Anti-thyroid Stimulating Hormone Receptor Antibodies Research Articles

Incidence of Graves' Disease with Validation and Completeness of the Diagnosis for Registry Extracts in the Danish National Patient Register.

Graves' disease (GD) is one of the most common causes of thyrotoxicosis. It has been proposed to identify incident GD by using the GD-specific code, E05.0, of the 10th revision of the International Classification of Disease (ICD-10) in the Danish National Patient Register (DNPR). We aimed to report the incidence of GD and to investigate the validity and completeness of E05.0 registration using Aalborg University Hospital (AaUH) as a single centre-sample. The study included registry data from 2020 to 2022. The study population (n=2,893) comprised all people (15-99 years) in the catchment area of AaUH (n=244,872) with either positive anti-thyroid stimulating hormone receptor antibodies (TRAb), or registered with a thyroid disease related ICD-10 code E03.0-E07.9, O99.2 or O90.5 at the Department of Endocrinology, AaUH. To identify incident cases, all subjects occurring for the first time in 2020 were excluded (n=2,339). The incident subjects were categorized into a general practice (n=63) or hospital care group (n=491) and underwent GD verification by biochemical tests and thyroid imaging. Validity was evaluated by positive (PPV) and negative (NPV) predictive values and completeness of E05.0 registration was estimated to the total number of verified GD subjects in hospital care only and in overall (groups combined). One hundred thirty-one incident GD subjects were identified corresponding to an incidence of 26.8 per 100,000/year. E05.0had a PPV of 90% [95% CI: 81;96] and a NPV of 90% [95% CI: 85;93] to identify incident cases of GD. Completeness was estimated to be 73% [95% CI: 63;82] in hospital care and 50-60% [95% CI: 41;68] in overall. We report on a similar incidence of GD as previous studies in Denmark. Despite a high PPV, incident cases of GD could not adequately be identified by E05.0 in DNPR due to low completeness. Researchers should rely on biochemical test results to identify incident GD.

A single-center retrospective study on the clinical features of thyrotoxic periodic paralysis.

Thyrotoxic periodic paralysis (TPP) is characterized by muscle paralysis and significant intracellular potassium movement resulting in hypokalemia. Since TPP is a rare condition, only a few studies have explicated the clinical characteristics of patients with this disease. This study aimed to elucidate the clinical characteristics of patients with TPP by comparing them with those with thyrotoxicosis without paralysis (non-TPP) and sporadic periodic paralysis (SPP). This was a single-center retrospective cohort study. Clinical data of patients with hyperthyroidism (n = 62) or periodic paralysis (n = 92) who were emergently admitted to our hospital was extracted from the electronic medical records and analyzed. All patients in the TPP group (15 males and 2 females) had Graves' disease, with 14 being newly diagnosed. The average serum potassium level on admission was 2.3±0.75 mEq/L. No significant correlation was observed among serum potassium level, amount of potassium required for normalization, and thyroid hormone levels. The TPP group showed significantly younger age, higher male ratio and body mass index (BMI), and lower serum potassium and phosphorus levels than the non-TPP group, which comprised 36 patients with Graves' disease. No significant differences were observed between the TPP and SPP (n = 11) groups in terms of age, sex, BMI, serum electrolyte levels, potassium requirement for normalization, and recovery time. Considering that most patients with TPP have undiagnosed Graves' disease, distinguishing TPP from SPP based on clinical information and course alone is difficult in emergency settings. Therefore, for early detection and launch of specific treatment of Graves' disease, screening for thyroid hormone and anti-thyroid stimulating hormone receptor antibody levels is necessary when treating patients with periodic paralysis.

Thyroid dysfunction and autoantibodies among patients infected with Covid 19 in Erbil city /IRAQ

