بیماری هاشیموتو

بیماری هاشیموتو

اسلاید 1: hAshimoto (ht)Dr. jadaliSEYEDEH FATEMEH SHAYESTEH

اسلاید 2: تیروئیدیت هاشیماتو نام دیگر: Chronic Lymphocytic Thyroiditis تعریف: - یکی از بیماری های رایج خود ایمنی است. - در این بیماری لنفوسیت ها علیه غده ی تیرویید آنتی بادی تولید میکنند و سبب التهاب مزمن آن میشوند. Ab- مهم در HT IgG4است. ورود لنفوسیت ها به تیرویید = تخریب سلول ها، بافت و رگ هی خونی نتیجه: از بین رفتن توانایی غده تیرووید در تولید هورمون های تیروییدی که باعث کاهش تدریجی عملکرد و سر انجام هیپوتیروییدیسم میشود. - روند تخریب ابتدا آهسته است به همین دلیل بسیاری از افرادی که این بیماری را دارند سال ها علامت قابل توجهی نمی بینند. - این بیماری دارای هم بستگی با گواتر و هیپو تیروییدیسم است. (ایجاد گواتر، هیپوتیروییدیسم یا هردو )

اسلاید 3: تاریخچه:نخستین بار در 1912 میلادی توسط پزشک ژاپنی به نام Hakaro Hashimato گزارش شد.تا سال 1950 یک بیماری نادر بود ولی اکنون از شایع ترین بیماری های خود ایمنی به حساب می آید.شیوع : 1 در هر 1000 نفر در سالدر همه سنین و جنس شیوع دارد ولی در زنان 5 – 10 برابر مردان است.شایع ترین فرم HTافزایش در اندازه غده (گواتر) همراه یا بدون هیپو تیروییدیسم – میتواند همراه سایر بیماری های خود ایمن مثل دیابت ملیتوس نوع 1 یا سندرم شوگرن بروز نماید.اخیرا گزارشات آن رو به افزایش بوده. بیشتر به علت جراحی ها و مصرف داروهای تعدیل کننده ی سیستم ایمنی بروز میکند.مثلا: درمان هپاتیت c با اینترفرون آلفا میتواند باعث القای تیروییدیت شود.HT Ethiology

اسلاید 4: علایم HT

اسلاید 5: تشخیص:علائم اولیه:ورم جلوی گردنابتدا برآمدگی بدون درد است ولی اگر درمان نشود یه جلوی گلو فشار می آورد.در مراحل پیشرفته گواتر بوجود آمده در تنفس و بلع دخالت میکند.سایر علائم: خشکی پوست و مو و ناخنdrowsinessبررسی وجود یا عدم وجود Ab های سرمی ضد آنتی ژن های تیروییدی ( تیروگلوبولین و تیرو پروکسیداز )

اسلاید 6: از مهم ترین عوامل محیطی موثر در :HTسیگار و ید!به طرز شگفت انگیزی مطالعات از اثرات مفید سیگار بر HT خبر میدهند. تنباکوی سیگار سطح اثر آنتی بادی های علیه تیرویید را کاهش میدهد!و موجب کاهش هیپو تیروییدیسم میگردد. مدل های آزمایشگاهی نشان داده است که ماده ای به نام آناتابین( anatabin ) که یکی از آلکالویید های تنباکو است، احتمالا با اثر بر اینفلامازوم های مسیر های ایمنی ذاتی موجب بهبودی هاشیموتو میگردد.( البته این توجیهی برای سیگار کشیدن نیست ! )

