Diagnosis Of Autoimmune Thyroid Disease Research Articles

Salivary Alterations in Autoimmune Thyroid Diseases: A Systematic Review

Autoimmune thyroid disease (AITD) is a dysregulation of the immune system that causes an attack on the thyroid gland. Two major clinical manifestations are Hashimoto's thyroiditis and Graves' disease. Saliva performs many functions and, importantly, has the potential for easy, non-invasive diagnostics of several systemic disorders. This systematic review was designed to answer the question whether salivary alterations are reliable for the diagnosis of autoimmune thyroid diseases. Following the inclusion and exclusion criteria, fifteen studies were included. Due to their heterogeneity, saliva analysis was divided into two subgroups: quantitative assessment analysing salivation and qualitative assessment concerning potential salivary biomarkers for AITD. In addition to detecting altered levels of thyroid hormones and antibodies, salivary changes were also observed in the concentrations of total protein, cytokines and chemokines, as well as markers of oxidative status. According to the saliva flow rate values, significantly reduced saliva secretion was observed in patients with HT. In conclusion, it is not possible to unequivocally state if salivary biomarkers can potentially be used in autoimmune thyroid disease diagnosis. Therefore, further investigations, including salivation disorders, are necessary to validate these findings.

Shear wave elastography as a quantitative method for thyroid gland elasticity assessment in pediatrics patients with autoimmune-related thyroid disease, diagnostic utility and laboratory correlation

BackgroundAutoimmune thyroiditis (AIT) is the most common thyroid pathology in pediatric patients among which Hashimoto’s thyroiditis has the highest prevalence. Along with size, measuring mechano-acoustic tissue elasticity is evolving as an important parameter in the evaluation of diffuse thyroid pathology. This study aims to investigate the role of shear wave elastography (SWE) in the diagnosis of autoimmune thyroid disease (AITD) in the pediatric population and also compare the elasticity between them and healthy individuals.ResultsThis case–control analytical study was carried out on 64 pediatric subjects ranging in age from 7 to 17 years. All the cases were diagnosed as AIT by anti-thyroid antibodies, and their thyroid function was evaluated by thyroid hormones. We performed thyroid Ultrasonography and Shear wave elastography. Patients with AIT had significantly higher elasticity values (35.6 kPa, IQR 8.43–103.7 kPa) than the control group (9.35 kPa, IQR 5.73–13.21 kPa). There was no correlation of elasticity values of thyroid gland in patients with AIT with autoantibodies and thyroid function test, respectively. The cutoff value for elasticity was 12.317 kPa with sensitivity and specificity of 96.9% and 100%, respectively.ConclusionsSWE is a highly sensitive imaging method integrating routine ultrasonography in the diagnosis of AITD which estimates the extent of fibrosis in numerical value.

A rapid homogenous bioassay for detection of thyroid-stimulating antibodies based on a luminescent cyclic AMP biosensor

Graves' disease (GD) is an autoimmune disease caused by antibodies to the thyroid stimulating hormone receptor (TSHR). The FDA-cleared Thyretain™ TSI bioassay is a highly specific method to detect thyroid stimulating antibodies (TSAb/TSI) in the blood of patients with autoimmune thyroid disease (AITD), particularly GD. To simplify the workflow of this bioassay and to support a semi-quantitative result, we have generated a stable CHO-K1 cell line expressing both a chimeric TSH receptor (TSHR-Mc4) and a luciferase-based homogeneous cAMP biosensor (GS luciferase). Here, we describe a rapid, real-time, homogenous bioassay (Turbo™ TSI Bioassay) to directly assess the functional activity of TSI and produce results in International Units of IU/L. The Turbo™ TSI bioassay works by measuring changes in the intracellular cAMP level induced by a G-protein coupled receptor (G-PCR) signaling cascade which is triggered by the binding of TSI to the TSHR. Upon binding to cAMP, the GS luciferase reporter is activated through conformational changes and generates light that can be measured in intact cells with a luminometer. The LoD and LoQ of the assay were determined to be 0.016 IU/L and 0.03 IU/L, respectively and the preliminary assay cutoff was determined to be 0.024 IU/L by ROC analysis using the Thyretain™ TSI bioassay results as reference. The analytical performance of the Turbo™ TSI bioassay is comparable to the Thyretain™ TSI bioassay as evidenced by similar EC50 values for a TSHR stimulating monoclonal antibody (M22). The specificity of the Turbo™ TSI bioassay was demonstrated by showing no response to a high concentration of a human monoclonal TSHR blocking antibody (K1–70). The precision of the assay was excellent with an overall within-laboratory precision <15% CV. When testing 198 clinical samples, the positive and negative percent agreement between the Turbo™ TSI and the Thyretain™ TSI bioassays were 98.7% and 93.5%, respectively. While both bioassays yield equivalent analytical and clinical performances, the Turbo™ TSI bioassay is much simpler to perform. It does not require cell culture, sample dilution, washing or cell lysis steps, resulting in a dramatically reduced turnaround time from about 21 h to 60 min. In addition, the same cell line showed its capability of detecting thyroid blocking antibodies (TBAb/TBI) in a competitive format. The Turbo™ TSI bioassay is user-friendly and is a very promising advancement to aid the diagnosis of autoimmune thyroid disease (AITD).

