas compatíveis com episódio de mania e exame físico sugestivo de tireotoxicose. Doença de Graves foi confirmada por exames subsequentes. A paciente foi tratada com sucesso com ablação por iodo radioativo, levando à remissão dos sintomas maníacos. Comentários: A esquizofrenia é uma doença crônica que afeta cerca de 1% da população mundial. Os principais sintomas do transtorno são o embotamento afetivo, alucinações e delírios. A doença de Graves é uma doença autoimune em que o estímulo humoral aumenta a produção e liberação de hormônios pela tireoide. Há relatos na literatura sobre o desenvolvimento de sintomas maníacos em pacientes com doença de Graves, os quais remitem mediante tratamento adequado. .

The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto’s thyroiditis but not in Graves’ disease

Hashimoto’s thyroiditis (HT) is considered to be mediated mainly by Th1 cells, but it is not known whether Graves’ disease (GD) is associated with Th1 or Th2 predominance. Th17 cells, a novel subset of Th cells, play a crucial role in the pathogenesis of various autoimmune disorders. In the present study, the expression of IL-17A and IFN-γ was investigated in patients with HT or GD. mRNA expression of IL-17A and IFN-γ in peripheral blood mononuclear cells (PBMC) from 43 patients with autoimmune thyroid disease (AITD) and in thyroid tissues from 40 AITD patients were measured by real-time qRT-PCR. The protein expression of IL-17A and IL-23p19 was examined by immunohistochemistry in thyroid tissues from 28 AITD patients. The mRNA levels of IL-17A and IFN-γ were higher in both PBMC and thyroid tissues of HT patients than in controls (mRNA levels are reported as the cytokine/β-actin ratio: IL-17 = 13.58- and 2.88-fold change and IFN-γ = 16.54- and 2.74-fold change, respectively, P < 0.05). Also, the mRNA levels of IL-17A and IFN-γ did not differ significantly in GD patients (P > 0.05). The high protein expression of IL-17A (IOD = 15.17 ± 4.8) and IL-23p19 (IOD = 16.84 ± 7.87) in HT was confirmed by immunohistochemistry (P < 0.05). The similar high levels of IL-17A and IFN-γ suggest a mixed response of Th17 and Th1 in HT, where both cells may play important roles in the destruction procedure by cell-mediated cytotoxicity.

Bone mineral density in patients of Graves disease pre- & post-treatment in a predominantly vitamin D deficient population.

Background & objectives: Hyperthyroidism causes bone loss, and its treatment may restore bone mass, however, concomitant vitamin D deficiency may prevent this. We undertook this study to measure the bone mineral density (BMD) 25 (OH) vitamin D levels in patients with Graves disease in our population which is predominently vitamin D deficient and how we change with when patients become euthyroid. Methods: The biochemical, thyroid functions, serum vitamin D levels and BMD were estimated in 80 consecutive patients with Graves and 80 euthyroid controls. Patients were treated and rendered euthyroid. Fifty four completed one year, and 27 completed two years of follow up. Results: Patients had significant reduced BMD during hyperthyroid state compared to normal healthy controls. The mean vitamin D levels at baseline were in the insufficient range both patients (12.67±6.24 ng/ml) and controls (10.99±7.05 ng/ml). The BMD improved at all sites with antithyroid treatment. But, the BMD adjusted for body mass index (BMI) and age at all sites showed significant decrease with time. Interpretation & conclusions: Age and body mass index positively correlated with BMD. There was improvement in absolute BMD of patients at one and two years of follow up. When the BMD was adjusted for age and BMI, there was a decrease in BMD at one year which was less in the second year including that the damage in BMD caused by thyroid hormone excess is not made up even after two years of patient being euthyroid. Whether vitamin D replacement would change this needs to be studied.

