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

AIM: The aim of this study was to determine the prevalence of maternal hypothyroidism in the first trimester from 11 to 14 weeks of gestation according to the American Thyroid Association (ATA) guidelines from 2017 and to compare the rates for singleton and twin pregnancies. METHODS: A total of 4965 consecutive Caucasian singleton pregnancies and 109 Caucasian twin pregnancies were included in the investigation. Patients with a history of thyroid gland disorder were excluded. Subclinical maternal hypothyroidism was defined as a thyroid stimulating hormone (TSH) concentration above the 97.5th percentile and free thyroxine (fT4) within the range of a reference population of women at 11-14 weeks of gestation. Overt maternal hypothyroidism was defined as a TSH concentration above the 97.5th percentile and an fT4 below the 2.5th percentile of the reference population.TSH, fT4, and anti thyroid peroxidase antibody (TPOAb) were measured by immunochemiluminescent assays on an 16200 Abbott Architect analyzer. RESULTS: The prevalence of hypothyroidism for twin pregnancies was no higher than that for singleton pregnancies; 6.42% (7/109) vs. 5.32% (264/4965), respectively; P=0.61. All twin pregnancies were subclinical. Singleton hypothyroid pregnancies included 4.91% (244 cases) of subclinical and 0.41% (20 cases) of overt hypothyroidism. The prevalence of TPOAb positive hypothyroid women for twin pregnancies and singleton pregnancies was 71% (5/7) vs. 52% (137/264 cases), respectively but the differences were not statistically significant; P=0.31. CONCLUSION: Each first trimester screening center should establish its TSH and fT4 reference ranges. Our center had higher upper reference limits of TSH than that of the universally fixed limit of 2.5 mU/L, which led to a lower measured prevalence of maternal hypothyroidism. A large number of hypothyroid women were TPOAb positive.

• Klíčová slova
• gestation, hypothyroidism, immunoassay, pregnancy, thyroid disease,
• MeSH
• dospělí MeSH
• hypotyreóza krev   diagnóza   MeSH
• imunoanalýza metody   MeSH
• jodidperoxidasa imunologie   MeSH
• komplikace těhotenství krev   diagnóza   MeSH
• lidé MeSH
• protilátky metabolismus   MeSH
• první trimestr těhotenství MeSH
• retrospektivní studie MeSH
• těhotenství s dvojčaty fyziologie   MeSH
• těhotenství MeSH
• thyreotropin metabolismus   MeSH
• thyroxin metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH
• Názvy látek
• jodidperoxidasa MeSH
• protilátky MeSH
• thyreotropin MeSH
• thyroxin MeSH

Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron α and interleukin 2) cause autoimmune thyroiditis in 2-10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.Key words: bexarotene - endocrine complication - hypophysitis - immune checkpoint inhibitors - immunotherapy.

• MeSH
• antigen CTLA-4 antagonisté a inhibitory   MeSH
• antikarcinogenní látky škodlivé účinky   MeSH
• autoimunitní tyreoiditida chemicky indukované   MeSH
• bexaroten MeSH
• hypofyzitida chemicky indukované   MeSH
• hypotyreóza chemicky indukované   MeSH
• imunoterapie MeSH
• inhibitory proteinkinas škodlivé účinky   MeSH
• ipilimumab MeSH
• lidé MeSH
• monoklonální protilátky škodlivé účinky   MeSH
• nádory farmakoterapie   MeSH
• nemoci štítné žlázy chemicky indukované   MeSH
• protinádorové látky škodlivé účinky   MeSH
• tetrahydronaftaleny škodlivé účinky   MeSH
• thyroxin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• antikarcinogenní látky MeSH
• bexaroten MeSH
• CTLA4 protein, human MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• ipilimumab MeSH
• monoklonální protilátky MeSH
• protinádorové látky MeSH
• tetrahydronaftaleny MeSH
• thyroxin MeSH

Associations of both hypothyroidism and subclinical hypothyroidism with metabolic syndrome are well established. Nowadays, more attention has been paid to the role of thyroid hormones and thyrotropin (TSH) within the euthyroid range on the development of cardiometabolic health risks. The paper summarizes current knowledge related to the associations of lower free thyroxine (fT4) level and higher levels of both free triiodothyronine (fT3) and TSH with body adiposity, metabolic syndrome and insulin resistance in euthyroid subjects. In our recent study of obese euthyroid adolescents, we revealed that fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) positively correlated with fT3 and TSH and negatively with fT4. The ratio of fT3 to fT4 was also significantly related to HOMA-IR both in girls (r = 0.347, p < 0.001) and boys (r = 0.267, p < 0.001). It is concluded that up-to-date conducted studies mostly confirmed that thyroid hormones and TSH even in euthyroid range may significantly affect the metabolic health and particularly insulin sensitivity.Key words: euthyroid range - insulin resistance - metabolic health - metabolic syndrome - obesity - thyrotropin - thyroxine - triiodothyronine.