Thyroid Autoimmune Disease-Impact on Sexual Function in Young Women.

The important prevalence of autoimmune thyroid disease (AITD) in the general population was the main motivation for conducting the present study. The present paper aims to estimate the possible comorbidities related to female sexual dysfunction (FSD) and depression related to AITD. The study group consisted of 320 patients: 250 cases known with untreated AITD, divided into subgroups (euthyroid subgroup, subclinical hypothyroidism subgroup and clinical hypothyroidism subgroup); respectively 70 healthy females in the control group. Patients underwent thyroid evaluation, ovarian evaluation and laboratory assays. At the time of the diagnosis of autoimmune thyroid disease, psychometric scales were filled in by the patients: the Female Sexual Function Index 6 (FSFI-6) and the Beck’s Depression Inventory-II (BDI-II). It was observed that healthy patients had significantly higher FSFI scores than patients with AITD (28 vs. 27; p = 0.006). In the AITD group, the risk of FSD increases with the severity of thyroid disease. The most affected areas were: sexual desire (p < 0.001), lubrication (p = 0.001) and orgasm (p = 0.008), followed by excitability and sexual satisfaction. The severity of hypothyroidism influences the degree of decrease in libido, central and peripheral excitability. Sexual satisfaction and orgasm were less influenced. The field related to pain seems uninfluenced by the presence of thyroid disease. The concomitant presence of depression and the value of thyroid-stimulating hormone (TSH) are risk factors in the development of FSD. Higher TSH value and BDI-II score increase the risk of female sexual dysfunction by 1.083 and 1.295 times, respectively. Our findings are significant and promising; they may help professionals dealing with sexual and reproductive health. Despite the importance of female sexual dysfunction and its prevalence, clinicians and patients often ignore it. In fact, only a small percentage of patients consult their doctors about sexual health, and their doctors do not often ask them questions related to this aspect.

HOSPITAL-BASED CLINICAL STUDY ON PREVALENCE OF TPO ANTIBODIES IN ASSOCIATION TO AUTOIMMUNE THYROID DISEASES IN TERTIARY CARE HOSPITAL

Objective: Autoimmune thyroid disease is one of the organs specific autoimmune disorders. The onset is much more common in women than in men. Worldwide, 2–4% of women and only 1% of men have affected and the rate increases with age. Thyroperoxidase (TPO) antibodies (Abs) level helps to diagnose autoimmune thyroid disease along with levels of thyroid stimulating hormone (TSH), Free Tri-iodotyrosine (Free T3), and Free Thyroxin(Free T4) and it helps in differentiation between subclinical and overt thyroidism. The core objective of clinical study was to evaluate prevalence of anti-TPO Abs in association to autoimmune thyroid disease in a tertiary care hospital – Punjab.&#x0D; Methods: A cross-sectional study of random patient (n=200 patients) at a tertiary care hospital, Mohall – Punjab was carried out. All the patients fall in the age group 12–89 years. The parameters, which were used for the diagnosis of autoimmune thyroid disease, were anti-TPO level, Free T3 level, and Free T4 level. The patients were divided in different group on the basis of their age, gender, and their clinical conditions. The level of TPO Abs, TSH, Free T3, and Free T4 was noted for each patient. Electrochemiluminescence immunoassay method was used for determination of TPO Abs and other thyroid parameters. After a period of 16 weeks, subjects from different groups had great difference in their anti-TPO values in the autoimmune thyroid disease.&#x0D; Results: TPO Abs positive is one of the most common associated with hypothyroidism which was 36.5%, among them 20.5% suffered from subclinical hypothyroidism, whereas other remaining suffered from clinical hypothyroidism, clinical hyperthyroidism, and other autoimmune disease.&#x0D; Conclusion: TPO Abs level helps to diagnose autoimmune thyroid disease, along with this the level of TSH, Free T3, and Free T4 helps in differentiation between subclinical and overt thyroidism.

Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake

ObjectivesSelenium (Se) deficiency is related to an increased risk of preterm labor, miscarriage, preeclampsia, gestational diabetes, and other obstetric complications. As the Se status declines during pregnancy, we hypothesized that the decline may be exacerbated in women with autoimmune thyroid disease (AITD). Material and methodsPregnant women (n=74; 30 [23–38] years) were consecutively recruited from the district of Warsaw, Poland, and divided into healthy subjects (HS, n=45), and women with a diagnosis of AITD (AITD, n=29). Thyroglobulin antibodies (TG-aAb), thyroid peroxidase antibodies (TPO-aAb), TSH, free T3, free T4, total T3, and total T4, as well as urine iodine excretion were determined. Se status was assessed by serum Se and selenoprotein P (SELENOP) concentrations. Thyroid volume was evaluated by ultrasonography. ResultsSerum Se and SELENOP concentrations were relatively low in both control and AITD women. A Se deficit according to WHO definition (<45μg/l) was observed in 0%, 3.4%, 28.6% and 4.5%, 18.2%, 35.5% of women in the AITD and HS group, respectively, during the 1st, 2nd, and 3rd trimester. From first to third trimester, TPO-aAb and TG-aAb declined in AITD by 71% and 60%, respectively. The decline in TPO- and TG-aAb was unrelated to the Se status. ConclusionsIn this area of habitual low Se intake, a high proportion of women developed a severe Se deficit during pregnancy, irrespective of AITD status. This decline must be considered as a preventable risk factor for pregnancy complications of relevance to both the unborn child and the pregnant mother.

Increased Risk of Chronic Spontaneous Urticaria in Patients With Autoimmune Thyroid Diseases: A Nationwide, Population-based Study.

There was no previous population-based study on the comparison of the risk of chronic spontaneous urticaria (CSU) between autoimmune thyroid diseases (AITD) and age- and gender-matched controls. The primary objective of this study was to evaluate the risk of CSU after diagnosis of AITD using national registry data from Korea. The secondary objective was to evaluate other risk factors of CSU. Based on the disease code diagnoses in 2003-2005, we composed an AITD group (n=3,659) and an age- and gender-matched control group (n=18,295). Each patient was tracked for whether CSU occurs or not until 2013. After adjusting for demographic differences and comorbidities, patients with AITD had a significantly higher rate of CSU compared to the control group (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.25-1.70; P<0.001). Among the AITD patients, the adjusted HR for CSU was higher in patients with Hashimoto's thyroiditis (HR, 1.50) than in those with Grave's disease (HR, 1.33), although the difference was not statistically significant (P=0.368). Analysis of CSU patients associated with AITD showed that female patients had a significantly higher risk of CSU compared to male ones (HR, 1.34; P=0.001) and that those with allergic rhinitis (HR, 1.51; P<0.001), atopic dermatitis (HR, 2.44; P<0.001), and asthma (HR, 1.50; P<0.001) had a significantly higher risk of CSU compared to patients without respective diseases. Our results demonstrated that AITD could be significantly associated with an increased risk of CSU.

In-House Solid-Phase Radioassay for the Detection of Anti-thyroglobulin Autoantibodies in Patients with Differentiated Thyroid Cancer.

