Many patients taking levothyroxine (the UK equivalent of Synthroid) wonder whether their thyroid medication could affect their liver health. Levothyroxine is the most commonly prescribed treatment for hypothyroidism in the UK, and whilst it undergoes liver metabolism, there is no established direct link between levothyroxine and fatty liver disease. This article examines the evidence on levothyroxine and liver health, explores the complex relationship between thyroid function and fatty liver, and identifies the true risk factors that may affect patients with thyroid conditions.

Understanding Levothyroxine and Its Role in Thyroid Treatment

Levothyroxine sodium is a synthetic form of thyroxine (T4), the primary hormone produced by the thyroid gland. In the UK, levothyroxine is the most commonly prescribed medication for hypothyroidism, a condition where the thyroid gland fails to produce sufficient thyroid hormone. Patients typically receive generic levothyroxine preparations through the NHS. (Note: 'Synthroid' is a US brand name; UK patients should refer to their medication as levothyroxine.)

The thyroid gland plays a crucial role in regulating metabolism, energy production, and numerous bodily functions. When thyroid hormone levels are inadequate, patients may experience symptoms including fatigue, weight gain, cold intolerance, constipation, and cognitive difficulties. Levothyroxine works by replacing the missing thyroid hormone, thereby restoring normal metabolic function and alleviating these symptoms.

Mechanism of action: Once absorbed, levothyroxine undergoes deiodination in peripheral tissues to triiodothyronine (T3), the active form of thyroid hormone. T3 binds to thyroid hormone receptors in cells throughout the body, influencing gene expression and regulating metabolic processes. The medication typically requires 6–8 weeks to reach steady-state levels in the bloodstream, which is why thyroid function tests are usually repeated after this interval when initiating or adjusting treatment.

According to NICE guidance (NG145), levothyroxine should be taken consistently, preferably on an empty stomach at least 30–60 minutes before breakfast, to ensure optimal absorption. Important: Separate levothyroxine from iron, calcium supplements, antacids, and proton pump inhibitors by at least 4 hours, as these can reduce absorption. Patients require regular monitoring through thyroid function tests—primarily TSH in primary hypothyroidism, with free T4 also measured—to ensure appropriate dosing. Both under-treatment and over-treatment can lead to adverse health consequences. The goal of treatment is to maintain thyroid hormone levels within the normal reference range whilst alleviating symptoms of hypothyroidism.

References: NICE NG145 Thyroid disease: assessment and management; NHS Medicines A–Z: Levothyroxine; BNF monograph: Levothyroxine.

Can Levothyroxine Cause Fatty Liver Disease?

There is no established direct causal link between levothyroxine and the development of fatty liver disease (hepatic steatosis). Fatty liver disease is not listed as a recognised adverse effect in UK regulatory product information (MHRA/EMC Summary of Product Characteristics). The medication is generally well-tolerated, with most side effects relating to inappropriate dosing rather than direct hepatotoxicity.

Levothyroxine undergoes substantial hepatic metabolism, including deiodination and conjugation (glucuronidation and sulfation), with enterohepatic recirculation. However, when used at appropriate replacement doses, it does not typically cause clinically significant liver enzyme elevations or hepatic injury. Whilst very rare idiosyncratic liver reactions have been described in case reports, these are exceptional and fatty liver disease has not been identified as a consequence of levothyroxine treatment in clinical trials or routine pharmacovigilance.

It is important to distinguish between direct drug effects and indirect metabolic consequences. Inappropriate levothyroxine dosing—particularly over-replacement leading to subclinical or overt hyperthyroidism—can influence metabolic parameters, though the relationship with liver health is complex and not fully characterised. Excessive thyroid hormone may alter lipid metabolism and body composition, but these effects do not directly cause fatty liver disease.

The confusion may arise because patients with thyroid disorders and those requiring levothyroxine treatment may have other risk factors for fatty liver disease, including obesity, metabolic syndrome, type 2 diabetes, and dyslipidaemia. These conditions frequently coexist with thyroid dysfunction but are not caused by the levothyroxine medication itself. If fatty liver disease develops in a patient taking levothyroxine, it is essential to investigate other underlying causes rather than attributing it solely to the thyroid medication. Patients concerned about liver health whilst taking levothyroxine should discuss their individual risk factors with their GP or endocrinologist.

