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1.
Drug Des Devel Ther ; 17: 2273-2285, 2023.
Article in English | MEDLINE | ID: mdl-37551407

ABSTRACT

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.


Subject(s)
Hashimoto Disease , Thyroiditis, Autoimmune , Animals , Rats , Autoantibodies/blood , NF-kappa B , Thyroglobulin/adverse effects , Thyroiditis, Autoimmune/chemically induced , Thyroiditis, Autoimmune/drug therapy , Thyrotropin/blood , Thyroxine/blood , Toll-Like Receptor 4 , TOR Serine-Threonine Kinases , Triiodothyronine/blood
2.
Nuklearmedizin ; 49(6): 216-24, 2010.
Article in English | MEDLINE | ID: mdl-20877918

ABSTRACT

UNLABELLED: The primary aim of this study was to compare pharmacoeconomic effects of hypothyroidism secondary to hormone withdrawal (THW) and recombinant human TSH (rhTSH) for follow-up WBS in patients with differentiated thyroid cancer (DTC). The second aim was to determine patients' preference for one procedure or the other. PATIENTS, METHODS: This retrospective survey included 327 patients with DTC who underwent at least one in-hospital WBS with rhTSH between 1999 and 2006. They had also undergone THW for WBS. Patients received a two-page questionnaire via mail addressing five symptoms and ten items regarding managing their daily life which was answered by 61.6%. The responder group did not differ from the entire group. The medical and societal cost of both procedures for diagnostic WBS was calculated including direct and all ascertainable indirect cost for the reference year 2005. A sensitivity analysis included the German DRG system of 2007 and 2010. RESULTS: After THW, 94% of patients reported hypothyroid symptoms. Using rhTSH, symptoms occurred significantly less. As a result, 97% of patients favored rhTSH over THW. Mean absence from salaried work was 12.3 days after THW compared to 4 days with rhTSH. Family members of salaried employees missed 3 and 0.7 workdays after THW and rhTSH, respectively. Almost twice as often, medical attention was sought after THW (36%) compared to rhTSH (19 %). Undergoing THW, 48% of patients still used their car while hypothyroid. Our cost calculation revealed a slight benefit of about 89.00 Euro in favour of rhTSH stimulation. CONCLUSION: Hypothyroidism after THW causes significant morbidity and safety risks. The clinical and societal benefits associated with rhTSH are roughly gained at equivalent overall cost to that of THW.


Subject(s)
Recombinant Proteins/therapeutic use , Thyroid Neoplasms/drug therapy , Thyrotropin/therapeutic use , Carcinoma , Carcinoma, Papillary , Fatigue/etiology , Female , Hospitalization , Humans , Hypothyroidism/chemically induced , Male , Recombinant Proteins/economics , Thyroglobulin/adverse effects , Thyroglobulin/blood , Thyroglobulin/drug effects , Thyroid Cancer, Papillary , Thyroid Neoplasms/blood , Thyrotropin/economics , Thyrotropin/genetics , Thyrotropin Alfa/therapeutic use
3.
Obstet Gynecol ; 112(1): 85-92, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18591312

ABSTRACT

OBJECTIVE: To estimate whether maternal thyroid hypofunction is associated with complications. METHODS: A total of 10,990 patients had first- and second-trimester serum assayed for thyroid-stimulating hormone (TSH), free thyroxine (freeT4), and antithyroglobulin and antithyroid peroxidase antibodies. Thyroid hypofunction was defined as 1) subclinical hypothyroidism: TSH levels above the 97.5th percentile and free T4 between the 2.5th and 97.5th percentiles or 2) hypothyroxinemia: TSH between the 2.5th and 97.5th percentiles and free T4 below the 2.5th percentile. Adverse outcomes were evaluated. Patients with thyroid hypofunction were compared with euthyroid patients (TSH and free T4 between the 2.5th and 97.5th percentiles). Patients with and without antibodies were compared. Multivariable logistic regression analysis adjusted for confounders was used. RESULTS: Subclinical hypothyroidism was documented in 2.2% (240 of 10,990) in the first and 2.2% (243 of 10,990) in the second trimester. Hypothyroxinemia was documented in 2.1% (232 of 10,990) in the first and 2.3% (247 of 10,990) in the second trimester. Subclinical hypothyroidism was not associated with adverse outcomes. In the first trimester, hypothyroxinemia was associated with preterm labor (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] 1.00-2.62) and macrosomia (aOR 1.97; 95% CI 1.37-2.83). In the second trimester, it was associated with gestational diabetes (aOR 1.7; 95% CI 1.02-2.84). Fifteen percent (1,585 of 10,990) in the first and 14% (1,491 of 10,990) in the second trimester had antithyroid antibodies. When both antibodies were positive in either trimester, there was an increased risk for preterm premature rupture of membranes (P=.002 and P<.001, respectively). CONCLUSION: Maternal thyroid hypofunction is not associated with a consistent pattern of adverse outcomes. LEVEL OF EVIDENCE: II.