• MeSH
• hypotyreóza epidemiologie   metabolismus   MeSH
• inzulin MeSH
• inzulinová rezistence * MeSH
• kardiovaskulární nemoci epidemiologie   metabolismus   MeSH
• lidé MeSH
• metabolický syndrom epidemiologie   metabolismus   MeSH
• mladiství MeSH
• obezita epidemiologie   metabolismus   MeSH
• rizikové faktory MeSH
• testy funkce štítné žlázy MeSH
• thyreotropin metabolismus   MeSH
• thyroxin metabolismus   MeSH
• trijodthyronin metabolismus   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin MeSH
• thyreotropin MeSH
• thyroxin MeSH
• trijodthyronin MeSH

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1(PV/+) mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1(PV/+) mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1(PV/+) mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation.

• MeSH
• fyziologická kalcifikace MeSH
• kostní denzita MeSH
• lidé MeSH
• mutace MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• thyroxin metabolismus   MeSH
• tyreoidální hormony, receptory alfa genetika   metabolismus   MeSH
• velikost těla MeSH
• vývojové onemocnění kostí genetika   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• thyroxin MeSH
• tyreoidální hormony, receptory alfa MeSH

Mercury is a prominent environmental contaminant that causes endocrine disorder to human and other organisms. But little is known about the response of the thyroid functions and hypothalamic-pituitary-thyroid (HPT) axis to mercury in teleosts and the few studies that are available have not yielded consistent results. In this study, expression profiles of corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshβ), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trβ) genes were determined in whole-body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Hg(2+) (0, 0.1 and 0.3 mg/l) for 4 days, as well as the thyroid hormones (THs) levels. Moreover, the 96-h lethal concentration of Hg(2+) on rare minnow larvae was determined as 0.32 mg/l. The results showed that crh, tg, trα and trβ mRNA levels were significantly up-regulated in the larvae, but the gene expression of tshβ and slc5a5 was not significantly changed in our study. Besides, the THs levels increased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Hg(2+) could alter some genes expression in the HPT axis which could be used as the potential biomarkers for evaluating the environmental Hg(2+)-induced stress in fish.

• Klíčová slova
• Chinese rare minnow, Gene expression, Hypothalamic–pituitary–thyroid axis, Mercury, Thyroid hormone,
• MeSH
• beta podjednotka tyreotropinu genetika   MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• chlorid rtuťnatý toxicita   MeSH
• Cyprinidae genetika   metabolismus   MeSH
• hormon uvolňující kortikotropin genetika   MeSH
• larva účinky léků   genetika   metabolismus   MeSH
• LD50 MeSH
• regulace genové exprese účinky léků   MeSH
• symportéry genetika   MeSH
• thyreoglobulin genetika   MeSH
• thyroxin metabolismus   MeSH
• trijodthyronin metabolismus   MeSH
• tyreoidální hormony, receptory alfa genetika   MeSH
• tyreoidální hormony, receptory beta genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta podjednotka tyreotropinu MeSH
• chemické látky znečišťující vodu MeSH
• chlorid rtuťnatý MeSH
• hormon uvolňující kortikotropin MeSH
• sodium-iodide symporter MeSH Prohlížeč
• symportéry MeSH
• thyreoglobulin MeSH
• thyroxin MeSH
• trijodthyronin MeSH
• tyreoidální hormony, receptory alfa MeSH
• tyreoidální hormony, receptory beta MeSH

Cadmium is a heavy metal abundant in the environment that can induce endocrine disorder and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in fish are still unclear. In this study, the thyroid hormone (TH) levels and the expression profiles of genes related to hypothalamic- pituitary-thyroid (HPT) axis, including corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshβ), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trβ), were determined in whole body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Cd(2+) (0, 0.5 and 2.5mg/L) for 4days. And the 96-h lethal concentration of Cd(2+) on rare minnow larvae was determined as 2.59mg/L. The results showed that crh, slc5a5, tg and tshβ mRNA levels were significantly up-regulated in the larvae, but the gene expression of trα and trβ was down-regulated in a concentration-dependent manner. Besides, the THs levels decreased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Cd(2+) could alter gene expression in the HPT axis that might subsequently contribute to thyroid disruption.

• Klíčová slova
• Cadmium, Chinese rare minnow, Gene expression, Hypothalamic–pituitary–thyroid axis, Thyroid hormone,
• MeSH
• chemické látky znečišťující vodu otrava   MeSH
• down regulace účinky léků   genetika   MeSH
• exprese genu účinky léků   MeSH
• hormony štítné žlázy metabolismus   MeSH
• kadmium škodlivé účinky   MeSH
• larva účinky léků   genetika   metabolismus   MeSH
• messenger RNA genetika   MeSH
• otrava kadmiem * MeSH
• ryby metabolismus   MeSH
• štítná žláza účinky léků   metabolismus   MeSH
• systém hypotalamus-hypofýza účinky léků   metabolismus   MeSH
• thyroxin metabolismus   MeSH
• upregulace účinky léků   genetika   MeSH
• vystavení vlivu životního prostředí MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• hormony štítné žlázy MeSH
• kadmium MeSH
• messenger RNA MeSH
• thyroxin MeSH

