Thyroid Autoantibody Titers Research Articles

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

Efficacy of selenium supplementation for mild-to-moderate Graves’ ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial

BackgroundThe therapeutic effect of selenium has been demonstrated in mild Graves’ ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea.MethodsThe SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6.DiscussionThe SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO.Trial registrationKCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160.

Thyroid Function Rather Than Thyroid Antibodies Affects Pregnancy and Perinatal Outcomes: Results of a Prospective Study.

Thyroid autoantibody positivity has been associated with an increased rate of obstetrical complications. We aimed to evaluate the role of thyroid autoantibodies in adverse pregnancy outcomes. This prospective study was conducted in the Endocrinology Unit of Pisa Hospital. A total of 975 pregnant women were studied from 2012 to 2021; 572 (59%) were diagnosed with autoimmune thyroid (AT) diseases; 403 (41%) served as controls. Levothyroxine (LT4) treatment was introduced when TSH was > 2.5 mIU/L in the AT group and when TSH was > 4 mIU/L in the controls. Rates of obstetrical complications in each group were measured. Although the frequency of miscarriage in the AT group was greater (4.8%) than in the controls (2.9%), no significant differences were detected (P = 0.181). There were no differences between the 2 groups concerning the other pregnancy complications, and no association with the titer of thyroid antibodies was observed. The frequency of congenital malformations was greater in the AT group than in the controls (P = 0.019), but no correlation with major congenital malformations was detected (P = 0.872). Given that thyroid hormone concentrations were strictly controlled in our population, we documented a tendency (not significant) toward an increase in miscarriage and preterm birth among women with TSH > 4 mIU/L. If thyroid function is adequately controlled, the presence and titer of thyroid autoantibodies does not negatively influence gestation. Although not significant, suboptimal thyroid hormone status seems to affect pregnancy outcomes more than thyroid autoimmunity.

Dijetarni faktori i tiroidna disfunkcija

Besides iodine deficiency, autoimmune Hashimoto thyroiditis is the leading cause of hypothyroidism globally, characterized by the increased titer of thyroid autoantibodies and destruction of thyroid cells. Graves' disease is the most common etiology of hyperthyroidism worldwide. Patients with thyroid dysfunction often require dietary modifications. Popular interventions include supplementation with certain vitamins and minerals, as well as trace elements such as iodine and selenium. The intake of food containing goitrogens should be limited. Goitrogens are substances of plant origin that interfere with the production of thyroid hormones, increasing the risk for goiter and hypothyroidism. The primary dietary sources of goitrogens are cruciferous vegetables, soy products, starchy plants, and some fruits. Beyond essential nutrients, there has been an increasing interest in using specific nutraceuticals, including myoinositol, Lcarnitine, melatonin, and resveratrol, as potential preventive and therapeutic agents in thyroid diseases. Even though current evidence promotes some beneficial outcomes of these nutraceuticals, further investigations are needed to clarify dose-dependent effects, duration of supplementation, combination in different clinical settings, and the exact mechanism of their action in thyroid disorders.

Assessment of Visual and Brainstem Auditory Evoked Potentials in Patients with Hashimoto's Thyroiditis.

Background The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto's thyroiditis (HT) patients without central nervous system involvement. Methods 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. Results The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. Conclusions There were changes in the brain's bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain's bioelectrical activity in the course of HT may be associated with an autoimmune process.