اسلاید 7: Anatabine Supplementation Decreases Thyroglobulin Antibodies in Patients With Chronic Lymphocytic Autoimmune (Hashimoto’s) Thyroiditis: A Randomized Controlled Clinical TrialContext: Hashimoto’s thyroiditis is less prevalent in tobacco smokers. Anatabine, an alkaloid foundin Solanaceae plants including tobacco, has been reported to ameliorate a mouse model of Hashimoto’s thyroiditis.Objective: The effects of anatabine in patients with Hashimoto’s thyroiditis were studied. Design, Setting, Patients, and Intervention: This was a double-blind, randomized, placebo-controlled multisite study. A total of 146 patients (70 treated with anatabine and 76 with placebo) completed the study. Approximately 50% of patients in each group were taking levothyroxine.Anatabine lozenges (9–24 mg/d) or placebo, each containing vitaminsAandD3, were administeredorally 3 times a day for 3 months.Main Outcome Measures: Serum thyroperoxidase antibody (TPOAb) and thyroglobulin antibody(TgAb) levels were assessed. Safety was assessed through adverse events, clinical laboratory evaluations, and vital sign measurements. Anatabine-treated patients had a significant reduction in absolute serum TgAb levels from baseline Results: by study end relative to those receiving placebo (P.027); however, there were no significant changes or differences in treatment group means for TPOAb or TgAb levels. Mean SD TgAb values decreased by 46.2 101.1 and 3.9 83.9 World Health Organization units for the anatabine and placebo groups, respectively. Significantly more patients had a20% drop in TgAb levels in the anatabine than placebo group (P.023). Overall, the anatabine supplement was safe and well tolerated, although significantly (P .05) more patients in the anatabine group reported adverse events.Conclusions: These results demonstrate an immunological effect of anatabine on TgAb levels.Further studies are warranted to determine the longer-term effects and possible actions of anatabine on the course of Hashimoto’s thyroiditis. (J Clin Endocrinol Metab 99: E137–E142, 2014)

اسلاید 8: Treatment for chronic lymphocytic (Hashimoto’s) thyroiditis consists of L-thyroxine replacement when hypothyroidism develops (1). Tobacco smoking has numerous effects on thyroid volume, function, and disease and a protective effect on development of Hashimoto’s thyroiditis and thyroid antibodies (2). Nicotine has anti-inflammatoryeffects (3) but cannot be recommended because it is addictive (4) and toxic (5, 6). Anatabine, another Solanaceaealkaloid with a similar chemical structure, may have immunomodulatory properties. In a mouse model ofthyroiditis, anatabine reduced the incidence and severity of thyroiditis and lowered the levels of thyroglobulin antibodies (TgAbs) (7). We designed a clinical trial to assess the effects of anatabine dietary supplementation in patients with Hashimoto’s thyroiditis.Materials and MethodsStudy sites, patients, and objectivesThis was a multicenter, double-blind, placebo-controlled, randomized clinical trial enrolling patients with Hashimoto’sthyroiditis. Institutional review board approval was obtained, and all study patients provided signed informed consent. Patients were recruited from 9 endocrinology clinics in the United States between March 2012 and August 2012.The primary objective was to collect information on the effects of anatabine supplementation in patients with Hashimoto’s thyroiditis. Patients taking L-thyroxine were included, but only if their dose was 1.0 g/kg/d to exclude individuals with thyroid destruction incapable of responding to any intervention.The main inclusion and exclusion criteria are provided in Supplemental Table 1 published on The Endocrine Society’s Journals

اسلاید 9: Study design and randomizationPatients underwent 5 study site visits over 4 months. At visit1 (screening), demographics, vital signs, medical and medication history, and blood and urine samples were collected, and ultrasonography was scheduled. At visit 2 (randomization), patients were randomly assigned to either the anatabine or placebo group. Thereafter, patients returned monthly for visits 3, 4, and 5 to complete the study procedures.Anatabine and placebo lozengeAnatabine was provided by Rock Creek Pharmaceuticals and formulated into a flavored mannitol granulation lozenge that also contained fractional replacement doses of vitamins A (834 IU) andD3 (66 IU), in both active and placebo units to reduce the chance that vitamin deficiencies might obscure an anatabine effect on autoimmunity. Anatabine lozenges were administered orally 3 times daily to a target total dose of 0.17 to 0.25 mg/kg/d.To reduce nicotinic type effects (eg, dizziness and nausea), patients started with 9 mg/d and advanced to the target dose during week 2. Patients who took less than 70% of assigned treatment(pill count) were excluded from the efficacy analysis.

