Serum Thyroid Autoantibody Levels Research Articles

Serum thyroid autoantibodies in malignant thyroid nodules

Background: Thyroid cancer is one of the most common malignant tumours of the endocrine system. Thyroid autoantibodies were reported to be associated with malignant thyroid nodules. This study aimed to assess the diagnostic accuracy of serum thyroid autoantibody levels for malignant thyroid nodules. Methods: From March 2023 to January 2024, we recruited 104 consecutive patients with thyroid nodules confirmed by ultrasonography in three departments of Bangabandhu Sheikh Mujib Medical University. Out of these, 52 were diagnosed with malignant thyroid nodules using fine needle aspiration cytology, while the remaining 52 had benign thyroid nodules. Serum thyroid autoantibodies were measured using the immunoassay technique. Results: The mean levels of serum thyroid peroxidase antibody (TPOAb) were significantly higher (P<0.001) in the malignant group compared to the benign group (36.1 versus 24.0 IU/mL). The mean levels of serum thyroglobulin antibodies (TgAb) were also significantly higher (P<0.001) in the malignant group (39.8 IU/mL versus 29.1 IU/mL). Elevated TPOAb (>40 IU/mL) and TgAb (>35 IU/mL) showed reasonable accuracy (60% to 65%) in detecting malignancy of thyroid nodules. Conclusions: Thyroid malignancy is positively associated with TgAb and TPOAb. Therefore, thyroid autoantibodies could be considered for screening malignancy in thyroid nodules.

Effects of high-fat diet on thyroid autoimmunity in the female rat

BackgroundWhile contributions of dyslipidemia to autoimmune diseases have been described, its impact on thyroid autoimmunity (TA) is less clear. Programmed cell death 1(PD-1)/PD-ligand 1 (PD-L1) immune checkpoint is crucial in preventing autoimmune attack while its blockade exacerbates TA. We thus unveiled the effect of high-fat diet (HFD) on TA, focusing on the contribution of PD-1/PD-L1.MethodsFemale Sprague Dawley (SD) rats were randomly fed with a regular diet or HFD (60% calories from fat) for 24 weeks. Then, thyroid ultrasonography was performed and samples were collected for lipid and thyroid-related parameter measure.ResultsHFD rats exhibited hyperlipemia and abnormal biosynthesis of the unsaturated fatty acid in serum detected by lipidomics. These rats displayed a relatively lower echogenicity and increased inflammatory infiltration in thyroid accompanied by rising serum thyroid autoantibody levels and hypothyroidism, mimicking human Hashimoto’s thyroiditis. These alterations were concurrent with decreased mRNA and immunostaining of intrathyroidal PD-1 and also serum PD-1 levels but not the PD-L1 expression, suggesting a role of a PD-1 pathway. Meanwhile, the infiltration of B and T cell, a key cellular event inhibited by the PD-1 signals, was enhanced in the thyroid of HFD rats, along with thyroid fibrosis and apoptosis.ConclusionsOur data suggest that HFD triggers TA through a mechanism possibly involving downregulation of PD-1-related immunosuppression, providing a novel insight into the link between dyslipidemia and autoimmune toxicities.

Hashimoto's Thyroiditis Induces Hippocampus-Dependent Cognitive Alterations by Impairing Astrocytes in Euthyroid Mice.

Background: Although studies have reported an increased risk for cognitive disorders in Hashimoto's thyroiditis (HT) patients, even in the euthyroid state, the mechanisms involved remain unclear. The hippocampus is a classic brain region associated with cognitive function, among which the formation of long-term potentiation (LTP) in the Schaffer collateral-CA1 pathway plays an important role in the process of learning and memory. Therefore, this study established a euthyroid HT model in mice and investigated whether and how HT itself has the ability to trigger LTP alterations accompanied by learning and memory abnormality. Methods: An experimental euthyroid HT model was established in NOD mice through immunization with porcine thyroglobulin (Tg). Morris water maze was measured to determine mice spatial learning and memory. We investigated the effect of HT on synaptic transmission and high-frequency stimulation-induced LTP in the Schaffer collateral-CA1 synapse of mice hippocampus in vivo. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with the induction of LTP. Results: HT mice showed intrathyroidal lymphocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function. The HT mice had poorer performance in Morris water maze than controls. These alterations were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. The integrity of the synaptic structure is the premise for the production of LTP. As detected by transmission electron microscopy, the ultrastructure of synapse and astrocyte in the hippocampus were impaired in euthyroid HT mice. Additionally, Western blot and real-time polymerase chain reaction analyses confirmed that in HT mice, GS, GLAST, and GLT-1, key elements in glutamate-glutamine circulation located in astrocyte, were downregulated, accompanied by elevated levels of glutamate in the hippocampus, which impaired the material basis for LTP induction. NMDR2B expression in the hippocampus was also downregulated. Conclusion: HT can induce damage of LTP in the hippocampal Schaffer collateral-CA1 pathway in the euthyroid state, and this can be attributed, at least partly, to astrocytes impairment, which may underlie the deleterious effects of HT itself on hippocampal-dependent learning and memory function.