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma

BackgroundLutetium 177 (177Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on 177Lu-DOTATATE-induced thyroid dysfunction is limited.Case DescriptionA 29-year-old male with SDHB positive metastatic paraganglioma enrolled under the 177Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to 177Lu-DOTATATE therapy. The TSH was suppressed [<0.01 µIU/ml (0.27–4.2 µIU/ml)], and FT4 was normal [1.3 ng/dl (0.9–1.7 ng/dl)]. The TSH receptor antibody and thyroid stimulating immunoglobulin index were undetectable [<1 IU/L (≤1.75 IU/L), and <1 (≤1.3) respectively], while the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were elevated [605 IU/ml (0.0–34.9 IU/ml), and 178 IU/ml (0.0-40.0 IU/ml) respectively]. Mass spectrometry on a stored (-80°C) plasma sample obtained one-month pre-PRRT revealed elevated total triiodothyronine (TT3) [235 ng/dl (65–193 ng/dl)] and FT4 [3.9 ng/dl (1.2–2.9 ng/dl)] levels. The patient was diagnosed with Hashimoto’s thyrotoxicosis. However, the patient was asymptomatic. One month after the first dose of 200mCi 177Lu-DOTATATE, the patient noted fatigue and a 2.6 Kg weight gain. The TSH (73.04 µIU/ml), anti-TPO antibodies (>1,000 IU/ml), and anti-Tg antibodies (668 IU/ml) had substantially increased, with reductions in FT4 (0.3 ng/dl) and TT3 [54 ng/dl (87–169 ng/dl)]. Diagnostic gallium 68 - DOTATATE positron emission tomography-computed tomography performed prior to 177Lu-DOTATATE treatment revealed diffuse thyroid uptake. Post-therapy single-photon emission computed tomography also revealed diffuse uptake of 177Lu-DOTATATE in the thyroid gland. Levothyroxine therapy was initiated, and the patient’s symptoms resolved.SummaryWe report, for the first time, a patient with asymptomatic primary hyperthyroidism who rapidly developed symptomatic primary hypothyroidism 1 month after 177Lu-DOTATATE therapy, accompanied by marked changes in TFTs and thyroid auto-antibody titers, with functional imaging evidence of diffuse uptake of 177Lu-DOTATATE in the thyroid gland.ConclusionsThyroid dysfunction can be associated with PRRT. Thyroid uptake patterns on pre-treatment diagnostic somatostatin analog scans might predict individual susceptibility to PRRT-associated TFT disruption. Therefore, periodic evaluation of TFTs should be considered in patients receiving PRRT.

Research on the Role of Th17Treg Cells and Their Factors in Graves&amp;apos; Disease with Different Iodine Nutritional Status

Introduction: At present, studies on the role of iodine nutrition in thyroid function stratification, antibody titer, Th17/Treg cells and related factors in the pathogenesis of GD have not been carried out. Objective: The acritical aims to investigate the correlation between thyroid function and autoantibody titers of Graves' disease (GD) patients with different iodine nutritional status with Th17/Treg cells, their cytokines and transcription factors, and the role of related factors in the pathogenesis of GD. Method: The levels of serum thyroid hormone, autoantibodies and urine iodine in 100 GD patients and 60 healthy subjects are detected by electrochemiluminescence instrument and iodine-catalyzed arsenic-cerium method, respectively. The ratio of Th17 cells to Treg cells and Th17/Treg ratio in peripheral blood mononuclear cells (PBMC) are detected by immunofluorescence-labeled monoclonal antibodies and flow cytometry. Real-time fluorescence quantitative PCR is used to detect the expression levels of retinoic acid-related orphan receptor (ROR-γt) and fork head/wing-shaped spiral transcription factor 3 (Foxp3) mRNA, and the serum IL-17 and TGF-β levels are detected by ELISA. Result: As a result, the proportion of Th17 cells, serum IL-17 and ROR-γt in PBMC of GD patients with different iodine nutritional status significantly increase, while the proportion of Treg cells, the expression of Foxp3mRNA and serum TGF-β significantly decrease. The ratio of Th17/Treg cells in GD patients is significantly positively correlated with the titers of TPOAb and TgAb, and the titers of TPOAb and TgAb antibodies are significantly correlated with Th17/Treg, IL-17 and ROR-γt. Conclusion: In conclusion, thyroid hormones, autoantibodies, Th17, Treg cell ratios and dysfunctions as well as corresponding cytokines and transcription factors in GD patients with different iodine nutritional status participate in the development of GD.

