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1.
Expert Rev Endocrinol Metab ; 16(5): 251-257, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34424110

RESUMO

OBJECTIVE: There is an increasing body of literature on the impact of COVID-19 on the pituitary-thyroid axis. Therefore, we conducted a systematic review to assess the prevalence of hypothyroidism in patients with COVID-19. METHODS: A literature review was conducted using LitCOVID for study selection in PubMed and MEDLINE till May 2021. All relevant original articles evaluating thyroid dysfunction were included and information regarding the prevalence of hypothyroid disease in COVID-19 was retrieved from the eligible articles. RESULTS: Out of 32 articles, six articles qualified for the final analysis which included 1160 patients. There was significant heterogeneity among the included articles. Most of the patients had lower mean triiodothyronine (T3) and normal or low thyroid-stimulating hormone (TSH). Increased TSH ranged from 5.1% to 8% while low T3 was present in up to 28% of the patients. In these studies, the prevalence of altered thyroid hormones was significantly more in COVID-19 patients as compared to control groups. A positive correlation between low mean T3 and clinical severity of COVID-19 was reported. CONCLUSION: This systematic review reveals a significant proportion of hypothyroidism associated with COVID-19. Therefore, routine assessment of thyroid function is warranted in hospitalized COVID-19 patients.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hormônios Tireóideos/sangue , COVID-19/diagnóstico , Humanos , Hipotireoidismo/diagnóstico , Glândula Tireoide/metabolismo , Glândula Tireoide/virologia
3.
J Med Life ; 14(2): 243-249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104248

RESUMO

The thyroid hormone plays a vital role in the development and maturation of the nervous system not only during prenatal and perinatal age but also in adults. "Peripheral marker hypothesis" revealed that gene expression changes in some regions of the brain are reflected into the peripheral blood lymphocytes. The objective of the study was to investigate changes in the gene expression profile of neuropeptides and their receptors in patients with different forms of thyroid pathology. One hundred fifty-three patients with thyroid pathology were enrolled in the study. They were divided into three groups: group 1 included 16 patients with postoperative hypothyroidism, group 2 included 65 patients with hypothyroidism resulting from autoimmune thyroiditis (AIT), and group 3 included 72 patients with AIT and elevated levels of anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies in the serum. We used a pathway-specific polymerase chain reaction (PCR) array (RT2 Profiler™ PCR Array Human Neurotrophins & Receptors, QIAGEN, Germany) to identify and verify neuropeptides and receptors pathway-focused gene expression in 12 individuals that were randomly selected from each group using real-time PCR. Our research identified that patients with postoperative hypothyroidism had a considerably increased expression of NPY1R, NTSR1, and NPY4R. The patients with hypothyroidism caused by autoimmune thyroiditis had considerably lower expression of NTSR1, while the expression of NPY1R increased. The mRNA levels of NPY2R and PNOC increased in the patients with elevated levels of autoantibodies anti-Tg and anti-TPO in the serum, and mRNA levels of NPY1R and NTSR1 decreased in this group of patients.


Assuntos
Neuropeptídeos/sangue , Neuropeptídeos/genética , Receptores de Neuropeptídeos/sangue , Receptores de Neuropeptídeos/genética , Glândula Tireoide/patologia , Transcrição Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Alemanha , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/genética , Pessoa de Meia-Idade , Neuropeptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Neuropeptídeos/metabolismo , Tireoidite Autoimune/sangue , Tireoidite Autoimune/genética
4.
J Biochem Mol Toxicol ; 35(8): e22814, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34047416

RESUMO

The aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)-induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU-induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T3 ), thyroxine (T4 ), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid-related protein targets, such as human thyroid hormone receptor ß (hTRß), and thyroid peroxidase (TPO) protein, were studied using molecular docking. Whereas in hypothyroid animals, T4 , T3 , and antioxidants were decreased, there was an increase in TSH, TNF-α, IL-6, ALT, AST, and hepatic LPO; administration of SA in PTU-induced animals reversed all these indices to near normal levels. SA also improved the histological features of liver and thyroid gland. Our study clearly demonstrates SA as a novel thyroid agonist for augmenting the thyroid functions in rats. Molecular docking analysis reveals that SA possesses good binding affinity toward both the targets, hTRß and TPO. Through this approach, for the first time we provide the evidence for SA as a novel thyroid agonist and suggest a receptor-mediated mechanism for its thyroid stimulatory potential.


