Quando o hipotireoidismo vem do fígado
Hipotireoidismo e fígado: tudo a ver
[Imagem: medportal.ru]
Praticamente, a maioria das pessoas com hipotireoidismo possui o que poderíamos chamar, eventualmente, de “hipotireoidismo hepático”, isto é não conseguem converter o T4 inativo no ativo T3. E é somente este – o hormônio ativo, T3 - que nossas células conseguem utilizar, de fato.
Portanto, se a tireoide está hígida, produz o T4 – acompanhado da correspondente pequena quantidade de T3 – mas, no entanto, o T4 não chega a ser ativado, a pessoa continua com hipotireoidismo.
É crucial, nesse caso, quando se vai suplementar com hormônio tireoidiano [T4+T3], que se tenha uma ideia prévia da saúde hepática, da capacidade do fígado de ativar o hormônio T4.
Ver mais sobre essa conexão fígado-tireoide-alimentação aqui, aqui e aqui.
Várias experiências mostraram que hormônios tireoidianos tendem a declinar quando se desenvolve disfunção hepática do tipo esteatose.
Mais esteatose, menores níveis do hormônio tireoidiano ativo [isso se dá em pacientes obesos ou com sobrepeso, embora nem sempre em magros][A]. Também se verificou que pacientes com hipotireoidismo têm tendência a maior incidência de doença do fígado gordo [esteatose não alcoólica ou NAFLD][B].
Ou seja, a hipótese é de que fígado gordo não alcoólico possa também ter como uma de suas causas o hipotireoidismo [C][D][E]. Ficou estabelecida a ponte, então, entre o hipotireoidismo e a hepatopatia, isto é, doença hepática pode ser causa de hipotireoidismo [L][M][N][O]Q]. E há estudos mais diretos, associando doença hepática a hipotireoidismo, este como causa [P].
Há quem associe fígado gordo a níveis de TSH, independente dos níveis de hormônios tireoidianos [G].
Mas como “há estudos para todos os gostos” é possível encomendar, digo, encontrar pesquisa negando que fígado esteatótico tipo NAFLD possa ser causado por hipotireoidismo [F][J].
Cabe lembrar que outro hipotireoidismo que pode vir do fígado é aquele derivado do estresse, causado pela inibição da entrada do hormônio tireoidiano ativo na célula, por conta do T3-reverso. Neste caso, o fígado possui enzimas que, acionadas pelo cortisol, irão converter o hormônio ativo, T3, em T3-reverso; e este bloqueará a ação da tireoide [do T3, no caso] sobre as células-alvo.
Importante sempre levar em conta as carências nutricionais que também impactam o fígado e, por tabela, prejudicam a tireoide, causando hipotireoidismo [açúcar, selênio são exemplos conhecidos, mas também proteína em baixa dose na alimentação]. Proteína de alto valor biológico, ao menos 80 g por dia é o necessário para um adulto pouco ativo, segundo R. Peat.
Neste caso, eventualmente não se trata de doença hepática, mas de uma carência nutricional que impacta diretamente o fígado, isto é, a conversão do hormônio inativo no fígado.
No caso do sexo feminino, por seus níveis-padrão mais altos de estrogênio, a mulher pode, na média, apresentar um fígado mais lento na conversão do T4, assim como também na detoxificação do álcool. Ela tende, por isso, a acumular mais T4, gerando, dessa forma, um efeito antitireoidiano, por conta de um fígado mais comprometido com os níveis de estrogênio.
E temos o açúcar, imprescindível na ativação do T4. Açúcar e fígado não são coisas desligadas. No entanto, quando alguns falam em praticar dieta low carb, ou em restringir açúcar na alimentação, pouco é lembrado a esse respeito. É como se nosso metabolismo pudesse ser tratado na base de modismos de qualquer natureza e ignorando as demandas da nossa fisiologia.
Mas o fato é que haverá, no caso de tais experimentos restritivos, um preço a ser cobrado: a supressão da tireoide. Será criado – por conta daquela escolha alimentar restritiva - um ambiente fisiológico mais tendente ao estresse, às crises de hipoglicemia.
É bom que isso seja lembrado, portanto: toda vez que a pessoa for planejar sua alimentação, planejar ciclos de jejum [fome], ao menos que procure ter consciência do trade off que está sendo efetuado e o custo em termos de inibição metabólica” [artigo O fígado necessita de açúcar para ativar o hormônio T4 produzido pela tireoide].
