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1.
Eur J Endocrinol ; 185(4): 553-563, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342595

RESUMO

Objective: Brown adipose tissue (BAT) controls metabolic rate through thermogenesis. As its regulatory factors during the transition from hyperthyroidism to euthyroidism are not well established, our study investigated the relationships between supraclavicular brown adipose tissue (sBAT) activity and physiological/metabolic changes with changes in thyroid status. Design: Participants with newly diagnosed Graves' disease were recruited. A thionamide antithyroid drug (ATD) such as carbimazole (CMZ) or thiamazole (TMZ) was prescribed in every case. All underwent energy expenditure (EE) measurement and supraclavicular infrared thermography (IRT) within a chamber calorimeter, as well as 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scanning, with clinical and biochemical parameters measured during hyperthyroidism and repeated in early euthyroidism. PET sBAT mean/maximum standardized uptake value (SUV mean/max), MR supraclavicular fat fraction (sFF) and mean temperature (Tscv) quantified sBAT activity. Results: Twenty-one (16 female/5 male) participants aged 39.5 ± 2.5 years completed the study. The average duration to attain euthyroidism was 28.6 ± 2.3 weeks. Eight participants were BAT-positive while 13 were BAT-negative. sFF increased with euthyroidism (72.3 ± 1.4% to 76.8 ± 1.4%; P < 0.01), but no changes were observed in PET SUV mean and Tscv. Significant changes in serum-free triiodothyronine (FT3) levels were related to BAT status (interaction P value = 0.04). FT3 concentration at hyperthyroid state was positively associated with sBAT PET SUV mean (r = 0.58, P = 0.01) and resting metabolic rate (RMR) (P < 0.01). Conclusion: Hyperthyroidism does not consistently lead to a detectable increase in BAT activity. FT3 reduction during the transition to euthyroidism correlated with BAT activity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Hipertireoidismo/metabolismo , Hipertireoidismo/reabilitação , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/efeitos dos fármacos , Adulto , Idoso , Antitireóideos/farmacologia , Antitireóideos/uso terapêutico , Composição Corporal/efeitos dos fármacos , Composição Corporal/fisiologia , Carbimazol/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Fluordesoxiglucose F18 , Doença de Graves/tratamento farmacológico , Doença de Graves/metabolismo , Doença de Graves/reabilitação , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Indução de Remissão , Singapura , Termogênese/efeitos dos fármacos , Termogênese/fisiologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiologia , Adulto Jovem
2.
Eur J Endocrinol ; 185(2): R65-R74, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34132199

RESUMO

Background and aims: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. Methods: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' Results: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. Conclusion: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.


Assuntos
Adenoma/metabolismo , Hipertireoidismo/metabolismo , Neoplasias Hipofisárias/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo , Adenoma/patologia , Adenoma/fisiopatologia , Adenoma/terapia , Fibrilação Atrial/fisiopatologia , Quimioterapia Adjuvante , Bócio/fisiopatologia , Gonadotropinas Hipofisárias/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Insuficiência Cardíaca/fisiopatologia , Hormônios/uso terapêutico , Humanos , Hipertireoidismo/fisiopatologia , Neoplasia Residual , Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/terapia , Prolactinoma/metabolismo , Radioterapia Adjuvante , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Carga Tumoral , Transtornos da Visão/fisiopatologia
3.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915895

RESUMO

Hyperthyroidism, which is characterized by increased circulating thyroid hormone levels, alters the body's metabolic and systemic hemodynamic balance and directly influences renal function. In this study, the urinary proteome of patients with hyperthyroidism was characterized using an untargeted proteomic approach with network analysis. Urine samples were collected from nine age-matched patients before and after carbimazole treatment. Differences in the abundance of urinary proteins between hyperthyroid and euthyroid states were determined using a 2D-DIGE coupled to MALDI-TOF mass spectrometry. Alterations in the abundance of urinary proteins, analyzed via Progenesis software, revealed a statistically significant difference in abundance in a total of 40 spots corresponding to 32 proteins, 25 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes associated with cellular metabolism, transport, and acute phase response. The notable upregulated urinary proteins were serotransferrin, transthyretin, serum albumin, ceruloplasmin, alpha-1B-glycoprotein, syntenin-1, and glutaminyl peptide cyclotransferase, whereas the three notable downregulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase, and serpin B3 (SERPINB3). Bioinformatic analysis using ingenuity pathway analysis (IPA) identified the dysregulation of pathways associated with cellular compromise, inflammatory response, cellular assembly, and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes.


