To systemically evaluate the clinical efficacy and safety of oral preparation of Xiakucao with levothyroxine(LT4) on Hashimoto's thyroiditis(HT), so as to provide the evidence for its clinical application in the future. All the included studies were retrieved from four Chinese databases and three English databases from their inception to December 2019. ROB assessment tool of cochrane system and the evidence classification recommended by GRADE were used to evaluate the quality of evidences in all included studies. RevMan 5.3 was used for Meta-analysis of the outcomes. Software TSA 0.9(trail sequential analysis) was used to estimate the sample size for Meta-analysis. The results showed that 11 randomized controlled trials and totaling 1 215 patients were included. Preparation of Xiakucao combined with LT4 was adopted as intervention in experimental group, while patients in control group were treated with LT4 alone. Meta-analysis results showed that as compared with control group, the rate of total efficacy in experimental group was significant improved, including improvement of thyroid function and thyroid autoantibodies, shrinkage of thyroid gland and nodule, and improvement of clinical symptoms such as fatigue and cold intolerance(RR=1.15, 95%CI[1.09, 1.21]). The experimental group significantly decreased the serum level of thyroperoxidase antibody TPO-Ab(SMD=-0.91, 95%CI[-1.40,-0.41]), and reduced the size of left thyroid lobe(MD=-1.46, 95%CI[-1.82,-1.11]), right thyroid lobe(MD=-1.45, 95%CI[-1.96,-0.94]) and isthmus of thyroid gland(MD=-1.08, 95%CI[-1.20,-0.95]). After evaluation based on GRADEpro, the results showed that the evidence quality of all included studies was low or very low. The result of TSA showed that the cumulative sample size had reached the expected value. However, the pooled results may be affected by one study with high bias risk, with not so high effect intensity of evidences. From this review, we can see that in treatment of HT, intervention of preparation of Xiakucao combined with LT4 has advantages on improvement of clinical efficiency, decreasing serum level of TPO-Ab and shrinkage of thyroid gland. However, due to the quality of evidence, more rigorously designed and high-quality trials are needed in the future to verify the clinical efficacy and safety of preparation of Xiakucao in treating HT.
Hashimoto Disease ; Humans ; Iodide Peroxidase ; Prunella ; Thyroxine

PURPOSE: The same autoimmune process is thought to cause thyroid associated ophthalmopathy (TAO) and Graves' disease. The aim of this study is to determine hether thyroid autoantibody is related to the development of thyroid associated ophthalmopathy. METHODS: A retrospective chart analysis was performed on patients with a newly diagnosed Graves' disease, who presented to our ophthalmology clinic between January 2006 and December 2009. Thyroid autoantibody titers were obtained at the time of diagnosis and were used to determine the presence or absence of TAO. In addition, any correlations between thyroid autoantibodies were analyzed in patients with TAO. RESULTS: Thyroid autoantibody levels correlated with the development of TAO. Fifty-eight (69%) out of 84 patients with positive thyroid-stimulating hormone receptor antibody (TRAB) levels at the time of diagnosis had TAO. Only 50 (51%) of the 99 patients with negative TRAB levels had TAO. This difference between the two groups was statistically significant (odds ratio, OR=2.2, p=0.013). A statistically significant correlation with the development of TAO was also found in thyroid peroxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb), respectively (OR=0.5, p=0.317; OR=0.3, p=<0.001). In patients with TAO, the correlation between TPOAb and TgAb levels was very high (r=0.64, p=<0.001). CONCLUSIONS: A significant association was determined to exist between the development of TAO and thyroid autoantibody level. This result demonstrates the clinical utility of thyroid autoantibody for the diagnosis of TAO in patients with newly diagnosed Graves' disease.
Autoantibodies ; Graves Disease ; Graves Ophthalmopathy ; Humans ; Iodide Peroxidase ; Ophthalmology ; Retrospective Studies ; Thyroid Gland ; Thyrotropin ; Troleandomycin