Efeitos agudos laringológicos e vocais da radioiodoterapia em pacientes com hipertireoidismo por doença de Basedow Graves / Acute effects of radioiodine therapy on the voice and larynx of Basedow-Graves patients

A Doença de Graves constitui a forma mais comum de hipertireoidismo e três abordagens terapêuticas são atualmente utilizadas: uso de medicamentos antitireoideanos, cirurgia e iodo radioativo (I 131). Os efeitos do o I 131 e a indução precoce de hipotireoidismo são conseqüências da destruição induzida do I131 sobre o parênquima tireoideano. São poucos relatos encontrados na literatura acerca dos efeitos da radioioterapia sobre a laringe e conseqüentemente na produção vocal. OBJETIVO: Avaliar os efeitos agudos sobre a voz da radioiodoterapia em pacientes com hipertireoidismo por Doença de Basedow Graves. MATERIAL E MÉTODO: Estudo de corte contemporâneo longitudinal, prospectivo. Procedimentos: Investigação vocal, mensuração do tempo máximo fonatório de /a/ e relação s/z, análise freqüência fundamental (Software Praat), laringoscopia e análise perceptivo-auditiva em três momentos: pré-dose, 4 dias e 20 dias pós dose. Momentos baseados no perfil inflamatório do tecido tireoideano. RESULTADOS: Não houve mudanças estatisticamente significantes nos aspectos vocais e laringológicos nos três momentos avaliados. CONCLUSÃO: A radioiodoterapia não afeta a qualidade vocal.

Graves's disease is the most common cause of hyperthyroidism. There are three current therapeutic options: anti-thyroid medication, surgery, and radioactive iodine (I 131). There are few data in the literature regarding the effects of radioiodine therapy on the larynx and voice. The aim and the AIM: os this study was: to assess the effect of radioiodine therapy on the voice of Basedow-Graves patients. MATERIAL AND METHOD: A prospective study was done. Following the diagnosis of Grave's disease, patients underwent investigation of their voice, measurement of maximum phonatory time (/a/) and the s/z ratio, fundamental frequency analysis (Praat software), laringoscopy and (perceptive-auditory) analysis in three different conditions: pre-treatment, 4 days, and 20 days post-radioiodine therapy. Conditions are based on the inflammatory pattern of thyroid tissue (Jones et al. 1999). RESULTS: No statistically significant differences were found in voice characteristics in these three conditions. CONCLUSION: Radioiodine therapy does not affect voice quality.

Frequency Of Pancreatic Beta-Cell Autoimmunity Markers In Patients With Autoimmune Thyroid Disease / Frecuencia de marcadores de autoinmunidad beta pancreática en pacientes con enfermedad tiroidea autoinmune

A total of 305 ambulatory patients recruited at the Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, with autoimmune thyroid disease (AITD) were studied to search for associations between autoimmune thyroid disease and presence of serum markers of autoimmune diabetes mellitus. Screening for markers of pancreatic beta-cell autoimmunity was performed by radioligand binding assays (RBA) as follows: autoantibodies to glutamic acid decarboxylase (GADA) and proinsulin (PAA) were determined in all sera, whereas autoantibodies to protein tyrosine phosphatase (IA-2A) and insulin (IAA) were additionally measured in 200 sera randomly selected from the total collection. In addition, every GADA positive serum among the remaining 105 sera was systematically tested for the presence of IA-2A and IAA. In the cohort of 305 AITD patients 22 (7.2%) were previously diagnosed as type 1, type 2 or insulin-requiring type 2 diabetics. Ten of these patients presented serum marker positivity specific for β-cell autoantigens and 12 were marker negative. On the other hand, considering the majority of non-diabetic AITD patients (n=283), β-cell marker positivity was detected in 17 individuals (6.0%). The prevalence of autoimmune diabetes markers was much higher in the studied population than in the general population utilized as a control group, and GADA was the most frequent marker.