Assuntos
Ácido Gálico/análogos & derivados , Hipotireoidismo , Propiltiouracila/efeitos adversos , Receptores beta dos Hormônios Tireóideos/agonistas , Animais , Feminino , Ácido Gálico/farmacologia , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Propiltiouracila/farmacologia , Ratos , Ratos Wistar , Receptores beta dos Hormônios Tireóideos/metabolismo
5.
Am J Med ; 134(9): 1115-1126.e1, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33872585

RESUMO

BACKGROUND: Few studies have scrutinized the spectrum of symptoms in subclinical hypothyroidism. METHODS: From 3 Danish Investigation on Iodine Intake and Thyroid Diseases (DanThyr) cross-sectional surveys performed in the period 1997 to 2005, a total of 8903 subjects participated in a comprehensive investigation including blood samples and questionnaires on previous diseases, smoking habits, alcohol intake, and education. From the 3 surveys we included patients with subclinical hypothyroidism (n = 376) and euthyroid controls (n = 7619). We explored to what extent patients with subclinical hypothyroidism reported 13 previously identified hypothyroidism-associated symptoms (tiredness, dry skin, mood lability, constipation, palpitations, restlessness, shortness of breath, wheezing, globus sensation, difficulty swallowing, hair loss, dizziness/vertigo, and anterior neck pain). In various uni- and multivariate regression models we searched for circumstances predicting why some patients have more complaints than others. RESULTS: Subclinically hypothyroid patients did not report higher hypothyroidism score [(median, interquartile range), 2 (0-4) vs 2 (0-4), P = .25] compared with euthyroid controls. Within the group of subclinical hypothyroid patients, comorbidity had the highest impact on symptoms (tiredness, shortness of breath, wheezing; all P < .001); TSH level had no impact on symptom score; and younger age was accompanied by higher mental burden (tiredness, P < .001; mood lability, P < .001; restlessness, P = .012), whereas shortness of breath was associated with high body mass index (P < .001) and smoking (P = .007). CONCLUSION: Patients with a thyroid function test suggesting subclinical hypothyroidism do not experience thyroid disease-related symptoms more often than euthyroid subjects. In subclinical hypothyroidism, clinicians should focus on concomitant diseases rather than expecting symptomatic relief following levothyroxine substitution.


Assuntos
Doenças Assintomáticas/epidemiologia , Hipotireoidismo , Avaliação de Sintomas , Tireotropina/análise , Tiroxina/uso terapêutico , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Dinamarca/epidemiologia , Escolaridade , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Hipotireoidismo/psicologia , Masculino , Saúde Mental , Pessoa de Meia-Idade , Fumar/epidemiologia , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
6.
Fertil Steril ; 116(1): 218-231, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33838869

RESUMO

OBJECTIVE: To investigate the impact of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) on thyroid function. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing conventional IVF or intracytoplasmic sperm injection. INTERVENTION(S): Systematic search of PubMed, MEDLINE, Embase, Scopus, and Web of Science from inception until November 2020. Studies could be included only if they met the following criteria: subjects were classified as euthyroid or hypothyroid; serum thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) levels were evaluated before COH; and the same thyroid function test was reassessed after COH (i.e., at the time of trigger for final follicle maturation and/or at pregnancy test). MAIN OUTCOME MEASURE(S): Mean difference (MD) between the serum TSH or FT4 levels assessed after COH and before COH. RESULT(S): In euthyroid women, the serum TSH levels assessed at the time of trigger and at the time of pregnancy test were significantly higher than those at baseline (MD: 0.69 mIU/L, 95% confidence interval [CI]: 0.30-1.08, I2 = 93% and MD: 0.67, 95% CI: 0.49-0.85, I2 = 72%, respectively). The serum FT4 levels did not undergo significant changes. Subanalysis confirmed an increase in the TSH level after restricting the analysis to women treated with gonadotropin-releasing hormone agonist protocols and to those who achieved pregnancy. A pronounced increase in the TSH level was observed in women treated for hypothyroidism (MD: 1.50 mIU/L, 95% CI: 1.10-1.89, I2 = 0%). CONCLUSION(S): Pooling of the results showed a significant increase in serum TSH level in women undergoing COH for IVF. This change was particularly pronounced in women treated for hypothyroidism. New thyroid function screening strategies for women undergoing COH are warranted.