BACKGROUND: The association between chronic urticaria and thyroid autoantibodies is now generally accepted, and some authors recommend screening for thyroid autoimmunity and function in all patients with chronic urticaria for early identification of patients who might require treatment of underlying thyroid dysfunction or follow-up. However, the prognostic significance of thyroid autoantibodies in urticaria patients is still unclear. OBJECTIVE: To evaluate antibody reactivity as a prognostic factor, the association between antibody positivity and disease duration were analyzed. METHODS: Medical records from March 2002 to October 2010 of urticaria patients (M: 41, F: 125), who were tested for thyroid auto-antibodies at their first visit, were collected and reviewed for the duration of urticaria. Patients with a 6-week or longer history of urticaria were categorized into the chronic urticaria group; patients whose urticaria resolved within 6 weeks were categorized into the acute urticaria group. RESULTS: A positive result to the thyroid autoantibody was shown by 28.9% of chronic urticaria patients and 10.7% of acute urticaria patients. Average duration of urticaria in patients who were thyroid autoantibody positive was 33.9 weeks, while patients with thyroid autoantibody negative tests had urticaria for 6.9 weeks on average. The frequency of a positive result to only the thyroid peroxidase antibody was different between the chronic urticaria group (15.6%) and the acute urticaria group (2.5%). CONCLUSION: According to our results, the average duration of urticaria in patients with thyroid autoantibodies was significantly longer than in urticaria patients without thyroid autoantibodies. Thyroid autoantibodies were statistically meaningful prognostic factors predicting the duration of urticaria.
Autoantibodies ; Autoimmunity ; Follow-Up Studies ; Humans ; Iodide Peroxidase ; Mass Screening ; Medical Records ; Thyroid Gland ; Urticaria

BACKGROUND: Tri-iodothyronine (T3) is the main active hormone, and 20% of this is derived from the thyroid gland and 80% is from the peripheral tissue according to 5'-monodeiodination of thyroxine (T4). In the previous studies, normal T3 levels were achieved with traditional levothyroxine (LT4) therapy alone in athyreotic patients, but there has been no data about the factors influencing peripheral conversion of LT4. The aim of this study was to determine the factor(s) influencing peripheral conversion of LT4 to T3 in athyreotic patients during LT4 replacement. METHODS: The patients who underwent total-thyroidectomy for any cause, and mostly for thyroid cancers, at Asan Medical Center between 2000 and 2008 were enrolled. The free T4, T3 and thyroid stimulating hormone (TSH) levels and age, gender, weight, height, body mass index (BMI) and the T4 dose were measured. Only patients with normal ranges of free T4 and TSH were included in the analysis. RESULTS: A total of 143 patients were enrolled. The mean T3, free T4 and TSH levels were 143.7 ng/dL, 1.4 ng/dL and 1.6 microU/mL, respectively. The mean weight and BMI were 62.9 kg and 24.6 kg/m2, respectively. We divided them into two groups according to the serum T3 level and we compared the characteristics of the groups. There were no differences in age, the gender distribution, the T4 dose/weight and the BMI between the low T3 group (T3 < or = 122 ng/dL, n = 14) and the normal T3 group (T3 > 122 ng/dL, n = 129). In the low T3 group, the mean body weight was significantly lower than that of the normal T3 group (59.0 +/- 6.0 vs. 63.4 +/- 9.9, respectively, P = 0.025). CONCLUSION: Lean body mass seems to be an important factor for determining the peripheral conversion of T4 to T3 in human. This suggest that a combination of T3/T4 is better than T4 only when we treat the patients with hypothyroidism and who have a negligible amount of functioning thyroid tissue, if they have a low lean body mass.
Body Height ; Body Weight ; Humans ; Hypothyroidism ; Iodide Peroxidase ; Reference Values ; Thyroid Gland ; Thyrotropin ; Thyroxine

BACKGROUND: Engineered cell sheet transplantation has been considered an alternative physiological therapy for endocrine disorders. In this study, we attempted to fabricate functional human thyroid cell sheets using the engineering technology by culturing primary thyrocytes in free-feeder monolayers and assessed their proliferation and function in two different media. METHODS: The non-tumorous tissues (approximately 2 g) were dissected during surgery. Primary human thyroid cells were isolated by mechanical dispersion and treatment with isolation solution. The cells were cultured on tissue culture dishes or temperature-responsive culture dishes to induce the formation of detached cell sheets. RESULTS: Primary thyroid cells isolated from nine patients were positive for thyroid transcription factor 1, thyroglobulin (TG) and cytokeratin 7. Cell sheets with follicles were fabricated by cells incubated in both Dulbecco's Modified Eagle Medium (DMEM) and hepatocyte-defined medium (HDM) culture medium. The diameter and thickness of sheets fabricated in HDM were larger and thicker than those fabricated from DMEM. Furthermore, the cells incubated in HDM secreted higher levels of fT3 and fT4 than those incubated in DMEM. The thyroid peroxidase and TG mRNA of cells maintained in HDM were higher than those in cells maintained in DMEM. CONCLUSION: HDM appears suitable as a culture medium for maintaining primary thyrocytes and fabricating functional cell sheets. These in vitro findings may contribute to the development of appropriate culture conditions for human thyrocytes as well as engineered functional cell sheets.
Eagles ; Humans ; In Vitro Techniques ; Iodide Peroxidase ; Keratin-7 ; RNA, Messenger ; Thyroglobulin ; Thyroid Gland ; Transcription Factors

