The acidobasic and complexing properties of 1-methyl-2-mercaptoimidazole (Methimazole, an anti-thyroid drug) were investigated. The pKa 11.49 ± 0.03 was estimated by molecular absorption spectroscopy (I = 0.10 M NaCl, t = 25.0 ± 0.1 °C). This value is in good agreement with the value 11.58 ± 0.05, obtained using the solvent-extraction technique. Theoretical (LFER and quantum chemical calculations) and experimental (1H/13C NMR spectroscopy) methods confirmed that the ligand prefers to be in the thion form, and the proton dissociation takes place on the nitrogen atom. Using glass electrode potentiometry, the complexation of the Pd(II) ion by the methimazole ligand occurs without the participation of protons. The best chemical model considers the [Pd(HL)]2+, [Pd(HL)2]2+ and [Pd(HL)3]2+ complex species, whose stability constants were also determined using spectroscopy and capillary zone electrophoretic (CZE) measurements. The metal complexes dissociate at -log [H+] > 7, where an uncharged palladium(II) hydroxide is formed. The formation kinetics of the palladium(II) complex with methimazole were studied in perchloric and hydrochloric acids (I = 1.00 M, t = 15-40 °C) and the determined rate constants and activation parameters are consistent with literature values determined for the reactions of the Pd(II) ion with thiourea derivatives. The rate constants decrease by two orders of magnitude in both media, which can be assigned to a lower tendency of the chloride ion to dissociate from the [PdCl4]2- complex species than the water molecule from the [Pd(H2O)4]2+ ion. The presented results can be utilized for the design of new Pd and Pt metallodrugs.

• Klíčová slova
• Anti-thyroid drug (methimazol, tapazol): 1-methyl-2-mercaptoimidazole, Complexation properties, Equilibria/kinetics, Metallodrug, Pd(II) ion, Protonation,
• MeSH
• kinetika MeSH
• komplexní sloučeniny * chemie   chemická syntéza   MeSH
• methimazol * chemie   MeSH
• palladium * chemie   MeSH
• termodynamika * MeSH
• thyreostatika chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• komplexní sloučeniny * MeSH
• methimazol * MeSH
• palladium * MeSH
• thyreostatika MeSH

Hyperthyreoidism is a clinical manifestation of excessive production of thyroid hormones. In most cases pacient ´s condition allows ambulant treatment. Rarely, it can develop into an acute, life- threatening thyrotoxic crisis which has to be treated in the intensive care unit. Main therapy includes antithyroid medication, corticosteroids, beta- blockers and rehydratation, mostly parenteral. If initial treatment fails, plasmapheresis provides effective strategy. Antithyroid medication may come with side effects as rash, digestive issues, joint pain.Agranulocystosis or acute liver lesion which leads to liver failure belong among the most severe ones. In this case we report a pacient with thyrotoxic crisis, atrial fibrilation which led to ventricular fibrilation, cor thyreotoxicum. The treatment was complicated by febrile neutropenia.

• Klíčová slova
• Lugol solution, agranulocytosis, hyperthyreoidism, hyperthyroidism, thyrotoxic crisis, total thyreoidectomy,
• MeSH
• febrilní neutropenie * komplikace   farmakoterapie   MeSH
• hypertyreóza * komplikace   MeSH
• lidé MeSH
• thyreostatika terapeutické užití   MeSH
• tyreotoxická krize * farmakoterapie   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• thyreostatika MeSH