Se investigó la asociación entre enfermedad tiroidea autoinmune y la presencia de marcadores séricos de diabetes mellitus en 305 pacientes ambulatorios con enfermedad tiroidea autoinmune reclutados en la División Endocrinología. La búsqueda de marcadores de autoinmunidad contra las células beta pancreáticas se realizó por la técnica de unión de radioligandos (RBA) como se detalla a continuación: se determinaron autoanticuerpos contra la decarboxilasa del ácido glutámico (GADA) y proinsulina (PAA) en todos los sueros, mientras que los anticuerpos contra la proteína tirosina fosfatasa (IA-2A) e insulina (IAA) fueron medidos en 200 de estos sueros tomados al azar de la colección total. Además, en los restantes 105 pacientes, la presencia de IA-2A y IAA fue evaluada en todos los sueros positivos para GADA. Del grupo de 305 pacientes con enfermedad tiroidea autoinmune 22 (7.2%) fueron diagnosticados previamente como diabéticos tipo 1, tipo 2 o tipo 2 insulino-requirientes. Diez de ellos presentaron positividad para marcadores específicos de autoantígenos de célula β, en tanto 12 fueron negativos. Por otra parte, en 17 de los 283 pacientes (6.0%) con enfermedad tiroidea autoimmune y sin diagnóstico previo de diabetes, se detectó positividad para marcadores de célula β. La prevalencia de marcadores de autoinmunidad asociados a diabetes fue mayor en la población estudiada que en la población general usada como grupo control, siendo GADA el marcador más frecuente.

Correlation between free thyroxin levels and left ventricular ejection fraction in Graves' disease (preliminary study).

AIM: to determine the correlation between free thyroid hormone level and left ventricular ejection fraction in newly diagnosed Graves' patients. METHODS: this is a preliminary study with an initial cross-sectional design using free thyroxine level as a parameter of thyroid hormone state and left ventricular ejection fraction (LVEF) as a parameter of left ventricular systolic function. Free thyroxine level was measured in the laboratory and the LVEF was assessed by Simpson's methods of echocardiography study. RESULTS: ten patients (7 men and 3 women; age 18-52 years old) were studied. Their average of fT4 was 5.75 (SD 0.96) ng/dL and their average of LVEF was 70.57 (SD 4.50)%. There was positive correlation coefficient between free thyroxine level and left ventricular ejection fraction (r=0.711, p=0.021) in newly diagnosed Graves' patients. CONCLUSION: in this study strong positive correlation was found between free thyroxine (fT4) and left ventricular ejection fraction (LVEF) in newly diagnosed Graves' patients.

The correlation between free thyroxine levels and left ventricular mass in Graves' disease.

AIM: to determine the correlation between free thyroxine level and left ventricular mass in newly diagnoses Graves' disease. METHODS: seventeen patients with newly diagnosed Graves' disease were studied. Inclusion criteria was new case of Graves' disease, no previous history or clinical evidence of coronary artery disease, cardiac valve disease, diabetes mellitus, chronic kidney disease, not taking antithyroid drugs and any drugs that could affect the heart (beta blockers, ACE inhibitor). Echocardiographic indices of left ventricular mass was obtained. RESULTS: there were no correlation between free thyroxine levels and left ventricular mass, systolic and diastolic blood pressure. There was a correlation between pulse rate and left ventricular mass in Graves' disease. CONCLUSION: there was no correlation between free thyroxine level and left ventricular mass in Graves' disease.

Valores inesperadamente elevados de TSH: a presença de formas de alto peso molecular ("macro TSH") deve ser investigada / Unexpected high values of TSH: the presence of high molecular weight forms (macro TSH) must be investigated