Background and objectives: Autoimmune thyroid diseases or specifically Anti-thyroid peroxidase antibodies increasing after corona virus infection pandemic. This study investigating Anti-thyroperoxidase, anti-thyroid stimulating receptor antibodies in conjunction with traditional thyroid markers after corona virus infection hoping that this would aid in reduction of enduring morbidity and associated health concerns. Methods: This cross-sectional study was conducted in Rizgary Teaching Hospital and Erbil Teaching Hospital in Erbil, Iraq, within the period of February to September 2022. The study comprised hundred patients; 80 females and 20 males, these patients had clinical symptoms suspecting thyroid abnormalities and were suspected for having a sort of thyroid disease. They had abnormal thyroid function tests, with investigating thyroid autoantibodies and corona virus infection. Investigations include thyroid function test and antithyroid antibodies. Results: The level of Anti-thyroid peroxidase antibodies was positive among 75 hypothyroidism patients than among hyperthyroidism cases 2, p-value 0.012. Positive Anti-thyroperoxidase antibodies and hypothyroidism were significantly more common among corona virus infected cases, p-value 0.012 and 0.0109 respectively. However; anti-thyroid stimulating hormone receptor antibody was positive only among hyperthyroidism group (18%); p-value was significant 0.019. Conclusions: This study confirmed the correlation between thyroid function test, Anti-thyroperoxidase antibodies values and corona virus infection. Autoimmune thyroid diseases are more common among female cases, in addition; antithyroid antibodies especially Anti-thyroperoxidase antibodies were more common among female patients. There was high prevalence of both hypothyroidism and positive anti-TPO Ab in COVID-19 cases.

Significance of the autoantibody assay in predicting the development of immune-related adverse events in patients receiving atezolizumab plus bevacizumab combination therapy for unresectable hepatocellular carcinoma.

Atezolizumab plus bevacizumab (AB) combination therapy is the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). The management of immune-related adverse events (irAEs) is an important issue associated with achieving a good therapeutic response in patients receiving AB therapy. However, few studies have reported irAE development in patients receiving AB therapy. This study focused on the association between irAE development and autoantibodies at baseline in patients receiving AB therapy. Sixty-one patients receiving AB therapy were enrolled. For autoantibodies, the following antibodies were tested before the start of AB therapy: antinuclear antibodies, rheumatoid factor (RF), anti-thyroglobulin antibodies, thyroid peroxidase antibodies, anti-thyroid stimulating hormone receptor antibodies, and acetylcholine receptor antibodies. A patient was considered to have pre-existing antibodies if any of the listed antibodies were present at baseline. Ten patients (16%) developed irAEs during the observation period. The irAEs included liver injury, hypothyroidism, adrenal insufficiency, adrenocorticotropic hormone deficiency, and rhabdomyolysis. Patients with irAE (n=10) were more likely to be positive for any autoantibody (hazard ratio [HR] 3.7, p=0.047) and RF at baseline (HR 5.4, p=0.035) and to achieve complete response (HR 5.8, p=0.027) than those without. The presence of autoantibodies at baseline was an independent factor associated with irAE development. In the real world, 16% of patients receiving AB therapy for u-HCC developed irAEs. Patients with autoantibodies at baseline are at high risk of developing irAEs and require cautious follow-up.

Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease.

Graves' disease (GD) is an autoimmune disorder caused by autoantibodies against the thyroid stimulating hormone receptor (TSHR) leading to overstimulation of the thyroid gland. Thyroid eye disease (TED) is the most common extra thyroidal manifestation of GD. Therapeutic options to treat TED are very limited and novel treatments need to be developed. In the present study we investigated the effect of linsitinib, a dual small-molecule kinase inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) and the Insulin receptor (IR) on the disease outcome of GD and TED. Linsitinib was administered orally for four weeks with therapy initiating in either the early ("active") or the late ("chronic") phases of the disease. In the thyroid and the orbit, autoimmune hyperthyroidism and orbitopathy were analyzed serologically (total anti-TSHR binding antibodies, stimulating anti TSHR antibodies, total T4 levels), immunohistochemically (H&E-, CD3-, TNFa- and Sirius red staining) and with immunofluorescence (F4/80 staining). An MRI was performed to quantify in vivo tissue remodeling inside the orbit. Linsitinib prevented autoimmune hyperthyroidism in the early state of the disease, by reducing morphological changes indicative for hyperthyroidism and blocking T-cell infiltration, visualized by CD3 staining. In the late state of the disease linsitinib had its main effect in the orbit. Linsitinib reduced immune infiltration of T-cells (CD3 staining) and macrophages (F4/80 and TNFa staining) in the orbita in experimental GD suggesting an additional, direct effect of linsitinib on the autoimmune response. In addition, treatment with linsitinib normalized the amount of brown adipose tissue in both the early and late group. An in vivo MRI of the late group was performed and revealed a marked decrease of inflammation, visualized by 19F MR imaging, significant reduction of existing muscle edema and formation of brown adipose tissue. Here, we demonstrate that linsitinib effectively prevents development and progression of thyroid eye disease in an experimental murine model for Graves' disease. Linsitinib improved the total disease outcome, indicating the clinical significance of the findings and providing a path to therapeutic intervention of Graves' Disease. Our data support the use of linsitinib as a novel treatment for thyroid eye disease.

