Autoimmune/inflammatory syndrome induced by adjuvants in a woman with Hashimoto thyroiditis and familial autoimmunity-a case report and literature review.

Introduction: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) consists of a wide spectrum of symptoms and immunological features that are believed to develop in predisposed individuals after exposure to an adjuvant, including a silicone breast implant (SBI). Different autoimmune diseases (AIDs) have been associated with ASIA, but ASIA development after SBI in women with Hashimoto thyroiditis (HT) and familial autoimmunity has rarely been described. Case report: A 37-year-old woman presented in 2019 with arthralgia, sicca symptoms, fatigue, + antinuclear antibody (ANA), + anti SSA, and + anticardiolipin Immunoglobulin G (IgG) antibodies. She was diagnosed with HT and vitamin D deficiency in 2012. The familial autoimmunity was present: the patient's mother had been diagnosed with systemic lupus erythematosus and secondary Sjogren's syndrome and her grandmother with cutaneous lupus and pernicious anemia. In 2017, the patient had a cosmetic SBI procedure that was complicated by repeated right breast capsulitis. After 2 years of irregular visits due to COVID-19, she presented with + ANA, + anticentromere antibodies both in sera and seroma, sicca syndrome, arthralgias, twinkling in extremities, abnormal capillaroscopic findings, and reduced diffusing capacity of the lungs for carbon monoxide. She was diagnosed with ASIA, and antimalarial and corticosteroid therapy were introduced. Conclusion: In patients with HT and familial autoimmunity, SBI should be carefully considered due to the possibility of ASIA development. Hashimoto thyroiditis, familial autoimmunity, and ASIA seem to be interconnected in the complex mosaic of autoimmunity in predisposed individuals.

Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis.

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto's thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

The effects of selenium supplementation on antibody titres in patients with Hashimoto's thyroiditis.

INTRODUCTION: The objective of this study was to evaluate the effect of selenium supplementation on autoantibody titres, thyroid ultrasonography, and thyroid function in patients with Hashimoto's thyroiditis (autoimmune thyroiditis) and normal thyroid reference range. MATERIAL AND METHODS: A total of 100 patients were given 200 ug/d selenium yeast orally, their thyroid function, levels of serum selenium, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and urine iodine were measured, and thyroid ultrasonography was performed before administration and three and six months afterwards, and the data were statistically analysed. RESULTS: The subjects exhibited a selenium deficiency before the administration of selenium, and the serum levels increased to moderate levels three and six months after the selenium supplementation (p < 0.05). The titres of TGAb decreased significantly in patients after six months of selenium supplementation (p < 0.05). In the high antibody group, TgAb decreased after 6 months compared with baseline (p = p < 0.05), and TPOAb decreased after 3 and 6 months of selenium supplementation compared with baseline (p < 0.05). CONCLUSION: In patients with autoimmune thyroiditis and normal thyroid reference range, there was a general selenium deficiency, but after six months of treatment it was shown that selenium supplementation may be effective in reducing the titres of TGAb and TPOAb.

Effect of selenium on thyroid autoimmunity and regulatory T cells in patients with Hashimoto's thyroiditis: A prospective randomized-controlled trial.

Selenium (Se) is an essential trace element in human. Recent studies of Se supplementation on the effect of Hashimoto's thyroiditis (HT) have been reported, but the exact benefit is unclear as well as the underlying immunologic mechanism. We aimed to evaluate the clinical effect of Se supplement in patients with HT, and explore the potential mechanism against thyroid autoimmunity. A prospective, randomized-controlled study was performed in patients with HT assigned to two groups. Se-treated group (n = 43) received selenious yeast tablet (SYT) for 6 months, whereas no treatment in control group (n = 47). The primary outcome is the change of thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TGAb). Second, thyroid function, urinary iodine, Se, Glutathione peroxidase3 (GPx3), and Selenoprotein P1 (SePP1) levels were measured during the SYT treatment. Meanwhile, regulatory T cells (Tregs) and their subsets activated Tregs (aTregs), resting Tregs, and secreting Tregs, as well as Helios and PD-1 expression on these cells were also detected. The results showed that SYT treatment significantly decreased TPOAb, TGAb, and thyroid stimulating hormone (TSH) levels, accompanied with the increased Se, GPx3, and SePP1, compared with the control group. Subgroup analysis revealed that subclinical HT may benefit more from this treatment in the decrease of TSH levels by interaction test. Moreover, the percentage of aTregs, Helios/Tregs, and Helios/aTregs were significantly higher in the Se-treated group than control. In conclusion, Se supplementation may have a beneficial effect on thyroid autoantibodies and thyroid function by increasing the antioxidant activity and upregulating the activated Treg cells.