Assuntos
Fertilização In Vitro , Hipotireoidismo/fisiopatologia , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/efeitos adversos , Ovulação/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Biomarcadores/sangue , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Masculino , Gravidez , Fatores de Risco , Injeções de Esperma Intracitoplásmicas , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Resultado do Tratamento
7.
Nutrients ; 13(3)2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33799943

RESUMO

Iodine is an essential micronutrient for the synthesis of thyroid hormones. The proper functioning of the thyroid axis is essential for the normal development of the nervous system, especially in the first trimester of gestation. The aim of the present study was to analyze the perinatal outcomes, anthropometry, and APGAR test scores of newborns and to relate them to maternal thyroid status. A total of 190 newborns participated in the study. No correlation was found between thyroid stimulating hormone (TSH) and maternal ioduria values in the first trimester of gestation with the weight or length of the newborn, or the APGAR score at one minute after birth. However, we found significant differences between the APGAR scores of children whose mothers had an iodine sufficiency level in the first trimester compared to the children of mothers with iodine deficiency. Similarly, the APGAR scores of children whose mothers had a TSH > 4 have significantly better APGAR scores than the children of mothers with a TSH < 4. Likewise, we found significant differences between the measurements of the newborns depending on whether their mothers smoked. The children of mothers who took iodine supplements or iodized salt obtained the highest APGAR score at one and five minutes after birth. It is essential to focus on recommending adequate consumption of iodine supplements and iodized salt prior to gestation and at least during the first trimester to achieve better fetal well-being.


Assuntos
Iodo/análise , Resultado da Gravidez , Primeiro Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/urina , Tireotropina/sangue , Adulto , Antropometria , Índice de Apgar , Suplementos Nutricionais/estatística & dados numéricos , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/urina , Recém-Nascido , Iodo/deficiência , Iodo/urina , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/urina , Cuidado Pré-Natal/estatística & dados numéricos , Cloreto de Sódio na Dieta/análise , Glândula Tireoide/fisiopatologia
8.
Medicine (Baltimore) ; 100(17): e25738, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907168

RESUMO

BACKGROUND: Whether hypothyroidism is related to non-alcoholic fatty liver disease (NAFLD) is controversial. Our aim was to investigate the relationship between NAFLD and hypothyroidism that may predict the NAFLD potential of these lesions and new prevention strategies in hypothyroidism patients. METHODS: Totally 51,407 hypothyroidism patients with average 28.23% NAFLD were analyzed by Revman 5.3 and Stata 15.1 softwares in the present study. The PubMed and Embase databases were systematically searched for works published through May 9, 2020. RESULTS: The blow variables were associated with an increased risk of NAFLD in hypothyroidism patients as following: increased of thyroid stimulating hormone (TSH) levels (odds ratio [OR] = 1.23, 1.07-1.39, P = .0001); old age (mean difference [MD] = 3.18, 1.57-4.78, P = .0001); increased of body mass index (BMI) (MD = 3.39, 2.79-3.99, P < .000001); decreased of free thyroxine 4 (FT4) levels (MD = -0.28, -0.53 to -0.03, P = .03). In addition, FT3 (MD = 0.11, -0.09-0.3, P = .29) had no association with the risk of NAFLD in hypothyroidism patients. CONCLUSION: Our systematic review identified results are as following: hypothyroidism was positively associated with the risk of NAFLD. The increased concentration of TSH levels maybe a risk factor that increased incidence of NAFLD. The BMI of NAFLD patients was significantly higher than that of non-NAFLD patients. Old age was significantly associated with the incidence of NAFLD. FT4 was significantly associated with the risk of NAFLD due to its negatively effect while FT3 was not significantly related to the risk of NAFLD. Taken together, the present meta-analysis provides strong evidence that hypothyroidism may play a vital role in the progression and the development of NAFLD.


Assuntos
Hipotireoidismo , Hepatopatia Gordurosa não Alcoólica , Tireotropina/sangue , Progressão da Doença , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Fatores de Risco , Testes de Função Tireóidea
9.
J Med Case Rep ; 15(1): 108, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33653380

RESUMO

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.


