Induction of remission in autoimmune polyglandular syndrome type three (APS III): An old drug with new perspectives

Allam, Magdy Mohamed; El‐Zawawy, Hanaa Tarek

doi:10.1002/ccr3.1827

Cited by 7 publications

(5 citation statements)

References 18 publications

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“…However, before such protocols are used in standard care, large-scale validation in a high-quality randomized trial is needed. Furthermore, there are some case reports that suggest the potential usefulness of AZA in severe cases of Graves’ hyperthyroidism ( 15 , 16 ). This study aimed to assess the efficacy of addition of AZA to the conventional ATDs in moderate and severe Graves’ hyperthyroidism.…”

Section: Introductionmentioning

confidence: 99%

Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial

et al. 2023

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IntroductionAzathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves’ disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.MethodsWe conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40–120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.ResultsA total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.ConclusionAZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.Trial registryThe trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).

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Section: Introductionmentioning

confidence: 99%

Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial

et al. 2023

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“…2 HT is associated with thyroid autoantibodies production, the most common are thyroid peroxidase antibodies (anti-TPO) and thyroglobulin antibodies with various degrees of thyroid dysfunction. 3 Formerly, HT was considered a T helper (Th) 1-mediated disease. After the identification of new Th cell subsets, including Th17 cells, HT was found to be mediated by Th17.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Improving Hashimoto’s thyroiditis by eradicating Blastocystis hominis: Relation to IL-17

El‐Zawawy

Farag

Tolba

et al. 2020

Therapeutic Advances in Endocrinology

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Background: Hashimoto’s thyroiditis (HT) is a common autoimmune disorder that causes significant morbidity. Interleukin (IL)-17 was identified as a major contributing factor in the pathogenesis of HT. Blastocystis hominis (BH) is a very common infection and has been shown to be associated with several diseases. Our aim was to determine serum IL-17 level in HT patients with and without BH infection and the effect of eradicating BH in patients with HT. Methods: A prospective cohort study was conducted on 20 HT patients not infected with BH (group I), 20 HT patients infected with BH (group II), and 20 healthy patients (group III). Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (anti-TPO), and IL-17 were performed by ELISA method and were repeated in group II after 6 weeks of eradication of BH. Results: Patients with HT showed a significantly higher serum IL-17 compared with controls. IL-17 was significantly higher in HT patients infected with BH compared with HT patients not BH infected (mean 6.93 ± 2.83 pg/ml versus 3.25 ± 1.55 pg/ml, p = 0.003). After BH eradication TSH, anti-TPO, and IL-17 were significantly decreased (mean 14.76 ± 11.11 µIU/ml versus 9.39 ± 7.11 µIU/ml, p < 0.001; mean 308 ± 175.6 IU/ml versus 295.4 ± 167.1 IU/ml, p = 0.006; and mean 6.93 ± 2.83 pg/ml versus 6.45 ± 2.48 pg/ml, p < 0.001), respectively. Multivariate analysis after treating BH infection showed that IL-17 was significantly negatively correlated with FT3 (adjusted p = 0.002) and significantly positively correlated with anti-TPO (adjusted p = 0.045). Conclusion: Treatment of BH infection ameliorates HT through reduction in IL-17, anti-TPO, and TSH. Clinical trial registration number: PACTR201909495111649

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“…However, the underlying pathological mechanisms remain unclear. Hypotheses suggest that autoimmune thyroiditis may be a part of an immune‐mediated disorder or an autoimmune polyglandular syndrome, which includes autoimmune vasculitis of the placental microvasculature . In addition, antithyroid antibodies can directly cause hypothyroidism in newborns via crossing the placental barrier …”

Section: Introductionmentioning

confidence: 99%

“…Hypotheses suggest that autoimmune thyroiditis may be a part of an immune-mediated disorder or an autoimmune polyglandular syndrome, which includes autoimmune vasculitis of the placental microvasculature. 6 In addition, antithyroid antibodies can directly cause hypothyroidism in newborns via crossing the placental barrier. 7 Recent guidelines recommend that thyroid status and TPOAb level to be taken into consideration separately regarding levothyroxine (LT4) treatment in infertile women especially those who are undergoing assisted reproductive techniques (ART).…”

Section: Introductionmentioning

confidence: 99%

A hidden cause of infertility in hypothyroid patients

Allam

El‐Zawawy

Barakat

et al. 2020

Clinical Case Reports

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Induction of remission in autoimmune polyglandular syndrome type three (APS III): An old drug with new perspectives

Cited by 7 publications

References 18 publications

Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial

Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial

Improving Hashimoto’s thyroiditis by eradicating Blastocystis hominis: Relation to IL-17

A hidden cause of infertility in hypothyroid patients

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