HLA typing of patients who developed subacute thyroiditis and Graves’ disease after SARS-CoV-2 vaccination: a case report

BackgroundCases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT.Case presentationWe conducted HLA typing of one patient with SAT and another with both SAT and Graves’ disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms.ConclusionHLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.

Stability of Anti-thyroid Stimulating Hormone Receptor Antibody in Whole Blood and Serum: Caution Required for Reflective and Batch Testing

Anti-thyroid stimulating hormone receptor antibody (TRAb) stability is stated as 7h at 20-25°C in the Roche Elecsys assay kit insert. The purpose of this study was to determine TRAb stability in whole blood and serum to assess the suitability of samples for reflective and weekly batch testing (with a single freeze-thaw cycle). In the first study, blood from n = 5 volunteers was used to assess: (1) stability in whole blood at room temperature up to 24h, and (2) stability in serum at 4-8°C up to 72h. In the second study, n = 21 patient samples were analysed in serum stored at 4-8°C for two and fivedays post-preliminary analysis. There was a statistically significant decrease in TRAb concentration caused by the single freeze-thaw cycle of -8.9% ± 5.2% (p = 0.03). TRAb concentration decreased in whole blood between 0 and 24h by -16.5% ±9.2%, and declined in serum over time by -11.6% ±6.6% (at 12h). In the patient samples, serum TRAb concentration decreased over time by -4.6% ± 2.5% at day two and -6.5% ± 4.0% at day five. TRAb concentration decreases over time in both whole blood at room temperature and serum samples stored at 4-8°C. A single freeze-thaw cycle also has a statistically significant effect on TRAb concentration.

Graves\u2019 disease coexisted with resistance to thyroid hormone: a case report

BackgroundResistance to thyroid hormone is a rare autosomal dominant disorder characterized by reduced responsiveness to thyroid hormone and can cause syndrome of inappropriate secretion of thyroid stimulating hormone. Although Graves’ disease is a common autoimmune thyroid disorder, the coexistence of these two diseases is extremely rare and makes the diagnosis and treatment complicated, leading to the delayed diagnosis of resistance to thyroid hormone. We describe the case of a Japanese man with resistance to thyroid hormone coexisting with Graves’ disease, in which the correct diagnosis of resistance to thyroid hormone was delayed by masking of the signs of syndrome of inappropriate secretion of thyroid stimulating hormone, with final diagnosis 30 years after the initial treatment for Graves’ disease.Case presentationA 30-year-old Japanese man presented with diffuse goiter and thyrotoxicosis. Anti-thyroid stimulating hormone receptor antibody was positive. He was diagnosed with Graves’ disease. Anti-thyroid medication was chosen as the initial treatment for Graves’ disease. However, this treatment failed to normalize the free triiodothyronine, free thyroxine, and thyroid stimulating hormone levels. His thyroid hormone levels indicated syndrome of inappropriate secretion of thyroid stimulating hormone. After cessation of methimazole treatment by remission of Graves’ disease, his state of syndrome of inappropriate secretion of thyroid stimulating hormone persisted. Magnetic resonance imaging revealed no pituitary tumor lesions. The results of thyroid stimulating hormone-releasing hormone stimulation test showed a normal response of thyroid stimulating hormone. He was suspected to have resistance to thyroid hormone. Direct sequencing analysis of the thyroid hormone receptor β gene identified a heterozygous missense mutation, R282S. Coexistence of resistance to thyroid hormone with Graves’ disease was confirmed. He has no signs of thyrotoxic symptoms, and is capable in activities of daily living at the present time.ConclusionWe described a rare case of resistance to thyroid hormone simultaneously existing with Graves’ disease. This case demonstrated that these diseases can coexist, and indicated some of the difficulties in diagnosis of resistance to thyroid hormone with coexisting Graves’ disease. The diagnosis of resistance to thyroid hormone did not become apparent until after anti-hyperthyroidism treatment. Although rare, careful follow-up after the initial treatment of Graves’ disease is necessary. The coexistence of these two diseases should be considered in patients showing occasional syndrome of inappropriate secretion of thyroid stimulating hormone.