Thyroglobulin autoantibodies (TgAb) are estimated to detect potential interferences in thyroglobulin (Tg) immunoassays and also for the diagnosis of autoimmune thyroid disease. A user friendly and robust in-house solid-phase radioassay was standardized and parameters like sensitivity, reproducibility and stability were assessed. Further, it was validated and evaluated for the detection of autoantibodies in differentiated thyroid cancer(DTC) patients. Totally 301 samples received in our laboratory for routine serum Tg estimation were studied. The samples were analyzed for TgAb by the solid-phase radioassay developed in-house and compared with commercial anti-hTg IRMA kit (Immunotech, France). The control group comprised of 37 euthyroid males from our Centre. The intra- and inter-assay CVs for the two quality control samples (Control A=104±12.6IU/mL and Control B=1029±114IU/mL) were found less than or equal to 6.05 and 13.85% respectively. Solid-phase radioassay showed a good agreement on comparison with Immunotech IRMA (r=0.99). Using the proposed cut-off thresholds (in-house solid-phase radioassay 52IU/mL and Immunotech IRMA 30IU/mL), 5.4% of the control subjects were positive for TgAb by both the methods. Prevalence of TgAb in DTC patients was 17.3 and 16.6% using the Immunotech kit and in-house solid-phase radioassay respectively. The in-house solid-phase radioassay has the requisite sensitivity for the evaluation of TgAb comparable to commercial kit and also suitable for routine use as it is rapid, user friendly and economical.

Coexistence of autoimmune diseases and autoantibodies in patients with myasthenia gravis.

In this study, we assessed 75 patients with myasthenia gravis (MG) for coexistent autoimmune diseases (ADs) and for the characteristic autoantibodies that are associated with the most relevant forms of ADs. The demographic and clinical characteristics of the patients were recorded. In all patients, thyroid function tests, thyroid autoantibodies, and other autoantibodies were studied. The diagnosis of autoimmune thyroid disease (AITD) was made based on the clinical features, physical examination, and laboratory findings. The diagnoses of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were made in accordance with the revised criteria of American College of Rheumatology. The presence of other ADs were also recorded which was based on whether or not the patient already had a diagnosis of ADs; or, whether it was detected during the period of the study based on clinical findings and/or laboratory abnormalities. Thirty-nine patients (52%) had autoantibody positivity in their sera. Thyroid autoantibodies and antinuclear antibodies were the main autoantibodies detected. In twenty one of these patients, a diagnosis of AD could not be confirmed. Eighteen patients (24%) had a confirmed diagnosis of a coexisting AD. These ADs included AITD (16%), RA (4%), SLE (2.6%), and Lambert-Eaton myasthenic syndrome (1.3%). In ten patients, the diagnosis of ADs had been established before the development of MG; 8 of the patients included those who were newly diagnosed with ADs in the course of the management of MG. MG has an increased frequency of coexisting ADs. Autoantibodies that are characteristic for ADs can be found in the patients without the presence of any of the clinical findings of ADs. Clinical attention towards the management of ADs is especially needed during the follow-up of patients with MG.

The value and controversy of thyroid peroxidase antibody in the diagnosis and treatment of autoimmune thyroid disease

Thyroid peroxidase antibody (TPOAb) play an important role in the diagnosis of autoimmune thyroid disease. Chemiluminescence immunoassay (CLIA) is a new method been strongly recommended in recent years. The definition of positive value of TPOAb is inconsistent. The definition of TPOAb positive value is important for exploring the development of autoimmune thyroid disease. TPOAb is significantly increased in Hashimoto′s disease and the titer is associated with the degree of infiltration and destruction of thyroid follicular. It is essential to monitor TPOAb in postpartum thyroiditis and early pregnancy. The positive of TPOAb is closely related to the adverse pregnancy outcomes caused by various risk factors. Graves disease combined with Hashimoto′s must to be considered. (Chin J Lab Med, 2015, 38: 884-887) Key words: Thyroid Diseases; Thyroiditis, autoimmune; Iodide peroxidase; Autoantibody

Diagnostic performance of thyroid ultrasonography screening in pediatric patients with a hypothyroid, hyperthyroid or euthyroid goiter.