Assuntos
Hipertireoidismo/metabolismo , Proteoma , Proteômica , Adulto , Biomarcadores , Pesos e Medidas Corporais , Biologia Computacional/métodos , Feminino , Humanos , Hipertireoidismo/etiologia , Hipertireoidismo/terapia , Masculino , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica/métodos , Eletroforese em Gel Diferencial Bidimensional
4.
Eur J Epidemiol ; 36(3): 335-344, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548002

RESUMO

Hypothyroidism and hyperthyroidism are observationally associated with sex hormone concentrations and sexual dysfunction, but causality is unclear. We investigated whether TSH, fT4, hypo- and hyperthyroidism are causally associated with sex hormones and sexual function. We used publicly available summary statistics from genome-wide association studies on TSH and fT4 and hypo- and hyperthyroidism from the ThyroidOmics Consortium (N ≤ 54,288). Outcomes from UK Biobank (women ≤ 194,174/men ≤ 167,020) and ReproGen (women ≤ 252,514) were sex hormones (sex hormone binding globulin [SHBG], testosterone, estradiol, free androgen index [FAI]) and sexual function (ovulatory function in women: duration of menstrual period, age at menarche and menopause, reproductive lifespan, and erectile dysfunction in men). We performed two-sample Mendelian randomization (MR) analyses on summary level, and unweighted genetic risk score (GRS) analysis on individual level data. One SD increase in TSH was associated with a 1.332 nmol/L lower (95% CI: - 0.717,- 1.946; p = 2 × 10-5) SHBG and a 0.103 nmol/l lower (- 0.051,V0.154; p = 9 × 10-5) testosterone in two-sample MR, supported by the GRS approach. Genetic predisposition to hypothyroidism was associated with decreased and genetic predisposition to hyperthyroidism with increased SHBG and testosterone in both approaches. The GRS for fT4 was associated with increased testosterone and estradiol in women only. The GRS for TSH and hypothyroidism were associated with increased and the GRS for hyperthyroidism with decreased FAI in men only. While genetically predicted thyroid function was associated with sex hormones, we found no association with sexual function.


Assuntos
Disfunção Erétil/etiologia , Hipertireoidismo/complicações , Hipotireoidismo/complicações , Análise da Randomização Mendeliana/métodos , Globulina de Ligação a Hormônio Sexual/metabolismo , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Psicogênicas/etiologia , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Adulto , Estradiol/sangue , Feminino , Hormônios Esteroides Gonadais , Humanos , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Masculino , Pessoa de Meia-Idade , Testosterona , Tireotropina/metabolismo , Tiroxina/metabolismo
5.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430047

RESUMO

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine ß hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.


Assuntos
Peso Corporal/efeitos dos fármacos , Hipertireoidismo/genética , Óxido Nítrico Sintase/genética , Óxido Nítrico/genética , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/crescimento & desenvolvimento , Animais , Peso Corporal/genética , Modelos Animais de Doenças , Estimulação Elétrica , Humanos , Hipertireoidismo/metabolismo , Hipertireoidismo/patologia , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/crescimento & desenvolvimento , Veias Mesentéricas/efeitos dos fármacos , Veias Mesentéricas/crescimento & desenvolvimento , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Wistar , Tiroxina/farmacologia , Vasoconstrição/genética
6.
J Nucl Med ; 62(3): 304-312, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33008929

RESUMO

Benign thyroid disorders, especially hyper- and hypothyroidism, are the most prevalent endocrine disorders. The most common etiologies of hyperthyroidism are autoimmune hyperthyroidism (Graves disease, GD), toxic multinodular goiter (TMNG), and toxic thyroid adenoma (TA). Less common etiologies include destructive thyroiditis (e.g., amiodarone-induced thyroid dysfunction) and factitious hyperthyroidism. GD is caused by autoantibodies against the thyroid-stimulating hormone (TSH) receptor. TMNG and TA are caused by a somatic activating gain-of-function mutation. Typical laboratory findings in patients with hyperthyroidism are low TSH, elevated free-thyroxine and free-triiodothyronine levels, and TSH-receptor autoantibodies in patients with GD. Ultrasound imaging is used to determine the size and vascularity of the thyroid gland and the location, size, number, and characteristics of thyroid nodules. Combined with lab tests, these features constitute the first-line diagnostic approach to distinguishing different forms of hyperthyroidism. Thyroid scintigraphy with either radioiodine or 99mTc-pertechnetate is useful to characterize different forms of hyperthyroidism and provides information for planning radioiodine therapy. There are specific scintigraphic patterns for GD, TMNG, TA, and destructive thyroiditis. Scintigraphy with 99mTc-sestamibi allows differentiation of type 1 from type 2 amiodarone-induced hyperthyroidism. The radioiodine uptake test provides information for planning radioiodine therapy of hyperthyroidism. Hyperthyroidism can be treated with oral antithyroid drugs, surgical thyroidectomy, or 131I-iodide. Radioiodine therapy is generally considered after failure of treatment with antithyroid drugs, or when surgery is contraindicated or refused by the patient. In patients with TA or TMNG, the goal of radioiodine therapy is to achieve euthyroid status. In GD, the goal of radioiodine therapy is to induce hypothyroidism, a status that is readily treatable with oral thyroid hormone replacement therapy. Dosimetric estimates based on the thyroid volume to be treated and on radioiodine uptake should guide selection of the 131I-activity to be administered. Early side effects of radioiodine therapy (typically mild pain in the thyroid) can be handled by nonsteroidal antiinflammatory drugs. Delayed side effects after radioiodine therapy for hyperthyroidism are hypothyroidism and a minimal risk of radiation-induced malignancies.


