Epilepsy associated with Graves' disease: Report of two cases.

We present two cases of epilepsy associated with Graves' disease. Case 1 is a 22-year-old woman. She had three epileptic seizures and was diagnosed with idiopathic generalized epilepsy. She was treated with valproic acid (VPA). She was later diagnosed with Graves' disease, and treated with antithyroid medication (thiamazole). We added a thyroid medication (levothyroxine) because of a decrease in free thyroxine observed with antithyroid medication. Case 2 is an 18-year-old woman. She had three epileptic seizures and was diagnosed with juvenile myoclonic epilepsy and treated with VPA. Then, she was diagnosed with Graves' disease and was treated with thiamazole. Levothyroxine was added due to low fT4 induced by thiamazole. Due to poor compliance with antithyroid medication, the thyroid functional status was not stable. Both patients became seizure-free and euthyroid after VPA and thiamazole treatments.

Progressive Thymic Hyperplasia With Graves' Disease: A Case Report.

We treated a 36-year-old man with thymic hyperplasia complicated with Graves' disease. Thymic hyperplasia was observed on thoracic computed tomography (CT) three months after the onset of thyrotoxicosis symptoms. One month after thiamazole initiation, he displayed drug-induced liver injury and underwent a total thyroidectomy. Seven months after surgery, we observed a dramatic reduction of thymic size associated with normalizing the soluble interleukin-2 receptor (sIL-2R) levels. The rapid development of hyperplasia after the onset of thyrotoxicosis and the restoration in thymus volume after total thyroidectomy associated with suppression of sIL-2R, in this case, suggests the complexity of the pathogenesis of thymic hyperplasia in the thyrotoxicosis.

Syringe Paper-Based Analytical Device for Thiamazole Detection by Hedysarum Polysaccharides-Mediated Silver Nanoparticles.

In this paper, silver nanoparticles (AgNPs) were successfully green-synthesized for the first time using Hedysarum polysaccharide (HPS) as a reducing agent, stabilizer, and modifier (HPS-AgNP). Thiamazole could induce the aggregation of HPS-AgNPs in the residue on a cellulose membrane. A syringe paper-based analytical device was creatively established to ensure the tightness, stability, and good repeatability of the test. The color information remaining on the cellulose membrane was converted into gray values using ImageJ software. Hence, the linear regression curve for thiamazole was established as y = 1 + 0.179x with a detection limit (LOD) of 24.6 nM in the relatively wide range of 0.1~10 µM. This syringe paper-based analytical device was successfully applied to the biological samples.

Radioiodine uptake after monotherapy with potassium iodide in patients with Graves' disease.

The effect of potassium iodide (KI) on radioiodine uptake (RAIU) before radioisotope therapy in Graves' disease (GD) patients was investigated. A total of 82 patients who had been treated with KI monotherapy before 24-hour RAIU (24 h RAIU) were evaluated and 354 of those who had been treated with thiamazole (MMI) monotherapy were extracted from the 1,130 GD patients who were identified as having had appropriate iodine restriction based on urinary iodine excretion. Urinary iodine excretion (UIE) <200 µg/day was confirmed in all subjects. Propensity score-matching was performed to identify the difference in 24 h RAIU between the KI group and the MMI group. In addition, multiple regression analysis was performed to evaluate related to 24 h RAIU. Propensity score-matching resulted in 57 matched patients in each group. After matching, 24 h RAIU was still significantly lower in the KI group than in the MMI group (median 53% (interquartile range 47-61%) vs. 63% (56-66%); p = 0.001). In addition, KI monotherapy was weakly negatively correlated with 24 h RAIU, whereas the female sex and FT3 were very weakly positively correlated on multiple regression analysis. The results suggest that KI monotherapy likely suppressed 24 h RAIU more than MMI monotherapy in GD patients with appropriate iodine restriction, given the difference in the mechanism of hormone suppression.

Evaluation of potential thiamazole exposure of owners of orally treated hyperthyroid cats.