OBJECTIVES: To examine the expression of serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in children with immune thrombocytopenia (ITP). METHODS: A total of 120 children with ITP who were admitted from October 2019 to October 2021 were enrolled as the ITP group. A total of 60 children without ITP were enrolled as the non-ITP group. According to the clinical classification of ITP, the children in the ITP group were further divided into a newly diagnosed ITP group, a persistent ITP group, and a chronic ITP group. The clinical data were compared between the ITP group and the non-ITP group and between the children with different clinical classifications of ITP. The expression levels of serum TGAb and TPOAb in children with ITP were measured and their association with the clinical classification of ITP was analyzed. RESULTS: Compared with the non-ITP group, the ITP group had significantly lower levels of CD3⁺, CD4⁺, and platelet count (PLT) and significantly higher levels of CD8⁺, TGAb, and TPOAb (P<0.05). The children with chronic ITP had significantly lower levels of CD3⁺, CD4⁺, and PLT and significantly higher levels of CD8⁺, TGAb, and TPOAb than those with newly diagnosed ITP or persistent ITP (P<0.05). The logistic regression analysis showed that CD3⁺, CD4⁺, CD8⁺, TGAb, and TPOAb were the influencing factors for chronic ITP (P<0.05). A decision curve was plotted, and the results showed that TGAb combined with TPOAb within the high-risk threshold range of 0.0-1.0 had a net benefit rate of >0 in evaluating the clinical classification of ITP in children. CONCLUSIONS TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.
Autoantibodies ; Child ; Humans ; Iodide Peroxidase ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Thrombocytopenia ; Thyroglobulin

BACKGROUND: Increased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO4), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice. METHODS: Eight-week-old 129S7/SvEvBrd-Mt1(tm1Bri) Mt2(tm1Bri)/J (MT-I/II KO) mice and background-matched wild type (WT) mice were used. RESULTS: By using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thiazolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 µM) can be relieved by 300 µM PTU, 30 µM KClO4, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice(P<0.05). CONCLUSION: We concluded that PTU, KClO4, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.
Animals ; Antioxidants ; Iodide Peroxidase ; Iodides ; L-Lactate Dehydrogenase ; Metallothionein* ; Mice ; Mice, Knockout* ; Oxidative Stress ; Potassium Iodide ; Propylthiouracil* ; Reactive Oxygen Species ; Superoxides* ; Suspensions ; Thyroid Diseases ; Thyroid Gland* ; Thyrotropin*

The present study was designed to investigate if antithyroid antibodies(ATA) could affect the pregnancy outcome in euthyroid women undergoing superovulation with intrauterine insemination(IUI). From January 1995 to September 1996, 18 euthyrouid women with ATA who undersent superovulation with IUI were suudied. Thirty-two euthyroid women without ATA who underwent superovulation with IVI were served as control. Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody(TGA) were assayed using radio ligand assay kits as ATA. All patient included in the study and the control groups had only ovulatory factor in infertility or had suffered from unexplained infertility. The infertile patients with ovulatory factor were resistant to clomiphene citrate(CC) or had previously failed to conceive despite 3 ovulatory cycles using CC. Long protocol of gonadotropin-releasing hormone agonist(GnRH-a) was used for superovulation in all patients. There were no significant differences between the study and the control groups in patient characteristics such as age, infertility duration and hormonal profil. There were also no significant differences between two groups with respect to the clinicalresponse to superovulation. The clinical pregnancy rate per cycle was significantly lower in the study group at 23.5%(8/34) compared with 44.4%(24/54) in the control group.l The biochemical pregnancy rate per cycle was significantly higher in the study group at 17.6%(6/34) compared with 3.7%(2/54) in the control group. The miscarriage rate seemed to be higher in the study group than in the control group(37.5% vs 8.3%), but the difference was not statistically significant. In the study group, both TPOA and TGA titers were higher in the miscarriage group than in the ongoing or delivery group, although statistical significance was not found. This study suggests that ATA in euthyroid women could be associated with the poor pregnancy outcome in superovulation with IUI cycles and ATA may serve as possible marker for reproductive failure.
Abortion, Spontaneous ; Antibodies* ; Clomiphene ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Infertility ; Insemination* ; Iodide Peroxidase ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Superovulation ; Thyroglobulin