As metodologias empregadas para a medida de TSH sérico apresentam níveis de especificidade e sensibilidade, tanto diagnósticas como analíticas, bastante elevadas. Adicionalmente, são metodologias bastante robustas, de maneira que resultados falso-positivos ou falso-negativos são raros e inesperados. Descrevemos neste trabalho dois casos de indivíduos descritos como eutiróideos, sem antecedentes de doenças autoimunes e sem referência ao uso de TSH exógeno, que apresentavam níveis de TSH de normais a muito elevados, dependendo da metodologia empregada. Em três métodos testados para a medida de TSH a diluição seriada das amostras mostrou que os níveis reais situavam-se entre 250 e 300 mUI/L. Nos dois casos, o aumento de TSH foi ocasionado pela presença de proteínas ligadoras de TSH no soro, formando formas de alto peso molecular ("macro TSH"), demonstradas por cromatografia de gel filtração em coluna de Superdex S-200. Em uma das pacientes a proteína ligadora foi caracterizada como IgG através de cromatografia em proteína G sepharose, na outra, a ligação em proteína G e em coluna de sepharose acoplada a monoclonal anti-IgM não conseguiu caracterizar a proteína ligadora sérica. Estes casos salientam a importância da correlação clínico-laboratorial e sugerem a necessidade de se pesquisar a presença de macro TSH em pacientes com níveis de TSH anormalmente elevados.

Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica / Cost-effectiveness of the clinical treatment of GraveÆs disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach

O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100æg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2 por cento) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60 por cento dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.

Avaliação do tratamento clínico da doença de Graves / Evaluation of the medical treatment of Graves' disease (GD)

O tratamento da doença de Graves (DG) com drogas antitireoidianas (DAT) associa-se à remissão da doença em metade dos indivíduos tratados por no mínimo 6 meses, e o índice de recidiva é alto, variando de 60 a 80 por cento. A presença de fatores prognósticos de sucesso do tratamento medicamentoso da DG é tema de discussão na literatura. Neste estudo avaliamos a incidência de remissão e recidiva em resposta ao tratamento clínico da DG com diferentes esquemas de tratamento com as duas DAT disponíveis no Brasil (propiltiouracil - PTU e metimazol - MMI), bem como determinar a presença de possíveis fatores preditivos de remissão e recidiva da doença e o perfil de efeitos colaterais. Revimos, no Hospital Universitário Clementino Fraga Filho (HUCFF), prontuários de todos os pacientes submetidos ao tratamento clínico da DG (sem história de tratamento prévio) por pelo menos 6 meses e seguidos após a suspensão da DAT por no mínimo 12 meses. Foram identificados 127 pacientes (idades de 18 a 88 anos; média 39,3±12,8), nos quais remissão da doença foi observada em 58 (45,7 por cento) e recidiva em 31 deles (53,4 por cento), num período médio de 14,5±16,1 meses. Sexo, idade e tempo de duração dos sintomas antes do tratamento clínico não interferiram significativamente sobre as taxas de remissão e recidiva, enquanto a presença de bócio >40 gramas, oftalmopatia de Graves (OG) e uso de doses diárias de DAT >600mg de PTU / 60mg de MMI influenciaram negativamente a taxa de remissão. Além disso, pacientes que apresentaram níveis de TSH <0,4æIU/mL entre 4 e 5 semanas após a suspensão da DAT apresentaram maior probabilidade cumulativa de recidiva da doença. Nossos resultados confirmam que a taxa de remissão em longo prazo da DG tratada com DAT é relativamente baixa. Concluímos que a combinação de oftalmopatia, bócio >40g e uso de dose diária de PTU >600mg ou MMI >60mg relacionou-se fortemente ã341; ausência de remissão da DG. Ademais, observamos que a dosagem de TSH entre 4 e 5 semanas após a suspensão da DAT parece ser uma ferramenta útil na determinação da chance de remissão ou recidiva da doença.

