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1.
J Int Med Res ; 52(4): 3000605241239856, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656269

RESUMO

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.


Assuntos
Anticorpos Monoclonais Humanizados , Doença de Graves , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/complicações , Psoríase/patologia , Feminino , Adulto , Doença de Graves/tratamento farmacológico , Doença de Graves/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento
4.
J Transl Med ; 22(1): 318, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553734

RESUMO

BACKGROUND: A subset of Graves' disease (GD) patients develops refractory hyperthyroidism, posing challenges in treatment decisions. The predictive value of baseline characteristics and early therapy indicators in identifying high risk individuals is an area worth exploration. METHODS: A prospective cohort study (2018-2022) involved 597 newly diagnosed adult GD patients undergoing methimazole (MMI) treatment. Baseline characteristics and 3-month therapy parameters were utilized to develop predictive models for refractory GD, considering antithyroid drug (ATD) dosage regimens. RESULTS: Among 346 patients analyzed, 49.7% developed ATD-refractory GD, marked by recurrence and sustained Thyrotropin Receptor Antibody (TRAb) positivity. Key baseline factors, including younger age, Graves' ophthalmopathy (GO), larger goiter size, and higher initial free triiodothyronine (fT3), free thyroxine (fT4), and TRAb levels, were all significantly associated with an increased risk of refractory GD, forming the baseline predictive model (Model A). Subsequent analysis based on MMI cumulative dosage at 3 months resulted in two subgroups: a high cumulative dosage group (average ≥ 20 mg/day) and a medium-low cumulative dosage group (average < 20 mg/day). Absolute values, percentage changes, and cumulative values of thyroid function and autoantibodies at 3 months were analyzed. Two combined predictive models, Model B (high cumulative dosage) and Model C (medium-low cumulative dosage), were developed based on stepwise regression and multivariate analysis, incorporating additional 3-month parameters beyond the baseline. In both groups, these combined models outperformed the baseline model in terms of discriminative ability (measured by AUC), concordance with actual outcomes (66.2% comprehensive improvement), and risk classification accuracy (especially for Class I and II patients with baseline predictive risk < 71%). The reliability of the above models was confirmed through additional analysis using random forests. This study also explored ATD dosage regimens, revealing differences in refractory outcomes between predicted risk groups. However, adjusting MMI dosage after early risk assessment did not conclusively improve the prognosis of refractory GD. CONCLUSION: Integrating baseline and early therapy characteristics enhances the predictive capability for refractory GD outcomes. The study provides valuable insights into refining risk assessment and guiding personalized treatment decisions for GD patients.


Assuntos
Doença de Graves , Hipertireoidismo , Adulto , Humanos , Prevenção Secundária , Estudos Prospectivos , Reprodutibilidade dos Testes , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Antitireóideos/uso terapêutico , Doença de Graves/tratamento farmacológico
5.
Eur Thyroid J ; 13(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38471303

RESUMO

Introduction: Secondary thyroid autoimmunity, especially Graves' disease (GD), frequently develops in patients with multiple sclerosis (MS) following alemtuzumab treatment (ALTZ; anti-CD52). Thyroid eye disease (TED) can also develop, and rituximab (RTX; anti-CD20) is a suitable treatment. Case presentation: A 37-year-old woman with MS developed steroid-resistant active moderate-to-severe TED 3 years after ALTZ, that successfully responded to a single 500 mg dose of i.v. RTX. Before RTX peripheral B-cells were low, and were totally depleted immediately after therapy. Follow-up analysis 4 years post ALTZ and 1 year post RTX showed persistent depletion of B cells, and reduction of T regulatory cells in both peripheral blood and thyroid tissue obtained at thyroidectomy. Conclusion: RTX therapy successfully inactivated TED in a patient with low B-cell count derived from previous ALTZ treatment. B-cell depletion in both thyroid and peripheral blood was still present 1 year after RTX, indicating a likely cumulative effect of both treatments.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Esclerose Múltipla , Feminino , Humanos , Adulto , Rituximab/efeitos adversos , Oftalmopatia de Graves/induzido quimicamente , Alemtuzumab/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Doença de Graves/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico
6.
Medicine (Baltimore) ; 103(11): e37456, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489722