BACKGROUND: Familial non-autoimmune hyperthyroidism is a rare disease caused by germline activating variants in the thyroid-stimulating hormone receptor (TSHR) gene. The c.1856A > G (p.Asp619Gly) pathogenic variant has been described in cases of toxic adenoma but never before, to our knowledge, in a case of familial non-autoimmune hyperthyroidism. PATIENT FINDINGS: A 3-year-old boy was admitted for acute gastroenteritis presenting with goiter and tall stature. Laboratory findings revealed peripheral hyperthyroidism and negativity for thyroid autoantibodies. Antithyroid drug treatment was effective, but relapses occurred shortly after attempts to decrease the drug dose. As the boy's father and paternal grandmother also experienced relapsing hyperthyroidism manifesting in early childhood, genetic testing of TSHR was indicated. The c.1856A > G (p.Asp619Gly) pathogenic variant was found in all three affected family members. Functional in vitro characterization of the variant verified that it enhances constitutional activation of the receptor, leading to increased production of cyclic adenosine monophosphate. Total thyroidectomy was indicated in the boy due to an unsatisfactory prognosis. Due to persistent positive thyroglobulin serum concentration, a diagnostic radioiodine scan was performed approximately 2 years later. Residual thyroid tissue was revealed; therefore, radioiodine ablative therapy was performed. Despite adequate thyroxine substitution over a long period of follow-up, TSH remained suppressed. CONCLUSIONS: Unlike Graves' disease, familial non-autoimmune hyperthyroidism cases present with antithyroid drug-dependence. Not ultrasound but positive thyroglobulin serum concentration indicated residual thyroid tissue. Early detection of residual thyroid tissue and radioiodine ablation prevented the subject from experiencing relapsing hyperthyroidism and undergoing unnecessary repeated surgery. Life-long hormone substitution should be adjusted to free thyroxine rather than TSH serum concentrations.

• Klíčová slova
• Activating TSHR pathogenic variant, Case report, Familial non-autoimmune hyperthyroidism, Functional study, Radioiodine ablative treatment, Repeated thyroid surgery,
• MeSH
• Gravesova nemoc * MeSH
• hypertyreóza * genetika   MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• předškolní dítě MeSH
• radioizotopy jodu MeSH
• receptory thyreotropinu genetika   metabolismus   MeSH
• thyreoglobulin chemie   MeSH
• thyreostatika farmakologie   MeSH
• thyreotropin chemie   MeSH
• thyroxin metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• radioizotopy jodu MeSH
• receptory thyreotropinu MeSH
• thyreoglobulin MeSH
• thyreostatika MeSH
• thyreotropin MeSH
• thyroxin MeSH

The knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.

• MeSH
• dánio pruhované MeSH
• embryo nesavčí účinky léků   metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• geneticky modifikovaná zvířata MeSH
• hydrofobní a hydrofilní interakce MeSH
• laboratorní automatizace * MeSH
• luminescentní proteiny genetika   metabolismus   MeSH
• počítačové zpracování obrazu MeSH
• preklinické hodnocení léčiv metody   MeSH
• štítná žláza účinky léků   metabolismus   MeSH
• thyreostatika farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• luminescentní proteiny MeSH
• thyreostatika MeSH

Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

• MeSH
• amiodaron škodlivé účinky   MeSH
• dospělí MeSH
• fibrilace síní farmakoterapie   MeSH
• glukokortikoidy terapeutické užití   MeSH
• hormony štítné žlázy MeSH
• hypertyreóza chemicky indukované   terapie   MeSH
• hypotyreóza chemicky indukované   farmakoterapie   MeSH
• kardiologie MeSH
• kardiovaskulární systém MeSH
• lidé MeSH
• methimazol terapeutické užití   MeSH
• radioizotopy jodu terapeutické užití   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• srdeční selhání MeSH
• thyreostatika terapeutické užití   MeSH
• thyroxin terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amiodaron MeSH
• glukokortikoidy MeSH
• hormony štítné žlázy MeSH
• methimazol MeSH
• radioizotopy jodu MeSH
• thyreostatika MeSH
• thyroxin MeSH

BACKGROUND: Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. METHODS: 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. RESULTS: Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. CONCLUSIONS: Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