Diagnostic Utility of Mean Peak Systolic Velocity of Superior Thyroid Artery in Differentiating Graves' Disease from Thyroiditis.

Background Differentiating Graves’ disease from thyroiditis can be at times clinically challenging. The gold standard test (thyroid nuclear imaging scan) is expensive, not routinely available, and has radiation exposure. Color Doppler ultrasonography of thyroid represents a suitable alternate which can be used for differentiating these conditions by studying thyroid blood flow parameters. Aim We aimed to investigate the use of thyroid blood flow parameters’ assessment of the superior thyroid artery (STA) and common carotid artery (CCA) with color Doppler ultrasonography for differentiating Graves’ disease from thyroiditis. Materials and Methods This is a cross-sectional study on 111 patients with newly diagnosed thyrotoxicosis (82 with Graves’ disease and 29 with thyroiditis) and 45 years of age and sex-matched healthy controls. All patients underwent detailed clinical and necessary investigations. Color Doppler ultrasonography of the thyroid gland and spectral flow analysis of both superior thyroid arteries was done using standard protocol. Sensitivity and specificity for mean peak systolic velocity of STA (STA-PSV) cut-offs were calculated using receiver operating characteristic curves. Results Patients with Graves’ disease have significantly higher free tri-iodothyronine (FT3) levels, free thyroxine (FT4) levels, antithyroid stimulating hormone receptor antibody (TRAb) levels, and thyroid volume as compared with those with thyroiditis. The mean STA-PSV of patients with Graves’ disease was significantly higher than thyroiditis and control group. Mean STA-PSV greater than 54.3 cm/s had 82.9% sensitivity and 86.2% specificity in diagnosing Graves’ disease. Mean PSV-STA/PSV-CCA ratio of 0.40 was 80.5% sensitive and 86.2% specific for Graves’ disease. Conclusion Mean STA-PSV has high sensitivity and specificity in differentiating Graves’ disease from thyroiditis and can be used routinely in clinical practice as a cheap and invaluable diagnostic tool.

The role of oxidative stress in the pathogenesis of Graves’ orbitopathy

Graves' disease (GD) is a chronic autoimmune condition, in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb corelate with severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema result in an increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to activation of the antioxidant system which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of antioxidative system parameters enables evaluation of oxidative stress severity, which in the future may be utilized for assessment of treatment efficacy and prognosis in patients with active OT.

Rola stresu oksydacyjnego w patogenezie orbitopatii Gravesa

Streszczenie Choroba Gravesa-Basedowa (chGB) jest przewlekłą chorobą autoimmunologiczną, której auto-antygenem jest receptor TSH (TSHR) umiejscowiony na tyreocytach, a jego pobudzenie przez przeciwciała przeciwko TSHR (TRAb) powoduje nadmierne wytwarzanie hormonów tarczycy. TSHR wykazuje także ekspresję w tkankach pozatarczycowych, przede wszystkim w tkankach oczodołu, a stężenie TRAb w surowicy krwi dodatnio koreluje z ciężkością oraz aktywnością orbitopatii tarczycowej (OT). OT jest najczęstszym pozatarczycowym objawem chGB. Jest to choroba autoimmunologiczna, w której dochodzi do zmian zapalnych w obrębie tkanek oczodołów, tj.: mięśniach okoruchowych, tkance tłuszczowej oczodołu czy gruczole łzowym. Wzrost proliferacji fibroblastów oczodołowych i adipocytów oraz nadmierne wytwarzanie glikozaminoglikanów, obrzęk mięśni okoruchowych zwiększają objętość tkanek oczodołu i powodują powstanie objawów klinicznych choroby. Patogeneza OT jest złożona i nadal pozostaje niewyjaśniona. Fibroblasty oczodołów wykazują ekspresję TSHR, który jest głównym miejscem ataku autoimmunologicznego. Zgodnie z szeroko akceptowaną hipotezą po pobudzeniu receptorów dochodzi do aktywacji limfocytów T, które naciekając tkanki oczodołu stymulują je do wytwarzania cytokin, czynników wzrostu oraz wolnych rodników tlenowych (WRT). WRT powodują uszkodzenie wielu składowych komórki m.in. błony komórkowej przez peroksydację lipidów oraz białek doprowadzając do utraty ich funkcji i aktywności enzymatycznej. Stres oksydacyjny uaktywnia układ antyoksydacyjny działający poprzez dwa mechanizmy: enzymatyczny oraz nieenzymatyczny. Ocena stężenia markerów stresu oksydacyjnego oraz stężenia lub aktywności parametrów układu antyoksydacyjnego umożliwia ocenę nasilenia stresu oksydacyjnego, co w przyszłości może być wykorzystywane do oceny skuteczności leczenia i rokowania u chorych z aktywną OT.

