Case report: Propylthiouracil-induced serious side effect: Perinuclear antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis?

INTRODUCTION: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease characterized by the inflammation and destruction of small blood vessels and circulating ANCAs. Drugs such as antithyroid drugs (ATDs), especially propylthiouracil (PTU), have been used for the production of ANCAs and cause the development of drug-induced AAV. The pathogenesis of this disease is unclear but could be related to the physiological processes affecting the degradation of neutrophil extracellular traps (NETs). At present, PTU is widely used in patients with Graves' disease (GD) who are preparing for pregnancy and whose condition has not been controlled. Once drug-induced AAV has occurred with important organ damage, considering NETs have a significant role in the immune system, whether the cessation of drugs could stop the progression of organ damage is unclear, and a consensus regarding standard treatment has not been established. PATIENT CONCERNS: In this case report, a female patient who planned pregnancy was hospitalized with multiple joint pain, impaired renal function, and hematuria. Immunofluorescence of the renal biopsy demonstrated spherical and diffuse mesangial distribution of IgA (3+). Autoimmune serology demonstrated positivity for autoantibodies against p-ANCA and an anti-MPO titer 74.72 RU/mL. DIAGNOSIS: She was diagnosed with PTU-induced p-ANCA-associated and IgA-associated vasculitis (IgAV). INTERVENTIONS: The patient accepted low doses of glucocorticoid, immunosuppressive therapy and RAI treatment. OUTCOMES: Both her kidney function and thyroid function remained were on the mend. CONCLUSION: The authors believe that this type of patient needs to fully consider their pregnancy preparation needs, suspend pregnancy when a small chance of GD remission is indicated, and avoid the use of drugs with reproductive toxicity and other serious adverse events. The multidisciplinary combination therapy of low-dose glucocorticoids and immunosuppressants combined with iodine radiotherapy is one reasonable scheme. At the same time, it is necessary to eliminate the organ damage caused by other reasons. This report provides a clinical treatment basis for patients with drug-induced vasculitis manifestations who cannot receive an accurate diagnosis.

Graves-PCD: protocol for a randomised, dose-finding, adaptive trial of the plasma cell-depleting agent daratumumab in severe Graves' disease.

INTRODUCTION: Severe Graves' disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating hormone receptor-stimulating antibodies (TRAb), which are secreted from plasma cells. The human anti-CD38 monoclonal antibody daratumumab was developed to target plasma cells which express high levels of CD38, and is currently licensed for treatment of the plasma cell malignancy, myeloma. However, it can also deplete benign plasma cells with the potential to reduce TRAb and alter the natural history of severe Graves' disease. This study aims to establish proof of concept that daratumumab has efficacy in patients with severe Graves' disease and will provide important data to inform a choice of dosing regimen for subsequent trials. METHODS AND ANALYSIS: The Graves-PCD trial aims to determine if daratumumab modulates the humoral immune response in patients with severe Graves' disease, and if so, over what time period, and to find an optimal dose. It is a single-blinded, randomised, dose-finding, adaptive trial using four different doses of daratumumab or placebo in 30 adult patients. Part 1 of the trial is dose-finding and, following an interim analysis, in part 2, the remaining patients will be randomised between the chosen dose(s) from the interim analysis or placebo. The primary outcome is the percentage change in serum TRAb from baseline to 12 weeks. ETHICS AND DISSEMINATION: The trial received a favourable ethical opinion from London-Hampstead Research Ethics Committee (reference 21/LO/0449). The results of this trial will be disseminated at international meetings, in the peer-reviewed literature and through partner patient group newsletters and presentations at patient education events. TRIAL REGISTRATION NUMBER: ISRCTN81162400.

Gut microbiome in the Graves' disease: Comparison before and after anti-thyroid drug treatment.

While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment.

Pearls & Oy-sters: Thyroid-Associated Ophthalmopathy and Transient Neuromuscular Junction Disorder Due to Graves Disease.

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.

Apathetic Graves' disease with severe hepatic and renal dysfunction induced by COVID-19 infection: Case report and literature review.

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.

Radioactive Iodine Therapy of Graves' Disease in Patients Pretreated With Methimazole Without Radioiodine Uptake for Dose Estimation.

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.

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience.

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.

Predictive factors for the outcome of radioiodine therapy in patients with benign thyroid diseases.