Assuntos
Hipertireoidismo , Medicina Nuclear , Técnicas de Laboratório Clínico , Humanos , Hipertireoidismo/diagnóstico por imagem , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Hipertireoidismo/radioterapia
7.
Front Endocrinol (Lausanne) ; 11: 615993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329408

RESUMO

GO is the most frequent extrathyroidal manifestation of Graves' disease, although it may rarely occur in euthyroid/hypothyroid patients with chronic autoimmune thyroiditis. It is a relatively infrequent disorder, and men tend to have more severe ocular involvement at an older age. The prevalence of GO is lower than in the past among patients with recent onset Graves' hyperthyroidism, and moderate-to-severe forms requiring aggressive treatments are no more than 5-6% of all cases of GO. After an initial inflammatory (active) phase and a phase of stabilization (plateau phase), GO tends to improve and eventually inactivates (inactive or burnt-out phase). Minimal-to-mild GO often remits spontaneously, but complete restitutio ad integrum almost never occurs when GO is more than mild. Several risk factors contribute to its development on a yet undefined genetic background. Cigarette smoking is the most important of them. Early diagnosis, control and removal of modifiable risk factors, early treatment of mild forms of GO may effectively limit the risk of progression to more severe forms, which have a profound and dramatic impact on the quality of life of affected individuals, and remain a therapeutic challenge, often requiring long-lasting and multiple medical and surgical therapies.


Assuntos
Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Oftalmopatia de Graves/epidemiologia , Estresse Oxidativo/fisiologia , Fatores Etários , Animais , Fumar Cigarros/metabolismo , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/metabolismo , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/epidemiologia , Hipertireoidismo/metabolismo , Fatores de Risco , Fatores Sexuais
8.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32944774

RESUMO

CONTEXT: Thyroid function is clinically evaluated by determination of circulating concentrations of thyrotropin (thyroid-stimulating hormone; TSH) and free thyroxine (fT4). However, a tissue-specific effector substrate of thyroid function is lacking. Energy-rich phosphorus-containing metabolites (PM) and phospholipids (PL) might be affected by thyroid hormone action and can be noninvasively measured by 31P nuclear magnetic resonance spectroscopy (NMRS). OBJECTIVES: To measure the actions of peripheral thyroid hormones on PM and PL tissue concentrations. DESIGN AND SETTING: A longitudinal, prospective pilot study was performed. PARTICIPANTS: Nine patients with hyperthyroidism (HYPER) and 4 patients with hypothyroidism (HYPO) were studied at baseline and 3 months after treatment. MAIN OUTCOME MEASURES: High-field 1H/31P NMRS was used to assess profiles of PM, PL, and flux through oxidative phosphorylase in liver and skeletal muscle, as well as ectopic tissue lipid content. RESULTS: The concentrations of total skeletal muscle (m-) and hepatic (h-) phosphodiesters (PDE) and one of the PDE constituents, glycerophosphocholine (GPC), were lower in HYPER compared with HYPO (m-PDE: 1.4 ±â€…0.4 mM vs 7.4 ±â€…3.5 mM, P = 0.003; m-GPC: 0.9 ±â€…0.3 mM vs 6.7 ±â€…3.5 mM, P = 0.003; h-PDE: 4.4 ±â€…1.4 mM vs 9.9 ±â€…3.9 mM, P = 0.012; h-GPC: 2.2 ±â€…1.0 mM vs 5.1 ±â€…2.4 mM, P = 0.024). Both h-GPC (rho = -0.692, P = 0.018) and h-GPE (rho = -0.633, P = 0.036) correlated negatively with fT4. In muscle tissue, a strong negative association between m-GPC and fT4 (rho = -0.754, P = 0.003) was observed. CONCLUSIONS: Thyroxine is closely negatively associated with the PDE concentrations in liver and skeletal muscle. Normalization of thyroid dysfunction resulted in a decline of PDE in hypothyroidism and an increase in hyperthyroidism. Thus, PDE might be a sensitive tool to estimate tissue-specific peripheral thyroid hormone action.