Hashimoto\u2019s thyroiditis impairs embryo implantation by compromising endometrial morphology and receptivity markers in euthyroid mice

BackgroundAlthough thyroid dysfunction caused by Hashimoto’s thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice.MethodsFemale NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot.ResultsHT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin β3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found.ConclusionsThese findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.

Hashimoto\u2019s thyroiditis induces neuroinflammation and emotional alterations in euthyroid mice

BackgroundAlthough studies have reported an increased risk for mood disorders in Hashimoto’s thyroiditis (HT) patients even in the euthyroid state, the mechanisms involved remain unclear. Neuroinflammation may play a key role in the etiology of mood disorders in humans and behavioral disturbances in rodents. Therefore, this study established a euthyroid HT model in mice and investigated whether HT itself was capable of triggering neuroinflammation accompanied by emotional alterations.MethodsExperimental HT was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Four weeks after the last challenge, mice were tested for anxiety-like behavior in the open field and elevated plus maze tests and depression-like behavior in the forced swimming and tail suspension tests. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with neuroinflammation. The changes in components of central serotonin signaling were also investigated.ResultsHT mice showed intrathyroidal monocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function, which defines euthyroid HT in humans. These mice displayed more anxiety- and depressive-like behaviors than controls. HT mice further showed microglia and astrocyte activation in the frontal cortex detected by immunohistochemistry, real-time RT-PCR, and transmission electron microscopy (TEM). These observations were also accompanied by enhanced gene expression of proinflammatory cytokines IL-1β and TNF-α in the frontal cortex. Despite this inflammatory response, no signs of neuronal apoptosis were visible by the TUNEL staining and TEM in the frontal cortex of HT mice. Additionally, IDO1 and SERT, key serotonin-system-related genes activated by proinflammatory cytokines, were upregulated in HT mice, accompanied by reduced frontal cortex serotonin levels.ConclusionsOur results are the first to suggest that HT induces neuroinflammation and alters related serotonin signaling in the euthyroid state, which may underlie the deleterious effects of HT itself on emotional function.

INTRODUCTING A RARE THYROID LYMPHOMA IN HASHIMOTO THYROIDITIS AIRWAY OBSTRUCTION AND RESPIRATORY AEERST

Primary thyroid lymphoma is an uncommon tumor that in almost the majority of patients occurs in the setting of lymphocytic thyroiditis or Hashimoto’s disease. Hashimoto thyroiditis is one of the autoimmune inflammatory diseases in the thyroid gland that is characterized with elevated levels of serum thyroid auto-antibodies. A 39-year-old woman was referred with dyspenea in last two months and in initial histological examination, Hashimoto thyroiditis was reported. Due to recurrence of symptoms and airway obstruction, she underwent total thyroidectomy. During surgery, a mass which was attached to the thrachea was seen, which was completely removed. In the final pathologic study, lymphoma arising from Hashimoto thyroiditis was introduced.

Autoimmune Thyroid Disease and Breast Cancer Prognosis.