اسلاید 10: Study outcomes and assaysThe main experimental outcomes were serum TgAb and thyroperoxidase antibody (TPOAb) levels. Other measures included serum TSH, freeT4, freeT3, and inflammatory biomarker(high-sensitivity C-reactive protein, IL-1, IL-6, and IL-18) levels and ultrasonographic thyroid volume, echogenicity, and vascularity. The North Coast Clinical Laboratory (Sandusky, Ohio) performed the measurements of thyroid function and highsensitivity C-reactive protein. Assays for TgAbs and TPOAbsand the 3 interleukins were performed at Johns Hopkins Immunological Disorder Laboratory (Baltimore, Maryland).Thyroid ultrasonography was performed at the 9 sites, and scans were sent to a central radiologist who read them blinded (Supplemental Table 2).Statistical analysisThe data set included thyroid-related variables (TgAbs, TPOAbs,TSH, free T4, free T3, volume, vascularity, and echogenicity), demographic variables (sex, age, race, and ethnicity), body mass index, inflammatory markers (high-sensitivity C-reactive protein, IL-1, IL-6, and IL-18), and safety outcomes. Urinaryiodine was not measured. We compared nonadjusted continuous variables between the 2 treatment groups using a paired t test when variables were normally distributed, a Wilcoxon rank sum test when variables were not normally distributed, and a 2 test for categoricalvariables. All statistical analyses were performed using Stata 12 (Stata-Corp) or JMP 7 (SAS Institute).

اسلاید 11: ResultsDemographics and baseline characteristicsAmong the 230 patients screened, 165 were randomly assigned in the study, and 146 completed the efficacy evaluation (70 receiving anatabine and 76 placebo) (Supplemental Figure 1). Patients were predominantly female,Caucasian, and non-Hispanic (Supplemental Table 2). Seventy-seven patients reported taking levothyroxine (36taking anatabine and 41 taking placebo). There were no significant differences between groups with respect to demographic and baseline characteristics.Thyroid autoantibodiesThe absolute change in mean TgAb levels between baseline and weeks 4, 8, and 12 revealed a significantlygreater reduction in TgAbs in patients taking anatabine relative to those taking placebo by week 12 (P .027)(Figure 1C). TgAb values decreased by 46.2 101.1 World Health Organization (WHO) units for the anatabinegroup and only 3.9 83.9 WHO units for the placebo group by week 12. The proportion of patients witha 20% decrease in TgAb levels was greater in the anatabine group (47%) than in the placebo group (28%) atweek 12 (P.023) (Figure 1D). Because of the significant heteroscedasticity in TgAb values, data were categorized

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اسلاید 13: based on the reduction from baseline: 25, 50, 75, and 100 WHO unit reductions. By week 12, the percentages of patients in the anatabine group with reductions in TgAb levels of 25, 50, 75, and 100 WHOunits were significantly greater than those in the placebo group for each category (all P .05) (Supplemental Figure 2). No significant differences were found for TPOAb levels.Subgroup analysis of patients taking levothyroxine (n 36) compared with those not taking levothyroxine (n 34) revealed a substantial decrease in TgAb levels from baseline at week 12 in the anatabine group receivinglevothyroxine therapy (P .008). Additional analysis conducted with 31 patients in the anatabine group takinglevothyroxine doses of1.0g/kg/d (range, 0.29–1.0g/ kg) revealed a greater effect of anatabine on TgAb levels.This analysis showed that decreases in TgAb levels from baseline at weeks 4, 8, and 12 were significant (P.05 forall). Further, there was a significant difference in mean TgAb levels for patients taking anatabine and levothyroxine1.0 g/kg/d vs those not taking levothyroxine (80.6 vs 23.1 WHO units, respectively; P .02). Norelationship between the anatabine dose and TgAb lowering was observed.Serological thyroid function tests, inflammatory biomarkers, and thyroid ultrasonographyThere were no significant changes or treatment group differences in serum thyroid function tests and inflammatory biomarkers or ultrasonography measures (Supplemental Table 3).

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اسلاید 15: Adverse events (AEs) and safety More patients in the anatabine group (81%) reported AEs relative to those in the placebo group (44%, P .05)(Table 1). The most common AEs in patients taking anatabine were dizziness (36%), nausea (8%), and headaches (7%) during dose titration and paresthesia (7%). Seven (8%) patients taking anatabine and 1 (1%) patient taking placebo withdrew from the study because of AEs; these were all considered mild or moderate. One patient taking anatabine reported a serious AE (chest pain) that was evaluated and found to be of noncardiac origin, considered unrelated to study treatment, resolved without complications, and did not recur with resumption of anatabine. There were no significant abnormalities in clinical laboratory values attributed to anatabine and no clinically significant effects of either treatment on vital sign measures.DiscussionThe results of this study show a selective decrease in TgAb but not TPOAb levels in patients with Hashimoto’s thyroiditis after 12 weeks of anatabine supplementation. Anatabine is an alkaloid found in plants of the Solanaceae family, including tobacco, tomatoes, potatoes, peppers, and eggplants (8). Although the mechanism of action ofdietary anatabine on thyroid autoimmunity remains to be elucidated, it may produce immunomodulatory effectsthrough activation of 42 or 7 cholinergic receptors similar to nicotine and other structurally related agonists(9 –11). In a mouse model of thyroiditis, anatabine decreases thyroidal IL-1 and IL-18 levels (7), and in otherexperimental disease models it suppresses the inflammatory transcription factors signal transducer and activatorof transcription 3 and nuclear factor-B (12–14). Multiple epidemiological studies have reported a protectiveeffect of smoking on autoimmune hypothyroidism and thyroid antibodies (Supplemental Table 4). Noteworthyare studies showing selective effects of smoking on TgAbs. Analysis of 4125 randomly selected Danes founda negative association between smoking and the presence of thyroid antibodies; the most pronounced association was found between smoking and TgAbs, irrespective of TPOAb status (15).