Assuntos
Fígado/metabolismo , Músculo Esquelético/metabolismo , Fósforo/metabolismo , Glândula Tireoide/fisiologia , Adolescente , Adulto , Ésteres/análise , Ésteres/metabolismo , Feminino , Humanos , Hipertireoidismo/diagnóstico por imagem , Hipertireoidismo/metabolismo , Hipotireoidismo/diagnóstico por imagem , Hipotireoidismo/metabolismo , Fígado/química , Fígado/diagnóstico por imagem , Estudos Longitudinais , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/química , Músculo Esquelético/diagnóstico por imagem , Fósforo/análise , Projetos Piloto , Estudos Prospectivos , Testes de Função Tireóidea , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-32733382

RESUMO

Background: Discrepant thyroid function tests (TFTs) are typical of inappropriate secretion of TSH (IST), a rare entity encompassing TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHß) due to THRB mutations. The differential diagnosis remains a clinical challenge in most of the cases. The objective of this study was to share our experience with patients presenting with discrepant TFTs outlining the main pitfalls in the differential diagnosis. Methods: medical records of 100 subjects with discrepant TFTs referred to Thyroid Endocrine Centers at the University of Milan were analyzed, retrospectively. Patients were studied by dynamic testing (TRH test, T3-suppression test, or a short course of long-acting somatostatin analog, when appropriate), THRB sequencing, and pituitary imaging. Results: 88 patients were correctly diagnosed as RTHß with (n = 59; 16 men, 43 women) or without THRB variants (n = 6; 2 men, 4 female) or TSHoma (n = 23; 9 men, 14 women). We identified 14 representative subjects with an atypical presentation or who were misdiagnosed. Seven patients, with spurious hyperthyroxinemia due to assays interference were erroneously classified as RTHß (n = 4) or TSHoma (n = 3). Three patients with genuine TSHomas were classified as laboratory artifact (n = 2) or RTHß (n = 1). Two TSHomas presented atypically due to coexistent primary thyroid diseases. In one RTHß a drug-induced thyroid dysfunction was primarily assumed. These patients experienced a mean diagnostic delay of 26 ± 14 months. Analysis of the investigations which can differentiate between TSHoma and RTHß showed highest accuracy for the T3-suppression test (100% specificity with a cut-off of TSH <0.11 µUI/ml). Pituitary MRI was negative in 6/26 TSHomas, while 11/45 RTHß patients had small pituitary lesions, leading to unnecessary surgery in one case. Conclusions: Diagnostic delay and inappropriate treatments still occur in too many cases with discrepant TFTs suggestive of central hyperthyroidism. The insistent pitfalls lead to a significant waste of resources. We propose a revised flow-chart for the differential diagnosis.


Assuntos
Hipertireoidismo/diagnóstico , Mutação , Receptores beta dos Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Hipertireoidismo/genética , Hipertireoidismo/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Adulto Jovem
10.
Reprod Fertil Dev ; 32(12): 1060-1066, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32758353

RESUMO

Follicle development is a complicated process regulated by thyroid hormone (TH). TH dysregulation is associated with reproductive disorders; however, the mechanism underlying these relationships remains unclear. Glucose-related protein 78 (GRP78) is a well-characterised endoplasmic reticulum stress protein related to ovarian cell apoptosis. To clarify whether GRP78 is regulated by TH and the involvement of GRP78 in follicle development, we established rat models of hypothyroidism and hyperthyroidism and investigated the effects of TH dysregulation on levels of GRP78, C/EBP homologous protein (CHOP) and cleaved caspase-3. TH dysregulation decreased levels of GRP78 and increased those of CHOP and cleaved caspase-3 in both rat models. However, treatment with equine chorionic gonadotrophin reversed these effects, as well as granulosa cell apoptosis induced by TH dysregulation. Together, these results provide evidence that TH dysregulation alters the GRP78 expression profile, triggering the apoptotic signalling pathway, and suggest that GRP78 is a novel mediator of TH in follicle development.


Assuntos
Apoptose/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Proteínas de Choque Térmico/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Folículo Ovariano/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Feminino , Proteínas de Choque Térmico/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
11.
FASEB J ; 34(9): 11970-11982, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32667083

RESUMO

Integrated metabolomics and proteomics analysis was carried out to study the effects of Poria and its split components (volatile oil, triterpenoid, oligosaccharide, amino acid, and crude polysaccharide) on rats of normal physiological model, hyperthyroidism model, and hypothyroidism model to explore the substance basis of Poria for hypothyroidism from the perspective of a holistic view in substance and energy metalism. The key pathways regulating substance and energy metabolism were screened, encompassing tricarboxylic acid cycle pathway, glycolysis/ gluconeogenesis pathways, biosynthesis of amino acid pathway, fatty acid biosynthesis pathway, pentose phosphate pathway, peroxisome proliferator-activated receptors pathway, etc Poria and its split components showed promoting effects on substance and energy metabolism in normal model, while showed amelioration effects on hypothyroidism model at different degrees, and had no significant improvement effects on hyperthyroidism in rats. Volatile oil, triterpenoid, and crude polysaccharide from Poria were regarded as substance basis of Poria ameliorating hypothyroidism other than hyperthyroidism. This work also revealed the feasibility of metabolomics and proteomics analysis to elucidate the effective substance basis of traditional Chinese medicine from a new viewpoint based on its effects on substance and energy metabolism.