Study on Th17/Treg Cells and Cytokines in Hashimoto&amp;apos;s Thyroiditis with Different Iodine Nutrition Status

<i>Background</i>: The incidence of AITDs increased with the increase of iodine nutrient levels in the population. HT is one of the most common AITDs. The role of thyroid function stratification, antibody titer, Th17/Treg cells and related factors in the pathogenesis of HT under different iodine nutritional conditions is still unclear. <i>Objective</i>: To investigate the correlation between the thyroid function stratification, autoantibody titer and Th17 cells, Treg cells, cytokines and transcription factors in hashimoto thyroiditis patients with different iodine nutritional status. <i>Methods</i>: Thyroid hormone, autoantibody and urinary iodine levels were measured in 100 hashimoto's thyroiditis (HT) patients and 60 healthy subjects by electrochemical immunoluminescence and iodine-catalyzed arseniummethod. Meanwhile, the proportion and ratio of Th17 cells and Tregs cells in peripheral blood mononuclear cells (PBMC) were determined by immunofluorescence labeling and flow cytometry. The qRT-PCR was used to detect the expression of ROR-γt mRNA and Foxp3 mRNA. Serum IL-17 and TGF-β levels were detected by ELISA. <i>Results</i>: Th17 cell proportion, serum IL-17 and ROR-γt mRNA expression levels in PBMC of HT patients with different iodine nutritional status were all higher than those in the control group (<i>P</i><0.05), while Tregs cell proportion, serum TGF-β and Foxp3 mRNA level were all lower than those in the control group (<i>P</i><0.05). <i>Conclusions</i>: The thyroid function, autoantibodies, Th17/Tregs cell proportion, cytokines and transcription factors of HT patients with different iodine nutrition status were changed, hich were involved in the development and progression of HT.

Correlation Analysis Between Thyroid Function and Autoantibodies in Hashimoto Thyroiditis Patients with Different Iodine Nutritional Status

Objective: In order to discuss the correlation between thyroid function stratification and autoantibody titer in HT patients under different iodine nutritional status. Methods: The serum TH, antibody and urinary iodine levels were measured by the electrochemical immune-luminescent apparatus and iodine-catalyzed arsenic-cerium method in 100 HT patients (HT-A, HT-B, HT-C) with different thyroid functions and 60 healthy subjects. Results: The urinary iodine level of HT patients from HT-A increased in turn along with the progression of the disease, while the levels of FT3, FT4, TT3, TT4 decreased gradually and the levels of TSH and thyroid autoantibodies increased gradually. The urinary iodine level of HT-C group was negatively correlated with the serum FT3, FT4, TT3 and TT4 (P<0.05), while the urinary iodine level of HT-B group was negatively correlated with the serum FT3 and TT4 (P<0.05), and positively correlated with TSH (P<0.05). Along with the progression of HT disease, the levels of serum TPOAb and TGAb increased successively, and there were significant differences among each group (P<0.01). The serum TSH level of high TPOAb group and high TgAb group were respectively higher than those of low TPOAb group, low TgAb group and the control group, the levels of FT3 and FT4 were respectively lower than the low TPOAb group and low TGAb group, but there were no statistically significant on the differences between the FT3 of low TgAb and the levels of T3 and T4 of the control group, high TPOAb group, high TGAb group, low TPOAb group and low TGAb group. Conclusions: Under different iodine nutritional status, if the TH and autoantibody levels of HT patients with different thyroid functions changed correspondingly, it could indicate that the iodine nutritional status is involved in the occurrence and development process of HT of different thyroid functions and antibody levels, and plays an important role in it.

The Impact of Glucocorticoid Co-Secretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease.