OBJECTIVES: The objective of this study was to evaluate the presence of traces of thiamazole in the urine of owners of hyperthyroid cats treated with antithyroid drugs. METHODS: Urine was collected from 24 owners of hyperthyroid cats, five human patients treated with thiamazole and five healthy humans without any contact with antithyroid drugs. All owners of hyperthyroid cats were asked to fill out a questionnaire. Urine of hyperthyroid cats was collected by spontaneous micturition. All urine samples were stored at -20°C until analysis by ultra-high-performance liquid chromatography coupled to high-resolution quadrupole Orbitrap mass spectrometry. RESULTS: These owners were assessed to have a lot of contact with their cat. Adherence to antithyroid medication handling guidelines was rather poor. High concentrations of thiamazole were detected in all feline samples (median concentration 2818 ng/ml; range 104-15,127) and in the urine of all human patients treated with thiamazole (median concentration 4153 ng/ml; range 1826-5009). No thiamazole was detected in the urine of owners of hyperthyroid cats (limit of detection 3.88 ng/ml; limit of quantification 11.75 ng/ml). CONCLUSIONS AND RELEVANCE: The results regarding the potential exposure of owners of hyperthyroid cats to antithyroid drugs are reassuring. Nevertheless, prudence is still warranted when administering antithyroid drugs. Whether these results can be extrapolated to the use of transdermal application requires further investigation.

A case of membranous nephropathy secondary to asymptomatic Graves' disease.

Although cases of secondary membranous nephropathy associated with autoimmune thyroid disease (AITD) have been reported, most of them, if not all, present with symptomatic thyroid disease. Here we report an asymptomatic case of AITD complicated with secondary membranous nephropathy. A 16-year-old girl was referred to our institute because of proteinuria found by an annual medical checkup. Urinalysis showed a urinary protein creatinine ratio (UPCR) of 3.0 g/gCre. Blood examination revealed that she had Graves' disease, although she did not have any symptoms of hyperthyroidism such as weight loss, anxiety, tremor, tachycardia, or eye symptoms. In a kidney biopsy, periodic acid silver-methenamine staining showed spike formation in the basement membrane. Electron microscopy showed electron-dense deposits on the epithelial side of the glomerular basement membrane. Immunofluorescent staining showed co-localization of thyroid peroxidase and IgG deposition along the glomerular capillary walls. A diagnosis of membranous nephropathy secondary to asymptomatic Graves' disease was made on the basis of results of the examinations. Treatment with thiamazole added to enalapril improved proteinuria (reduction of UPCR to 0.83 g/gCr) and hypoalbuminemia. Consideration should be given to the possibility of AITD in differential diagnosis of etiologies of membranous nephropathy even when typical symptoms of AITD are lacking.

Survey of the actual administration of thiamazole for hyperthyroidism in Japan by the Japan Thyroid Association.

To clarify the actual administration of thiamazole (MMI), the first choice of antithyroid drugs, the actual therapy provided by the Japan Thyroid Association (JTA) members for the following conditions was surveyed. The subjects included adult patients, pregnant women, and pediatric patients with Graves' disease who visited each medical institution from September 2019 to February 2020. Initial doses, frequency of administration, maintenance doses, maximum doses, consultation intervals for pregnant women, and dosages administrated to breastfeeding mothers were surveyed. The total number of cases collected was 11,663. Administration of 15 mg once a day was the most common initial therapy, constituted 74.4% (2,526/3,397 cases) of adults, 33.8% (44/130) of pregnant women, and 50.8% (61/120) of children. The maintenance dose before discontinuation was equivalent to 2.5 mg/day in 52.3% (3,147/6,015). The most common maximum dose for adults and children was 30 mg/day, administrated to 57.5% of adults (223/388) and 59.6% (28/47) of children; for pregnant women, it was 15 mg/day, administrated to 71.1% (27/38). The most common consultation interval for pregnant women was every four weeks (32.1%, 341/1,063). In lactating mothers, the dose was 10 mg/day or less in 366 of 465 cases (78.7%). Breastfeeding was also allowed 4-6 hours after the administration of 15-20 mg/day in 69 patients (14.8%). Breastfeeding was prohibited in 26 patients (5.6%). In conclusion, initial MMI therapy was started with 15 mg once a day in most patients, and MMI was also administrated to lactating mothers following the Graves' disease treatment guidelines by the JTA.

Prevention of Iodinated Contrast Media-Induced Hyperthyroidism in Patients with Euthyroid Goiter.