Assuntos
Hipertireoidismo , Hipotireoidismo , Óleos Voláteis/farmacologia , Poria/química , Triterpenos/farmacologia , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/metabolismo , Hipertireoidismo/patologia , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Masculino , Metabolômica , Óleos Voláteis/química , Proteômica , Ratos , Ratos Sprague-Dawley , Triterpenos/química
12.
Bull Exp Biol Med ; 169(2): 224-228, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32654002

RESUMO

We analyzed structural and functional features of the main mitochondrial Ca2+-transporting systems, mitochondrial Ca2+ uniporter complex (MCUC) and Ca2+-dependent cyclosporin A-sensitive mitochondrial permeability transition pore (MPT pore), in rats with hyperthyroid state. It was found that, the rate of Ca2+ accumulation by rat liver mitochondria in this pathology increases by 1.3 times, which can be associated with higher level of the channel-forming subunit of the uniporter MCU and lower content of dominant-negative subunit of this complex MCUb. At the same time, the level of the regulatory subunit MICU1 remained unchanged. It was shown that calcium retention capacity of liver mitochondria in rats with experimental hyperthyroidism decreased by 2 times in comparison with the control, which attested to reduced resistance of liver mitochondria of hyperthyroid rats to induction of the MPT pore. The observed changes are consistent with the data on increased amount of cyclophilin D, a mitochondrial matrix peptidyl-prolyl isomerase that is known to modulate the MPT pore opening and expression of the Ppif gene that encodes mitochondrial cyclophilin D in rats with experimental hyperthyroidism.


Assuntos
Canais de Cálcio/metabolismo , Hipertireoidismo/metabolismo , Mitocôndrias Hepáticas/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Animais , Cálcio/metabolismo , Ciclofilina D/metabolismo , Masculino , Poro de Transição de Permeabilidade Mitocondrial/metabolismo , Ratos , Ratos Wistar
13.
Eur Rev Med Pharmacol Sci ; 24(11): 6380-6389, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32572935

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effect of ß-casomorphin-7 (ß-CM-7) on myocardial hypertrophy (MH) in hyperthyroidism-induced cardiomyopathy in vivo and in vitro. MATERIALS AND METHODS: Thirty C56BL/6 mice were randomly divided into three groups: control group, hyperthyroidism group, and ß-CM-7 treatment group. An animal model of cardiac hypertrophy of hyperthyroid heart disease (HHD) was constructed by continuous intraperitoneal injection of 100 µg of L-thyroxine (L-Thy) for 28 days, and the serum TT3 and TT4 concentrations were measured. After that, myocardial specimens were collected to measure left and right ventricular MH index, and the myocardial cell structure was observed under hematoxylin and eosin (HE) staining. Thereafter, Masson staining was adopted to determine collagen volume fraction, and hydroxylamine method was used to measure superoxide dismutase (SOD) activity, Meanwhile, DTNB direct method was applied to measure GSH-Px activity, thio-malonylurea method was utilized to measure malondialdehyde (MDA) content, and the level of reactive oxygen species (ROS) was detected by flow cytometry. Finally, the expressions of oxidative stress (OS) and inflammation-related factors in vivo and the nuclear factor-κB (NF-κB) pathway in vitro were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared with those in control group, TT3 and TT4 were remarkably increased, the structure of myocardial cells was disordered, the interstitial fibrosis and the ventricular MH index were significantly increased, the OS and inflammatory responses were increased, and the NF-κB pathway was activated in the Hyperthyroidism group. In the ß-CM-7 group, the content of TT3 and TT4 was decreased, the myocardial cell structure was slightly disturbed, the fibrosis and the ventricular MH index were reduced, OS and inflammatory response were reduced, and the NF-κB pathway was inhibited. CONCLUSIONS: ß-CM-7 can prevent and treat MH in mice with L-Thy-induced HHD probably through regulating the NF-κB signaling pathway.