Assuntos
Hipotireoidismo/diagnóstico , Tireoidite Autoimune/diagnóstico , Alopecia/fisiopatologia , Apetite , Autoanticorpos/imunologia , Constipação Intestinal/fisiopatologia , Depressão/fisiopatologia , Fadiga/fisiopatologia , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Achados Incidentais , Iodeto Peroxidase/imunologia , Menorragia/fisiopatologia , Índice de Gravidade de Doença , Glândula Tireoide/diagnóstico por imagem , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Tireoidite Autoimune/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Ultrassonografia , Ganho de Peso , Adulto Jovem
10.
Ann R Coll Surg Engl ; 103(5): 367-373, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33682437

RESUMO

INTRODUCTION: It has been established that thyroid-stimulating hormone (TSH) stimulates the growth and development of thyroid malignancy, and a higher serum TSH level is associated with the incidence of thyroid cancer and an advanced tumour stage. This study aimed to evaluate the association of preoperative subclinical hypothyroidism with the prognosis of papillary thyroid cancer (PTC). METHODS: A total of 466 patients who underwent surgery for PTC between December 2006 and June 2009 were enrolled. Among them, 44 patients had subclinical hypothyroidism, while 422 did not have subclinical hypothyroidism, as diagnosed using the preoperative thyroid function test. We compared the recurrence rate and association with clinicopathological features in the two groups. RESULTS: The median patient age was 46.9 years (17-74 years). There were 420 female and 46 male patients. The median follow-up duration was 81.4 months. There were no statistical differences between the two groups with respect to age, sex, tumour size, extrathyroidal extension, multifocality, lymph node metastasis, TNM stages, recurrence and disease-free survival, despite a significant difference in the average TSH concentrations of the two groups. CONCLUSIONS: Our results suggest that preoperative subclinical hypothyroidism was not associated with tumour aggressiveness and recurrence in PTC.


Assuntos
Hipotireoidismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/mortalidade , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/mortalidade , Tireotropina/sangue , Adulto Jovem
11.
JAMA Netw Open ; 4(2): e2036645, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566107

RESUMO

Importance: Previous trials on the effect of levothyroxine on depressive symptom scores in patients with subclinical hypothyroidism were limited by small sample sizes (N = 57 to 94) and potential biases. Objective: To assess the effect of levothyroxine on the development of depressive symptoms in older adults with subclinical hypothyroidism in the largest trial on this subject and to update a previous meta-analysis including the results from this study. Design, Setting, and Participants: This predefined ancillary study analyzed data from participants in the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism (TRUST) trial, a double-blind, randomized, placebo-controlled, parallel-group clinical trial conducted from April 2013 to October 31, 2016. The TRUST trial included adults aged 65 years or older diagnosed with subclinical hypothyroidism, defined as the presence of persistently elevated thyroid-stimulating hormone (TSH) levels (4.6-19.9 mIU/L) with free thyroxine (T4) within the reference range. Participants were identified from clinical and general practitioner laboratory databases and recruited from the community in Switzerland, the Netherlands, Ireland, and the UK. This ancillary study included a subgroup of 472 participants from the Netherlands and Switzerland; after exclusions, a total of 427 participants (211 randomized to levothyroxine and 216 to placebo) were analyzed. This analysis was conducted from December 1, 2019, to September 1, 2020. Interventions: Randomization to either levothyroxine or placebo. Main Outcomes and Measures: Depressive symptom scores after 12 months measured with the Geriatric Depression Scale (GDS-15), with higher scores indicating more depressive symptoms (minimal clinically important difference = 2). Results: A total of 427 participants with subclinical hypothyroidism (mean [SD] age, 74.52 [6.29] years; 239 women [56%]) were included in this analysis. The mean (SD) TSH level was 6.57 (2.22) mIU/L at baseline and decreased after 12 months to 3.83 (2.29) mIU/L in the levothyroxine group; in the placebo group, it decreased from 6.55 (2.04) mIU/L to 5.91 (2.66) mIU/L. At baseline, the mean (SD) GDS-15 score was 1.26 (1.85) in the levothyroxine group and 0.96 (1.58) in the placebo group. The mean (SD) GDS-15 score at 12 months was 1.39 (2.13) in the levothyroxine and 1.07 (1.67) in the placebo group with an adjusted between-group difference of 0.15 for levothyroxine vs placebo (95% CI, -0.15 to 0.46; P = .33). In a subgroup analysis including participants with a GDS-15 of at least 2, the adjusted between-group difference was 0.61 (95% CI, -0.32 to 1.53; P = .20). Results did not differ according to age, sex, or TSH levels. A previous meta-analysis (N = 278) on the association of levothyroxine with depressive symptoms was updated to include these findings, resulting in an overall standardized mean difference of 0.09 (95% CI, -0.05 to 0.22). Conclusions and Relevance: This ancillary study of a randomized clinical trial found that depressive symptoms did not differ after levothyroxine therapy compared with placebo after 12 months; thus, these results do not provide evidence in favor of levothyroxine therapy in older persons with subclinical hypothyroidism to reduce the risk of developing depressive symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT01853579.


