General cause severe cirrhosis cases (Child-Pugh B/C and/or MELD >20).
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Request TSH, FT4, and FT3 exams. |
Low FT3 as a possible factor for worse prognosis in liver disease. |
Correlate low FT3 levels with the severity and prognosis of liver cirrhosis. |
IV |
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In case of suspected Euthyroid Sick Syndrome (ESS): consider reverse T3. |
More severe cases, considering the Child-Pugh scale, especially B, C, and MELD, especially above 20 years old, in addition to risk for complications such as ascites, encephalopathy, and hemorrhagic varicose veins, in addition to laboratory markers of INR, albumin, PGT, bilirubins, and platelets in patients with low FT3 level. |
Do not treat FT3 in isolation. |
Novis, Vaisman e Coelho (2001) |
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Most common laboratory standard of main thyroid dysfunctions: |
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In case of Euthyroid Sick Syndrome, evaluate thyroid hormones after liver transplant or cirrhosis stabilization to check whether normality was achieved. |
Penteado et al. (2015) |
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1.ESS: |
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When suspecting primary thyroid disease, check observations at the end of the bundle*. |
Mansour-Ghanaei et al. (2012) |
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-Low total and/or free T3; |
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Verma et al. (2017) Kayacetin, |
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-Normal or low FT4; |
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Kisakol e Kaya (2003) |
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-Normal or high TSH; |
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Shakoor, Kaneez e Iftikhar (2012) |
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-High reverse T3. |
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Taş et al. (2012) |
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Punekar, Sharma e Jain (2018) |
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Manka et al. (2019) |
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Piantanida et al. (2020) |
Cirrhosis from Hepatitis C (CHC)
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Request TSH, FT4, and FT3 exams. |
Patients with cirrhosis due to HCC seem more likely to have positive results for anti-TPO and anti-TG antibodies, and hypothyroidism. |
Carefully monitor thyroid function during the follow up of patients with HCC infection. |
VI |
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If the TSH is high, consider asking for anti-thyroperoxidase (anti-TPO) and anti-thyroglobulin (anti-TG) tests; |
Cases are more severe according with Child-Pugh and MELD scales in patients with low total and free T3. |
Evaluate thyroid hormones after liver transplant or cirrhosis stabilization to check whether normality was returned. |
Antonelli et al. (2006) |
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In case of suspected Euthyroid Sick Syndrome (ESS): consider reverse T3. |
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Correlate low FT3 levels with the severity and prognosis of the liver cirrhosis. |
Piantanida et al. (2020) |
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Most common laboratory standard of main thyroid dysfunctions: |
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Do not treat FT3 in isolation. |
Yang et al. (2011) |
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1.ESS: |
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When suspecting primary thyroid disease, check observations at the end of the bundle*. |
Novis, Vaisman e Coelho (2001) |
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-Low FT3; |
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Mansour-Ghanaei et al., (2012) |
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-Normal or low FT4; |
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Verma et al. (2017) |
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-Normal or high TSH; |
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-High reverse T3. |
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2. Associated with the C virus: |
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-Higher prevalence of thyroid autoantibodies. |
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Non-alcoholic fatty liver disease
(NAFLD)
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Request TSH, FT4, and FT3 exams. |
NAFLD patients have higher TSH levels. Hypothyroidism may be associated with higher risks for NAFLD and for non-alcoholic steatohepatitis (NASH) or fibrosis. |
Correlate low FT3 levels with the severity and prognosis of liver cirrhosis. |
VI |
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In case of suspected Euthyroid Sick Syndrome (ESS): consider reverse T3. |
Levothyroxine supplementation may have a positive effect over NAFLD in patients with clinical or mild subclinical hypothyroidism and dyslipidemia. |
Correlate low FT3 levels with fibrosis and advanced non- alcoholic steatohepatitis (NASH). |
Tahara et al. (2019) |
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Most common laboratory standard of main thyroid dysfunctions: |
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Supplement levothyroxine in patients with severe subclinical hypothyroidism** (TSH>10 mUI/L) to improve clinical characteristics of the metabolic syndrome and potential impact in NAFLD control. |
Kim et al. (2018) |
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1.Associated with NAFLD |
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Consider supplementing levothyroxine in patients with mild subclinical hypothyroidism (TSH between the upper limit and 10 mUI/L) with NAFLD and dyslipidemia, with a potential beneficial effect over the prevalence of NAFLD. |
Liu et al. (2017) |
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-High or borderline-high TSH; |
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Check general observations for the treatment of subclinical hypothyroidism** |
Bano et al. (2016) |
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-Normal or low FT3; |
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When suspecting primary thyroid disease, check observations at the end of the bundle*. |
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-Normal or low FT4; |
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2.ESS: |
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-Low FT3; |
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-Normal or low FT4; |
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-Normal or high TSH; |