INTRODUCTION: Iodinated contrast media (ICM)-induced hyperthyroidism is an underestimated, potentially severe condition; however, its prevention has not been sufficiently investigated. The aim of this study was to evaluate the influence of ICM on thyroid status, the advantages of prophylactic therapy for iodine-induced hyperthyroidism (IIH) in patients with euthyroid goiter and cardiovascular comorbidities, and the association between the incidence of IIH and thyroid volume. METHODS: Thirty-six euthyroid patients undergoing procedures involving ICM administration were divided into 2 groups: the first group (n = 13) received prophylactic treatment with thiamazole or thiamazole combined with sodium perchlorate during ICM exposure; the second group (n = 23) did not receive prophylaxis. Thyroid-stimulating hormone levels were evaluated before and after ICM, and thyroid hormone levels were assessed after ICM at different points in time. The morphology of the thyroid was evaluated by ultrasonography. RESULTS: Twenty-one patients (58%) developed hyperthyroidism after ICM. Hyperthyroidism was observed more frequently in the group without prophylactic treatment than in the group with prophylaxis (65 vs. 15%, respectively; p = 0.006). No cases of overt hyperthyroidism were observed in the group receiving thiamazole with sodium perchlorate. IIH persisted for a median time of 52.5 days. Larger thyroid volume was associated with a significantly higher occurrence of ICM-induced hyperthyroidism (p = 0.04). CONCLUSIONS: Patients with euthyroid goiter receiving ICM are at risk of developing hyperthyroidism. The occurrence of hyperthyroidism after ICM in euthyroid patients with goiter is higher in those with larger thyroid volume. The frequency of ICM-induced hyperthyroidism in euthyroid patients with goiter is lower in those receiving prophylactic therapy with thiamazole in monotherapy or in combination with sodium perchlorate than in those not receiving prophylactic treatment.

Effect of thiamazole on kainic acid-induced seizures in mice.

Kainic acid (KA) induced epileptic seizures in mice is a commonly used experimental model of epilepsy. Previous studies have suggested the roles of various neurotransmitters and oxidative stress in KA-induced seizures. An important role of hypothyroidism has also been suggested in epilepsy. Thiamazole (TZ) is an anti-hyperthyroid drug with antioxidant property. This study reports the effect of TZ on KA-induced epileptic seizures in mice, produced by intraperitoneal (IP) injection of KA (18 mg/kg). Prior to KA injection, the animals were treated with TZ (12.5, 25 and 50 mg/kg IP). Our results showed that in KA alone group, about half of the animals developed seizures. Pre-treatment of mice with TZ significantly increased the frequency of seizures in dose-dependent manner. Administration of TZ significantly reduced the latency time and aggravated the severity of seizures. TZ also increased the mortality in KA-treated mice. Striatal dopamine and serotonin levels were markedly increased in KA alone treated mice, which were not significantly affected by TZ treatment. Among the indices of oxidative stress, we observed a significant reduction in cerebral vitamin E whereas the levels of cerebral malondialdehyde and conjugated dienes were significantly increased in animals with high severity of seizures. In conclusion, TZ potentiated the frequency and severity of experimental seizure in mice. There is a possibility of altered metabolism of KA in presence of TZ that might have potentiated the toxicity of KA. These findings suggest a caution while administering anti-hyperthyroid drugs in epileptic seizures.

[Iodine-induced thyroid dysfunction]. / Jodinduzierte Schilddrüsendysfunktion.

BACKGROUND: Iodine-induced thyroid dysfunctions are, despite their rare occurrence, important clinical syndromes. Their immediate recognition can avoid serious consequences. Important triggers can be iodine-containing contrast agents, amiodarone or iodine-containing disinfectants. Iodine-induced hypothyroidism and hyperthyroidism need to be distinguished, whereby the former is usually self-limiting. OBJECTIVES: The aim of this article is to present current knowledge on the pathogenesis, therapy, and prophylaxis of iodine-induced thyroid dysfunction. MATERIALS AND METHODS: We performed a literature search of current publications and linked them to daily clinical experience. RESULTS AND CONCLUSION: In iodine-induced hyperthyroidism, antithyroid drugs and perchlorate are primarily used to decrease thyroid hormone synthesis and further iodine uptake into the thyroid. For the prophylaxis of x­ray contrast agent-induced hyperthyroidism, perchlorate can be administered in high-risk settings in combination with antithyroid drugs, if possible starting one day before the iodine exposure.

Detection of Ag+ ions via an anti-aggregation mechanism using unmodified gold nanoparticles in the presence of thiamazole.