The association of breast cancer and thyroid autoimmunity has been suggested by many studies in the literature, but the causality still needed to be proven. With this study we aimed to search the correlation between thyroid autoimmunity and breast cancer prognostic factors. To this prospective cohort study 200 consecutive breast cancer patients, who were operated in our clinic were included. Patients' serum thyroid hormone, anti-thyroglobuline (anti-TG) and anti-thyroid peroxidase (anti-TPO) levels and tumors' prognostic parameters (tumor size, axillary involvement, histological grade, lymphovascular invasion, receptor status, Ki-67 proliferation index) were collected. The correlation between serum thyroid autoantibody levels and tumor's prognostic factors were studied. The prevalence of thyroid autoimmunity (high levels of serum anti-TPO and/or anti-TG) was 18.5% (n=37). Patients with thyroid autoimmunity had a significant lower rate of axillary involvement and a lower rate of Ki-67 proliferation index (22% vs. 46% [p=0,007] and 12.73% vs. 20.72% [p=0.025], respectively) and were more commonly included to the "low-risk" group (<14%) according to their Ki-67 scores (68% vs. 46%; p=0.015). Other parameters did not differ between the two groups. We found a favorable correlation between thyroid autoimmunity and axillary involvement and also Ki-67 proliferation index score, which are two crucial and strongly predictive parameters of breast cancer prognoses. This supports the idea of thyroid autoimmunity being a favorable prognostic parameter. Further studies are necessary to investigate the reasons of protective or predictive effect of high thyroid peroxidase levels in breast cancer patients.

The role of preoperative serum thyroglobulin and thyroid auto-antibody levels before histopathological diagnosis of thyroid cancers

If a frozen section pathological examination is not performed in unilateral thyroid nodule surgery and the postoperative pathological diagnosis is cancer, a second operation may be required. Therefore, it was studied whether serum thyroid auto-antibody levels are useful or not in determining preoperative malignancy in patients with thyroid disorders. Materials and methods: It was investigated retrospectively whether there was a correlation between preoperative serum thyroglobulin (Tg), anti-thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase antibody (anti-TPO) levels and thyroid cancer in patients who had undergone thyroidectomy. Results: Two hundred and eighty-seven patients who had undergone thyroid surgery and whose preoperative serum levels of Tg, anti-Tg, and anti-TPO had been recorded were included in this study. Only 54 (18.8%) of the patients had a malignant diagnosis in the postoperative histopathological examination. Sixteen of the patients who had a postoperative malignant thyroid disease diagnosis (29.6%) had high serum Tg, anti-TPO, and/or anti-Tg levels. The rate of high serum Tg levels was significant in patients with a benign pathology (49.4% vs. 31.5%, P = 0.018). Conclusion: It appears that preoperative measurement of serum Tg, anti-TPO, and anti-Tg levels is not a useful method to predict malign thyroid diseases.

Changed Presentation of Hashimoto's Thyroiditis in North-Eastern Sicily and Calabria (Southern Italy) Based on a 31-Year Experience

To quantify the yearly prevalence of Hashimoto's thyroiditis at our Division and evaluate changes in its clinical presentation over the period 1975-2005. We have reviewed retrospectively the clinical records of patients admitted to a university hospital located in Messina, Sicily (Italy), from January 1, 1975, through December 31, 2005. This facility attracts patients from North-Eastern Sicily and most of Calabria, the Italian region across the Straits. HT was diagnosed based on various combinations of clinical, laboratory, and instrumental findings. The study group consisted of 4064 HT patients diagnosed during these 31 years. We evaluated these indexes on a yearly basis: number of new HT diagnoses; age at presentation; male-to-female ratio; functional status; goitrous or nongoitrous variants with or without nodule(s); above-normal titers or levels of serum thyroid autoantibodies (thyroglobulin antibodies and thyroperoxidase antibodies). Several indexes have changed over those 31 years. Particularly, HT has become 10 times more common than it was until the early 1990s and males are relatively more represented. Patients are relatively younger, with a nongoitrous thyroid; the rate of S-Hypo exceeds largely the rate of O-Hypo. Serum thyroid autoantibodies have become less frequently positive, and when positive, they are present at a lower concentration. Only environmental changes, as opposed to genetic changes, can account for such alterations in the presentation of HT in our geographical area.

A study of thyroid function and prevalence of thyroid autoantibodies in an African diabetic population