RESUMO

RATIONALE: A rare and intractable case of apathetic Graves' disease (GD) with severe liver and kidney damage induced by coronavirus disease 2019 (COVID-19) carries a certain risk of missing diagnosis and delayed treatment during the COVID-19 pandemic. PATIENT CONCERN: A 60-year-old female patient developed anorexia, exhaustion, jaundice, nausea, and vomiting 10 days after COVID-19 infection. She was admitted to the Infectious Diseases Department because of recurring symptoms for more than a month. DIAGNOSIS: Based on the patient's epidemiological history, clinical symptoms, and prior history, she was preliminarily diagnosed with GD induced by COVID-19 with severe hyperthyroid-related liver injury and chronic kidney disease stage 4. Drug-induced and radiation-induced liver injuries occurred sequentially throughout the therapy. INTERVENTION: Methimazole (MMI) (10 mg/d) was administered for 1 week, and the patient's symptoms, thyroid function, and liver and kidney function improved. Nevertheless, the aforementioned symptoms and liver and kidney function deteriorated 20 days after increasing the MMI dose (20 mg/d). Therefore, in the presence of an artificial liver, hemodialysis, and other medical conditions, the treatment schedule was adjusted to individualized 131I anti-hyperthyroidism therapy. OUTCOME: After 131I treatment, the patient's liver function returned to almost normal levels after a month, but worsened when the hepatoprotective drugs were stopped. Renal function did not deteriorate significantly and returned to baseline after 3 months. Thyroid function was restored to normal approximately 4 months later. CONCLUSION: COVID-19 may induce GD. Multidisciplinary collaboration can be initiated as early as possible. Individualized 131I therapy or long-term low-dose MMI (10 mg/d) can be considered to manage hyperthyroidism in GD patients with liver and kidney dysfunction and to prolong liver protection therapy appropriately.


Assuntos
COVID-19 , Doença de Graves , Hipertireoidismo , Feminino , Humanos , Pessoa de Meia-Idade , Radioisótopos do Iodo/uso terapêutico , Pandemias , COVID-19/complicações , Doença de Graves/tratamento farmacológico , Hipertireoidismo/tratamento farmacológico , Metimazol/uso terapêutico , Antitireóideos/uso terapêutico , Fígado
7.
Neurology ; 102(8): e209282, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38513158

RESUMO

The concomitant presentation of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis is well documented. In the course of Graves disease (GD), symptomatic transient neuromuscular junction disorder may occur due to the effect of thyroid hormones at the neuromuscular synapse. Diagnostic clues are the clinical and electrophysiologic remission synchronous with restoration of euthyroidism. Furthermore, the occurrence of thymic hyperplasia in GD poses further diagnostic and therapeutic considerations. These points are discussed in the case report of a 43-year-old male patient suffering from TAO and transient neuromuscular junction disorder due to GD.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Miastenia Gravis , Masculino , Humanos , Adulto , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/diagnóstico , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Miastenia Gravis/complicações
8.
Endocr Pract ; 30(4): 333-339, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38307459

RESUMO

OBJECTIVE: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole. METHODS: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies. RESULTS: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response. CONCLUSION: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.


Assuntos
Doença de Graves , Neoplasias da Glândula Tireoide , Humanos , Feminino , Adulto , Masculino , Metimazol/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Doença de Graves/tratamento farmacológico , Doença de Graves/radioterapia
9.
Nuklearmedizin ; 63(2): 69-75, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38190997