Assuntos
Cardiomegalia/tratamento farmacológico , Endorfinas/farmacologia , Hipertireoidismo/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Células Cultivadas , Modelos Animais de Doenças , Endorfinas/administração & dosagem , Hipertireoidismo/metabolismo , Hipertireoidismo/patologia , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos
14.
Radiat Environ Biophys ; 59(3): 553-558, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32449015

RESUMO

COTI (collar therapy indicator) has been recently introduced for the detection of gamma rays with emphasis on thyroid investigations. The aim of this study was to test the feasibility of a prototype version of COTI including activity detectors with low sensitivity in performing thyroid uptake measurements for a large group of patients. Consequently, thyroid uptake tests were carried out for a total of 89 patients (22 males and 67 females; age: 44 ± 13 years) with thyroid cancer (n = 74), hyperthyroidism (n = 16) at 2 and 24 h after administration of 0.44-2 MBq of 131I. Eight individuals among the thyroid cancer patients were monitored up to 96 h after administration. The COTI device was equipped with two CsI (Tl) detectors, known as LoHi type, sensitive to activity ranges from 0.02 to 30 MBq of 131I. The uptake values from COTI were compared with those measured with a standard probe. It was found that the mean uptake of thyroid activity in thyroid cancer patients was 2.1 ± 1.3% at 2 h when measured with the standard probe, while it was 2.2 ± 1.2% when measured with COTI. In addition, the average uptake at 24 h after administration was 2.5 ± 3.2% and 3.2 ± 3.8% measured with COTI and the standard probe, respectively. A strong correlation was found at 24 h between the results obtained with COTI and the standard probe, while a weaker correlation was seen at 2 h. Overall, there was no significant difference between the results obtained with the standard probe and those obtained with COTI at both 2 and 24 h (Pvalue ≥ 0.05). Besides, 85% of the uptake values measured with COTI were less than those measured with the standard probe at the 24 h after administration. The average uptake value was 0.9 ± 0.8% after 96 h by COTI, and 1.4 ± 1.3% by the standard probe. Pertaining to the hyperthyroidism patients, COTI showed mean uptake values of 20 ± 16% and 23 ± 18% at 2 and 24 h, respectively. In contrast, the standard probe suggested higher mean uptake values of 26 ± 18% and 30 ± 22%, respectively. It is concluded that the prototype of COTI used in the present study has been proved to be a feasible and promising tool in thyroid investigations. It is noted, however, that the next COTI generation should include detectors equipped with collimator and energy discrimination.


Assuntos
Radioisótopos do Iodo , Traçadores Radioativos , Glândula Tireoide/metabolismo , Administração Oral , Adulto , Feminino , Humanos , Hipertireoidismo/metabolismo , Hipertireoidismo/radioterapia , Hipertireoidismo/cirurgia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
15.
Mitochondrion ; 52: 190-196, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32278087

RESUMO

The aim of the present work was to investigate the energy metabolism and antioxidant status of rat liver mitochondria using a model of hyperthyroidism. In experimental animals, the level of triiodothyronine and thyroxine was increased 3- and 4-fold, respectively, in comparison with that in the control group, indicating the development of hyperthyroidism in these animals. Oxygen consumption was found to be higher in rats with experimentally induced hyperthyroidism (from 20 to 60% depending on the experimental scheme used), with a slight decrease in the efficiency of oxidative phosphorylation and respiratory state ratio. It was shown for the first time that the level the respiratory complexes of the electron transport chain in hyperthyroid rats increased; however, the quantity of complexes III and V changed unreliably. The assay of respiratory chain enzymes revealed that the activities of complexes I, II, and citrate synthase increased, whereas the activities complexes II + III, III, IV decreased in liver mitochondria of the experimental animals. Alterations in the oxidative state in liver mitochondria were found: a 60% increase in the hydrogen peroxide production rate and a 45% increase in lipid peroxidation. The activities of superoxide dismutase and catalase in the liver of experimental rats were higher than in the control. At the same time, the activity of glutathione peroxidase did not change. The data obtained indicate that the known activation of metabolism and changes in the oxidative status in thyrotoxicosis are associated with variations in the respiratory chain functioning and the antioxidant enzymes of mitochondria.


Assuntos
Hipertireoidismo/metabolismo , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias/metabolismo , Tiroxina/efeitos adversos , Tri-Iodotironina/sangue , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Metabolismo Energético , Peróxido de Hidrogênio/metabolismo , Hipertireoidismo/induzido quimicamente , Peroxidação de Lipídeos , Masculino , Fosforilação Oxidativa , Estresse Oxidativo , Consumo de Oxigênio , Ratos , Superóxido Dismutase/metabolismo , Tiroxina/sangue
16.
Int J Mol Sci ; 21(8)2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32325836