The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disease (ATD) worldwide and is strongly associated with miscarriage and even recurrent miscarriage (RM). Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. Based on these findings, research investigating some potentially more effective treatments, such as selenium (Se), vitamin D3, and intravenous immunoglobulin (IVIG), has been well developed over the past few years. In this review, we highlight some of the latest advances in the possible immunological pathogenesis of HT-related miscarriage and focus on the efficacies of treatments that have been widely introduced to clinical trials or practice described in the most recent literature.

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

Selenomethionine potentiates the impact of vitamin D on thyroid autoimmunity in euthyroid women with Hashimoto's thyroiditis and low vitamin D status.

BACKGROUND: Both exogenous vitamin D and selenium reduce thyroid antibody titers. The aim of the study was to investigate whether the impact of vitamin D on thyroid autoimmunity is affected by selenium intake. METHODS: The study included 47 euthyroid women with Hashimoto's thyroiditis and low vitamin D status, 23 of whom had been treated with selenomethionine (200 µg daily) for at least 12 months before the beginning of the study. During the study, all patients were treated with vitamin D preparations (4000 IU daily). Serum titers of thyroid peroxidase and thyroglobulin antibodies, as well as circulating levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D were measured before vitamin D supplementation and 6 months later. Moreover, at the beginning and at the end of the study, we calculated Jostel's thyrotropin index, the SPINA-GT index and the SPINA-GD index. RESULTS: With the exception of the free triiodothyronine/free thyroxine ratio and the SPINA-GD index, there were no differences between the study groups. In both groups, vitamin D increased 25-hydroxyvitamin D levels, reduced thyroid peroxidase and thyroglobulin antibody titers, as well as increased the SPINA-GT index. The effects on antibody titers and the SPINA-GT index were more pronounced in women receiving selenomethionine. Neither in selenomethionine-treated nor in selenomethionine-naïve women vitamin D affected serum hormone levels, Jostel's index and the SPINA-GD index. CONCLUSIONS: The results of the study suggest that selenium intake enhances the effect of vitamin D on thyroid autoimmunity.

The effect of vitamin D and selenomethionine on thyroid antibody titers, hypothalamic-pituitary-thyroid axis activity and thyroid function tests in men with Hashimoto's thyroiditis: A pilot study.

BACKGROUND: Both selenium and vitamin D were found to reduce thyroid antibody titers in women with Hashimoto's thyroiditis. METHODS: The study enrolled 37 young drug-naïve euthyroid men with autoimmune thyroiditis, who were treated for 6 months with either exogenous vitamin D (group A, n = 20) or selenomethionine (group B, n = 17). Serum titers of thyroid peroxidase and thyroglobulin antibodies, serum levels of thyrotropin and free thyroid hormones, serum levels of 25-hydroxyvitamin D, as well Jostel's thyrotropin, the SPINA-GT and the SPINA-GD indices were determined at the beginning and at the end of the study. RESULTS: At baseline, there were no differences between the study groups. Both vitamin D and selenomethionine reduced antibody titers and increased the SPINA-GT index. Only selenomethionine affected the SPINA-GD index, while only vitamin D increased 25-hydroxyvitamin D levels. Neither selenomethionine nor vitamin D significantly affected thyrotropin and free thyroid hormone levels. The effect of vitamin D on antibody titers correlated with baseline and treatment-induced changes in serum levels of 25-hydroxivitamin D. CONCLUSIONS: Both vitamin D and selenomethionine have a beneficial effect on thyroid autoimmunity in drug-naïve men with Hashimoto's thyroiditis.

Effects of vitamin D supplements on frequency of CD4+ T-cell subsets in women with Hashimoto's thyroiditis: a double-blind placebo-controlled study.