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn’s Registry were included. Anti-TPO and anti-TG levels were measured pre and 6–12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

SAT-LB76 Impact of Glucocorticoid Cosecretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease

Context: Excess aldosterone is associated with the increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects.The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation.Patients and Methods: 97 PA patients (43 with unilateral, 54 with bilateral PA) from the database of the German Conn’s Registry were included. Anti-TPO and anti-TG levels were measured pre and 6 to 12 months post therapeutic intervention. Patients were assessed for ACS according to their 24h urinary cortisol excretion, late night salivary cortisol and low-dose dexamethason suppression test.Results: Abnormal test results in line with ACS were identified in 74.2% of patients. Significant increases in anti-TPO levels were observed in adrenalectomized patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy.Conclusion: ACS appears to be a relevant factor in PA affecting thyroid autoimmune disease. The biochemical and clinical course maybe be exacerbated after resolution of hypercortisolism by adrenalectomy in PA.

Effect of Vitamin D Supplementation on Thyroid Autoimmunity among Subjects of Autoimmune Thyroid Disease in a Coastal Province of India: A Randomized Open-label Trial.

Objective:Hashimoto's thyroiditis (HT) is a variant of autoimmune thyroid disorders (AITD) which has been associated with vitamin D (vit-D) deficiency. However, whether vit-D supplementation is linked to reduction of thyroid autoantibodies and improvement of thyroid function is not well characterized. The present study was planned to evaluate the effect of vit-D supplementation on possible improvement of thyroid autoantibody titer and thyroid hormone profile in patients with AITD subjects.Methods:Twenty-three patients of HT were given weekly supplementation of 60,000 IU vit-D for 8 weeks followed by once a month for another 4 months. After 6 months of vit-D supplementation, thyroid autoantibody titer (TPO antibody) and thyroid hormone profile was rechecked.Results:Mean serum vit-D was increased significantly from 15.33 ± 5.71 to 41.22 ± 12.24 ng/mL (normal levels) after supplementation. There was significant increase in thyroid autoantibody titre (from 746.8 ± 332.2 to 954.1 ±4 59.8 IU/ml; P = 0.006) and TSH level (7.23 ± 3.16 to 3.04 ± 2.62 (mIU/L); P = 0.01) following 6 months of vit-D supplementation.Conclusion:Vitamin-D levels were low in AITD patients in eastern India and, its supplementation in HT patients increased thyroid antibody titer and there was significant reduction in serum TSH and increased in free T4.

Correlation Analysis of Thyroid Function and Autoantibodies in Graves’ Disease Patients with Different Iodine Nutritional Status

Objective: To investigate the correlation between thyroid function stratification and autoantibody titers in patients with Graves’ disease (GD) under different iodine nutrition conditions. Methods: The levels of serum thyroid hormones, autoantibodies and urinary iodine in 100 patients with different thyroid function GD [GD-A, GD-B] and 60 healthy subjects are detected by electrochemical immunoluminescence and iodine-catalyzed arsenic-cerium method. Results: The proportion of GD patients with the sum of iodine overdosage and iodine overdosage group is consistent with iodine adequate group, which is significantly higher than iodine deficiency group, and the (Median Urine Iodine, MUI) of GD-A group is significantly higher than GD-B group. Urinary iodine levels in GD group and GD-A group are positively correlated with serum FT3 and FT4 (P<0.05), and negatively correlated with (thyroid stimulating hormone, TSH) (P<0.05). The levels of serum (thyroid peroxidase antibody, TPOAb) and (thyroid globulin antibody, TGAb) in each GD group are significantly higher than those in the control group. Serum TSH levels in the high TPOAb group and high TgAb group are lower than those in the low TPOAb group, low TgAb group and control group, respectively. The levels of FT3 and FT4 are higher than those of the low TPOAb group and the low TgAb group, however, there is no significant difference between the FT3 of low TgAb and T3 and T4 levels that belong to the control group, high TPOAb group, high TgAb group, low TPOAb group, and low TgAb group. In conclusion: GD patients with different thyroid functions have corresponding changes in their thyroid hormone and autoantibody levels under different iodine nutrition conditions, which indicates that iodine nutrition status involve in and play an important role in the development of GD with different thyroid functions and different antibody levels.

Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.

The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. Iodine deficiency (UIC < 100μg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

BS14. Visual and brainstem auditory evoked potentials in Hashimoto’s thyroiditis

Introduction A normal thyroid gland activity is essential for the optimal development, maturation and function of the nervous system. Neurological syndromes can develop in certain thyroid diseases that may have normal levels of thyroid hormones. One such example is Hashimoto’s thyroiditis (HT), which is currently considered to be the most common autoimmune disease in humans. The exact cause of those symptoms has not yet fully been explained. Their pathomechanism is still being studied. Precise and non-invasive methods of assessment of the nervous system function is evoked potentials study (EP). It is a sensitive technique that enables the evaluation of the brain bioelectrical activity also in patients with HT. EPs are particularly useful in patients with mild or without clinical neurological symptoms. The aim of the study was to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic HT patients without clinical neurological deficit, and without ophthalmological and otolaryngological abnormalities. Methods 100 HT patients (92 women, 8 men) from 20 to 68 years old (mean 46.9 years). They did not suffer from concurrent diseases that could have affected the brain electrical activity. The visual and auditory receptors were not damaged in any of the patients and the patients did not suffer from any central nervous system damage. The matched control group comprised 50 healthy subjects. HT patients underwent a subjective and objective neurological examination, thyroid hormone levels and thyroid autoantibody titers, brain imaging (CT or MRI), VEP and BAEP. Results Abnormal VEP and BAEP were recorded in 34% of the patients. The mean P100, relative P100, N145 VEP latencies were significantly longer and P100 amplitude significantly higher in HT patients than in the control group. HT patients also had a longer mean wave V latency and mean wave III-V and I-V interpeak latencies and significantly lower mean wave I and V amplitudes than the controls. There were no statistically significant correlations between the mean VEP parameters and the levels of TSH, free thyroid hormones, antithyroid antibody titers and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. The number of abnormal VEP and BAEP depended on the dose of L-thyroxine and was the highest in patients without treatment and decreased with the increase in the dose of levothyroxine. Conclusion 1. There were changes in the brain bioelectrical activity in the form of abnormal VEP and BAEP in one third of the patients with Hashimoto’s disease who did not have central nervous system deficits. 2. The increased amplitude of the VEP in the course of HT may indicate increased cerebral cortex activity. 3. Disorders of the brain bioelectrical activity in the course of HT may be associated with an ongoing autoimmune process. 4. The analysis of the VEP and BAEP may be useful in assessing the brain bioelectrical activity in the course of HT.

Thyroid function and autoantibody status in Bangladeshi patients with type 2 diabetes mellitus

Background: Thyroid dysfunction is common in patients with type 2 diabetes mellitus (T2DM), and data on thyroid autoimmunity in T2DM are scarce. This study was designed to observe the frequency of thyroid dysfunction and autoimmune thyroid disease in Bangladeshi T2DM patients. Materials and Methods: In this cross-sectional study, we investigated 1056 T2DM patients with unknown thyroid function status throughout the country. Serum thyroid stimulating hormone (TSH) and free T4 (FT4) and antithyroid antibodies (antithyroid peroxidase or antimicrosomal) were measured. Statistical analysis was done using IBM SPSS Statistics for Windows, version 23.0 software. P ≤ 0.05 was considered statistically significant. Results: The observed frequency of thyroid dysfunction in our study was 21.9% (subclinical hypothyroid 14.1%, primary hypothyroid 4%, subclinical hyperthyroid 1.9%, overt hyperthyroid 1%, and secondary hypothyroid 0.9%). 32.9% of the participants were positive for thyroid autoantibodies. The patients with thyroid dysfunction had a higher body mass index (BMI), higher TSH, lower FT4, and higher thyroid autoantibody titer than euthyroid ones. Thyroid dysfunction was more common in females and autoantibody-positive individuals. TSH had an inverse negative correlation with FT4 in both euthyroid and thyroid dysfunction groups and had a positive correlation with age in the euthyroid group only. FT4 had an inverse correlation with age and duration of diabetes in both groups and with BMI in euthyroid diabetic patients. Conclusion: Thyroid dysfunction and autoimmunity are common in Bangladeshi T2DM patients. Thyroid dysfunction was more common in females and autoantibody-positive diabetic patients.

