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Background: Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; I 2  = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; I 2  = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; I 2  = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; I 2  = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. Conclusions: In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.

Background: Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions., Methods: A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction., Results: Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases., Conclusions: Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Background: Although most studies of levothyroxine-liothyronine combination therapy employ once-daily hormone administration, the kinetics of once-daily liothyronine have been studied infrequently. The aim of this study was to document both the peak and trough serum triiodothyronine (T3) levels that occur with once-daily liothyronine administration, along with changes in thyroid-responsive parameters., Methods: Participants with hypothyroidism were studied prospectively at an academic institution. Patients were switched from levothyroxine monotherapy to liothyronine monotherapy with 15 μg liothyronine for two weeks, and then continued liothyronine at doses of 30-45 μg for a further four weeks in an open-label, single-arm study. Weekly trough levels of T3 were documented. In addition, hourly T3 concentrations immediately following liothyronine tablet administration were documented for eight hours during the sixth week of therapy. Serum thyrotropin (TSH) and free thyroxine (fT4) concentrations were documented. Biochemical markers, markers of energy metabolism, anthropometric parameters, well-being, and hyperthyroid symptoms were also assessed., Results: Mean serum TSH levels increased from 1.56 ± 0.81 mIU/L at baseline to 5.90 ± 5.74 mIU/L at two weeks and 3.84 ± 3.66 mIU/L at six weeks. Trough T3 levels decreased from 99.5 ± 22.9 to 91.9 ± 40.2 at two weeks and recovered to 96.1 ± 32.2 at six weeks. The peak T3 concentration after dosing of liothyronine during week 6 was 292.8 ± 152.3 ng/dL. fT4 levels fell once levothyroxine was discontinued and plateaued at 0.44 ng/dL at week 4. The sex hormone binding globulin (SHBG) concentration decreased at week 2 (p = 0.002). Hyperthyroid symptoms and SF36-PCS scores increased significantly at weeks 4-5 of liothyronine therapy (p = 0.04-0.005). Preference for liothyronine therapy increased from 6% to 39% over the study period., Conclusions: Once-daily dosing of liothyronine at doses of 30-45 μg did not return serum TSH to the values seen during levothyroxine therapy. There were significant excursions in serum total and free T3 concentrations with once-daily therapy. Trials of combination therapy are likely to be associated with similar excursions, albeit of a lesser magnitude. Only the physical component score of the SF36 questionnaire and hyperthyroid symptoms changed significantly with conversion to liothyronine monotherapy. Sustained release preparations with stable serum T3 profiles may have entirely different outcomes.

Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby report a case of Hashimoto's thyroiditis, presenting as an acute painful thyroiditis, and as a complication of IRIS., Summary: A painful acute thyroiditis with thyrotoxicosis occurred in a 37-year-old HIV-infected woman 10 months after initiation of ART. This thyroiditis was associated with the appearance of a high titer of anti-thyroid peroxidase (anti-TPO) antibodies and was followed by persistent hypothyroidism, requiring thyroxine replacement therapy., Conclusions: Hashimoto's thyroiditis may present as an acute thyroiditis with thyrotoxicosis in HIV-infected patients after initiation of ART. Clinicians caring for HIV-infected patients should be aware of this possible association.

Background: Evidence suggests that selenium (Se) supplementation could be useful as an adjunctive therapy to levothyroxine (LT₄) in the treatment of Hashimoto's thyroiditis (HT). To summarize evidence regarding its effect on thyroid autoantibodies' titers, demands in LT₄ replacement therapy, ultrasonographic thyroid morphology, and mood in patients with HT under LT₄ treatment, a systematic review and meta-analysis of relevant literature were performed., Methods: Systematic review of prospective studies involving patients with HT under LT₄ treatment and meta-analysis of studies on randomized, placebo-controlled, blinded trials were performed., Results: Patients with HT assigned to Se supplementation for 3 months demonstrated significantly lower thyroid peroxidase autoantibodies (TPOab) titers (four studies, random effects weighted mean difference: −271.09, 95% confidence interval: −421.98 to −120.19, p< 10⁻⁴) and a significantly higher chance of reporting an improvement in well-being and/or mood (three studies, random effects risk ratio: 2.79, 95% confidence interval: 1.21-6.47, p= 0.016) when compared with controls. Demands in LT₄ replacement therapy and ultrasonographic thyroid morphology were found either unaltered or underreported., Conclusions: On the basis of the best available evidence, Se supplementation is associated with a significant decrease in TPOab titers at 3 months and with improvement in mood and/or general well-being. Evidence suggests a different pattern of response to Se supplementation in HT relative to baseline TPOab titers, and this, if confirmed, could be used to identify which patients would benefit most from treatment. An improvement in thyroid function and morphology should be demonstrated before Se routine supplementation can be recommended in the treatment of HT.