The profile of autoimmunity in Type 1 diabetes patients.

Background:Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by pancreatic β-cells destruction. Anti-pancreatic antibodies are the witness of β-cell destruction and their dosage is mainly used for etiological diagnosis. Patients with T1DM are at increased risk of developing other autoimmune reactions, which may involve other organs, resulting in organ specific autoimmune disease. The most frequently encountered are autoimmune thyroid disease, followed by celiac and gastric disease and other rare autoimmune diseases.Objectives:The purpose of this study is to investigate the prevalence of autoimmune markers in patients with T1DM.Methods:The study was conducted at the Department of Endocrinology of the Military Hospital Moulay Ismail in Meknes Morocco, from January 2016 to December 2018. All Type 1 diabetes patients consulting during the study period were included in the study. Their clinical and biochemical data were collected at their first presentation, made up of anti-pancreatic antibodies (glutamic acid decarboxylase [GAD] antibody, tyrosine phosphatase antibody, and islet cell antibody) and other organ-specific antibodies: the thyroid (antithyroid peroxidase antibody, antithyroglobulin antibody, and antithyroid-stimulating hormone receptor antibody), the intestine (IgA antitissue transglutaminase antibody), the adrenal gland (anti-21 hydroxylase antibody), and the stomach (antigastric parietal cell antibody and anti-intrinsic factor antibody).Results:Fifty-four patients were included, with an average age of 26 years. GAD, tyrosine phosphatase, and islet cell antibodies were detected in 74%, 22%, and 3.7%, respectively, of the 54 patients examined. The prevalence of extrapancreatic autoimmunity was 45% with a large preponderance among different immunities of those from thyroid and celiac diseases (CDs).Conclusion:Our results confirm that patients with Type 1 diabetes should be investigated for the presence of autoimmune diseases mainly from thyroid and CDs.

Short-Term Versus 6-Week Prednisone In The Treatment Of Subacute Thyroiditis: A Randomized Controlled Trial

Moderate-to-severe subacute thyroiditis is clinically managed with 6 to 8 weeks of glucocorticoid therapy. However, no studies have evaluated short-term prednisone treatment for subacute thyroiditis. This 24-week, prospective, single-blind, randomized controlled study enrolled patients (aged 18 to 70 years) with subacute thyroiditis who were hospitalized between August, 2013, and December, 2014. Patients with moderate-to-severe symptoms were randomly assigned to receive either 30 mg/day prednisone for 1 week, followed by 1 week of nonsteroidal anti-inflammatory drugs, or the conventional 6-week prednisone therapy. The primary endpoint was intergroup differences in treatment efficacy at the end of the treatment course. Secondary endpoints included between-group differences in post-withdrawal adverse effect parameters and thyroid function at weeks 6, 12, and 24. We screened 96 patients, randomized 52 participants, and 50 participants completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P = .65). At treatment discontinuation, parathyroid hormone (28.8 versus 38.9 pg/mL; P = .011) and systolic blood pressure (113.9 versus 122.4mm Hg; P = .023) were significantly lower in the experimental group than in the control group. There were no significant intergroup differences in other secondary endpoints at withdrawal and in thyroid function at weeks 6, 12, and 24. Fewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with the 6-week treatment for subacute thyroiditis. Short-term prednisone, with a better safety profile, may be an alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis. BPPG = breakfast postprandial plasma glucose; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; GA = glycated albumin; NSAIDs = nonsteroidal anti-inflammatory drugs; OC = osteocalcin; PINP = type I procollagen amino-terminal peptide; PTH = parathyroid hormone; RCT = randomized controlled trial; SAT = subacute thyroiditis; SBP = systolic blood pressure; TC = total cholesterol; TSH = thyroid-stimulating hormone; TBG = thyroid-binding globulin; TG = triglyceride; TGAb = antithyroglobulin antibody; TPOAb = antithyroid peroxidase antibody; TRAb = antithyroid-stimulating hormone receptor antibody.