Increased leptin levels correlate with thyroid autoantibodies in nonobese males.

Leptin is an adipokine that regulates body weight and appetite. It is also an inflammatory cytokine that influences immune reactivity and autoimmunity. Leptin levels are increased in obesity and are higher in women than in men. We aimed to determine whether leptin levels, independent of sex and body mass index (BMI), are associated with thyroid autoimmunity. This study uses data from The Third National Health and Nutrition Examination Survey (NHANES III) to test the association of leptin and thyroid autoimmunity, independent of BMI. Thyroid-stimulating hormone, thyroxine, antithyroid peroxidase (TPO) antibodies and leptin levels were measured in 2902 men and 3280 women within the NHANES III population. BMI was calculated from height and weight. Women had significantly higher leptin levels and anti-TPO antibody titres than men. Correlation analyses demonstrated that leptin levels were associated with anti-TPO antibody levels in the total population, but when men and women were analysed separately, this association was lost. We then stratified men and women into obese (BMI > 30) or nonobese (BMI ≤ 30) subgroups and determined the association between leptin levels and anti-TPO antibody titres for each subgroup. Using regression analysis, we found that increased leptin levels correlated with thyroid autoantibodies in nonobese males, but not in obese males or in females. Leptin levels correlated with thyroid autoantibody titres in nonobese males. This association was not found in females. Sex and body habitus should therefore be considered in studying the role of leptin in other autoimmune conditions.

Effects of Selenium Supplementation on Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice.

Recent clinical studies have demonstrated the suppressive effect of selenium (Se) treatment on serum thyroid-specific antibody titers in patients with autoimmune thyroiditis (AIT), but the mechanism underlying this process is not clear. The aim of the present study was to investigate the effects of selenium on the incidence and severity of AIT, titers of thyroid autoantibodies, and selenoprotein expression in thyroid in a spontaneous autoimmune thyroiditis (SAT) model. NOD.H-2(h4) mice at four weeks of age were randomly divided into control, iodine supplement (SAT), and selenium supplement groups (SAT+Se). Mice were given 0.005% sodium iodide water for eight weeks to induce SAT and then 0.3 mg/L sodium selenite in drinking water for 8 weeks and 16 weeks. The severity of lymphocytic infiltration in the thyroid, serum thyroglobulin antibody (TgAb) titers, serum selenium concentration, expression of glutathione peroxidase-1 (GPx1), thioredoxin reductase-1 (Txnrd1), and peroxiredoxin 5 were measured. Serum selenium concentration significantly increased after selenium supplementation. Serum TgAb levels were significantly lower in the selenium group compared with the SAT group (p<0.05). The prevalence of thyroiditis and the degree of infiltration of lymphocytes decreased gradually over time in the group provided with selenium supplementation. The expression of GPx1 and Txnrd1 by Western blotting were found to be significantly higher in the SAT+Se group than in other groups (p<0.05). These results indicate that selenium treatment can increase the function of antioxidation by upregulating the expression of selenoproteins in the thyroid and have an inhibitory effect on TgAb titers, which may have an impact on AIT.

Thyroid-specific changes following treatment with biological therapies in patients with rheumatic diseases.