Em suma, o Dr Broda Barnes já chamou a atenção para esta “conexão, para o vínculo tireoide-coração, tireoide-doença crônico-degenerativa” e também para o inverso: como o hipotireoidismo vai deteriorando o fígado.
É dele um interessante livro mostrando como doenças cardiovasculares são engendradas a partir do hipotireoidismo”. [Ver vídeo do Dr Barnes falando sobre hipoglicemia e tireoide aqui, no artigo: Você está com hipotireoidismoɁ Pode ser o fígado]”.
Em suma, não é aconselhável que o doutor aborde o “problema da tireoide” apenas girando em torno da glândula, procurando o problema nela, muito menos com exames invasivos [RX, radioisótopos, biópsias].
Antes de mais nada, importante procurar ver de conjunto, entender os elos da totalidade tireoidiana que podem estar com problema. E, como esta e outra nota procuraram argumentar, muito frequentemente, o problema da tireoide pode estar lá no fígado.
GM Fontes, Brasília, 11-5-24
As informações aqui presentes não pretendem servir para uso diagnóstico, prescrição médica, tratamento, prevenção ou mitigação de qualquer doença humana. Não pretendem substituir a consulta ao profissional médico ou servir como recomendação para qualquer plano de tratamento. Trata-se de informações com fins estritamente educativos. Nenhuma das notas aqui presentes, neste blog, conseguirá atingir o contexto específico do paciente singular, nem doses, modo de usar etc. Este trabalho compete ao paciente com seu médico. Isso significa que nenhuma dessas notas - necessariamente parciais - substitui essa relação.
Referências _______________
[A] CHEN S JIN Y XU M, 2022. Relationship Between Thyroid Hormone and Liver Steatosis Analysis Parameter in Obese Participants: A Case-Control Study. Diabetes Metab Syndr Obes. 2022; 15: 887–896. Published online 2022 Mar 22. doi: 10.2147/DMSO.S356882 PMCID: PMC8957298 PMID: 35345544. “Objective - The thyroid hormone has been demonstrated to be associated with nonalcoholic fatty liver disease (NAFLD) in different populations. However, the relationship between thyroid hormone and the degree of liver steatosis in overweight/obese subjects is still unclear. Liver ultra-sound attenuation (LiSA) is a newly developed ultrasound attenuation parameter for the analysis of hepatic steatosis. The study aimed to characterize the relationship between thyroid hormone and LiSA in overweight/obese participants.
Methods - This case-control study was performed in Ningbo First Hospital, China. A total of 24 lean, 66 overweight and 49 obese participants were consecutively recruited from January 2021 to May 2021. Thyroid hormone and other clinical features were measured. LiSA was acquired by using a Hepatus ultrasound machine. Multiple linear regression analyses were performed to examine associations of LiSA and clinic indices.
Results - Obese subjects had higher LiSA, fT3 and TSH levels than lean participants of similar age and sex (P < 0.05). LiSA was positively associated with the fT3 level. The multiple linear regression analyses showed that fT3 (ß = 0.353, P < 0.001) was independently associated with LiSA in overweight/obese participants. Conclusion - The fT3 level was independently associated with the degree of liver steatosis among the overweight/obese participants.
------Thyroid hormones included triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4). Thyroid hormones are mostly bound to thyroxine-binding globulin in peripheral blood. The main thyroid hormones that play a physiological role are FT4 and FT3, and the physiological activity of FT3 is three to four times that of FT4. In our study, we found no significant correlation between other thyroid hormones (fT4, T3, T4 and TSH) and LiSA. This is partly due to the relatively small sample size of our study. Studies with larger sample sizes and prospective studies are needed in our future research. In addition, FT3 plays a direct role in the physiological function, and its level is more directly related to the metabolic state of the body. Therefore, the statistical results of FT3 are more sensitive than other thyroid hormone indicators (fT4, T3, T4 and TSH).