The present study was designed to investigate if antithyroid antibodies(ATA) could affect the pregnancy outcome in euthyroid women undergoing superovulation with intrauterine insemination(IUI). From January 1995 to September 1996, 18 euthyrouid women with ATA who undersent superovulation with IUI were suudied. Thirty-two euthyroid women without ATA who underwent superovulation with IVI were served as control. Thyroid peroxidase antibody (TPOA) and thyroglobulin antibody(TGA) were assayed using radio ligand assay kits as ATA. All patient included in the study and the control groups had only ovulatory factor in infertility or had suffered from unexplained infertility. The infertile patients with ovulatory factor were resistant to clomiphene citrate(CC) or had previously failed to conceive despite 3 ovulatory cycles using CC. Long protocol of gonadotropin-releasing hormone agonist(GnRH-a) was used for superovulation in all patients. There were no significant differences between the study and the control groups in patient characteristics such as age, infertility duration and hormonal profil. There were also no significant differences between two groups with respect to the clinicalresponse to superovulation. The clinical pregnancy rate per cycle was significantly lower in the study group at 23.5%(8/34) compared with 44.4%(24/54) in the control group.l The biochemical pregnancy rate per cycle was significantly higher in the study group at 17.6%(6/34) compared with 3.7%(2/54) in the control group. The miscarriage rate seemed to be higher in the study group than in the control group(37.5% vs 8.3%), but the difference was not statistically significant. In the study group, both TPOA and TGA titers were higher in the miscarriage group than in the ongoing or delivery group, although statistical significance was not found. This study suggests that ATA in euthyroid women could be associated with the poor pregnancy outcome in superovulation with IUI cycles and ATA may serve as possible marker for reproductive failure.
Abortion, Spontaneous ; Antibodies* ; Clomiphene ; Female ; Gonadotropin-Releasing Hormone ; Humans ; Infertility ; Insemination* ; Iodide Peroxidase ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Superovulation ; Thyroglobulin

BACKGROUNDThyroid peroxidase (TPO) is an important autoantigen in Hashimoto's thyroiditis (HT), and almost all epitopes are located in TPO ectodomain. The glycosylation of TPO might contribute to breaking self-tolerance, therefore, purified glycosylated recombinant TPO ectodomain is prerequisite of elucidating its role in the pathogenesis of HT. The aim of our study was to investigate whether the glycosylation has influence on the antigenic determinants of recombinant TPO.

METHODSBac-to-Bac baculovirus expression system was used to generate recombinant human TPO ectodomain. The antigenicity was analyzed by antigen specific enzyme-linked immunosorbant assays (ELISAs). The glycosylation of recombinant human TPO ectodomain of High Five insect cell origin was detected by lectin-ELISAs.

RESULTSTPO ectodomain was recovered from the culture media as a soluble protein, and it was fused with a hexahistidine tag which allowed purification by nickel-affinity chromatography. The recombinant TPO ectodomain could be recognized by all the 54 HT patients and three TPO monoclonal antibodies. Fucose, sialic acid and galactose were all detected on the recombinant TPO ectodomain. Sera TPOAb binding decreased slightly after non-specific deglycosylation of TPO by periodic acid.

CONCLUSIONSHigh Five insect cells derived recombinant human TPO ectodomain had N-glycosylation sites, which might have little effect on recognition by serum TPOAb.

Animals ; Antibodies, Monoclonal ; immunology ; Baculoviridae ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Glycosylation ; Humans ; Insecta ; cytology ; Iodide Peroxidase ; immunology ; Recombinant Proteins