Goiter is frequently the first indicator of thyroid disease in children. To evaluate the usefulness of ultrasonography (US) in the identification of potential malignant nodules and autoimmune thyroiditis in children with diffuse goiter. This study consisted of 113 patients <20years with a diffuse goiter who underwent thyroid US. Parenchymal echogenicity and the presence of nodules and abnormal lymph nodes were evaluated on US; if a thyroid nodule was detected, its characteristics were analyzed. The diagnostic accuracy of the US findings in the diagnosis of autoimmune thyroid disease was assessed. Thyroid nodules were detected on US in 72 of the 113 (63.7%) patients. Of these, 65 (90.3%) had probably benign nodules and 4 (5.6%) patients had nodules suspicious of malignancy. The remaining had indeterminate nodules only. In one child with suspected malignant nodules, papillary thyroid cancer with coexisting autoimmune thyroiditis was confirmed. Hypoechogenicity was visualized in 23 (88.5%) patients with autoimmune thyroiditis and 12 (85.7%) with Graves disease. The sensitivity and specificity of micronodulation for autoimmune thyroiditis were 53.9% and 98.3%, respectively. Although the potential for malignant nodules is relatively low in children with diffuse goiter, US can detect focal thyroid disease and characterize the nodules. US thus plays a useful role in excluding autoimmune thyroiditis in this population.

Type 1 Diabetes Mellitus Associated with Autoimmune Thyroid Disease, Celiac Disease and Facial Asymmetry

Patients with type 1 diabetes mellitus are at a great risk of developing other autoimmune diseases.Ten -year-old girl was brought to our clinic with complaints of polydipsia, polyuria and weight loss and was diagnosed as diabetic ketoacidosis due to autoimmune type 1 DM. On physical examination, on the left side of her face mild facial asymmetry was noticed. She had the asymmetry since the birth. Elevated thyroid antibodies associated with diffuse goiter and hypothyroidism led to the diagnosis of autoimmune thyroid disease, and elevated antiendomysial antibodies, anti-gliadin antibodies and abnormal intestinal biopsy findings led to the diagnosis of celiac disease . To our knowledge, this is the first report on a child with a combination type 1 diabetes mellitus, autoimmune thyroid disease, celiac disease and facial asymmetry. Further research is clearly required both to study associations between autoimmune diseases and facial asymmetry and the link between autoimmune diseases and facial asymmetry.

The clinical role of serum concentrations of selected cytokines: IL-1β, TNF-α and IL-6 in diagnosis of autoimmune thyroid disease (AITD) in children

Chronic autoimmune thyroiditis (cAIT) leads to hypothyroidism due to T cell-mediated cytotoxicity in most cases. By contrast, Graves’ disease (GD) with thyrotropin receptor stimulatory autoantibodies cause hyperthyroidism. Cytokines play a crucial role in modulating immune response in both disorders. The aim of study was to evaluate the concentrations of cytokines: IL-1β, TNF-α and IL-6 in these two opposite clinical and hormonal thyroid diseases. The study group consisted of 64 children, 44 newly diagnosed, untreated children with cAIT (n = 22; with hypothyroidism) and GD (n = 22; hyperthyroidism), and the control group of 20 healthy children. Cytokine concentrations were evaluated using the ELISA technique. The studied groups of children did not differ significantly in concentrations of IL-6 (p = 0.48) and TNF-α (p = 0.067). In children with hypothyroidism, we found significantly higher concentrations of IL-1β (median 2.16 pg/ml, IQR 0.87) compared to hyperthyroidism (median 1.39 pg/l, IQR 1.27) (p < 0.01) and the control group (median 1.88 pg/ml, IQR 1.04) (p < 0.05). The results of ROC curve analysis demonstrated the usefulness of IL-1β (AUC = 0.77, p = 0.003) and TNF-α (AUC = 0.691, p = 0.034) as diagnostic parameters in cAIT which enable discrimination of children with autoimmune thyroid disease from healthy individuals. Concentrations of these markers are increased in autoimmune hypothyroidism. We found no significant sex differences in the tested parameters. In conclusion, IL-1β and TNF-α may be considered as markers of hypothyroidism, and could efficiently discriminate between healthy and autoimmune hypothyroid children. Significantly higher concentrations of IL-1β in children with hypothyroidism may be used to distinguish children with cAIT from GD patients.