RESUMO

A perennial task is to prevent the occurrence and/or recurrence of most frequent or life-threatening cardiac arrhythmias such as atrial fibrillation (AF) and ventricular fibrillation (VF). VF may be lethal in cases without an implantable cardioverter defibrillator or with failure of this device. Incidences of AF, even the asymptomatic ones, jeopardize the patient's life due to its complication, notably the high risk of embolic stroke. Therefore, there has been a growing interest in subclinical AF screening and searching for novel electrophysiological and molecular markers. Considering the worldwide increase in cases of thyroid dysfunction and diseases, including thyroid carcinoma, we aimed to explore the implication of thyroid hormones in pro-arrhythmic signaling in the pathophysiological setting. The present review provides updated information about the impact of altered thyroid status on both the occurrence and recurrence of cardiac arrhythmias, predominantly AF. Moreover, it emphasizes the importance of both thyroid status monitoring and AF screening in the general population, as well as in patients with thyroid dysfunction and malignancies. Real-world data on early AF identification in relation to thyroid function are scarce. Even though symptomatic AF is rare in patients with thyroid malignancies, who are under thyroid suppressive therapy, clinicians should be aware of potential interaction with asymptomatic AF. It may prevent adverse consequences and improve the quality of life. This issue may be challenging for an updated registry of AF in clinical practice. Thyroid hormones should be considered a biomarker for cardiac arrhythmias screening and their tailored management because of their multifaceted cellular actions.


Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Hipertireoidismo/complicações , Hipertireoidismo/metabolismo , Transdução de Sinais , Hormônios Tireóideos/metabolismo , Arritmias Cardíacas/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etiologia , Cálcio/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Metabolismo Energético/efeitos dos fármacos , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/etiologia , Canais Iônicos/metabolismo , Terapia de Alvo Molecular , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/terapia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia
17.
Clin Nucl Med ; 45(6): 439-441, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32349091

RESUMO

A 74-year-old woman with hyperthyroidism was referred for radioiodine therapy. The patient was accidentally given 60 mCi of Lu-PSMA orally instead of I. Upon discovery of this medical event, we immediately started radiation protective actions including hydration, antiemetics, and laxatives. The patients did not have any symptoms. Static acquisition was performed from the abdominal-pelvic and head and neck regions at 20 and 90 hours after ingestion, which showed prominent intestinal activity and mild systemic activity in the kidneys, bladder, salivary, and lacrimal glands.


Assuntos
Hipertireoidismo/radioterapia , Lutécio/administração & dosagem , Erros Médicos , Radioisótopos/administração & dosagem , Administração Oral , Idoso , Feminino , Humanos , Hipertireoidismo/metabolismo , Radioisótopos do Iodo/uso terapêutico , Lutécio/efeitos adversos , Lutécio/farmacocinética , Masculino , Radioisótopos/efeitos adversos , Radioisótopos/farmacocinética
18.
Sci Rep ; 10(1): 6992, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332761

RESUMO

The aim of the research is to explore the relationship between hyperthyroidism, iodine, antithyroid drugs (propylthiouracil) and vascular endothelial injury. In total, 136 SD rats were randomly allocated into the control group, the hyperthyroidism group, the hyperthyroidism propylthiouracil group, the hyperthyroidism low iodine group, the high iodine group, and the endothelial injury group. Rats were raised for 60 days. Afterward, indicators concerning endothelial damage were determined, including the von Willebrand Factor (vWF), thrombomodulin (TM), nitric oxide (NO), endothelin 1 (ET-1), and P-selectin, as well as the plant hemagglutinin sample type oxidized low-density lipoprotein receptor 1 (LOX-1) from the aorta and the number of endothelial progenitor cells (EPCs) in whole blood. The hyperthyroidism group had significantly higher values for vWF, TM, NO, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with the control group, similar to the LOX-1 expression in abdominal aorta. The hyperthyroidism low iodine group had significantly higher values for vWF, ET-1, and P-selectin in serum and a higher number of EPCs in whole blood compared with those of the control group, as was the case for LOX-1 expression in the abdominal aorta. The hyperthyroidism propylthiouracil group had significantly higher values for FT4 in the serum compared with those in the control group. The electron microscope showed that hyperthyroidism caused a certain degree of endothelial injury to the abdominal aorta in rats. Hyperthyroidism can damage the vascular endothelium and is a high-risk factor for cardio-cerebrovascular disease. Propylthiouracil could be used in the treatment of hyperthyroidism, thus protecting endothelial cells from damage.