Assuntos
Doenças Assintomáticas , Depressão/psicologia , Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/psicologia , Masculino , Tireotropina/sangue , Tiroxina/sangue , Resultado do Tratamento
12.
Mol Cell Endocrinol ; 525: 111173, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33549603

RESUMO

The hypothalamus-pituitary-thyroid axis is one of several hormone regulatory systems from the hypothalamus to the pituitary and ultimately to the peripheral target organs. The hypothalamus and the pituitary gland are in close anatomical proximity at the base of the brain and extended through the pituitary stalk to the sella turcica. The pituitary stalk allows passage of stimulatory and inhibitory hormones and other signal molecules. The target organs are placed in the periphery and function through stimulation/inhibition by the circulating pituitary hormones. The several hypothalamus-pituitary-target organ axis systems interact in very sophisticated and complicated ways and for many of them the interactive and integrated mechanisms are still not quite clear. The diagnosis of central hypothyroidism is complicated by itself but challenged further by concomitant affection of other hypothalamus-pituitary-hormone axes, the dysfunction of which influences the diagnosis of central hypothyroidism. Treatment of both the central hypothyroidism and the other hypothalamus-pituitary axes also influence the function of the others by complex mechanisms involving both central and peripheral mechanisms. Clinicians managing patients with neuroendocrine disorders should become aware of the strong integrative influence from each hypothalamus-pituitary-hormone axis on the physiology and pathophysiology of central hypothyroidism. As an aid in this direction the present review summarizes and highlights the importance of the hypothalamus-pituitary-thyroid axis, pitfalls in diagnosing central hypothyroidism, diagnosing/testing central hypothyroidism in relation to panhypopituitarism, pointing at interactions of the thyroid function with other pituitary hormones, as well as local hypothalamic neurotransmitters and gut-brain hormones. Furthermore, the treatment effect of each axis on the regulation of the others is described. Finally, these complicating aspects require stringent diagnostic testing, particularly in clinical settings with lower or at least altered à priori likelihood of hypopituitarism than in former obvious clinical patient presentations.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Glândula Tireoide/fisiopatologia , Animais , Hormônios/sangue , Hormônios/metabolismo , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/patologia , Hipopituitarismo/fisiopatologia , Sistema Hipotálamo-Hipofisário/patologia , Hipotireoidismo/sangue , Hipotireoidismo/patologia , Hipotireoidismo/fisiopatologia , Modelos Biológicos , Glândula Tireoide/patologia
13.
Res Vet Sci ; 136: 6-10, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550147

RESUMO

Hypothyroidism is one of the most commonly diagnosed endocrine disease in dogs. The clinical signs are caused by a deficiency of the active thyroid hormones triiodothyronine (T3) and thyroxine (T4) and have a negative impact on dog's quality of life. We hypothesized that serum metabolic profile varies between healthy dogs and dogs with hypothyroidism. Twenty serum samples from dogs with hypothyroidism and 20 from healthy dogs were used for untargeted metabolomics analysis performed by LC/MS analysis. Fifteen metabolites showed significant changes between hypothyroid and healthy dogs, being the pentose phosphate pathway (PPP), aminoacyl-tRNA biosynthesis and pyrimidine metabolism the principal pathways altered in hypothyroidism. Specifically, metabolites such as D-gluconic acid and L-Isoleucine may potentially act as biomarkers of disease.