The emergence of systemic lupus erythematosus in hypothyroid patients: two case reports and mini review

Systemic lupus erythematosus (SLE) is a multi-systemic autoimmune disease that involves almost all the organs in the human body and is characterized by auto antibodies formation. Autoimmune thyroid diseases (AITD) are organ-specific diseases that are associated with a production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies, anti-cardiolipin antibodies, and others. The diagnosis of AITD in patients with SLE is well known, but the reverse is rarely reported. We present two cases of adolescent girls in whom SLE evolved one year after being diagnosed with hypothyroidism.

Value of the Left Inferior Thyroid Artery Peak Systolic Velocity in Diagnosing Autoimmune Thyroid Disease

The purpose of this study was to calculate a number of thyroid grayscale and Doppler sonographic parameters in healthy individuals and patients with Hashimoto thyroiditis or Graves disease and assess their sensitivity and specificity for the diagnosis of autoimmune thyroid disease using receiver operating characteristic curves. A consecutive series of 153 patients (70 euthyroid and 54 hypothyroid patients with Hashimoto thyroiditis and 29 patients with Graves disease), all selected from an outpatient endocrine clinic, and 48 age- and sex-matched healthy control participants were evaluated with grayscale and power Doppler sonography. An irregular echo pattern in the thyroid parenchyma had 92.8% sensitivity for the diagnosis of autoimmune thyroid disease, and a left inferior thyroid artery peak systolic velocity (PSV) greater than 26.11 cm/s had 91.7% specificity. Of 8 patients with Hashimoto thyroiditis and normal grayscale sonographic characteristics, 6 had a left inferior thyroid artery PSV greater than 26.11 cm/s. A left inferior thyroid artery PSV greater than 61.65 cm/s had 82.8% sensitivity and 86.9% specificity for differentiating Hashimoto thyroiditis from Graves disease. The left inferior thyroid artery PSV was the most accurate sonographic parameter for the diagnosis of autoimmune thyroid disease. Measurement of the inferior thyroid artery PSV could be used in patients with a normal grayscale sonographic appearance and inconclusive clinical and biochemical parameters to substantiate the diagnosis of autoimmune thyroid disease. Further studies are needed to evaluate and expand the use of this index.

A hospital-based study of anti-TPO titer in patients with thyroid disease

Context: Autoimmunity against the thyroid gland is one of the most important causes for thyroid dysfunction. Anti-thyroid antibody test is an important tool in the evaluation of autoimmune thyroid disorders. Aims: To study the prevalence of thyroid hormone dysfunction and positive anti-TPO antibody titers in patients being evaluated for thyroid-related disorders. Settings and Design:This retrospective cross-sectional study was done in Father Muller Medical College. Materials and Methods: The TSH (Thyroid stimulating hormone), FT 4 (Free thyroxine), and anti-TPO titer reports of 74 subjects undergoing evaluation for thyroid-related disorders were analyzed. Statistical Analysis Used: Statistical significance was estimated by P value. Results: About two-third (60%) of hypothyroid patients showed raised TPO antibody titer. The titer was significantly higher in hypothyroid subjects when compared to the euthyroid subjects, and a majority of the hypothyroid subjects had a titer at least twice the upper limit of normal. Two of the three subjects with hyperthyroidism also had elevated anti-TPO titers. Conclusions: The commonest cause of hypothyroidism in our study subjects was autoimmune-related thyroid disease. Anti-TPO antibody estimation is a very useful test for establishing the etiological diagnosis of autoimmune thyroid diseases in our population. In situations where there is a diffuse non-progressive goiter, anti-TPO antibody estimation can substitute for an invasive FNAC.

Autoimmune encephalitis associated with Graves’ disease: a case report

Almost all patients who developed autoimmune thyroid disease associated with encephalopathy were diagnosed to have Hashimoto's thyroiditis, but a few patients with Graves' disease who developed encephalopathy have been reported. A 36-year-old female with a 10-year history of Graves' disease had experienced three episodes of tonic-clonic seizure. At admission, the patient's status was confused, and she also developed tactile and visual hallucinations. The cranial MRI confirmed white-matter lesion and showed subcortical high signal lesions on T2-weighted images. In EEG record, diffuse slow activity was noticed in both sides. T3 and TSH were decreased, T4 remained normal and thyroid peroxidase antibody (TPO) was evaluated to be more than 2,000 (T4=8.4, T3=12/9, TSH=0/14, TPO >2,000). The diagnosis of autoimmune thyroid disease is probable in all patients with signs of encephalopathy with unknown origin, while they have a previous history of thyroid disease.