RESUMO

PURPOSE: Radioiodine therapy (RIT) of benign thyroid diseases is an established therapy. This study aimed to identify factors predictive for outcome in patients with non-toxic goiter (NTG), unifocal (UFA), multifocal (MUFA) or diffuse autonomy (DISA) and Graves' disease (GD). METHODS: Retrospective analysis of 205 patients with benign thyroid disease (54 NTG, 46 MUFA, 24 DISA, 26 UFA, 55 GD) who underwent RIT. Follow up time was 12 months for determining treatment outcome. RESULTS: The type of disease was predictive for volume reduction after 12 months (NTS 66%, DISA 67%, MUFA 58%, UFA 51%, GD 71%, p<0.001) and post-treatment hypothyroidism (NTS 48%, DISA 33%, MUFA 15%, UFA 15%, p=0.006). Initial volume, intra-therapeutic uptake and intra-therapeutic half-life were independent prognostic factors for volume reduction 12 months after RIT. In patients with NTG, UFA, MUFA, DISA post-treatment hypothyroidism was significantly correlated with extent of volume reduction 12 months after RIT, achieved dose, higher pre-therapeutic TSH values and younger age. Two different strategies for pre-therapeutic dosimetry used in MUFA showed no differences regarding the therapeutic outcome. In GD, effective half-life, initial volume and Graves' ophthalmopathy were predictive for treatment failure. CONCLUSION: Reduction of thyroid volume and the percentage of hypothyroid patients one year after RIT was primarily dependent on the type of disease. In MUFA and DISA we could identify volume reduction after 3 months as a reliable predictor for hypothyroidism while in patients with GD a short intra-therapeutic half-life, a large pre-therapeutic volume and active Graves' ophtalmopathy were relevant predictors for treatment failure suggesting an intensified follow-up scheme in these patients.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Hipertireoidismo , Hipotireoidismo , Doenças da Glândula Tireoide , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Doenças da Glândula Tireoide/radioterapia , Doença de Graves/radioterapia , Doença de Graves/tratamento farmacológico , Hipertireoidismo/induzido quimicamente , Oftalmopatia de Graves/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico
10.
J Ethnopharmacol ; 324: 117753, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38218499

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: For numerous years, the Xiehuo Xiaoying decoction (XHXY), a traditional Chinese medicine formula, has demonstrated substantial promise in treating Graves' disease (GD) in clinical settings, showcasing significant potential. However, the therapeutic mechanism and efficacy material basis of XHXY remains obscure. AIM OF THE STUDY: This work aims to investigate the underlying mechanisms and to study the efficacy material basis of XHXY in anti-GD effect using a combination of TMT quantitative proteomics and molecular docking method. MATERIALS AND METHODS: GD model was initiated by administering Ad-TSH289. Subsequently, the mice underwent a four-week regimen that included oral gavage of XHXY at doses of 17 g/kg·d and 34 g/kg·d, along with intraperitoneal injections of Gentiopicroside (GPS). Utilizing the principles of pharmacological chemistry in traditional Chinese medicine, we employed high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS) to discern prescribed prototype composition of XHXY in serum samples from mouse. TMT proteomics research provided evidence of XHXY's putative targets and important pathways in vivo. The binding activity of probable action targets and prototype composition was detected by molecular docking. Finally, Immunohistochemistry (IHC) and TUNEL staining were used to verify the mechanism of XHXY and GPS in anti-GD. RESULTS: XHXY and GPS alleviated GD by ameliorating the pathological changes and reducing thyroxine and TRAb levels. In mouse serum, a total of 31 prototypical XHXY ingredients were detected, and the majority of these components were from monarch and minister medicine. Proteomics study results indicated that the XHXY may mainly regulate targets including FAS-associated death domain protein (FADD), Apolipoprotein C-III, etc. and main pathways are Apoptosis, Cholesterol metabolism, TNF signalling pathway, etc. Strong binding activity of the prototypical active ingredient and GPS towards FADD, Caspase 8, and Caspase 3 was demonstrated by molecular docking. XHXY and its primary component, GPS, elevated the expression of FADD, Caspase 8, and Caspase 3, and enhance apoptosis in thyroid cells, as lastly validated by TUNEL and IHC staining. CONCLUSIONS: XHXY exhibits a favorable therapeutic effect in treating GD by promoting apoptosis in thyroid cells through the upregulation of FADD, Caspase 8, and Caspase 3 expression. And GPS is the main efficacy material basis for its therapeutic effect in anti-GD.


Assuntos
Medicamentos de Ervas Chinesas , Doença de Graves , Animais , Camundongos , Caspase 3/metabolismo , Caspase 8/metabolismo , Simulação de Acoplamento Molecular , Proteômica , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
11.
Pharmacol Rep ; 76(1): 185-194, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38273183