If you suspect a side effect: Report it via the MHRA Yellow Card scheme at https://yellowcard.mhra.gov.uk or search for 'Yellow Card' in the Google Play or Apple App Store.

References: MHRA/EMC SmPC for levothyroxine; NHS Medicines A–Z: Levothyroxine.

The Link Between Thyroid Function and Liver Health

The relationship between thyroid function and liver health is complex and bidirectional. Both hypothyroidism and hyperthyroidism can influence liver function, though the mechanisms and clinical significance differ considerably. Understanding this relationship is important for patients taking levothyroxine, as optimising thyroid hormone levels may support liver health rather than harm it.

Hypothyroidism and the liver: Untreated or inadequately treated hypothyroidism can negatively affect liver function through several mechanisms. Reduced thyroid hormone levels slow metabolic processes, including lipid metabolism, which can contribute to dyslipidaemia (elevated cholesterol and triglycerides). This metabolic disruption may be associated with increased risk of non-alcoholic fatty liver disease (NAFLD). (Note: Recent international consensus has introduced the term 'metabolic dysfunction-associated steatotic liver disease' or MASLD, though UK guidance currently uses NAFLD.) Additionally, hypothyroidism can cause mild elevations in liver enzymes, particularly alkaline phosphatase and transaminases, which typically normalise with appropriate levothyroxine treatment. Some observational studies suggest associations between untreated hypothyroidism and increased hepatic fat accumulation, though the evidence base is heterogeneous and further research is needed.

The potential role of appropriate treatment: Restoring normal thyroid function through levothyroxine replacement may help normalise lipid profiles and improve metabolic parameters in patients with hypothyroidism. Some studies suggest potential improvements in hepatic fat content when hypothyroidism is adequately treated, though this evidence is limited and levothyroxine is not indicated as a treatment for NAFLD in euthyroid patients. Management of NAFLD follows standard pathways focused on weight loss, physical activity, and control of metabolic risk factors, as outlined in NICE guidance (NG49).

Thyroid hormone and metabolic regulation: Thyroid hormones play essential roles in regulating hepatic glucose and lipid metabolism, mitochondrial function, and overall energy expenditure. When thyroid function is optimised, these metabolic processes function more efficiently. Therefore, appropriate levothyroxine therapy typically supports overall metabolic health by correcting the abnormalities associated with hypothyroidism, which may indirectly benefit liver health.

References: NICE NG49 Non-alcoholic fatty liver disease; systematic reviews on hypothyroidism and NAFLD (e.g., Mantovani et al.); BSG guidelines on abnormal liver blood tests.

Risk Factors for Fatty Liver in Thyroid Patients

Patients with thyroid disorders, including those taking levothyroxine, may have multiple risk factors for developing non-alcoholic fatty liver disease (NAFLD) that are independent of their thyroid medication. Recognising these risk factors is essential for comprehensive health management and prevention strategies.

Metabolic risk factors are particularly important:

• Obesity and increased body mass index (BMI): Excess body weight, especially central adiposity, is the strongest risk factor for NAFLD

• Type 2 diabetes and insulin resistance: These conditions significantly increase the likelihood of hepatic fat accumulation

• Dyslipidaemia: Elevated triglycerides and low HDL cholesterol are commonly associated with fatty liver

• Metabolic syndrome: The clustering of obesity, hypertension, dyslipidaemia, and insulin resistance substantially increases NAFLD risk

Thyroid-specific considerations: Patients with hypothyroidism often experience weight gain before diagnosis and treatment, which may persist if lifestyle modifications are not implemented alongside levothyroxine therapy. Additionally, autoimmune thyroid disease (such as Hashimoto's thyroiditis) may coexist with other autoimmune or metabolic conditions that independently affect liver health.