Autoimmune thyroid diseases andHelicobacter pylori: The correlation is present only in Graves's disease

To investigate the correlation between autoimmune thyroid diseases (ATDs) and the prevalence of Cag-A positive strains of Helicobacter pylori (H. pylori) in stool samples. Authors investigated 112 consecutive Caucasian patients (48 females and 4 males with Graves' disease and 54 females and 6 males with Hashimoto's thyroiditis HT), at their first diagnosis of ATDs. Authors tested for H. pylori in stool samples using an amplified enzyme immunoassay and Cag-A in serum samples using an enzyme-linked immunoassay method (ELISA). The results were analyzed using the two-sided Fisher's exact test and the respective odds ratio (OR) was calculated. A marked correlation was found between the presence of H. pylori (P ≤ 0.0001, OR 6.3) and, in particular, Cag-A positive strains (P ≤ 0.005, OR 5.3) in Graves' disease, but not in Hashimoto's thyroiditis, where authors found only a correlation with Cag-A strains (P ≤ 0.005, OR 8.73) but not when H. pylori was present. The marked correlation between H. pylori and Cag-A, found in ATDs, could be dependent on the different expression of adhesion molecules in the gastric mucosa.

The Roche Elecsys and Siemens-Centaur Thyroglobulin Autoantibody Assays Show Comparable Clinical Performance to the Recently Unavailable Beckman-Coulter Access Thyroglobulin Autoantibody Assay in Identifying Samples with Potentially False-Low Thyroglobulin Measurements Due to Thyroglobulin Autoantibody Interference

Dear Editor: Approximately 25% of thyroid cancer patients have circulating antithyroglobulin autoantibodies (anti-TgAB), which can cause false-low interference in Tg assays (1). It is therefore recommended that all Tg measurements are accompanied by TgAB testing (1). The Beckman-Coulter Access Tg- and TgAB assays have become perhaps the most widely used assay combination for thyroid cancer follow-up in the United States, because they run on the same automated instrument and they are more sensitive than most alternative Tg/TgAB assays. Unfortunately, Beckman-Coulter has recently indicated that their TgAB assay will be unavailable for the foreseeable future, necessitating a switch to other TgAB assays to accompany Tg testing. Such a change has a high risk of interfering with patient management. Different TgAB assays show at best a moderate numerical agreement with each other, have different detection sensitivities, and have different cutoffs for TgAB positivity (2–4). We have therefore performed a comparison study of the Beckman-Coulter TgAB assay with three other automated TgAB assays: Roche Elecsys TgAB, Siemens-Centaur TgAB, and Siemens-Immulite TgAB. As these assays are primarily marketed for the diagnosis of autoimmune thyroid disease, the manufacturer-provided diagnostic cutoffs are not optimized for the detection of interference in Tg assays. Therefore, we first determined optimal cutoffs for these assays by comparing them with the Beckman-Coulter assay in 100 archival patient samples. Next, we performed a clinical validation of these cutoffs in 130 samples from 113 Mayo Clinic patients. These samples were selected to include patients with (43 patients with 51 samples) and without (70 patients with 79 samples) definitive persistent/recurrent disease (clinical or imaging proven) (see Supplementary Methods; Supplementary Data are available online at www.liebertonline.com/thy). We found poor numerical agreement between the Beckman-Coulter assay and the other TgAB assays, but receiver-operating characteristics (ROC) curve analysis, using the Beckman-Coulter TgAB results as the “gold standard” (negative: <4 IU/mL, N = 32; positive: ≥4 IU/mL, N = 68), showed comparable areas under the curves (see Supplementary Fig. S1): Siemens-Centaur 0.88 (95% confidence interval [CI]: 0.79–0.97), Siemens-Immulite 0.86 (95% CI: 0.81–0.92), and Roche 0.87 (95% CI: 0.77–0.95). At their respective ROC curve–derived cutoffs, the Siemens-Centaur (44 IU/mL) and Roche (22 IU/mL) missed only 1 and 3 samples, respectively, which had been positive with the Beckman-Coulter assay, whereas the Siemens-Immulite (20 IU/mL) missed 18. The Roche assay showed the best agreement with the Beckman-Coulter assay in the clinical validation sample set with verified disease status (see Supplementary Table S1), with a negative and positive agreement of 96% and 95%, respectively. The Siemens-Immulite assay showed the worst agreement (negative and positive agreement of 79% and 78%). The Siemens-Centaur assay's performance fell in between these two with 92% negative agreement and 94% positive agreement. All 16 samples from 15 patients with clinical recurrent/persistent disease, who had undetectable serum Tg levels (<0.1 ng/mL), were positive for TgAB in all four assays, using the respective cutoffs. However, of 31 samples from 26 patients with clinical recurrence and a Tg of <2 ng/mL, a total of 3 samples from 3 patients (1 per patient) had a negative TgAB result in the Beckman-Coulter, Roche, and Siemens-Centaur TgAB assays, whereas 6 samples from 5 patients (1 patient with 2 samples) had a negative TgAB result by the Siemens-Immulite assay. We conclude that the automated Roche Elecsys (cutoff: 22 IU/mL) and Siemens-Centaur (cutoff: 44 IU/mL) TgAB assays show comparable clinical performance to the Beckman-Coulter Access TgAB assay (cutoff: 4 IU/mL). The Siemens-Immulite assay (cutoff: 20 IU/mL) had lesser TgAB detection sensitivity than the other assays. Incidentally, all these cutoffs are much lower than those listed in the respective package inserts, which are targeted at diagnosis of autoimmune thyroid disease. These manufacturer-stated cutoffs would miss many cases of clinically relevant TgAB levels that could cause interferences in Tg measurements. The satisfactory performance of the Roche and Siemens-Centaur TgAB assays in identifying samples with TgAB levels that might interfere with Tg measurements does not solve all problems related to the sudden unavailability of the Beckman-Coulter TgAB assay. In particular, it remains important for laboratorians and clinicians to be mindful of the poor numerical agreement between the Beckman-Coulter assay and the other TgAB assays, when analyzing patient samples. Practitioners, who have used serial TgAB measurements with the Beckman-Coulter assay as a semiquantitative follow-up marker in TgAB-positive patients, need to re-baseline these patients with one of the alternative assays and should ensure that subsequent samples are measured using the same assay.