Background: Although it is known that Hashimoto's thyroiditis in children and adolescents can go into long-term remission, and that treatment with thyroxine (T4) may not be necessary, it is difficult to quantify changes in the degree of autoimmune destruction of the thyroid. Here we report a patient in whom there was a relationship between functional and anatomical changes as assessed by hormone measurements and ultrasonography., Summary: The patient was a 12-year-old girl with Hashimoto's thyroiditis who was initially euthyroid and later treated with 50 µg levo-T4 when her free T4 (fT4) had declined from 17 to 7 pmol/L (normal range, 8-22 pmol/L). At this time her thyroid-stimulating hormone (TSH) was 4.1 mIU/L (normal range, 0.30-4.0 mIU/L) and thyroid ultrasonography demonstrated features of early inflammation. Two years later, while on the same dose of T4, ultrasound examination revealed severe end-stage Hashimoto's thyroiditis and thyroid function tests showed a T4 of 14.0 pmol/L and TSH of 0.81 mIU/L. Twelve months later, however, the thyroid ultrasound had returned to almost normal with only minimal features of inflammation. Thyroid function tests showed a fT4 of 12.8 pmol/L and TSH of 0.75 mIU/L. Her T4 treatment was then stopped. Eight, 17, and 30 weeks after this, her fT4 was 16.8, 9.7, and 13.9 pmol/L, respectively, and her respective TSH values at the same times were 0.10, 2.24, and 0.75 mIU/L., Conclusions: This is the first recording of serial thyroid ultrasound changes in a patient with Hashimoto's thyroiditis that paralleled changes in thyroid function. This indicates that thyroiditis can go into remission in some children. Thyroid ultrasound may be useful to make presumptive therapeutic decisions in children and adolescents with Hashimoto's thyroiditis whose dose of thyroid hormone seems to be less than is full replacement. Thyroid function tests, however, should ultimately guide T4 dosage.

Background: The thyroidal response of pregnant patients with established Hashimoto's thyroiditis remains poorly described. The aim of this study was to determine the impact of pregnancy on Hashimoto's thyroiditis as revealed by changes in postpregnancy levothyroxine requirements., Methods: We performed a retrospective study of 799 hypothyroid patients in a university hospital. We reviewed the clinical records and selected a group of well-documented pregnant (n = 34) and nonpregnant (n = 32) hypothyroid women for study. We reviewed levothyroxine intake and serum thyrotropin (TSH) levels during three consecutive 9-month time intervals that were immediately before, during, and after pregnancy. We compared the percent change in levothyroxine dose between the prepregnancy level and each trimester during and after pregnancy., Results: There were two patterns of levothyroxine supplementation during gestation. In pattern 1 (n = 11) there was either no change or a single levothyroxine dose increase with no subsequent changes in each trimester (T1 = T2 = T3). In pattern 2 (n = 18), multistep levothyroxine dose increases were required throughout pregnancy (T1 < T2 < T3) to maintain desired TSH levels (<2.0 mU/L). Women with pattern 2 had mean TSH levels during gestation that differed significantly from pattern 1 (2.8 +/- 0.5 vs. 1.3 +/- 0.1 mU/L respectively; p < 0.03). Further, in multivariate logistic regression, women with pattern 2 were 62 times more likely than women with pattern 1 to have a levothyroxine dose at least 20% above baseline at 3 months postpartum (p = 0.04)., Conclusions: We showed that >50% of hypothyroid women with Hashimoto's thyroiditis experienced an increase in levothyroxine requirements in the postpartum compared to pregestational doses. This pattern of enhanced levothyroxine need was most likely dependent on the preexisting thyroid functional reserve and postpartum progression of autoimmune destruction.