RESUMO

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune disorder of the orbit and retro-ocular tissues and the primary extrathyroidal manifestation of Graves' disease. In moderate-to-severe and active GO iv glucocorticoids (GCs) are recommended as first-line treatment. The aim was to assess the safety profile of methylprednisolone administered intravenously for three consecutive days at 1 g in patients with active, moderate-to-severe or sight-threatening Graves' orbitopathy. METHODS: We retrospectively evaluated 161 medical records of patients with GO treated with high-dose systemic GCs in the Department of Endocrinology, Metabolic Disorders, and Internal Medicine in Poznan between 2014 and 2021. Clinical data included age, gender, laboratory results, activity and severity of GO, smoking status, disease duration, and presented side effects. RESULTS: The presence of mild side effects was observed during 114 (71%) hospitalizations. The most common complications were hyperglycemia (n = 95) and elevated aminotransferases (n = 31). Increased levels of aminotransferases were more likely observed in smokers and GO duration above 12 months. Based on the multivariate logistic regression, higher TRAb and CAS values were significantly associated with lower odds of hyperglycemia. In turn, the increased odds of elevated aminotransferases were significantly correlated with higher initial ALT levels, female gender, and GO duration above 12 months. In addition, the multidimensional correspondence analysis (MPA) showed that GO patients who declared smoking and had not L-ornithine L-aspartate applied demonstrated a higher probability of elevated aminotransferases. CONCLUSIONS: Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Hiperglicemia , Humanos , Feminino , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/etiologia , Estudos Retrospectivos , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Glucocorticoides/efeitos adversos , Metilprednisolona/efeitos adversos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Transaminases
12.
Exp Clin Endocrinol Diabetes ; 132(1): 17-22, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38237612

RESUMO

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. RESULTS: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). CONCLUSIONS: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.


Assuntos
Agranulocitose , Doença de Graves , Hipertireoidismo , Humanos , Agranulocitose/induzido quimicamente , Agranulocitose/genética , Agranulocitose/tratamento farmacológico , Antitireóideos/efeitos adversos , Doença de Graves/tratamento farmacológico , Doença de Graves/genética , Hipertireoidismo/tratamento farmacológico , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/uso terapêutico , Polimorfismo de Nucleotídeo Único
13.
Mini Rev Med Chem ; 24(3): 265-271, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37069724

RESUMO

Coronavirus disease 2019 (COVID-19) affects thyroid function. These changes are due to the direct impact of the virus on thyroid cells via angiotensin-converting-enzyme 2 (ACE2) receptors, inflammatory reaction, apoptosis in thyroid follicular cells, suppression of hypothalamus-pituitarythyroid axis, an increase in activity of adrenocortical axis, and excess cortisol release due to cytokine storm of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Euthyroid sick syndrome (ESS), thyroiditis, clinical and subclinical hypothyroidism, central hypothyroidism, exacerbation of underlying autoimmune thyroid disease, and clinical and subclinical hyperthyroidism can be associated with coronavirus. Adjuvants in coronavirus vaccines induce autoimmune/inflammatory syndrome known as vaccine adjuvants (ASIA) syndrome. Thyroiditis and Graves' disease have been reported to be associated with ASIA syndrome after some coronavirus vaccinations. Some coronavirus medications, such as hydroxychloroquine, monoclonal antibodies, lopinavir/ritonavir, remdesivir, naproxen, anticoagulants, and glucocorticoids can also affect thyroid tests, and correct diagnosis of thyroid disorders will be more difficult. Changes in thyroid tests may be one of the most important manifestations of COVID-19. These changes can be confusing for clinicians and can lead to inappropriate diagnoses and decisions. Prospective studies should be conducted in the future to increase epidemiological and clinical data and optimize the management of thyroid dysfunctions in patients with COVID-19.


Assuntos
COVID-19 , Doença de Graves , Hipotireoidismo , Tireoidite , Humanos , COVID-19/complicações , Estudos Prospectivos , SARS-CoV-2 , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Tireoidite/diagnóstico
14.
Intern Med ; 63(4): 521-526, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37380454

RESUMO

A 20-year-old woman with a 10-month history of treatment for Graves' disease (GD), developed hypothyroidism with a high level of thyrotropin (TSH) receptor-blocking antibodies (TBAbs). She conceived at 28 years old and was clinically euthyroid in the first and second trimester, while taking L-thyroxine. However, at 28 weeks she became hyperthyroid with an unexpected rise in TSH receptor-stimulating antibody (TSAb) levels. She was diagnosed with GD, and methimazole was initiated. Her thyroid function normalized, but the neonate became hyperthyroid. We herein report the first case of a shift in dominance from TBAbs to TSAbs in late pregnancy.