The present study proposed a novel and highly selective and sensitive method for Ag+ ion detection based on gold nanoparticles (AuNPs) anti-aggregation. Thiamazole can induce AuNPs aggregation due to electrostatic interactions, which result in color transitions in the AuNPs solution from red to blue. However, the presence of Ag+ ions results in the preferential combination of the pyridinic nitrogen of thiamazole with the Ag+ ions. In addition, the Ag+ ions oxidize the sulfhydryl groups(-SH), which inhibit AuNPs aggregation and prompt a color change from blue to red. As a result, the present study established a method for Ag+ ion determination by AuNPs-thiamazole colorimetric probe based on the aforementioned anti-aggregation mechanism. The probe dynamic range was easily tuned via adjustments of the thiamazole amount. The relationship between the Ag+ concentration and AuNPs aggregation was monitored by ultraviolet-visible light (UV-Vis) spectroscopy at a dynamic range of 0.1 nM-9 µM and at a detection limit of 0.042 nM. The river water and tap water recovery analysis validated the successful operation of this colorimetric sensor in environmental monitoring.

[Thiamazole-induced arthritis]. / Thiamazol-induzierte Arthritis.

We report the case of a 42-year-old male patient with acute onset of asymmetrical polyarthritis of the medium and large joints as well as fever and elevated serological inflammation markers. The symptoms began shortly after initiation of thiamazole treatment for newly diagnosed Graves' disease. Antithyroid arthritis syndrome (AAS) is a rare but serious adverse side effect of antithyroid treatment with thioamides such as thiamazole. Clinically, AAS may present with myalgia, arthralgia, fever, exanthema and polyarthritis. In the case of suspected AAS, when possible the thionamide medication should be rapidly discontinued or modified in consultation with the endocrinologist. In some cases anti-inflammatory therapy with NSAID or corticosteroids may be required for symptom control.

Graves' disease in children.

R1 The diagnosis of Graves' disease in children is based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies. 1/+++. R2 Thyroid ultrasound is unnecessary for diagnosis, but can be useful for assessing the size and homogeneity of the goiter. 2/+. R3. Thyroid scintigraphy is not required for the diagnosis of Graves' disease. 1/+++. R4. The measurement of T4L and T3L levels is not necessary for the diagnosis of Graves' disease in children but can be useful for the management and assessment of prognosis. 1/++. R5. In the absence of TSH receptor autoantibodies, the possibility of genetically inherited hyperthyroidism must be considered. 1/++. R6. Drug therapy is the primary line of treatment for children and consists of imidazole, carbimazole or thiamazole, with an initial dosage of 0.4 to 0.8mg/kg/day (0.3 to 0.6mg/kg/day for thiamazole) depending on the initial severity, up to maximum of 30mg. 1/++. R7. Propylthiouracil is contraindicated for children with Grave's disease. 1/+++. R8. Before starting treatment, it may be useful to perform a CBC in order to assess the degree of neutropenia caused by hyperthyroidism. It is not necessary to perform systematic CBCs during follow-up. 2/+. R9. An emergency CBC should be performed if symptoms include fever or angina. If neutrophil counts are <1000/mm3, synthetic antithyroid therapy should be discontinued or decreased and may be permanently contraindicated in severe (<500) and persistent neutropenia. Otherwise treatment may be resumed. 1/++. R10. Transaminases levels should be measured before initiating treatment. Systematic monitoring of liver function is not consensually validated. 2/+. R11. In cases of jaundice, digestive disorders or pruritus, measuring liver enzymes (AST, ALT), total and conjugated bilirubin and alkaline phosphatases is indicated. 1/++. R12. Patients and parents should be informed of the possible side effects of antithyroid agents. 1/+. R13. Therapeutic education of parents and children is important in ensuring the best possible treatment compliance. 2/++. R14. Given the specificities involved in the treatment of Graves' disease in children, medical care should be provided by a specialist accustomed to treating endocrinopathies in pediatric patients. 2/+. R15. Depending on patient age, the severity of the disease at diagnosis and the persistence of anti-TSH receptor antibodies, the initial course of treatment must take place over an extended period of 3 to 6 years. R16.The anticipated success rates of medical treatment (50% of patients in remission following several years of treatment) should be explained to the family and the child. The possibility that radical treatment may be required in case of failure or intolerance of medical treatment should also be discussed. 1/++. R17.In females with Graves' disease, it is important to explain that they must undergo an assessment by an endocrinologist before planning future pregnancies, from the start of pregnancy and during the course of pregnancy. This is true in all female patients, even those in remission after medical treatment, or those who have undergone radical treatment. R18.Indications for a radical treatment can arise in cases of: 1/+: contraindication to antithyroid agents; poorly controlled hyperthyroidism due to lack of compliance; relapse despite prolonged medical treatment; a request made by the family and child for personal reasons. R19.Surgery is the radical method of treatment used in children under 5 years of age, or in cases of very large, nodular, or compressive goiters. 2/++. R20. The surgeon's experience in dealing with thyroidectomies in children is likely to be the most significant determining factor in limiting the morbidity of the procedure (alongside any collaboration between a pediatric surgeon and an adult surgeon). 1/++. R21 When radical treatment is indicated, I-131 treatment may be discussed after 5 years (but more often after puberty), if the goiter is not too large. Experience from monitoring Graves' disease in North American children is reassuring. 1/++.