Our study was unique and different from the previous studies. First of all, we selected lean participants as the control group, and found no correlation between LiSA and thyroid hormone, suggesting that the correlation between LiSA and thyroid hormones only existed in overweight/obese participants. In the second place, the lean group and overweight/obese group in our research are similar in age, which greatly eliminates the influence of confounding factors of age differences. Thirdly, we conducted the subgroup analyses according to the degree of liver steatosis to further explore the clinical characteristics of different subgroup. In addition, we conducted the stepwise multivariate analyses to further evaluate the relationship of fT3 with LiSA and to eliminate the influence of other confounding factors. Last but not least, LiSA was used to evaluate the degree of NAFLD in our study, and the effectiveness and stability of LiSA are currently superior to other ultrasonic attenuation parameter. Fonte: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957298/
[B] RITTER M J AMANO I, 2020. Thyroid Hormone Signaling and the Liver. Hepatology. 2020 Aug;72(2):742-752. doi: 10.1002/hep.31296. PMID: 32343421 DOI: 10.1002/hep.31296 “Thyroid hormone (TH) plays a critical role in maintaining metabolic homeostasis throughout life. It is well known that the liver and thyroid are intimately linked, with TH playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Indeed, patients with hypothyroidism have abnormal lipid panels with higher levels of low-density lipoprotein levels, triglycerides (triacylglycerol; TAG), and apolipoprotein B levels. Even in euthyroid patients, lower serum-free thyroxine levels are associated with higher total cholesterol levels, LDL, and TAG levels. In addition to abnormal serum lipids, the risk of nonalcoholic fatty liver disease (NAFLD) increases with lower free thyroxine levels. As free thyroxine rises, the risk of NAFLD is reduced. This has led to numerous animal studies and clinical trials investigating TH analogs and TH receptor agonists as potential therapies for NAFLD and hyperlipidemia. Thus, TH plays an important role in maintaining hepatic homeostasis, and this continues to be an important area of study. A review of TH action and TH actions on the liver will be presented here”.
[C] VIDAL-CEVALLOS P GALL S M-B, 2023. Understanding the Relationship between Nonalcoholic Fatty Liver Disease and Thyroid Disease. Int J Mol Sci. 2023 Sep 27;24(19):14605. doi: 10.3390/ijms241914605. PMID: 37834051 PMCID: PMC10572395 DOI: 10.3390/ijms241914605 “The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-β in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-β agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-β agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-β agonists have on hepatic lipid metabolism.
[D] TANASE D M GOSAV E M, 2020. Hypothyroidism-Induced Nonalcoholic Fatty Liver Disease (HIN): Mechanisms and Emerging Therapeutic Options. Int J Mol Sci. 2020 Aug 18;21(16):5927. doi: 10.3390/ijms21165927. PMID: 32824723 PMCID: PMC7460638 DOI: 10.3390/ijms21165927 “Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide problem and its association with other metabolic pathologies has been one of the main research topics in the last decade. The aim of this review article is to provide an up-to-date correlation between hypothyroidism and NAFLD. We followed evidence regarding epidemiological impact, immunopathogenesis, thyroid hormone-liver axis, lipid and cholesterol metabolism, insulin resistance, oxidative stress, and inflammation. After evaluating the influence of thyroid hormone imbalance on liver structure and function, the latest studies have focused on developing new therapeutic strategies. Thyroid hormones (THs) along with their metabolites and thyroid hormone receptor β (THR-β) agonist are the main therapeutic targets. Other liver specific analogs and alternative treatments have been tested in the last few years as potential NAFLD therapy. Finally, we concluded that further research is necessary as well as the need for an extensive evaluation of thyroid function in NAFLD/NASH patients, aiming for better management and outcome”.
[E] KIZIVAT T MARIC I, 2020. Hypothyroidism and Nonalcoholic Fatty Liver Disease: Pathophysiological Associations and Therapeutic Implications. J Clin Transl Hepatol. 2020 Sep 28;8(3):347-353. doi: 10.14218/JCTH.2020.00027. Epub 2020 Jul 21. PMID: 33083258 PMCID: PMC7562794 DOI: 10.14218/JCTH.2020.00027 “Nonalcoholic fatty liver disease (NAFLD) is a complex clinical entity which can be secondary to many other diseases including hypothyroidism, characterized by lowering of thyroid hormones and increased thyroid stimulating hormone (TSH). A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity, even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications. In addition, a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment, currently in phase 3 clinical trials. In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment, specifically thyroid hormone receptor (THR) agonist and its metabolites.