Assuntos
Doenças do Cão/sangue , Hipotireoidismo/veterinária , Animais , Doenças do Cão/diagnóstico , Cães , Feminino , Hipotireoidismo/sangue , Masculino , Metaboloma , Metabolômica , Qualidade de Vida , Tiroxina/sangue , Tri-Iodotironina/sangue
14.
Int J Radiat Oncol Biol Phys ; 110(2): 462-472, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412261

RESUMO

PURPOSE: To study the hypothyroidism risk after adjuvant radiation therapy (RT) and the association of different RT targets with hypothyroidism risk. METHODS: We studied 4073 women treated with adjuvant RT for breast cancer from 2007 to 2016. The primary endpoint was hypothyroidism development after RT. Patients were divided and analyzed into 3 groups: whole breast (WB)-alone (n = 2468), regional node irradiation (RNI)-Lv.4 (n = 215; cranial border at the subclavian artery, according to the European Society for Radiotherapy and Oncology consensus guideline), and RNI-supraclavicular lymph node (SCL) (n = 1390; cranial border at the cricoid cartilage). In general, RNI-Lv.4 was used in the patients with high-risk pN0 and pN1 breast cancer. In auxiliary analysis, the mean thyroid dose was estimated in each group (total n = 600, 200 from each group). All the doses were converted to the equivalent dose in 2 Gy fractions (EQD2) with α/ß ratios of 3. RESULTS: The median follow-up duration was 84 months (WB-alone, 84 months; RNI-Lv.4, 44 months; RNI-SCL, 91 months). The 3-year hypothyroidism incidence rate differed significantly between the RNI-SCL and WB-alone groups (2.2% vs 0.8%; Bonferroni corrected P [Pc] < .001) but not between the RNI-Lv.4 and WB-alone groups (0.9% vs 0.8%; Pc > .05). The Cox model revealed an adjusted hazard ratio of 2.25 (95% CI, 1.49-3.38) for RNI-SCL vs WB-alone, 1.69 (95% CI, 1.12-2.56) for adjuvant systemic therapies, and 2.07 (95% CI, 1.07-3.99) for age <60 years. In the subgroup analysis, the hypothyroidism risk became more prominent in patients aged <60 years. The mean exposure doses to the thyroid were 0.23 versus 1.93 versus 7.89 Gy (EQD2) for the WB-alone versus RNI-Lv.4 versus RNI-SCL groups (P < .001). No statistically different locoregional recurrence rates were seen between groups (5-year rate: <3%). CONCLUSIONS: The risk of hypothyroidism increases after RNI-SCL for breast cancer but not after RNI-Lv 4. These data support routine contouring of the thyroid in the RNI setting, and future studies are required to develop optimal dose-volume constraints.


Assuntos
Neoplasias da Mama/radioterapia , Hipotireoidismo/etiologia , Glândula Tireoide/efeitos da radiação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Incidência , Irradiação Linfática/efeitos adversos , Mastectomia , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Modelos de Riscos Proporcionais , Doses de Radiação , Radioterapia Adjuvante/efeitos adversos , Radioterapia de Intensidade Modulada , Risco , Hormônios Tireóideos/sangue , Fatores de Tempo , Adulto Jovem
15.
Artif Cells Nanomed Biotechnol ; 49(1): 61-70, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33410369

RESUMO

Determination of thyroid-stimulating hormone (TSH) level in serum or plasma is defined as a sensitive method for the diagnosis of hyperthyroidism and hypothyroidism and also in many diseases thought to be related to TSH levels. In this study, a novel simple impedimetric immunosensor based on polyamidoamine dendrimer was developed. Anti TSH antibody was immobilized on the gold electrode by using cysteamine self-assembled monolayer strategy. In constructing the immunosensor, a polyamidoamine dendrimer was used to increase the surface area in which Anti-TSH was immobilized and glutaraldehyde was used as a cross-linker. After each immobilization step, the electrode surface was monitored by electrochemical impedance spectroscopy, cyclic voltammetry, scanning electron microscopy and energy-dispersive X-ray spectroscopy techniques and optimization studies were performed. The reproducibility, repeatability, linearity and sensitivity of the immunosensor were examined. Also, the interference experiments for glucose, salts and proteins in serum were performed. The limit of detection and limit of quantification values of the proposed immunosensor were 0.026 mIUL-1 and 0.086 mIUL-1, respectively and it was able to detect the amount of TSH within a linear range of 0.1-0.6 mIUL-1.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Hipotireoidismo/sangue , Tireotropina/sangue , Humanos , Imunoensaio , Limite de Detecção
16.
Mol Cell Endocrinol ; 524: 111157, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33421531