Thyrotoxic graves' disease-induced by interferon-ribavirin therapy in a patient with amiodarone-induced hypothyroidism on thyroxine replacement

An unusual type of drug-induced thyroid dysfunction is described. Thyrotoxicosis was seen in association with the use of interferon therapy despite prior established amiodarone-induced hypothyroidism. A 63-year-old female patient with a history of hypertension, high-grade ventricular arrhythmia on sotalol 80 mg daily was diagnosed to have amiodarone-induced hypothyroidism previously. She has been receiving thyroxine replacement therapy for 4 years. During the second cycle of interferon for hepatitis C virus relapse. She developed autonomous thyrotoxicosis. Her anti-thyroid peroxidase antibody was persistently negative before, during, and after either amiodarone or interferon while anti-thyroid stimulating hormone receptor antibody titer. Thyroid Tc-99m scan showed a high uptake during interferon therapy. To the best of the author's knowledge, this is the first report of a case of long-term hypothyroidism-induced by amiodarone therapy evolving into thyrotoxic Graves' disease-induced by interferon/ribavirin combination therapy in Libya reflecting an interaction of drugs and the background autoimmune disease.

Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.

BackgroundAnti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole.MethodsWe included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups.ResultsThe mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness.ConclusionIn patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

Variables Affecting the Long-Term Outcome of Graves Orbitopathy Following High-Dose Intravenous Glucocorticoid Pulse Therapy in Patients not Treated with Orbital Radiotherapy

Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.

Clinical, Endocrinological and Immunological Characteristics of Japanese Patients With Autoimmune Polyglandular Syndrome Type 3a

Background: Autoimmune polyglandular syndrome (APS) is an autoimmune disease that involves multiple organ failure. In APS3, autoimmune thyroid disease occurs with other autoimmune diseases, but not with Addison disease. APS3a is defined as APS3 including autoimmune diabetes. The information about clinical backgrounds of APS3a is very limited. We studied to understand clinical, endocrinological and immunological characteristics of Japanese patients with APS3a. Methods: We reviewed our previously published case reports about APS3a, and picked up patients with type 1 diabetes and autoimmune diabetes, who showed the positivity for anti-glutamic acid decarboxylase antibody (anti-GAD ab) or anti-islet antigen 2 antibody (anti-IA2 ab) or anti-thyroglobulin antibody (anti-TG ab) or anti-thyroid peroxidase antibody (anti-TPO ab) or anti-thyroid stimulating hormone receptor antibody (anti-TR ab) between January 2010 and January 2016. We collected data including age, sex, anti-GAD ab, anti-IA2 ab, HbA1c, serum fasting C-peptide immunoreactivity (CPR), urinary CPR, treatment for diabetes, anti-TPO ab, anti-TG ab, anti-TR ab, thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), findings of thyroid ultrasonography and treatment for thyroid diseases. Results: Present study revealed a remarkable female predominance in APS3a. Among patients with autoimmune diabetes, slowly progressive insulin-dependent diabetes mellitus (SPIDDM) was the most common type of diabetes, and almost 80% of patients with APS3a showed the positivity for anti-GAD ab. Among patients with autoimmune thyroid diseases, almost 80% of patients had possible Hashimoto thyroiditis. Almost 70% of patients with APS3a showed the positivity for anti-TPO ab. Almost 20% of APS3a patients had possible Grave’s disease, and 83% of patients with possible Grave’s disease showed overt Grave’s disease. In patients with possible Grave’s disease, the positive rate of anti-TR ab was 100%. Conclusion: We revealed clinical, endocrinological and immunological characteristics of patients with APS3a in Japan. J Endocrinol Metab. 2016;6(2):46-51 doi: http://dx.doi.org/10.14740/jem348e