Thyroid hormones (TH) are powerful modulators of heart function, but their arrhythmogenic effects are less elucidated. We have examined both acute and long-term action of TH on the heart susceptibility to the ventricular fibrillation (VF) and on the heart ability to terminate VF and restore a sinus rhythm. Triiodothyronine (T3) was applied in the range of 10(-9)-10(-6) mol/l in acute experiments using isolated perfused aged (14-month-old) guinea pig hearts. L-thyroxine (T4) was applied in the dose of 50 microg/100g/day to young (3-month-old) and aged (20-month-old) rats for 2 weeks. The T4 treatment resulted in an increased susceptibility of young, but not adult rat hearts to a hypokalemia-induced VF and facilitated a spontaneous sinus rhythm (SSR) restoration in the latter group. The acute T3 administration in the range of 10(-9)-10(-7) mol/l significantly decreased the susceptibility of an isolated heart to an electrically induced VF and also facilitated the sinus rhythm restoration. The SSR restoration was, however, not affected by 10(-6) mol/l concentration of T3, which also led to an increased VF susceptibility. Results indicate that TH can affect the susceptibility of the heart to VF and its ability to restore the sinus rhythm via acute (non-genomic) and long-term (genomic) actions. Furthermore, an anti- and pro-arrhythmic potential of TH appears to be age- and dose-dependent.

• MeSH
• časové faktory MeSH
• fibrilace komor metabolismus   patofyziologie   prevence a kontrola   MeSH
• kardiomyocyty metabolismus   patologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• morčata MeSH
• potkani Wistar MeSH
• převodní systém srdeční patofyziologie   MeSH
• srdeční frekvence MeSH
• thyroxin aplikace a dávkování   metabolismus   MeSH
• trijodthyronin aplikace a dávkování   metabolismus   MeSH
• věkové faktory MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• thyroxin MeSH
• trijodthyronin MeSH

BACKGROUND: Differentiated thyroid cancers (DTC) often form metastases in neck lymph nodes, lungs and bones. Other metastases--to the brain, kidneys, skin and liver are rare. Liver metastases of DTC occur in the terminal phase of the disease and predominantly do not accumulate radioiodine. Functional (accumulating radioiodine) metastases are very rare. MATERIAL AND METHODS: In an 85 year old patient with DTC of the follicular type after removal of the thyroid and lymph nodes metastases on the neck and after the elimination of thyroid remnants by radioiodine, a functional metastasis in the liver was detected by combination of whole-body scintigraphy following administration of 131I and liver scintigraphy by using 99mTc-colloid, supplemented by bone scintigraphy after administration of 99mTc-MDP. At first, the high thyroglobulin serum level was falsely negative after repeated radioiodine treatment. The patient was treated for this hepatic accumulating metastasis eight times by 59.2 GBq total dose of radioiodine. Radioiodine treatments were repeated for 7 years, the patient died at the age of 92 years. CONCLUSIONS: It is necessary to distinguish between diffuse and focal radioiodine accumulation in a liver. Only a focal accumulation is characteristic for functional liver metastasis in which thyroxin synthesis is preserved. The correspondence of focal accumulation of radioiodine on whole-body scintigraphy with "cold" area on liver scintigraphy is specific for diagnosis of this metastasis. At the same time, it confirms the fact that radioiodine therapy can be both promising and successful, as we can see in the case of our patient.

• MeSH
• buněčná diferenciace MeSH
• játra diagnostické zobrazování   MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• karcinom patologie   MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• metastázy nádorů MeSH
• nádory jater diagnostické zobrazování   radioterapie   sekundární   MeSH
• nádory štítné žlázy patologie   chirurgie   MeSH
• radioisotopová scintigrafie MeSH
• radioizotopy jodu terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thyroxin metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• radioizotopy jodu MeSH
• thyroxin MeSH

To obtain information about whether nutrient and hormonal factors are critical for the developmental pattern of electrogenic amiloride-sensitive Na+ transport (NaSCC) in rat distal colon, we studied the effect of adrenalectomy, high dietary Na+ intake, and hypothyroidism on colonic NaSCC in weanling rats. Adrenalectomy and high dietary Na+ intake inhibited NaSCC, decreased plasma level of aldosterone, and did not influence plasma level of thyroxine. Hypothyroidism inhibited NaSCC without significant changes of plasma aldosterone. These results suggest that the high activity of NaSCC during weaning period reflects the relatively low Na+ intake, and that thyroid hormones have an important permissive role in the developmental changes of NaSCC.

• MeSH
• aldosteron metabolismus   MeSH
• amilorid farmakologie   MeSH
• biologický transport účinky léků   MeSH
• hypotyreóza metabolismus   MeSH
• kolon účinky léků   růst a vývoj   metabolismus   MeSH
• krysa rodu Rattus MeSH
• nadledviny fyziologie   MeSH
• potkani Wistar MeSH
• sodík dietní farmakologie   MeSH
• thyroxin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldosteron MeSH
• amilorid MeSH
• sodík dietní MeSH
• thyroxin MeSH