BACKGROUND: Vitamin D is a modulator of immune functions. Investigations on the mechanisms of vitamin D action and pathogenesis of Hashimoto's thyroiditis (HT) have revealed that vitamin D can reduce damages to thyroid cells caused by autoreactive immune cells. METHODS: Totally, 48 female patients with HT disease were introduced to the study by endocrinologists. Patients were divided into two major groups of 24 individuals and treated weekly with 50,000 IU of cholecalciferol (vitamin D group) or placebo (placebo group) using oral administration for 3 months. Eventually, 17 of the 24 patients in each group finished the study. Before and after supplementation, frequencies of Th1, Th17, Th2 and Tr1 cells and mean fluorescent intensity (MFI) of the associated cytokines, including IFN-γ, IL-17, IL-4 and IL-10, were assessed using flow cytometry. Furthermore, gene expression of IL-10 was assessed using real-time PCR. RESULTS: Results of this study showed that cholecalciferol supplementation caused a significant decrease in Th17/Tr1 ratio. The proportion and MFI of Th1, Th2, Tr1 and Th17 cells included no significant changes in vitamin D group, compared to those in placebo group. Expression rate and MFI of IL-10 increased in both groups. This increase was higher in vitamin D group than placebo group with no significance. CONCLUSIONS: In this novel preliminary clinical trial study, supplementation with cholecalciferol in HT patients for 3 months changed the balance of CD4+ T-cell subsets to improve the disease control. However, further studies are necessary to investigate effects of vitamin D on immune functions in HT patients.

Multiple nutritional factors and thyroid disease, with particular reference to autoimmune thyroid disease.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are examples of autoimmune thyroid disease (AITD), the commonest autoimmune condition. Antibodies to thyroid peroxidase (TPO), the enzyme that catalyses thyroid-hormone production and antibodies to the receptor for the thyroid-stimulating hormone, are characteristic of HT and GD, respectively. It is presently accepted that genetic susceptibility, environmental factors, including nutritional factors and immune disorders contribute to the development of AITD. Aiming to investigate the effect of iodine, iron and selenium in the risk, pathogenesis and treatment of thyroid disease, PubMed and the Cochrane Library were searched for relevant publications to provide a narrative review. Iodine: chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly-iodinated thyroglobulin (Tg) is more immunogenic. The recent introduction of universal salt iodisation can have a similar, although transient, effect. Iron: iron deficiency impairs thyroid metabolism. TPO is a haem enzyme that becomes active only after binding haem. AITD patients are frequently iron-deficient since autoimmune gastritis, which reduces iron absorption and coeliac disease which causes iron loss, are frequent co-morbidities. In two-thirds of women with persistent symptoms of hypothyroidism despite appropriate levothyroxine therapy, restoration of serum ferritin above 100 µg/l ameliorated symptoms. Selenium: selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases remove excessive hydrogen peroxide produced there for the iodination of Tg to form thyroid hormones. There is evidence from observational studies and randomised controlled trials that selenium, probably as selenoproteins, can reduce TPO-antibody concentration, hypothyroidism and postpartum thyroiditis. Appropriate status of iodine, iron and selenium is crucial to thyroid health.

The pathogenesis of thyroid autoimmune diseases: New T lymphocytes - Cytokines circuits beyond the Th1-Th2 paradigm.

Autoimmune thyroid disease (AITD) is one of the most common organ-specific autoimmune disorders. It mainly manifests as Hashimoto's thyroiditis (HT) and Graves' disease (GD). HT is characteristic of hypothyroidism resulting from the destruction of the thyroid while GD is characteristic of hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor-specific stimulatory autoantibodies. T lymphocytes and their secretory cytokines play indispensable roles in modulating immune responses, but their roles are often complex and full of interactions among distinct components of the immune system. Dysfunction of these T cells or aberrant expressions of these cytokines can cause the breakdown of immune tolerance and result in aberrant immune responses during the development of AITDs. This review summarizes recently identified T subsets and related cytokines and their roles in the pathogenesis of AITDs with the hope to provide a better understanding of the precise roles of notably identified T subsets in AITDs and facilitate the discovery of functional molecules or novel immune therapeutic targets for AITDs.

Moderate-dose simvastatin therapy potentiates the effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and vitamin D insufficiency.