RESUMO

Both the cholinergic pathway and oxidative stress are important mechanisms involved in the pathogenesis of hypothyroidism, a condition characterized by low levels of thyroid hormone that predispose the patient to brain dysfunction. Phenolic compounds have numerous health benefits, including antioxidant activity. This study evaluates the preventive effects of resveratrol in the cholinergic system and redox status in rats with methimazole-induced hypothyroidism. Hypothyroidism increases acetylcholinesterase (AChE) activity and density in the cerebral cortex and hippocampus and decreases the α7 and M1 receptor densities in the hippocampus. Hypothyroidism also increases cellular levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), but reduces total thiol content, and catalase and superoxide dismutase activities in the serum. In the cerebral cortex and hippocampus, hypothyroidism increases the levels of ROS and nitrites. In this study, resveratrol (50 mg/kg) treatment prevents the observed increase in AChE in the cerebral cortex, and increases the protein levels of NeuN, a marker of mature neurons. Resveratrol also prevents changes in serum ROS levels and brain structure, as well as the levels of TBARS, total thiol content, and serum catalase enzyme activity. These collective findings suggest that resveratrol has a high antioxidant capacity and can restore hypothyroidism-triggered alterations related to neurotransmission. Thus, it is a promising agent for the prevention of brain damage resulting from hypothyroidism.


Assuntos
Colinérgicos/metabolismo , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Neuroproteção/efeitos dos fármacos , Resveratrol/farmacologia , Transdução de Sinais , Acetilcolinesterase/metabolismo , Animais , Antígenos Nucleares/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/metabolismo , Hipotireoidismo/sangue , Masculino , Proteínas do Tecido Nervoso/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Receptores Colinérgicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiroxina/sangue , Tri-Iodotironina/sangue
17.
Clin Hemorheol Microcirc ; 77(2): 133-142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33074218

RESUMO

BACKGROUND: Inflammation has an important role in the pathogenesis of atherosclerosis. Lymphocyte-to-monocyte ratio (LMR) is accepted as an indicator of inflammation. OBJECTIVE: Our aim was to scrutinize the relationship between LMR and subclinical atherosclerosis (SubAth) measured by carotid intima-media thickness (CIMT) in subclinical hypothyroidism (SubHT). METHODS: Newly identified 190 SubHT patients were prospectively included into the study. Blood samples were taken for measuring laboratory parameters. Then, CIMT was computed. Patients were seperated into 2 groups by their CIMT value (Group-1: ≤0.9 and Group-2: >0.9 mm), and then stratified into tertiles pursuant to LMR and thyroid-stimulating hormone (TSH) levels, respectively. RESULTS: 59 patients had an increased CIMT value (Group-2), and 131 patients had a normal CIMT value (Group-1). Group-2 had a lower LMR and a greater high-sensitivity C-reactive protein (hsCRP), CIMT and TSH than Group-1 (for all, p < 0.05). Patients in the lowest tertile of LMR had a higher hsCRP, TSH and CIMT than those in the highest tertile (for all, p < 0.05). LMR was negatively associated with hsCRP, CIMT and TSH (for all, p < 0.05). LMR and TSH were independent predictors of increased CIMT. CONCLUSIONS: Pre-ultrasonographic LMR, which is a simple and inexpensive inflammatory marker, may give additional predictive information to determine SubAth in SubHT.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Espessura Intima-Media Carotídea/normas , Hipotireoidismo/sangue , Linfócitos/metabolismo , Monócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Am J Cardiol ; 139: 57-63, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33115640