Assuntos
Doença de Graves , Hipertireoidismo , Hipotireoidismo , Recém-Nascido , Feminino , Gravidez , Humanos , Adulto Jovem , Adulto , Estimulador Tireóideo de Ação Prolongada , Receptores da Tireotropina , Hipertireoidismo/complicações , Hipertireoidismo/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Tireotropina , Autoanticorpos
15.
HIV Med ; 25(3): 398-403, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37990629

RESUMO

BACKGROUND: Comorbidity of Myasthenia gravis (MG) and Graves' disease (GD) in treated HIV-infected individuals has rarely been described and little study has been done on the link between HIV-related immune reconstitution and autoimmune diseases occurring post antiretroviral therapy. CASE PRESENTATION: Here we report on a 33-year-old Chinese man with HIV infection who had been virologically suppressed since 2018. The patient was diagnosed with GD and was treated in 2020. Early in 2022, he developed fluctuating weakness and fatigue involving the bilateral extraocular muscles and limbs. With a positive neostigmine test, he was considered to have MG, but showed a poor response to oral medication. After multiple failed medication attempts, a thymectomy was finally performed to resolve his symptoms. The consecutive onset of immunological events may have partially resulted from immune reconstitution after viral control. CONCLUSIONS: This is a rare case of HIV-related immune reconstitution-associated autoimmune disease (IRAD) with comorbidity of MG and GD which was reported initially. Cooperation with multidisciplinary teams is essential to avoid misdiagnosis and to promote the overall health of HIV-infected patients.


Assuntos
Doença de Graves , Infecções por HIV , Síndrome Inflamatória da Reconstituição Imune , Reconstituição Imune , Miastenia Gravis , Masculino , Humanos , Adulto , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Comorbidade
16.
J Clin Endocrinol Metab ; 109(2): 344-350, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37708353

RESUMO

OBJECTIVE: Atypical Graves disease (GD) is a common complication in multiple sclerosis (MS) patients treated with alemtuzumab. We present epidemiological, clinical, and biochemical characteristics of alemtuzumab-induced GD. METHODS: Retrospective follow-up study of MS patients treated with alemtuzumab from 2014 to 2020, including clinical course of GD, pregnancy outcome, and thyroid eye disease (TED). RESULTS: We enrolled 183 of 203 patients (90%, 68% women) treated with alemtuzumab at 4 hospitals in Norway. Seventy-five (41%) developed thyroid dysfunction, of whom 58 (77%) had GD. Median time from the first dose of alemtuzumab to GD diagnosis was 25 months (range, 0-64). Twenty-four of 58 GD patients (41%) had alternating phases of hyper- and hypothyroidism. Thyrotropin receptor antibodies became undetectable in 23 of 58 (40%) and they could discontinue antithyroid drug treatment after a median of 22 (range, 2-58) months. Conversely, 26 (44%) had active disease during a median follow-up of 39 months (range, 11-72). Two patients (3%) received definitive treatment with radioiodine, 6 (10%) with thyroidectomy. Nine developed TED (16%), 7 had mild and 2 moderate to severe disease. Four patients completed pregnancy, all without maternal or fetal complications. Patients who developed GD had a lower frequency of new MS relapses and MRI lesions than those without. CONCLUSION: GD is a very common complication of alemtuzumab treatment and is characterized by alternating hyper- and hypothyroidism. Both remission rates and the prevalence of TED were lower than those reported for conventional GD. Pregnancies were uncomplicated and GD was associated with a lower risk of subsequent MS activity.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Hipotireoidismo , Esclerose Múltipla , Humanos , Feminino , Gravidez , Masculino , Alemtuzumab/efeitos adversos , Estudos Retrospectivos , Radioisótopos do Iodo/uso terapêutico , Prevalência , Seguimentos , Doença de Graves/tratamento farmacológico , Doença de Graves/epidemiologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/epidemiologia , Oftalmopatia de Graves/tratamento farmacológico , Oftalmopatia de Graves/epidemiologia , Fatores de Risco
17.
Klin Monbl Augenheilkd ; 241(1): 48-68, 2024 Jan.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-37799096

RESUMO

Graves' orbitopathy is an autoimmune disease of the orbit that most frequently occurs with Graves' hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and more or less pronounced inflammation. Consequently, patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus restrictive motility impairment with double vision. In recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the recognition that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition of antibody development must be included in the therapeutic concept, especially in severe cases.