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.

Effects of block-replace regimen in patients with autoimmune hypothyroidism converted to Graves' disease.

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.

Effect of previous administration of potassium iodine and different durations of low iodine diets for radioiodine therapy on the treatment of Graves' disease in iodine-rich areas.

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.

Comorbidity of Myasthenia gravis and Graves' disease as immune reconstitution-associated autoimmune disease in HIV infection: A case report and literature review.

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.

The Potential Role of Pyrroloquinoline Quinone to Regulate Thyroid Function and Gut Microbiota Composition of Graves' Disease in Mice.

Graves' disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD's intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

The influence of thionamides on intra-thyroidal uptake of 131I during radioiodine-131 treatment of Graves' disease.

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

Case Report of Graves' Disease in a 45-Year-Old Woman Secondary to Herceptin Treatment for Breast Cancer.

Graves' disease is the most common cause of thyrotoxicosis and is characterized by ophthalmopathy with proptosis, chemosis, or conjunctival injection; pretibial myxedema; and thyroid acropachy. It is an autoimmune disease that can be genetic or influenced by coexisting environmental factors such as exposure to anticancer drugs, including immune checkpoint inhibitors. The incidence rate of breast cancer is increasing due to rising awareness of risk factors and screening for breast cancer, and the mortality rate is decreasing due to recent advances in cancer treatment. However, there are side effects that are attributed to these treatment modalities, manifesting in various forms in breast cancer survivors, which are reflected in the patient in this case study.

[Clinical and immunological predictors of Graves' orbitopathy after radioiodine therapy of Graves' disease].

BACKGROUND: Data on the effect of 131I on the course of Graves' orbitopathy (GO) are contradictory. A number of studies indicate a deterioration in the course of GO against the background of RAIT, in other studies such a connection has not been established. Cytokines that regulate inflammation could potentially be biomarkers for assessing GO activity and predicting the course of GO after RAIT. AIM: The purpose of this study was to evaluate the dynamics of eye symptoms and analyze immunological parameters: cytokine TGF-ß1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, sIL-6R over time after RAIT, as possible predictors of GO activation. MATERIALS AND METHODS: The study included 59 patients (118 orbits) with GD in the state of euthyroidism and subclinical hyperthyroidism and low active and inactive GO, aimed at conducting RAIT. Concentrations of cytokine TGF-ß1, sTNFα-RI and sTNFα-R2, sIL-2R, sIL-6R, TSH receptor antibodies (rTSH-Ab), free thyroxine (FT4) and free triiodothyronine (FT3), -thyroid-stimulating hormone (TSH) in the blood serum were determined. Ultrasound examination of the thyroid gland, multispiral computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits was performed. The examination was carried out 3, 6, 12 months after the RAIT. RESULTS: The deterioration of the course of the GO (1-2 points according to CAS) was noted after 3 months. (32.5%) and to a lesser degree after 6 and 12 months (13.2% and 8.45%, respectively). Dynamics were not noted, approximately, in the same number of patients (40.5%, 41.5%, 45.8%, respectively). An improvement in the course of the GO was noted after 6 and 12 months (45.3, 45.8, respectively). After 3 and 6 months, the achievement of hypothyroidism and a significant increase in the level of rTSH-Ab were noted. In the analysis of cytokines and their receptors a significant decrease in the level of TGF-ß1 was noted after 3, 6 and 12 months. There was also a significant decrease in sTNF-R1 and sIL-2R at 3 and 6 months. The level of sTNFα-R2 significantly decreased 3 months after RAIT. The level of sIL-6R has not changed significantly. After 3 months in patients with positive dynamics of image intensification, the level of TGF-ß1 did not significantly change compared with the level before RAIT, in patients with worsening of the course of GO or without dynamics, the level of TGF-ß1 significantly decreased. After 6 months, there was the same trend, not reaching statistical significance. The IgG4 level and the IgG4/IgG ratio increased to 6 and 12 months, which corresponded to an increase in diplopia index. CONCLUSION: The main limiting factor in the conduct of RAIT is the activity of the autoimmune process in the orbits. Since patients with inactive (CAS 0-2) or low activity (CAS 3-4) GO were referred for RAIT, there was no pronounced activation of GO after RAIT. There was a slight deterioration in the course of GO by only 1-2 points according to CAS after 3 months. (32.5%) and to a lesser degree after 6 months (13.2%). In the study, it was found that the main predictors of the deterioration of the course of GO after RAIT are uncompensated hypothyroidism, a high level of rTSH-Ab and a decrease in the level of cytokine TGF-ß1.