Anti-thyroglobulin and anti-thyroid microsomal antibodies in thyroid disorders

High titers of antibodies to thyroglobulin [ATA] and thyroid microsomal antigen [ATMA] are the hallmarks of human autoimmune thyroid diseases. The clinical significance of these autoantibodies in other thyroid disorders is still unclear. The aim of this study was to analyze the prevalence and titres of these antibodies in Omani patients [mean age 32, range 5-81 years] with different thyroid disorders. This was done in order to investigate any correlation regarding clinical manifestations that may be unique to patients attending Sultan Qaboos University Hospital [SQUH]. Serum levels of ATA and ATMA in 400 cases involving four groups of thyroid disorders [one hundred each with Hashimoto's disease, Graves' disease, thyroid cancer and goitre] and 100 cases of non-thyroid disorders were studied. The antibodies were tested using a commercial haemagglutination assay [Thymune-T and Thymune-M]. The overall prevalence of ATA or ATMA antibodies with thyroid disease was 47% and in non-thyroid disorders was 8%. The ATA was positive in 27% of all the patients with thyroid disorders compared to only 4% of those in the non-thyroid groups while ATMA was positive in 42% and 8% respectively. Among all patients, ATA and ATMA were positive in 64% of patients with Graves's disease, 81% in those with Hashimoto's, 30% of goiter patients, and 20% of those with thyroid carcinoma. The prevalence according to the age within each group for the three ranges: less than 20 years, between 20-40 years and over 40 years, showed the following results: within Graves were 12, 49 and 39% respectively; in the goitre group: 23, 55 and 22%; in the Hashimotos' group: 18, 54 and 28% and 7, 56 and 37% among the patients with thyroid carcinoma. The female to male ratio prevalence was 68% and 32% in Graves disease, 92% and 8% in Hashimotos', 75% and 25% in thyroid cancer and 88% and 12% in goiter. This study confirms the prevalence of a high level of thyroid autoantibodies in these Omani patients as in Caucasians, and its correlation to age and gender. It also indicated the importance of screening for ATA and ATMA in non-autoimmune thyroid disorders. Their significance in thyroid cancers needs further elucidation

Antineutrophilic cytoplasmic antibody-positive systemic vasculitis associated with propylthiouracil therapy: report of 2 children with Graves' disease.

Systemic vasculitis is a rare complication of therapy with antithyroid medication. Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis has been described in patients treated with propylthiouracil (PTU) and methimazole (MMI). The majority of cases have underlying Graves' disease. The authors report 2 children who developed ANCA-associated systemic vasculitis during PTU therapy of Graves' disease. One patient, after PTU treatment for 3 years, developed severe systemic vasculitis. After 3 weeks of arthritis, she abruptly presented with hematuria, proteinuria and edema concomitant with anemia. Her serum creatinine was elevated, to 6 mg/dl. Renal biopsy revealed crescentic glomerulonephritis. After admission, she developed intracerebral hemorrhage and pulmonary hemorrhage. She had positive perinuclear-ANCA (p-ANCA) with a titer of 1:160. Despite intensive therapy with immunosuppressive agents and plasmapheresis, as well as discontinuation of PTU, she died of the complications of severe systemic vasculitis. The other patient developed fever, arthralgia and leukocytoclastic vasculitis of the skin during treatment with PTU for about 2 years. Her symptoms and skin lesions disappeared after discontinuation of PTU. However, she has had a persistently high titer of p-ANCA 1:320 through 17 months follow-up time. Thus, patients who are treated with PTU can develop ANCA-positive vasculitis in a mild or severe form. Therefore, they should be carefully followed and monitored, not only for their thyroid status but also the serious complications of PTU.

Serum cytokine levels in autoimmune and non-autoimmune hyperthyroid states

Although the role of interleukin-2 (IL-2) and interferon gamma (yIFN) is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD) than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; P

Positividade dos anticorpos antitiroidianos na doença de Graves / Positivity of antithyroid antiboidies in Graves' disease

Os auto-anticorpos descritos na doença de Graves säo imunoglobulinas pertencentes à classe IgG que dirigem-se especificamente a certos antígenos tiroidianos, destacando-se entre eles: tireoglobulina (antitireoglobulina), peroxidade tiroidiana (antimicrossomia/antiperoxidade) e receptor do hormônio tireotrófico (TRab). Com o objetivo de avaliar a prevalência dos auto-anticorpos na doença de Graves descompensada, estudamos 46 pacientes virgens de tratamento. Concordante com os dados da literatura, o anticorpo anti-receptor de TSH mostrou-se o melhor marcador da doença de Graves, com 92,4 por cento de positividade