Biological anti-rheumatic agents (BAA) may induce autoimmune phenomena. Evidence on thyroid-specific effects of these agents is relatively limited. We studied prospectively, over 3 years, 36 rheumatic patients treated with BAA (18 Infliximab and 18 Rituximab) and no prior exposure to biological therapies (group-1), with respect to their thyroid function, thyroid antibody titers, and thyroid ultrasonographic parameters, such as left inferior thyroid artery peak systolic velocity (ITA PSV), left thyroid lobe vascularity index (TL VI), and echogenicity. Twenty-eight rheumatic patients treated with disease-modifying anti-rheumatic drugs and/or glucocorticoids (group-2), 21 rheumatic patients not receiving any treatment (group-3), and 49 healthy individuals (group-4) were used for comparison. Thyroid function and autoantibody titers were not significantly altered at any stage irrespectively of the administered BAA, previously unknown autoimmune thyroid disease (AITD) status, and/or concomitant treatment with glucocorticoids. Left ITA PSV was significantly increased in group-1 patients (mean ± SD start: 25.5 ± 14.1 cm/s vs. end: 29.8 ± 11.1 cm/s, p = 0.038 and p < 0.001, respectively). Six group-1, 7 group-2, and 3 group-3 patients developed reduced thyroid echogenicity during follow-up (start: p = 0.003 and end: p < 0.001). Left ITA PSV, left TL VI, and echogenicity changes were not related to alterations in thyroid volume, thyrotropin hormone levels, and/or underlying AITD. Infliximab and Rituximab do not cause any alterations in thyroid function and/or autoimmunity, even in patients with previously undiagnosed AITD. Elevated left ITA PSV and reduced thyroid echogenicity may be early features signaling progression to AITD in patients treated with BAA.

Reference ranges for TSH and thyroid hormones

Though TSH remains the most commonly used endocrine test in clinical practice, the issue of an appropriate TSH, and to a lesser extent, free T4 and free T3 reference ranges is still under debate. First of all the distribution of TSH reference range is not normal, with median values (also depending on population iodine intake) usually between 1-1.5 mU/L [1-3]. On the other hand, upper TSH reference limit is (assay-dependent) usually around 4.2-4.5 mU/L. There is also an argument that significant number of patients (up to 30%) with TSH above 3.0 mU/L have an occult autoimmune thyroid disease [4]. On the other hand the upper normal TSH reference range in elderly subjects (i.e. 70 plus years) may extend up to around 6.0 mU/L, with relative small changes in free hormones. This phenomenon also applies to elderly patients, where autoimmune thyroid disease had been ruled out [1,2]. Furthermore, there is little evidence of any adverse effects of autoimmune thyroid disease in the elderly in the absence of an overt hypothyroidism. Indeed, Wang et al [5] surprisingly demonstrated decreased frailty in elderly subjects with raised titres of thyroid autoantibodies. It is also well known that in the setting of subclinical hypothyroidism, concentrations of free T4 start to decline below 10 pmol/L only with TSH above 6-7 mU/L in elderly subjects, though a decline in free T4 is more pronounced in the young (particularly in those aged 20-29 years), where free T4 starts to decline for TSH concentrations above 4.5 mU/l [6]. Another issue pertains to the risk of cardiovascular disease in subjects with subclinical hypothyroidism. There are data from post-menopausal women enrolled into the Women Health Initiative study, where an increase in the risk of myocardial infarction was demonstrated only for TSH concentrations above 7.0 mU/L [7]. A separate issue, extensively discussed elsewhere [8], pertains to alterations of TSH and free thyroid hormones during pregnancy. In particular there is decrease in TSH in the first trimester followed by a gradual return to pre-pregnancy values. In contrast, there is an increase in free T4 in the first trimester, while in the third trimester free T4 concentrations are usually at the lower end of the standard (i.e. pre-pregnancy) reference range, or even just below the lower reference limit. Hence, there is an urgent need (postulated in the Endocrine Society Guidelines [8]) to create separate reference ranges for TSH and free thyroid hormones during pregnancy, possible with reference to each trimester. There are also recent data from China [9], where the authors demonstrated that the above-mentioned first trimester-related alterations in TSH and free T4, become only really visible after about 5th-6th week of gestation. The authors of this study suggest that standard reference ranges for TSH and free T4 can be applied up to this point of gestation.