It is generally believed that autoimmune disorders are uncommon in Africans. Some workers have argued that insulin-dependent diabetes mellitus (IDDM) is rare in Africa on account of this reduced proneness to autoimmunity. However, it is undetermined whether or not Africans with IDDM have increased prevalence of thyroid dysfunction and autoimmunity, two phenomena strongly associated with Caucasian IDDM. We determined thyroid function and the prevalence of thyroid autoimmunity in IDDM Africans. The results are compared with those of a nondiabetic group and a group with non-insulin-dependent diabetes mellitus (NIDDM). Thyroid hormone levels were significantly lower in IDDM patients than in the control population and the NIDDM population. Subclinical hypothyroidism was present in 21% of the 28 IDDM patients. One patient was hypothyroid and another hyperthyroid. Of the 60 NIDDM patients, 5 (8.3%) had subclinical hypothyroidism. Forty-six percent of the IDDM patients had significant levels of serum thyroid autoantibodies (TAAB). This was significantly higher than the 1.4% and 1.7%, respectively, in the controls and NIDDMs. Presence of TAAB in the patients was strongly associated with thyroid dysfunction, female preponderance, and duration of diabetes mellitus. Thyroid dysfunction and autoimmunity are common in Nigerians clinically diagnosed as IDDM, and have prevalence rates comparable to other populations but higher than rates previously reported from some other African groups. The increased prevalence of thyroid autoimmunity in the IDDM supports the view that these patients are true IDDMs rather than variants of NIDDM or malnutrition-related diabetes mellitus (MRDM) as has been suggested by some workers.

Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease.

The iodine-rich antiarrhythmic drug, amiodarone, can induce both thyrotoxicosis and hypothyroidism, the former being more frequent in iodine-deficient areas, the latter in iodine-sufficient areas. In this study we evaluated prospectively thyroid function in amiodarone-treated patients with positive or negative baseline thyroid autoantibody test results who resided in a moderately iodine-deficient area of Italy. Two groups of patients received long-term amiodarone treatment: Group 1 included 13 patients with negative thyroid autoantibody test results. Group 2 consisted of seven patients with positive thyroid autoantibody test results and thyroid ultrasound patterns compatible with Hashimoto's thyroiditis. The control group (group 3) included 16 untreated euthyroid patients with Hashimoto's thyroiditis. All subjects resided in a mildly iodine-deficient area of Italy (Southern Sardinia) and had low urinary iodine values. Patients in groups 1 and 2 had markedly elevated urinary iodine excretion during treatment. The follow-up period ranged from 6 to 29 months in group 1, from 4 to 9 months in group 2, and from 12 to 55 months in group 3. Two (15%) of 13 patients in group 1 with nodular goiter developed thyrotoxicosis. No patient in this group developed circulating thyroid autoantibodies. Five (71%) of seven patients in group 2 became hypothyroid after 4 to 9 months of amiodarone treatment associated with a rise in serum thyroid autoantibody levels. No patient in group 3 became hypothyroid. (1) Amiodarone administration can cause both thyrotoxicosis and hypothyroidism. (2) Hypothyroidism is far more frequent in patients with preexisting thyroid autoimmune disease. (3) Amiodarone can modify the natural history of Hashimoto's thyroiditis. (4) Circulating thyroid autoantibodies do not appear in amiodarone-treated patients who have negative test results prior to therapy.

Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves' disease.

Thyrostatic drug treatment of Graves' disease suppresses excessive thyroid hormone synthesis and causes a parallel decrease in serum thyroid autoantibody levels. The mechanism of this immunosuppression is unknown. We studied methimazole-induced immunoregulatory effects prospectively in 14 patients with Graves' disease treated for up to six months. The numbers of circulating activated, HLA-DR-positive T helper/inducer cells decreased gradually, from 8.3+1.7 percent (+SD) to 1.0+1.7 percent (P less than 0.001). HLA-DR-positive T suppressor/cytotoxic cells increased transiently at one month, from 2.0+1.9 percent to 12.6+6.4 percent (P less than 0.001), and returned to 2.9+3.7 percent at six months. Methimazole did not alter the HLA-DR expression of T cells in vitro. In two patients, the helper activity of T cells in inducing autoantibody secretion in vitro was substantially reduced after one month of methimazole treatment. Before treatment, large proportions of thyroid-infiltrating T-cell subsets expressed the activation markers HLA-DR, interferon-gamma, and interleukin-2 receptors, which were partially lost during therapy. Methimazole treatment was accompanied by a gradual reduction in circulating levels of thyrotropin-receptor, microsomal, and thyroglobulin autoantibodies. These results are compatible with the view that methimazole-induced immunoregulation in Graves' disease is mediated by a direct inhibitory effect on thyrocytes. This inhibition is in turn accompanied by marked changes in the proportions of activated T helper-like and T suppressor-like cells. This altered T-cell activation profile reflects, at least in part, the functional suppression of autoantibody production observed in methimazole-treated patients with Graves' disease.