اسلاید 16: Analysis of a prospective populationbased cohort of 9362 pregnant mothers in Finland showed that mothers who smoked before pregnancy had a lower TgAb prevalence than nonsmokers (2.5% vs 4.7%, P .001), whereas prevalences of TPOAb were similar (16). Although TPOAbs and TgAbs are typically both measured for diagnostic purposes and often fluctuate in parallel with the disease course, the quantitative correlation between them is rather poor. Carlé et al (17) analyzed 145 patients with newly diagnosed autoimmune hypothyroid-ism and noted a correlation between TPOAbs and TgAbs (P .001), but a low Pearson r2 value (0.11). Analysis of National Health and Nutrition Examination Survey data from 2007 to 2008 showed a similarly low r2 value of 0.21 in 6200 Americans (unpublished data). A retrospective chart review study found that surgical removal or radioiodine ablation of the thyroid leads to gradual reductions in both TgAbs and TPOAbs over several years, with TgAb levels initially declining more rapidly than TPOAb levels (18). Based on those findings, it is possible that the differential response of TgAbs and TPOAbs that we observed after 12 weeks of treatment might have become less apparent after several additional months of anatabine supplementation, although that remains to be tested. It is also possible that anatabine specifically and directly affects thyroglobulin secretion resulting in a drop in TgAbproduction, as has been suggested regarding the effects of smoking on thyroid autoimmunity (15). Regardless of mechanism, anatabine in the diet reduced TgAbs much like smoking, without nicotine or exposure to toxic smoke constituents.

اسلاید 17: Anatabine supplementation was safe and well tolerated. Patients in the anatabine group reported more Aes relative to those in the placebo group during upward dose titration, mostly mild nicotinic effects that resolved with dose adjustment. The primary limitation of this study is its short duration. Longer treatment is required to show a clinically meaningful effect on thyroid gland function and structure.In addition, vitamin D is known to affect immune function (19), and the addition of this vitamin to both the active and placebo formulations may have obscured a treatment effect because TPOAb levels decreased in both groups. Third, the dose of anatabine may have been too low, although the amount taken per day (0.17– 0.25 mg/kg) was expected to be safe and effective based on case reports of individuals who experienced positive immunomodulatory effects within this dose range.Fourth, the inclusion of patients who were taking levothyroxine could have influenced the results, because TgAb levels were lower in individuals in the anatabine group who were receiving levothyroxine therapy. Furtherstudies are needed to determine whether anatabine could be an adjunctive therapy to levothyroxine or whether its effects would be more or less robust without the addition of vitamins A and D3. Finally, because urinary iodide measurements were not performed, a potential effect of dietary iodine status on anatabine responsivenesscould not be assessed. This study shows that nutritional supplementation with anatabine significantly reduces circulating TgAb levels in patients with Hashimoto’s thyroiditis. These results confirm an immunological effect of anatabine in humans as shown previously in a preclinical model of Hashimoto’s thyroiditis (7). Collectively, the results of this trial suggest that further studies of anatabine in Hashimoto’s thyroiditis and other autoimmune disorders, including studies that monitor changes noted above for longer time periods and elucidate its mechanismof action, are warranted.

اسلاید 18: References :https://www.endocrineweb.com/conditions/hashimotos-thyroiditis/symptoms-hashimotos-thyroiditis https://www.thyroid.org/hashimotos-thyroiditis/https://www.sciencedaily.com/releases/2019/03/190318222147.htmhttp://ImmunologyToday.ir

اسلاید 19: Thank you