BACKGROUND: Vitamin D preparations reduce titers of thyroid antibodies in women with autoimmune thyroiditis. The same effect was induced by high-dose, but not moderate-dose-, statin therapy. No previous study has investigated the impact of concomitant treatment with a statin and vitamin D on thyroid autoimmunity. METHODS: The study included three matched groups of women with Hashimoto's thyroiditis and low vitamin D status. Groups B (n=19) and C (n=20) were treated with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia, groups A (n=18) and B received simvastatin (40mg daily). Plasma lipids, serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. RESULTS: At baseline, 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. In groups A and B, simvastatin reduced plasma levels of total and LDL cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D decreased titers of thyroid peroxidase antibodies, as well as tended to decrease titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this effect was stronger than the effect of simvastatin and vitamin D administered alone. Treatment-induced changes in thyroid antibody titers correlated with baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment-induced changes in 25-hydroxyvitamin. CONCLUSIONS: The obtained results indicate that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity in vitamin D-deficient women with Hashimoto's thyroiditis.

Hashimoto encephalopathy in pediatric patients: Homogeneity in clinical presentation and heterogeneity in antibody titers.

OBJECTIVE: Hashimoto encephalopathy is an autoimmune encephalopathy characterized by elevated antithyroid antibodies and a favorable response to corticosteroid. This study delineated the clinical characteristics of pediatric Hashimoto encephalopathy and the significance of low antithyroid antibody titers in diagnosis and treatment. SUBJECTS AND METHODS: Clinical manifestations, antibody titers, and treatment responses were retrospectively reviewed in six consecutive children diagnosed with Hashimoto encephalopathy between August 2008 and July 2016. RESULTS: Age at diagnosis was 10-17years. Presenting symptoms were seizures, altered consciousness, behavioral changes, psychosis, tremor, and dystonia. Thyroid function was normal in five patients, and one had hypothyroidism prior to the encephalopathy. Antithyroid antibody titer was increased at presentation in five patients and one week later in the other. Antibody levels were extremely varied (anti-thyroglobulin, 20.5-2318.0U/ml; anti-thyroid peroxidase, 12.5-2231.0U/ml; reference range, <60U/ml) and <180U/ml in two patients. Electroencephalogram was abnormal in five patients. Brain magnetic resonance imaging was unremarkable. Four patients responded to high-dose corticosteroid and one improved with additional intravenous immunoglobulin. The remaining patient did not respond to both treatments and normalized after plasmapheresis. Autoantibody titers decreased with treatment response in the acute stage. Two patients with low antibody titers showed similar clinical presentations and responses. CONCLUSIONS: The clinical presentations and treatment responses in Hashimoto encephalopathy were similar, irrespective of antithyroid antibody titer. Because the initial antithyroid antibody titers can be normal or mildly-elevated, follow-up testing of antithyroid antibodies is required in patients who are clinically suspect for Hashimoto encephalopathy.

Multiple Nutritional Factors and the Risk of Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is considered to be the most common autoimmune disease. It is currently accepted that genetic susceptibility, environmental factors, and immune disorders contribute to its development. With regard to nutritional factors, evidence implicates high iodine intake and deficiencies of selenium and iron with a potential relevance of vitamin D status. To elucidate the role of nutritional factors in the risk, pathogenesis, and treatment of HT, PubMed and the Cochrane Library were searched for publications on iodine, iron, selenium, and vitamin D and risk/treatment of HT. SUMMARY: Chronic exposure to excess iodine intake induces autoimmune thyroiditis, partly because highly iodinated thyroglobulin (Tg) is more immunogenic. Recent introduction of universal salt iodization can have a similar, though transient, effect. Selenoproteins are essential to thyroid action. In particular, the glutathione peroxidases protect the thyroid by removing excessive hydrogen peroxide produced for Tg iodination. Genetic data implicate the anti-inflammatory selenoprotein S in HT risk. There is evidence from observational studies and randomized controlled trials that selenium/selenoproteins can reduce thyroid peroxidase (TPO)-antibody titers, hypothyroidism, and postpartum thyroiditis. Iron deficiency impairs thyroid metabolism. TPO, the enzyme responsible for the production of thyroid hormones, is a heme (iron-containing) enzyme which becomes active at the apical surface of thyrocytes only after binding heme. HT patients are frequently iron deficient, since autoimmune gastritis, which impairs iron absorption, is a common co-morbidity. Treatment of anemic women with impaired thyroid function with iron improves thyroid-hormone concentrations, while thyroxine and iron together are more effective in improving iron status. Lower vitamin D status has been found in HT patients than in controls, and inverse relationships of serum vitamin D with TPO/Tg antibodies have been reported. However, other data and the lack of trial evidence suggest that low vitamin D status is more likely the result of autoimmune disease processes that include vitamin D receptor dysfunction. CONCLUSIONS: Clinicians should check patients' iron (particularly in menstruating women) and vitamin D status to correct any deficiency. Adequate selenium intake is vital in areas of iodine deficiency/excess, and in regions of low selenium intake a supplement of 50-100 µg/day of selenium may be appropriate.