The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases

During recent years, researchers have been focusing on the concept of an infectious etiology of autoimmune diseases. The most discussed theory is molecular mimicry, i.e. the emergence of autoreactive clones of T- and B-lymphocytes as a result of cross-immune response to homologous bacterial or viral antigen. Information on the role of probiotic microorganisms (PM) in the molecular mechanisms of autoimmune thyroid diseases (ATD) is limited. Using proteins and immunogenic peptides databanks and relevant computer programs, the homology between the amino acid sequences of thyroid peroxidase (TPO) and thyroglobulin (Tg), which are potential B- and T-cell epitopes of these antigens, and proteins of bifidobacteria and lactobacilli was established. Moreover, we have found components of cells of Bifidobacterium bifidum 791, Bifidobacterium adolescentis 94 BIM, Bifidobacterium longum B379M and Lactobacillus plantarum B-01 that selectively bind human antibodies to TPO (anti-TPO) and antibodies to Tg (anti-Tg) and compete with natural antigens for the binding of anti-TPO and anti-Tg in ELISA. Additionally, a three-fold difference was observed between the probability of detecting antibodies (Abs) to the antigens of L. plantarum B-01 and B. bifidum 791 in serum samples containing and those not containing anti-TPO. On the whole, our data are arguments in favour of the assumption of the possible role of PM of the genera Bifidobacterium and Lactobacillus in triggering ATD by the mechanism of molecular mimicry. The data obtained in silico and in vitro should be proven by use of animal models and clinical studies for extrapolations to the whole body. Possible antigenic properties of components/proteins of bifidobacteria and lactobacilli, selectively binding anti-TPO and anti-Tg should be taken into consideration. Natural human Abs to these bacterial components are probably able to cross-react with the TPO and Tg in the ELISA for detection of anti-TPO and anti-Tg, which are serologic markers of ATD. It can lead to unspecific false positive results and, hence, to an incorrect diagnosis.