Thyroid-Related Autoantibodies in Tunisian Patients with Type 1 Diabetes

Aim. To evaluate, retrospectively, the frequency of antithyroid antibodies (ATA) in patients with type 1 diabetes (T1D). Materials and methods. Antithyroperoxidase antibodies (TPO-Ab), antithyroglobulin antibodies (TG-Ab), and antithyroid-stimulating hormone receptor antibodies (TSHR-Ab) were determined by enzyme-linked immunosorbent assay. Sera of 312 patients (166 children and 146 adults) with T1D were analyzed. Sera of 276 healthy subjects (87 children and 189 blood donors) served as controls. Results. Out of 312 patients with T1D, 44 (14%) had ATA (TPO-Ab or TG-Ab or TSHR-Ab). The frequency of ATA in patients with T1D was significantly higher than in the control group (14% vs. 2.8%; p < 10−5). ATA were significantly more frequent in adult patients with T1D than in the blood donor group (20% vs. 1.6%; p < 10−8). The frequency of ATA in adult patients was significantly higher than in pediatric patients (20% vs. 9%; p = 0.006). The frequency of TPO-Ab and TG-Ab was significantly higher in patients with T1D than in the control group (13.5% vs. 2%; p < 10−8 and 7% vs. 2.2%, p = 0.008), respectively. Out of 312 patients with T1D, only one had TSHR-Ab. The simultaneous presence of three autoantibodies was found in one patient with T1D. Conclusion. ATA were frequent in patients with T1D. Serological screening of autoimmune thyroid disease is suggested in patients with T1D.

Thyroid-related autoantibodies in Tunisian patients with coeliac disease

The aim of our study was to evaluate, retrospectively, the frequency of anti-thyroid antibodies (ATA) in coeliac disease (CD) patients. ELISA was used to determine the frequency of anti-thyroid stimulating hormone receptor antibodies, thyroperoxidase antibodies and thyroglobulin antibodies in sera of 104 adult patients with CD. Patients were divided into three groups: group I, 56 untreated patients; group II, 21 patients on a strict gluten-free diet (GFD); and group III, 27 patients who did not comply with a GFD. Sera of 189 healthy blood donors served as controls. Out of 104 patients with CD, five (4.8%) had ATA. The frequency of ATA found in the control group (1.6%) was not significantly different from that found in all CD patients. However, the frequency of ATA in CD patients on a GFD was significantly higher than that found in the control group (8.3% vs. 1.6%, p=0.03). The frequency of ATA in groups I, II and III was 1.8%, 9.5% and 7.4%, respectively. ATA were found in CD patients even on a GFD.

Clinical Significance of Thyroid Disease in Patients With Inflammatory Myopathy

We conducted the current study to determine the prevalence, incidence density, and clinical significance of thyroid disease in a series of 109 patients diagnosed with idiopathic inflammatory myopathy. We analyzed 109 patients diagnosed with idiopathic inflammatory myopathy during a 20-year period (1986-2006). Routine determination of thyroid profile, including hormone levels and antithyroid antibodies (antithyroid peroxidase and antithyroglobulin antibody systematically, and antithyroid-stimulating hormone receptor antibody when appropriate) was carried out at onset and at least once again during the follow-up period. Human leukocyte antigen (HLA) study was performed by polymerase chain reaction sequence-specific oligonucleotide typing. Six patients (5.5%) developed thyroid disease (hypo- or hyperthyroidism), with an incidence density of 8.7 new cases per 1000 person-years; 4 of the 6 cases were of autoimmune origin (3.6%). Thyroid dysfunction, whether autoimmune or not, was clearly related with onset or relapse of disease activity. Neoplastic disease was detected in 3 of 4 (75%) patients with autoimmune thyroid disease, a significantly higher frequency than was observed in the remaining patients in the series (12 of 103, 11.7%; p < 0.05; RR: 22.8; 95% confidence interval, 2.2-236.6). HLA DRB1*04 was found in 4 of the 6 patients with thyroid disease and inflammatory myopathy. Thyroid disorders are clinically relevant in patients with inflammatory myopathies. An association was observed between autoimmune thyroid disease and cancer. Thyroid assessment is strongly recommended in patients with idiopathic inflammatory myopathy and clinical relapse.