Iodine-enhanced ultrasound degradation of sulfamethazine in water.

This study investigated sulfamethazine (SMT) ultrasound degradation, enhanced by iodine radicals, generated by potassium iodide (KI) and hydrogen peroxide (H2O2) in situ. The results showed that the ultrasound/H2O2/KI (US/H2O2/KI) combination treatment achieved an 85.10 ±â€¯0.45% SMT removal (%) in 60 min under the following conditions: pH = 3.2, ultrasound power of 195 W, initial SMT concentration of 0.04 mmol·L-1, H2O2 concentration of 120 mmol·L-1, and KI concentration of 2.4 mmol·L-1. UV-Vis spectrophotometric monitoring of molecular iodine (I2) and triiodide (I3-) revealed a correlation between the SMT degradation and the iodine change in the solution. Quenching experiments using methanol, t-butanol and thiamazole as radical scavengers indicated that iodine radicals, such as I and I2-, were more important than hydroxyl radicals (HO) for SMT degradation. SMT degradation under the US/H2O2/KI treatment followed pseudo-first order reaction kinetics. The activation energy (Ea) of SMT degradation was 7.75 ±â€¯0.61 kJ·mol-1, which suggested the reaction was controlled by the diffusion step. Moreover, TOC removal was monitored, and the obtained results revealed that it was not as effective as SMT degradation under the US/H2O2/KI system.

Familial Dysalbuminemic Hyperthyroxinemia that was Inappropriately Treated with Thiamazole Due to Pseudo-thyrotoxic Symptoms.

We herein report the case of a Japanese woman with familial dysalbuminemic hyperthyroxinemia (FDH) who was initially diagnosed with Graves' disease. Direct genomic sequencing revealed a guanine to cytosine transition in the second nucleotide of codon 218 in exon 7 of the albumin gene, which then caused a proline to arginine substitution. She was finally diagnosed with FDH, which did not require treatment. FDH is - superficially - an uncommon cause of syndrome of inappropriate secretion of thyrotropin (SITSH) in Japan. A misdiagnosis of pseudo-hyperthyroidism will lead to inappropriate treatment. Thus, physicians should strongly note the possibility of FDH as a differential diagnosis of SITSH.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

BACKGROUND: Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. CASE PRESENTATION: A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. CONCLUSIONS: The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

[Hyperthyroid and acute tonsillitis in a 23-year-old woman]. / Hyperthyreose und akute Tonsillitis bei einer 23-jährigen Patientin.

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G­CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

Sunitinib-induced thyrotoxicosis - a not so rare entity.

BACKGROUND/AIM: The tyrosine kinase inhibitor (TKI) sunitinib malate is nowadays a standard first-line treatment option for patients with metastatic clear-cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the incidence and clinical course of thyrotoxicosis in our cohort of patients treated with sunitinib. PATIENTS AND METHODS: Medical records of all patients treated with first-line sunitinib for mRCC at our Institution between November 2008 and March 2014 were retrospectively reviewed. Thyroid function was assessed after every 2 cycles of therapy, during the 2 weeks off period. RESULTS: Out of the 62 included patients, hypothyroidism has developed during therapy in 12 patients (19%) and it was preceded by thyrotoxicosis in 2 (3.2%). CONCLUSION: Sunitinib-induced thyrotoxicosis (SIT), a not so rare entity, was followed by hypothyroidism. The patterns of occurrence and possible significance of SIT, as predictive marker of better treatment response to sunitinib, need to be validated in further studies.