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-High reverse T3. |
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Primary biliary cholangitis (PBC)
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Request TSH, FT4, FT3, and anti-TPO exams. |
Hypothyroidism is commonly found in PBC. |
Suspect PBC in patients with cholestatic liver disease and autoimmune thyroiditis. |
VI |
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In case of suspected Euthyroid Sick Syndrome (ESS): consider reverse T3. |
The presence of thyroid dysfunction does not seem to influence on the rate of hepatic complications or PBC natural history. |
Regularly check thyroid function of patients with euthyroid sick syndrome with positive thyroid autoantibodies. |
Elta et al. (1983) |
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Most common laboratory standard of main thyroid dysfunctions: |
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In case of Euthyroid Sick Syndrome, evaluate thyroid hormones after liver transplant or cirrhosis stabilization to check whether normality was achieved. |
Floreani et al. (2016) |
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1. Associated with primary biliary cholangitis: |
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When suspecting primary thyroid disease, check observations at the end of the bundle*. |
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-Higher prevalence of thyroid autoantibodies (anti-TPO) |
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2.ESS: |
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-Low FT3; |
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-Normal or low FT4; |
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-Normal or high TSH; |
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-High reverse T3. |
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Hepatocellular carcinoma (HCC)
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Request TSH, FT4, and FT3 exams. |
Correlation between clinical*** or subclinical** hypothyroidism with worse advanced HCC prognosis. |
Correlate the presence of hypothyroidism with worse HCC prognosis |
IV |
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In case of suspected Euthyroid Sick Syndrome (ESS): consider reverse T3. |
High prevalence of hypothyroidism in advanced HCC patients. |
Treat clinical hypothyroidism before specific HCC medication is started. |
Sahin et al. (2020) |
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Most common laboratory standard of main thyroid dysfunctions: |
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Evaluate the need for subclinical hypothyroidism treatment**. |
Shao, Cheng e Hsu (2021) |
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1.Associated with HCC: |
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When suspecting primary thyroid disease, check observations at the end of the bundle*. |
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-Higher prevalence of clinical*** and subclinical** hypothyroidism; |
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-Normal or high FT3. |
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2.ESS: |
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-Low FT3; |
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-Normal or low FT4; |
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-Normal or high TSH; |
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-High reverse T3. |
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General observations
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Evidence level/references
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There is a biological variation in TSH levels. Levels can increase as a result of stress, transitory diseases, and with age. |
VII |
This biological variation in TSH levels means that the finding of abnormal TSH levels should be followed by another blood test to confirm diagnosis. Patients with TSH > 10 mUI/L may have underlying thyroid disease. |
Jonklaas et al. (2014) |
*In case of suspected primary thyroid disease, evaluate the need for anti-TPO test and thyroid ultrasound. Positive results for thyroid autoantibodies (anti-TPO is the most sensitive) and, in some cases, hypoechoic, non-homogeneous patterns found in the ultrasound can provide evidence for autoimmune thyroiditis. |
Bekkering et al. (2019) |
Consider the institution or adjust levothyroxine replacement in patients with already established clinical and subclinical hypothyroidism. |
Pearce et al. (2013) |
Some medication can interfere on the interpretation of thyroid hormones, such as diuretics, glucocorticoids, beta blockers, amiodarone, interleukin-2, interferon alpha, among others. Consider thyroid ultrasound and antibodies dosage in case of doubt in the diagnosis. |
Garber et al. (2012) |
**Subclinical hypothyroidism - serum TSH above normal range, combined with normal FT4 levels. Applicable when the thyroid function has been stable for weeks or longer, the hypothalamus-pituitary-thyroid is normal, and there is no current or recent severe illness. In this case, consider the following clinical management: |
Nice et al. (2019) |
TSH > =10 mUI/L: |
Burch (2019) |
- Age <70 years: treat. |
Vilar (2020) |
- Age > =70 years: consider treatment in case of hypothyroidism symptoms or high cardiovascular risk. |
Piantanida et al. (2020) |
TSH <10 mUI/L: consider treatment in case of hypothyroidism symptoms, positive anti-TPO, or evidence of atherosclerotic cardiovascular disease, cardiac failure, or risk factors for these diseases. Observation: in patients aged >70 years with TSH <7 mUI/L, keep patient under observation. |
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***Clinical hypothyroidism - TSH above normal range and FT4 below normal range. Consider adding or adjusting levothyroxine replacement in clinical hypothyroidism patients. Dosage adjustments are carried out according with serum TSH determinations 4-8 weeks after the beginning of the therapy or dosage adjustments. |
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Captions: anti-TG: anti-thyroglobulin; anti-TPO: anti-thyroperoxidase, PBC: Primary Biliary Cirrhosis; HCC: hepatocellular carcinoma; NAFLD: |
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Non-Alcoholic Fatty Liver Disease; NASH: Non-Alcoholic Steatohepatitis; HCV: Hepatitis C Virus; TH: Thyroid Hormones; INR: International Normalized Ratio; MELD: Model for End-Stage Liver Disease; ESS > Euthyroid Sick Syndrome; FT3: Free Triiodothyronine; TT3: Total T3; FT4: Free Thyroxine; OGT: Oxaloacetic Glutamic Transaminase; PGT: Pyruvic Glutamic Transaminase; TSH: Thyroid-Stimulating Hormone. |
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