The management of pediatric Graves' disease.

PURPOSE OF REVIEW: Graves' disease (GD) constitutes a significant proportion of thyroid disorders seen during childhood. Several specialties may be closely involved in the management of pediatric patients with GD and emerging research in each field contributes to variations in the approach over time. Here we review the recent literature on the management of the disease, with the hope that this can be a valuable resource for treating specialists who need to be continuously updated on new data obtained in relevant fields. RECENT FINDINGS: Genetic, postinfectious and environmental factors may play a role in the immunological pathophysiology of GD. Research performed during the COVID-19 pandemic supports that viral-induced immune dysregulation may be a possible trigger for the disease. The various current treatment options all have positive and negative factors to consider. Antithyroidal drug therapy (ATD) is generally recommended as the initial treatment, although remission rates are only 20-30% at 2 years and 75% at 9 years. Unfortunately, about half of patients will relapse within 1 year of discontinuing therapy. Radioactive iodine therapy (RAI) is an effective treatment option and can be considered in certain pediatric patients. There continues to be no definitive evidence that the doses used for GD lead to a higher risk of cancer. Surgical treatment via thyroidectomy is effective and safe when performed by a high-volume surgeon. Recent studies show improvement in quality-of-life after surgery in adolescents and young adults. Future medical treatment options for GD currently being studied include antigen-specific immunotherapy and monoclonal antibodies. SUMMARY: Although the future holds promising new therapeutic options for autoimmune diseases including GD, the current choices continue to be ATD, usually first-line, and definitive treatments including RAI and surgery. While all three offer the possibility of remission or cure, drug therapy and RAI have a possibility of relapse. Risks of each approach should be broached in detail with patients and their families, and the nuances of treating this disease specifically in children should be familiar to all treating providers.

Psychosis secondary to thyrotoxicosis that persisted post-thyroidectomy: a case report.

BACKGROUND: This case report is of a patient with psychosis secondary to thyrotoxicosis that persisted and reemerged after definitive treatment of thyroidectomy, which is a unique occurrence in the literature. CASE PRESENTATION: This patient is a male between 30 and 35 years of age with a history of Graves Disease and no past psychiatric history who was admitted to the hospital due to psychosis secondary to thyrotoxicosis. The thyrotoxicosis was treated with surgical removal, but the psychotic symptoms persisted after surgery and normalization of standard thyroid functional measures. The symptoms were of sufficient significance for inpatient psychiatric hospitalization, a rare occurrence. Ultimately after an extended stay in the psychiatric unit, the patient's symptoms stabilized with a second-generation antipsychotic, and the patient was discharged from the psychiatric unit. CONCLUSION: This case is evidence that the link between psychosis and hyperthyroidism is still poorly understood due to the patient's psychotic symptoms persisting after the definitive treatment of thyroidectomy and the fact that it required anti-psychotic medications for normalization.

The EANM guideline on radioiodine therapy of benign thyroid disease.

This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

[Alemtuzumab-induced Graves' disease].

Multiple sclerosis (MS) is a severe chronic autoimmune demyelinating disease of the central nervous system, mediated by Th1/Th17 lymphocytes as well as B lymphocytes, macrophages and other immune cells. Some patients with MS are treated with alemtuzumab, a monoclonal antibody against CD52+ cells, which belongs to the disease-modifying therapies (DMTs). The main effect of alemtuzumab is related to changes in immune recruitment. Alemtuzumab therapy can induce secondary autoimmunity against the background of immune rebalancing. The thyroid gland is generally involved in the autoimmune process. Graves' disease (GD) develops most often, followed by autoimmune thyroiditis.We present a clinical case of a patient with GD developed after alemtuzumab therapy for MS. The patient was referred to a radiologist at the Department of Radionuclide Therapy of Endocrinology Research Centre for radioiodine therapy (RAIT) due to relapse of thyrotoxicosis after anti-thyroid drug therapy for GD. The goal of treatment was achieved in 2 months, thyroid hormone therapy was initiated, against the background of this, there was compensation of thyroid function.