• MeSH
• apolipoprotein A-I krev   izolace a purifikace   MeSH
• apolipoprotein B-100 krev   izolace a purifikace   MeSH
• autoimunitní tyreoiditida MeSH
• dospělí MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• Hashimotova nemoc krev   farmakoterapie   MeSH
• hypertyreóza krev   farmakoterapie   MeSH
• LDL-cholesterol krev   izolace a purifikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny VLDL krev   izolace a purifikace   MeSH
• methimazol terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thyreostatika terapeutické užití   MeSH
• thyroxin terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• APOA1 protein, human MeSH Prohlížeč
• APOB protein, human MeSH Prohlížeč
• apolipoprotein A-I MeSH
• apolipoprotein B-100 MeSH
• LDL-cholesterol MeSH
• lipoproteiny VLDL MeSH
• methimazol MeSH
• thyreostatika MeSH
• thyroxin MeSH

• MeSH
• agranulocytóza chemicky indukované   MeSH
• Gravesova nemoc farmakoterapie   MeSH
• lidé MeSH
• radioizotopy jodu * MeSH
• thyreostatika škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH
• Názvy látek
• radioizotopy jodu * MeSH
• thyreostatika MeSH

INTRODUCTION: Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit. PATIENTS AND METHODS: We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU). RESULTS: Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8). CONCLUSION: Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

• MeSH
• agranulocytóza chemicky indukované   MeSH
• dospělí MeSH
• Gravesova nemoc komplikace   farmakoterapie   radioterapie   MeSH
• karbimazol aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• methimazol aplikace a dávkování   škodlivé účinky   MeSH
• propylthiouracil aplikace a dávkování   škodlivé účinky   MeSH
• radioizotopy jodu * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• thyreostatika aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• karbimazol MeSH
• methimazol MeSH
• propylthiouracil MeSH
• radioizotopy jodu * MeSH
• thyreostatika MeSH

Antithyroid drugs are relatively simple molecules known as thionamides, which contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure. Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one) and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid drugs used in the United States. Methimazole is used in most of Europe and Asia, and carbimazole - methimazole analogue, is used in the United Kingdom and parts of the former British Commonwealth. Their primary effect is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin and is an important step in the synthesis of thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or carbimazole), can block the conversion of thyroxine to triiodothyronine within the thyroid and in peripheral tissues. Antithyroid drugs may have clinically important immunosuppressive effects. Side effects of thionamides are usually mild, serious untoward effects are observed in < 5% of cases, more frequently during the initial phases of treatment, when the drug daily dose is higher.

• MeSH
• hormony štítné žlázy krev   MeSH
• hypertyreóza krev   farmakoterapie   MeSH
• karbimazol škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• methimazol škodlivé účinky   terapeutické užití   MeSH
• propylthiouracil škodlivé účinky   terapeutické užití   MeSH
• thyreoglobulin krev   MeSH
• thyreostatika škodlivé účinky   chemie   terapeutické užití   MeSH
• thyroxin krev   MeSH
• trijodthyronin krev   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• hormony štítné žlázy MeSH
• karbimazol MeSH
• methimazol MeSH
• propylthiouracil MeSH
• thyreoglobulin MeSH
• thyreostatika MeSH
• thyroxin MeSH
• trijodthyronin MeSH

A sensitive and selective analytical method for the determination of four thyreostats (tapazol, thiouracil, methylthiouracil and propylthiouracil) in cow's milk, lamb's milk, and goat's milk was developed and validated according to 2002/657/EC criteria. Proteins in milk samples were precipitated by acetonitrile and analytes were derivatised with 3-iodobenzylbromide. Afterwards, derivatives were separated from the matrix by liquid-liquid extraction with ethyl acetate as an organic solvent and analysis was carried out using LC-MS/MS in a positive electrospray mode. The method provides, for all determined analytes, decision limits CCα below 1 ng ml(-1) and a detection capability CCβ value below 1.5 ng ml(-1). The stability of analytes in sample extracts stored at various conditions was also tested and evaluated.

• MeSH
• chromatografie kapalinová metody   MeSH
• mléko chemie   MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• thyreostatika analýza   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH
• Názvy látek
• thyreostatika MeSH