Assuntos
Exoftalmia , Doença de Graves , Oftalmopatia de Graves , Hipertireoidismo , Humanos , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Hipertireoidismo/complicações , Autoanticorpos/uso terapêutico , Exoftalmia/etiologia
18.
Hormones (Athens) ; 23(1): 107-111, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37831339

RESUMO

PURPOSE: We present two cases of autoimmune hypothyroidism converted to Graves' disease (GD) and their medical management. METHODS: We tested thyroid function and thyroid antibodies and performed an ophthalmologic examination and neck ultrasound in two patients with autoimmune hypothyroidism converted to GD during a follow-up of several years. CASE REPORTS: The first case is a 33 year-old woman with hypothyroidism due to Hashimoto's thyroiditis (HT). She developed signs and symptoms of hyperthyroidism after 7 years of treatment with the same dose of levothyroxine (LT4). Even when LT4 therapy was discontinued, she remained thyrotoxic, with mild Graves' ophthalmopathy (GO) and very high thyroid-stimulating hormone receptor antibodies (TRAb > 40 IU/L, reference range: <1.75 IU/L). Antithyroid medication was started on a titration regimen, without achievement of euthyroidism. She was switched to a block and replace regimen, using 20 mg of methimazole (MMI) and 75 mcg of LT4 daily, with normalization of thyroid hormones and improvement of GO without steroids. The second case is a 57 year-old man with a 2-year positive medical history of HT and 6 months of LT4 treatment. He developed hyperthyroidism and moderate-severe GO. Despite stopping LT4 and initiating antithyroid medication in a titration regimen, he did not achieve euthyroidism and had active GO. Pulse glucocorticoid therapy and switching to a block-replace regimen was required to achieve euthyroidism and reduce ocular proptosis and diplopia. CONCLUSION: Spontaneous autoimmune conversion of hypothyroidism to hyperthyroidism can occur at any time: it is important to promptly identify these cases so as to manage them effectively.


Assuntos
Doença de Graves , Oftalmopatia de Graves , Doença de Hashimoto , Hipertireoidismo , Hipotireoidismo , Tireoidite Autoimune , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Doença de Graves/tratamento farmacológico , Hipotireoidismo/diagnóstico , Antitireóideos/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico
19.
Eur J Nucl Med Mol Imaging ; 51(4): 1060-1069, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38008728

RESUMO

PURPOSE: To examine whether adherence to a low-iodine diet (LID) enhances the therapeutic efficacy of radioiodine therapy (RAI) in Graves' hyperthyroidism (GH) in iodine-rich areas. METHODS: We retrospectively evaluated 185 patients with GH from Aichi (n = 114) and Hokkaido (n = 71) Prefectures. Patients aged ≥ 18 years with GH who underwent RAI between December 2012 and March 2022 were divided into subgroups based on pretreatment with anti-thyroid drug (ATD) or potassium iodide (KI). Patients were followed up with LID from 18 days (group A) or 7 days (group H) before RAI to 3 days after RAI. The dose of radioactive iodine 131 (131I) was adjusted to deliver > 100 Gy to the thyroid. The associations between urinary iodine concentration on UIC2 vs. 24hRU and UIC2 vs. the 1-year RAI success rate (SR) were investigated. RESULTS: Compared with UIC1, UIC2 was significantly decreased in all subgroups (P < 0.01). An inverse correlation between UIC2 and 24hRU was observed in the four groups; however, the difference was insignificant. The SR in groups A and H was 85% and 89%, respectively. Univariate analysis revealed no association between UIC2 and SR in each group. Additionally, stratification of the 185 patients into quartiles using UIC2 yielded no significant differences in SR (p = 0.79). CONCLUSIONS: LID sufficiently reduced UIC in patients undergoing RAI. Although a lower UIC2 may increase 24hRU, it did not increase the success of RAI. The benefit of LID in enhancing the efficacy of RAI in GH treatment remains uncertain.


Assuntos
Doença de Graves , Hipertireoidismo , Iodo , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo/efeitos adversos , Iodo/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Doença de Graves/radioterapia , Doença de Graves/tratamento farmacológico , Dieta , Potássio , Resultado do Tratamento
20.
J ASEAN Fed Endocr Soc ; 38(2): 135-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38045669

RESUMO

Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves' disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs' formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.


Assuntos
Fraturas do Fêmur , Doença de Graves , Humanos , Feminino , Fraturas do Fêmur/induzido quimicamente , População do Leste Asiático , Fêmur , Povo Asiático , Doença de Graves/tratamento farmacológico
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