RESUMO

Thyroid dysfunction is common in patients with chronic heart failure (CHF), but there is conflicting evidence regarding its prognostic significance. We investigated the relation between thyroid function and prognosis in a large, well characterized cohort of ambulatory patients with CHF. Heart failure was defined as signs and symptoms of the disease and either left ventricular systolic dysfunction (LVSD) mild or worse (heart failure with reduced ejection fraction [HFrEF]), or no LVSD and raised amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L; heart failure with normal ejection fraction [HFnEF]). Euthyroid state was defined as a thyroid-stimulating hormone (TSH) level between 0.35 and 4.70 mIU/l, hypothyroidism as TSH >4.70 mIU/l, and hyperthyroidism as TSH <0.35 mIU/l. 2997 patients had HFrEF and 1995 patients had HFnEF. 4491 (90%) patients were euthyroid, 312 (6%) were hypothyroid, and 189 (4%) were hyperthyroid. In univariable analysis, both hypothyroid patients (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.08 to 1.45) and hyperthyroid patients (HR 1.21, 95% CI 1.01 to 1.46) had a greater risk of death compared with euthyroid patients. There was a U-shaped relation between TSH and outcome. Increasing TSH was a predictor of mortality in univariable analysis (HR 1.02, 95% CI 1.01 to 1.03), but the association disappeared in multivariable analysis. The three strongest predictors of adverse outcome were increasing age, increasing NT-proBNP, and higher NYHA class. In conclusion, although thyroid dysfunction is associated with worse survival in patients with CHF, it is not an independent predictor of mortality.


Assuntos
Insuficiência Cardíaca/mortalidade , Hipotireoidismo/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Sistema de Registros , Volume Sistólico/fisiologia , Glândula Tireoide/fisiopatologia , Tireotropina/sangue , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipotireoidismo/etiologia , Hipotireoidismo/fisiopatologia , Masculino , Prognóstico , Precursores de Proteínas , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Glândula Tireoide/metabolismo , Reino Unido/epidemiologia
19.
Eur J Endocrinol ; 184(2): C1-C3, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33306038

RESUMO

Since the introduction of sensitive assays for serum thyroid-stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at the tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that the implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.


Assuntos
Hipotireoidismo/diagnóstico , Hipotireoidismo/terapia , Planejamento de Assistência ao Paciente , Tiroxina/uso terapêutico , Endocrinologia/métodos , Endocrinologia/normas , Endocrinologia/tendências , Prática Clínica Baseada em Evidências , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/normas , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/mortalidade , Ciência da Implementação , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos , Medicina de Precisão/normas , Prognóstico , Valores de Referência , Fatores de Risco , Inquéritos e Questionários , Hormônios Tireóideos/sangue , Tireotropina/sangue
20.
Toxicol Appl Pharmacol ; 411: 115367, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33340518

RESUMO

Pexacerfont is a corticotrophin-releasing factor subtype 1 receptor (CRF-1) antagonist developed for potential treatment of anxiety and stress-related disorders. In male rats, pexacerfont caused hepatic enzyme induction leading to increased thyroxine (T4) clearance. When administered to pregnant rats on gestation day 6 to 15, pexacerfont at 300 mg/kg/day (30× mean AUC in humans at 100 mg/day) produced similar effects on thyroid homeostasis with serum T4 and thyroid-stimulating hormone levels that were 0.3-0.5× and 3.3-3.7× of controls, respectively. At this dose, fetuses of pexacerfont-treated dams presented findings associated with maternal hypothyroidism including growth retardation and increased skeletal alterations. Additionally, there were unexpected great vessel malformations that were mostly derived from the 4th pharyngeal arch artery in 5 (4.3%) fetuses from 3 (15.8%) litters. The etiology was unclear whether the vascular malformations were related to insufficient thyroid hormones or another mechanism. To better understand this relationship, pregnant rats were implanted with a subcutaneous L-thyroxine pellet designed to provide a sustained release of T4 throughout organogenesis in rat embryos (GD 6 to 15; the dosing period of pexacerfont). T4 supplementation produced a near euthyroid state in pexacerfont-treated dams and completely prevented the fetal vascular malformations. These results suggest maternal T4 levels during organogenesis may have a role in great vessel morphogenesis associated with patterning and/or regression of pharyngeal arch arteries. Although previous clinical reports have speculated a potential relationship between thyroid hormone homeostasis and early cardiovascular development, this is the first report to experimentally demonstrate this relationship in great vessel morphogenesis.


Assuntos
Aorta/efeitos dos fármacos , Antagonistas de Hormônios/toxicidade , Pirazóis/toxicidade , Tiroxina/farmacologia , Triazinas/toxicidade , Malformações Vasculares/prevenção & controle , Animais , Aorta/anormalidades , Implantes de Medicamento , Feminino , Idade Gestacional , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Exposição Materna , Morfogênese , Organogênese , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/prevenção & controle , Ratos , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Toxicocinética , Malformações Vasculares/sangue , Malformações Vasculares/induzido quimicamente
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