The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto's Thyroiditis and Normal Vitamin D Status.

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimoto's thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naïve patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and normal vitamin D status.

Hashimoto's encephalopathy: A rare proteiform disorder.

Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature.

A patient-specific model of the negative-feedback control of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis.

The purpose of modelling the negative-feedback control mechanism of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis is to describe the clinical course of euthyroidism, subclinical hypothyroidism and overt hypothyroidism for patients. Thyroid hormone thyroxine (T4) and triiodothyronine (T3) levels are controlled by negative-feedback control through thyroid-stimulating hormone (TSH). T4, like other hormones, can be bound or unbound; the unbound T4 (FT4) is used as a marker for hypothyroidism. Autoimmune thyroiditis is a disease in which the thyroid-infiltrating lymphocytes attack autoantigens in follicle cells, destroying them over a long time. To describe the operation of the feedback control, we developed a mathematical model involving four clinical variables: TSH, FT4, anti-thyroid peroxidase antibodies and the thyroid gland's functional size. The first three variables are regularly measured while the last variable is determined through relationships between the other three variables. The problem of two different time scales for circulating hormones and thyroid damage is addressed using singular perturbation theory. Analysis of the mathematical model establishes stability and conditions under which the diseased state can maintain the slow movement toward diseased state equilibrium. Although we have used four variables in modelling the feedback control through the HPT axis, the predicted clinical course given any set of parameters is shown to depend on the steady-state levels of TSH and FT4. This observation makes possible the development of the clinical charts based only on the levels of TSH, time and potential steady-state values. To validate the model predictions, a dataset obtained from a Sicilian adult population has been employed.

Dehydroepiandrosterone in women with premature ovarian failure and Hashimoto's thyroiditis.

We evaluated dehydroepiandrosterone sulfate (DHEAS) levels in premature ovarian failure (POF) patients with and without Hashimoto's thyroiditis, and the impact of DHEA supplementation on thyroid autoantibodies. In a retrospective case series, we included 67 women with spontaneous POF who received estrogen/gestagen replacement with or without DHEA (30 mg/day) for 3 months. Women who were seropositive for thyroglobulin antibodies and/or thyroperoxidase autoantibodies (n = 30) revealed lower pretherapeutic DHEAS levels (1.2 µg/ml, range 0.4-2.9 µg/ml vs. 1.9 µg/ml, range 0.2-3.9 µg/ml; p < 0.001). DHEAS showed an inverse correlation with both thyroglobulin antibodies (r = -0.426, p < 0.001) and thyroperoxidase autoantibodies (r = -0.362, p = 0.002). When treated with additional DHEA, significant decreases were found for thyroperoxidase autoantibodies (median 85.0 IU/ml, range 41-600 IU/ml vs. median 51.0 IU/ml, range 20-589 IU/ml; p = 0.005) but not for thyroglobulin antibodies.

Effects of green tea polyphenols on iodide-induced autoimmune thyroiditis in nonobese diabetic mice.

Because green tea polyphenols (GTPs) possess anti-inflammatory properties and are effective in inhibiting autoimmune diseases in experimental settings, we examined whether GTPs prevented the development of autoimmune thyroiditis in iodide-treated nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis (HT). Mice were given 0.05% iodide water or iodide water supplemented with 0.2% GTPs for 8 weeks. GTPs administration led to an enhanced production of interleukin-10 by concanavalin A-stimulated splenocytes but did not interfere with thyroiditis development. Serum thyroxine levels were not influenced by GTPs. Our data suggest that administration of GTPs may not be an effective strategy for the prevention of HT.