Lifestyle and dietary factors also play crucial roles:

• Excessive alcohol consumption: The UK Chief Medical Officers advise that to keep health risks from alcohol low, it is safest not to drink more than 14 units per week on a regular basis, spread over 3 or more days with several drink-free days each week

• Sedentary lifestyle: Physical inactivity impairs metabolic health and increases NAFLD risk

• High-calorie, high-sugar diets: Particularly those rich in fructose and refined carbohydrates

• Weight management: Gradual, sustained weight loss of 5–10% of body weight is beneficial for NAFLD; very rapid weight reduction should be avoided

Medication considerations: Whilst levothyroxine itself does not cause fatty liver, patients with thyroid disorders may take other medications that affect liver health or metabolism. Some medicines (e.g., corticosteroids, certain antipsychotics, amiodarone, tamoxifen, methotrexate) have been associated with hepatic steatosis, whilst others used in diabetes management (e.g., GLP-1 receptor agonists, pioglitazone in selected patients) may reduce liver fat. According to NICE guidance on multimorbidity (NG56), comprehensive medication review should be part of routine care for patients with multiple conditions. Patients concerned about their liver health should discuss all medications and supplements with their healthcare provider to identify any potential contributing factors.

References: NICE NG49 Non-alcoholic fatty liver disease; UK Chief Medical Officers' Low-Risk Drinking Guidelines; NICE NG56 Multimorbidity: clinical assessment and management; BSG guidance on abnormal liver blood tests.

When to Seek Medical Advice About Liver Concerns

Patients taking levothyroxine should be aware of signs and symptoms that warrant medical evaluation regarding liver health, though it is important to emphasise that serious liver problems are uncommon in those taking thyroid medication alone.

Contact your GP if you experience:

• Persistent upper abdominal discomfort or pain, particularly in the right upper quadrant

• Unexplained fatigue that is disproportionate to your thyroid status or worsens despite stable thyroid function tests

• Jaundice: Yellowing of the skin or whites of the eyes

• Dark urine or pale stools: These may indicate bile flow problems

• Unexplained nausea, loss of appetite, or unintentional weight loss

• Easy bruising or bleeding: This may suggest impaired liver synthetic function

Seek urgent same-day medical assessment if you develop:

• New or worsening jaundice with confusion or drowsiness

• Vomiting blood or passing black, tarry stools

• Severe right upper abdominal pain with fever

Routine monitoring considerations: According to NHS and NICE guidance, patients taking levothyroxine require regular thyroid function monitoring but do not routinely need liver function tests unless there are specific clinical indications. However, if you have additional risk factors for liver disease—such as obesity, diabetes, excessive alcohol use, or a family history of liver problems—discuss with your GP whether periodic liver function testing would be appropriate.

UK primary care NAFLD assessment pathway: If NAFLD is suspected or incidentally detected, your GP will typically calculate a non-invasive fibrosis risk score (such as FIB-4 or NAFLD Fibrosis Score), taking into account your age and blood test results. Patients at low risk receive lifestyle advice and monitoring; those at indeterminate or high risk may be offered further testing (per NICE NG49, the Enhanced Liver Fibrosis or ELF test) and/or referral to hepatology services according to local pathways. It is important to note that normal liver function tests do not exclude NAFLD or liver fibrosis; non-invasive fibrosis assessment tools provide additional information.

Before your appointment, prepare information about:

• Your current levothyroxine dose and recent thyroid function test results

• Other medications, supplements, or herbal remedies you take

• Alcohol consumption patterns (in UK units per week)

• Any recent weight changes

• Family history of liver disease or metabolic conditions

Investigations your GP may arrange include liver function tests (measuring ALT, AST, alkaline phosphatase, bilirubin, and albumin), full blood count, lipid profile, glucose or HbA1c testing, and potentially liver ultrasound if fatty liver is suspected. If significant liver abnormalities or advanced fibrosis risk are identified, referral to a hepatologist or gastroenterologist may be appropriate. Remember that most patients taking levothyroxine will not develop liver problems, and maintaining optimal thyroid function through appropriate medication adherence, combined with a healthy lifestyle, supports overall metabolic and liver health.

References: NICE NG49 Non-alcoholic fatty liver disease; BSG 2018 guideline on abnormal liver blood tests; NHS: Non-alcoholic fatty liver disease page.

Frequently Asked Questions