Subject(s)
Hypothyroidism/complications , Pregnancy Complications , Pregnancy Outcome , Adult , Autoantibodies/adverse effects , Female , Fetal Membranes, Premature Rupture/etiology , Humans , Hypothyroidism/immunology , Odds Ratio , Pregnancy , Pregnancy Complications/immunology , Pregnancy Trimester, First , Pregnancy Trimester, Second , Risk , Thyroglobulin/adverse effects , Thyroid Function Tests
4.
Hum Immunol ; 63(4): 301-10, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12039412

ABSTRACT

In contrast to H2-based susceptibility to experimental autoimmune thyroiditis (EAT) induced with thyroglobulin (Tg), human leukocyte antigen (HLA) association with Hashimoto's thyroiditis, the human counterpart, is less clear, and determining association is further complicated by DR/DQ linkage disequilibrium. Previously, we addressed the controversial implication of HLA-DR genes by introducing HLA-DRA/DRB1*0301 (DR3) transgene into endogenous class II negative H2Ab(0) mice. EAT induction with either human (h) or mouse (m) Tg demonstrated the permissiveness of DR3 molecules for shared Tg epitopes. Here, we examined the participation of HLA-DQ genes by introducing DQA1*0301/DQB1*0302 (DQ8) transgene into class II negative Ab(0) or class I and II negative beta(2)m((-/-)) Ab(0) mice. About 50% and 80% of HLA-DQ8(+) Ab(0) and beta(2)m(-) Ab(0) mice, respectively, developed moderate EAT after hTg immunization, but only minimal response to mTg. The hTg presentation to hTg-primed cells was blocked by anti-DQ mAb in vitro. By contrast, HLA-DRB1*1502 (DR2) and *0401 (DR4) transgenes contributed little to hTg induction. Similarly, DQA1*0103/DQB1*0601 or DQA1*0103/DQB1*0602 (DQ6) transgenic Ab(0) mice were unresponsive to hTg induction and carried no detectable influence in DQ8/DQ6 double transgenic mice. Thus, both HLA-DR and -DQ polymorphism exists for hTg in autoimmune thyroiditis. The use of defined single or double transgenic mice obviates the complications seen in polygenic human studies.


Subject(s)
HLA-DQ Antigens/immunology , HLA-DR3 Antigen/immunology , Thyroglobulin/adverse effects , Thyroiditis, Autoimmune/immunology , Animals , Disease Susceptibility , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , HLA-DR3 Antigen/genetics , HLA-DRB1 Chains , Humans , Immunity, Innate , Mice , Mice, Transgenic , Polymorphism, Genetic , Thyroiditis, Autoimmune/chemically induced
5.
Am J Dis Child ; 133(1): 71-2, 1979 Jan.
Article in English | MEDLINE | ID: mdl-760516

ABSTRACT

Hypertriiodothyroninemia during therapy with thyroglobulin was noted in six hypothyroid patients aged 9 to 25 years. Causes of hypothyroidism were thyroiditis, congenital athyreosis, cryptothyroidism, or goitrous hypothyroidism. Serum thyroxine level, measured at the same time, was below normal in three patients. Findings attributable to excess of thyroid hormones were none other than slight nervousness or transitory heat intolerance. Substitution of levothyroxine for thyroglobulin was done in all patients and was associated with return to normal of serum triiodothyronine (T3) values in those tested. A high content of T3 in thyroglobulin used for medication seems the most probable cause of the observed hypertriiodothyroninemia. Since similar findings have been reported previously for hypothyroid patients treated with desiccated thyroid preparations, it seems clear that therapy with levothyroxine offers a significant advantage over the use of desiccated thyroid or thyroglobulin.


Subject(s)
Hypothyroidism/drug therapy , Thyroglobulin/adverse effects , Triiodothyronine/blood , Adolescent , Adult , Child , Female , Humans , Male , Thyroglobulin/therapeutic use , Thyroxine/therapeutic use
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