[F] JARUVONGVANICH V SANGUANKEO A, 2017. Nonalcoholic Fatty Liver Disease Is Not Associated with Thyroid Hormone Levels and Hypothyroidism: A Systematic Review and Meta-Analysis. Eur Thyroid J. 2017 Jul;6(4):208-215. doi: 10.1159/000454920. Epub 2017 Jan 21. PMID: 28868261 PMCID: PMC5567115 DOI: 10.1159/000454920 “Background: Whether hypothyroidism is related to nonalcoholic fatty liver disease (NAFLD) is unclear. Thyroid dysfunction is closely related with components of metabolic syndrome. Given the hepatic manifestation of metabolic syndrome, several studies have investigated the association between NAFLD and thyroid dysfunction and have demonstrated inconsistent results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between NAFLD and thyroid dysfunction. Methods: MEDLINE and Embase were searched through July 2016. The primary outcome was the association between NAFLD and subclinical, overt, and overall hypothyroidism. The secondary outcome was the difference in thyroid hormone levels (free triiodothyronine [FT3], free thyroxine [FT4], or thyroid-stimulating hormone [TSH]) between NAFLD patients and non-NAFLD controls. Pooled odds ratios (OR) and 95% CI were calculated using a random-effects model. All continuous data are summarized as the mean difference along with 95% CI. Results: Data were extracted from 14 studies involving 7,191 NAFLD patients and 30,003 controls. NAFLD was not associated with subclinical, overt, or overall hypothyroidism compared with non-NAFLD controls. Patients who had NAFLD did not show a significant difference in FT3, FT4, or TSH compared with non-NAFLD controls. Conclusions: Our meta-analysis demonstrates no significant association between NAFLD and subclinical, overt, or overall hypothyroidism, and we also found no significant difference in thyroid hormone levels between participants with and without NAFLD”. O problema aqui é esquecer que níveis de T3 e T4 podem estar perfeitamente normais e a pessoa, ainda assim, estar com hipotireoidismo pela não entrada do T3 nas células...
[G] GUO Z LI M HAN B, 2018. Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis. Dig Liver Dis . 2018 Nov;50(11):1153-1162. doi: 10.1016/j.dld.2018.08.012. Epub 2018 Aug 23. PMID: 30224316 DOI: 10.1016/j.dld.2018.08.012 “Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The relationship of NAFLD with thyroid function parameters and hypothyroidism remains controversial. Aim: To clarify the effect of thyroid function parameters and hypothyroidism on the development of NAFLD and progression to nonalcoholic steatohepatitis (NASH). Methods: PubMed, EMBASE, and Cochrane library databases were searched. Study quality was assessed. Weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated. Results: Twenty six studies involving 61,548 participants were eligible, most of which were of high quality. NAFLD/NASH patients had significantly higher TSH levels than controls in adults (NAFLD versus health: WMD = 0.105, 95%CI = 0.012-0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI = 0.005-0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136-0.944) and children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104-1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267-.703). Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180-2.183; NASH versus NAFLD: OR = 2.317, 95%CI = 1.425-3.768) and children/adolescents (NAFLD versus overweight/obese controls: OR = 2.015, 95%CI = 1.246-3.258). However, the statistical results were inconsistent among the subgroup meta-analyses of subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4 levels was heterogeneous among population. Conclusion: TSH level may be an important risk factor for the development and progression of NAFLD, independent of thyroid hormones”. Parece pouco consistente a ideia de separar TSH de hormônios tireoidianos, já que o feedback entre eles é real.
[H] MANDATO C D´ACUNZO I, 2018. Thyroid dysfunction and its role as a risk factor for non-alcoholic fatty liver disease: What's new. Dig Liver Dis. 2018 Nov;50(11):1163-1165. doi: 10.1016/j.dld.2018.08.026. Epub 2018 Sep 1. PMID: 30262159 DOI: 10.1016/j.dld.2018.08.026 No abstract available
[I] EFSTATHIADOU Z KITA M D, 2018. Thyroid dysfunction and non-alcoholic fatty liver disease Minerva Endocrinol. 2018 Sep;43(3):367-376. doi: 10.23736/S0391-1977.17.02617-7. Epub 2017 Feb 9. PMID: 28181781 DOI: 10.23736/S0391-1977.17.02617-7 “Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Non-alcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels, including values within or in proximity to the reference range and NAFLD incidence and severity remains a contradictory subject in the literature. On the other hand, attempts to treat NAFLD with thyromimetic drugs remain at an early stage. In this review, data derived from observational studies along with evidence on possible treatment with thyroid hormone analogues are presented”.