Background: T helper type 1 (Th1), Th2, and Th17 cells produce interferon (IFN)-gamma, interleukin (IL)-4, and IL-17A, respectively. We reported that IFN-gamma and IL-4 gene polymorphisms, which are related to higher IFN-gamma and lower IL-4 production, respectively, are more frequent in patients with severe Hashimoto's disease (HD) than in those mild HD. We now aim to investigate the proportion of peripheral Th1, Th2, and Th17 cells in patients with autoimmune thyroid disease (AITD)., Methods: We studied 17 patients with HD who developed hypothyroidism and were treated with l-thyroxine, referred to as severe HD; 17 untreated patients with HD who were euthyroid, referred to as mild HD; 18 euthyroid patients with Graves' disease (GD) who remained positive for anti-thyrotropin receptor antibody (TRAb) despite being treated with anti-thyroid drugs for more than 5 years, referred to as intractable GD; and 17 patients with GD who were euthyroid and negative for TRAb for more than 2 years after cessation of anti-thyroid drugs, referred to as GD in remission; and 10 control subjects without AITD. By the definitions in this study Th1 cells were CD4(+)IFN-gamma(+)IL-4(-)IL-17A(-) cells, Th2 cells were CD4(+)IFN-gamma(-)IL-4(+)IL-17A(-) cells, and CD4(+)IFN-gamma(-)IL-4(-)IL-17A(+) cells were Th17 cells., Results: The proportion of peripheral Th1 cells was higher in patients with severe HD than in patients with mild HD (p < 0.05), and the proportion of peripheral Th2 cells was lower in patients with severe HD than in patients with mild HD (p < 0.001). Therefore the Th1/Th2 ratio was higher in severe than in mild HD patients (p < 0.001). The proportion of peripheral Th17 cells in patients with AITD was higher than in control subjects and the proportion of these cells in patients with intractable GD was higher than in patients with GD in remission (p < 0.05)., Conclusions: The peripheral Th1/Th2 cell ratio is related to the severity of HD, and the proportion of Th17 cells is related to the intractability of GD. We hypothesize that these patterns of peripheral Th cell subsets may be expressed within the thyroid.

Background: A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto's thyroiditis decline during levothyroxine treatment, but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative ("normalization percentage"). The objective of the present study was to provide this information., Methods: This was a retrospective study of TPO-Ab concentrations in 36 women and 2 men (mean age 51 +/- 16 years; range 19-81 years) with Hashimoto's thyroiditis as defined by the following criteria: elevated plasma TPO-Ab and typical hypoechogenicity of the thyroid in high-resolution sonography at first presentation or during follow-up and low pertechnetate uptake in thyroid scintigraphy. When first studied 17 women and 1 man were not yet taking levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial examination 18 patients had serum thyroid-stimulating hormone (TSH) concentrations above normal. Results of up to eight (mean = 5.8) measurements obtained over a mean period of 50 months while patients were receiving levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3), and free thyroxine (fT4) were measured, and ultrasound of the neck was performed at each follow-up examination., Results: In terms of TPO-Ab levels, 35 of 38 patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient had an inverse hyperbolic increase in her TPO-Ab levels. In the 35 patients in whom there were decreasing TPO-Ab values, the mean of the first value was 4779 IU/mL with an SD of 4099 IU/mL. The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 +/- 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%. There were no correlations between changes in thyroid volume and changes in TPO-Ab., Conclusion: Serum TPO-Ab levels decline in most patients with Hashimoto's thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.

Although hypothyroid myopathy is seen frequently and the relationship with autoimmune hypothyroidism and myasthenia gravis is well known, specific forms of hypothyroid myopathy such as Hoffman's syndrome (HS) are rarely described. Here we describe a 40-year-old patient with Hashimoto thyroiditis showing symptoms and signs of two discrete forms of hypothyroid myopathy (HS and myasthenic syndrome) together. To our knowledge this is the first reported case with features of both of these syndromes. We discuss the diagnosis, speculate whether this patient may represent a unique form of hypothyroid myopathy, and report the 6-month follow-up of the patient both clinically and electrophysiologically.

Objective: We studied the effects of selenium (Se) treatment on serum anti-thyroid peroxidase (TPO) levels in Greek patients with Hashimoto's thyroiditis (HT)., Design: We prospectively studied 80 women with HT, median age 37 (range 24-52) years, for 1 year. All patients received 200 microg Se in the form of l-selenomethionine orally for 6 months. At the end of the 6-month period, 40 patients continued taking 200 microg Se (Group A) and 40 patients stopped (Group B). Serum thyrotropin (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4)), anti-TPO, and anti-thyroglobulin (Tg) levels were measured at baseline and at the end of each 3-month period., Main Outcome: There was a significant reduction of serum anti-TPO levels during the first 6 months (by 5.6% and 9.9% at 3 and 6 months, respectively). An overall reduction of 21% (p < 0.0001) compared with the basal values was noted in Group A. In Group B, serum anti-TPO levels were increased by 4.8% (p < 0.0001) during the second 6-month period., Conclusions: Our study showed that in HT patients 6 months of Se treatment caused a significant decrease in serum anti-TPO levels, which was more profound in the second trimester. The extension of Se supplementation for 6 more months resulted in an additional 8% decrease, while the cessation caused a 4.8% increase, in the anti-TPO concentrations.

Background: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+) and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12)., Methods: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry., Results: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound., Conclusions: We show that CD4(+) and CD8(+) T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).