Assuntos
Células Endoteliais/metabolismo , Hipertireoidismo/sangue , Hipertireoidismo/patologia , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/patologia , Animais , Células Progenitoras Endoteliais/metabolismo , Endotelina-1/metabolismo , Feminino , Hipertireoidismo/metabolismo , Masculino , Óxido Nítrico/metabolismo , Selectina-P/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Fatores de Risco , Receptores Depuradores Classe E/metabolismo , Trombomodulina/metabolismo , Doenças da Glândula Tireoide/metabolismo , Fator de von Willebrand/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-32300332

RESUMO

Purpose: Lipid metabolism has been poorly explored in subclinical hyperthyroidism. The aim was to examine the effects of exogenous subclinical hyperthyroidism in women under levothyroxine treatment upon plasma lipids and aspects of HDL metabolism. Methodology: Ten women were studied in euthyroidism and again in exogenous subclinical hyperthyroidism. Thyroid function tests and plasma lipids were studied. Results: HDL-cholesterol (increased 21.6%, p = 0.0004), unesterified cholesterol (increased 12.3%, p = 0.04) and Lp(a) (increased 33,3%, P = 0.02) plasma concentrations were higher in subclinical hyperthyroidism compared to euthyroidism, but total cholesterol, LDL, non-HDL cholesterol, triglycerides, apo A-I, apo B were unchanged. PON1 activity (decreased 75%, p = 0.0006) was lower in subclinical hyperthyroidism. There were no changes in HDL particle size, CETP and LCAT concentrations. The in vitro assay that estimates the lipid transfers to HDL showed that esterified cholesterol (increased 7.1%, p = 0.03), unesterified cholesterol (increased 7.8%, p = 0.02) and triglycerides (increased 6.8%, p = 0.006) transfers were higher in subclinical hyperthyroidism. There were no changes in phospholipid transfers to HDL in subclinical hyperthyroidism. Conclusions: Several alterations in the plasma lipid metabolism were observed in the subclinical hyperthyroidism state that highlight the importance of this aspect in the follow-up of those patients. The increase in HDL-C and in the transfer of unesterified and esterified cholesterol to HDL, an important anti-atherogenic HDL function are consistently protective for cardiovascular health. The increase in Lp(a) and the decrease in PON-1 activity that are important risk factors were documented here in subclinical hyperthyroidism and these results should be confirmed in larger studies due to great data variation but should not be neglected in the follow-up of those patients.


Assuntos
Adenocarcinoma/cirurgia , Colesterol/sangue , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/metabolismo , Lipoproteínas/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Tiroxina/efeitos adversos , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adulto , Doenças Assintomáticas , Brasil , Estudos de Casos e Controles , HDL-Colesterol/sangue , Feminino , Terapia de Reposição Hormonal , Humanos , Hipertireoidismo/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/sangue , Pessoa de Meia-Idade , Testes de Função Tireóidea , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/metabolismo , Tireoidectomia/reabilitação , Tiroxina/farmacologia
20.
Int J Cancer ; 147(7): 1895-1903, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32215913

RESUMO

Whether thyroid dysfunction plays a causal role in the development of cancer remains inconclusive. We conducted a two-sample Mendelian randomization study to investigate the associations between genetic predisposition to thyroid dysfunction and 22 site-specific cancers. Single-nucleotide polymorphisms associated with four traits of thyroid function were selected from a genome-wide association meta-analysis with up to 72,167 European-descent individuals. Summary-level data for breast cancer and 21 other cancers were extracted from the Breast Cancer Association Consortium (122,977 breast cancer cases and 105,974 controls) and UK Biobank (367,643 individuals). For breast cancer, a meta-analysis was performed using data from both sources. Genetically predicted thyroid dysfunction was associated with breast cancer, with similar patterns of associations in the Breast Cancer Association Consortium and UK Biobank. The combined odds ratios of breast cancer were 0.94 (0.91-0.98; p = 0.007) per genetically predicted one standard deviation increase in TSH levels, 0.96 (0.91-1.00; p = 0.053) for genetic predisposition to hypothyroidism, 1.04 (1.01-1.07; p = 0.005) for genetic predisposition to hyperthyroidism and 1.07 (1.02-1.12; p = 0.003) per genetically predicted one standard deviation increase in free thyroxine levels. Genetically predicted TSH levels and hypothyroidism were inversely with thyroid cancer; the odds ratios were 0.47 (0.30-0.73; p = 0.001) and 0.70 (0.51-0.98; p = 0.038), respectively. Our study provides evidence of a causal association between thyroid dysfunction and breast cancer (mainly ER-positive tumors) risk. The role of TSH and hypothyroidism for thyroid cancer and the associations between thyroid dysfunction and other cancers need further exploration.


Assuntos
Neoplasias da Mama/epidemiologia , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Análise da Randomização Mendeliana/métodos , Neoplasias da Glândula Tireoide/epidemiologia , Bancos de Espécimes Biológicos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Masculino , Polimorfismo de Nucleotídeo Único , Testes de Função Tireóidea , Glândula Tireoide/fisiologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/fisiopatologia , Tireotropina/metabolismo
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