[J] ESHAGHIAN A JAHROMI A H, 2014. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol. 2014 Jul 7;20(25):8102-9. doi: 10.3748/wjg.v20.i25.8102. PMID: 25009382 PMCID: PMC4081681 DOI: 10.3748/wjg.v20.i25.8102 “Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH). In this study, we reviewed the current literature on the association between thyroid dysfunction and NAFLD/NASH. A search for English language medical literature reporting an association between thyroid dysfunction and NAFLD/NASH in humans was conducted across PubMed, ISI Web of Science, and Scopus in August, 2013. Out of 140 studies initially identified through the search, 11 relevant articles were included in the final review. Thyroid dysfunctions in the form of overt or subclinical hypothyroidism are prevalent among patients with NAFLD/NASH. Hypothyroidism appears to be an independent risk factor for NAFLD/NASH in some studies; however, other newly published studies failed to find such an association. The results of the studies on the role of thyroid abnormalities in NAFLD/NASH are inconsistent, and further research is recommended to determine the relationship between hypothyroidism and NAFLD/NASH and the underlying mechanisms”. Quem leia os trabalhos questionando o vínculo entre hipotireoidismo a esteatose hepática poderá chegar às suas próprias conclusões, se são “inconsistentes” ou não.
[K] MANSOURIAN A R, 2013. A review of literatures on the adverse effects of thyroid abnormalities and liver disorders: an overview on liver dysfunction and hypothyroidism. Pak J Biol Sci. 2013 Dec 1;16(23):1641-52. doi: 10.3923/pjbs.2013.1641.1652. PMID: 24506031 DOI: 10.3923/pjbs.2013.1641.1652 “The healthy thyroid is vital for the liver metabolism. The liver also plays an important role in the metabolism of thyroid hormones. Thyroid and liver diseases can apparently have an adverse effects on each other organs. The main concept behind this present review is to analyze the coordination existed among thyroid and liver and the pathophysiology surrounding these two vital organs in human metabolismo”.
[L] MALIK R HODGSON H, 2002. The relationship between the thyroid gland and the liver. QJM. 2002 Sep;95(9):559-69. doi: 10.1093/qjmed/95.9.559. PMID: 12205333 DOI: 10.1093/qjmed/95.9.559 “Thyroxine and tri-iodothyronine are essential for normal organ growth, development and function. These hormones regulate the basal metabolic rate of all cells, including hepatocytes, and thereby modulate hepatic function; the liver in turn metabolizes the thyroid hormones and regulates their systemic endocrine effects. Thyroid dysfunction may perturb liver function, liver disease modulates thyroid hormone metabolism, and a variety of systemic diseases affect both organs. We highlight the intricate relations between the thyroid gland and the liver in health and disease”.
[M] BORZIO M CALDARA R, 1983. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut. 1983 Jul;24(7):631-6. doi: 10.1136/gut.24.7.631. PMID: 6407905 PMCID: PMC1420033 DOI: 10.1136/gut.24.7.631 “To further evaluate thyroid function in patients with liver disease, we have measured total and free T3 and T4, thyroxine binding globulin, basal and thyrotropin releasing hormone-stimulated thyrotropin and thyroglobulin antibodies in 33 patients with liver cirrhosis, in 22 with chronic hepatitis and in 30 healthy controls. All the patients but one were clinically euthyroid. T3, FT3, T3/thyroxine binding globulin and T4/thyroxine binding globulin ratios and thyrotropin after thyrotropin releasing hormone were significantly reduced, while FT4, thyroxine binding globulin and thyrotropin were significantly increased in liver cirrhosis. In chronic hepatitis group, FT3 and T3/thyroxine binding globulin ratio were significantly lower and thyroxine binding globulin and FT4 were higher than in healthy controls. The between patients comparison revealed a significantly lower T3, FT3, T3/thyroxine binding globulin and T4/thyroxine binding globulin ratios and delta thyrotropin in cirrhotics. Thyroglobulin antibodies were present at high titre only in two patients one of whom having evidence of Hashimoto's thyroiditis with subclinical hypothyroidism. The correlation coefficient between T4/thyroxine binding globulin ratio and FT4 were lower in patients than in controls. Furthermore an abnormal thyrotropin response to thyrotropin releasing hormone was shown in 10 cirrhotics and in four patients with chronic hepatitis. Serum T3 significantly correlated with serum bilirubin, albumin, and prothrombin time in both groups of patients. The present data confirm the existence of several abnormalities of thyroid function tests in patients with chronic liver disease, although showing that euthyroidism is almost always maintained, probably as a result of low-normal FT3 and high-normal FT4. Furthermore, T3 serum levels appear to parallel the severity of liver dysfunction”.
[N] HUANG M J LIAW Y F, 1995. Clinical associations between thyroid and liver diseases. J Gastroenterol Hepato. 1995 May-Jun;10(3):344-50. doi: 10.1111/j.1440-1746.1995.tb01106.x. PMID: 7548816 DOI: 10.1111/j.1440-1746.1995.tb01106.x “The liver has an important role in thyroid hormone metabolism and the level of thyroid hormones is also important to normal hepatic function and bilirubin metabolism. Besides the associations between thyroid and liver diseases of an autoimmune nature, such as that between primary biliary cirrhosis and hypothyroidism, thyroid diseases are frequently associated with liver injuries or biochemical test abnormalities. For example, thyroid diseases may be associated with elevation of alanine aminotransferase and alkaline phosphatase, which is mainly of bone origin, in hyperthyroidism and aspartate aminotransferase in hypothyroidism. Liver diseases are also frequently associated with thyroid test abnormalities or dysfunctions, particularly elevation of thyroxine-binding globulin and thyroxine. Hepatitis C virus infection has been connected with thyroid abnormalities. In addition, antithyroid drug therapy may result in hepatitis, cholestasis or transient subclinical hepatotoxicity, whereas interferon (IFN) therapy in liver diseases may also induce thyroid dysfunctions. These thyroid-liver associations may cause diagnostic confusions. Neglect of these facts may result in over of under diagnosis of associated liver or thyroid diseases and thereby cause errors in patient care. It is suggested to measure free thyroxine (FT4) and thyroid-stimulating hormone (TSH) which are usually normal in euthyroid patients with liver disease, to rule out or rule in coexistent thyroid dysfunctions, and consider the possibility of thyroid dysfunctions in any patients with unexplained liver biochemical test abnormalities. It is also advisable to monitor patients with autoimmune liver disease or those receiving IFN therapy for the development of thyroid dysfunctions, and patients receiving antithyroid therapy for the development of hepatic injuries”.
[O] BABB RR 1984. Associations between diseases of the thyroid and the liver. Am J Gastroenterol. 1984 May;79(5):421-3. PMID: 6720663 PMID: 6720663 “There are clinical and laboratory associations between thyroid and liver disease. Patients with chronic liver disease may have thyroiditis, hyperthyroidism, or hypothyroidism. Occasionally, alcoholics with active cirrhosis will show eye signs or laboratory evidence of hyperthyroidism, and yet be euthyroid on further testing. Patients with subacute thyroiditis or hyperthyroidism may have abnormalities in liver function tests which return to normal as the thyroid condition improves. In similar fashion, patients with acute or chronic liver disease may have changes in thyroid function tests which improves as the liver inflammation resolves. These interrelationships must be remembered if errors in patient care are to be avoided”.
[P] BAYRAKTAR M THIEL D H Van 1997. Abnormalities in measures of liver function and injury in thyroid disorders. Hepatogastroenterology. 1997 Nov-Dec;44(18):1614-8. PMID: 9427032 “Thyroid hormones exert their effect on all tissue and modulate the rate of metabolic activity appropriate for each situation. As a result of their actions, alterations in thyroid function can affect the liver and perturb measures of hepatic function and injury in the absence of liver disease. These alterations in the measure of hepatic function and injury may be difficult to recognize as being caused by thyroid dysfunction rather than hepatic disease. As a result, they may be quite troublesome for patients and physicians if their cause is not properly identified. Importantly, abnormalities in liver function tests return to normal once the primary thyroid pathology is recognized and treated”.
[Q] SHERIDAN P, 1983. Thyroid hormones and the liver. Clin Gastroenterol. 1983 Sep;12(3):797-818. PMID: 6616940 “Close relationships exist between the liver and the thyroid. The liver is important in the transport, metabolism, storage and excretion of thyroid hormones as well as being an important site for hormone activity. Liver disease alters thyroid function and thyroid function tests at all levels of the hypothalamic-pituitary-peripheral axis. Since thyroid disorders occur more frequently than expected in certain kinds of liver disease, awareness of the limitations of thyroid function tests in this situation are necessary. Drugs active in controlling hyperthyroidism may themselves cause liver disease due to hypersensitivity, but have also been used in treatment of alcoholic hepatitis. Clearly, these areas will stimulate further basic and clinical research”.
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