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The human liver is considered both the largest solid organ and the biggest gland in the body. In fact, your skin is the only organ that is larger and heavier than the liver.

Your liver is located beneath the diaphragm on the upper-right side of the body; it is reddish-brown in color and has a rubbery texture.

This organ participates in more than 500 functions in a human body. The strong and functioning liver is vital for overall health, prevention of many health conditions, and even for thyroid function.

Thyroid and liver are strongly connected to one another and this post provides a deeper insight into their relationship.

Thyroid hormone production and metabolism

In healthy persons, thyroid secretes about 100 nmol (nanomole) of thyroxine (T4) and 10 nmol of triiodothyronine each day[1].

The hormone T3 has a higher affinity and about ten times bigger efficacy than T4 for the nuclear receptor, even though the latter is produced in significantly greater amounts than its counterpart.

It’s also important to mention that T4 requires conversion and deiodination to T3 in order to become active biologically[2] and exhibit its effects.

Metabolism of thyroid hormones is regulated by three groups of enzymes that together form a unique iodothyronine-seleno-deiodinase enzyme system. These particular enzymes convert T4 to T3, conversion of rT3 (reverse T3) and T3 to T2, and inactivation of T4 to rT3.

No, T2 isn’t a typo; it is a lesser known thyroid hormone which can suppress TSH at high doses, but it doesn’t exhibit major manifestations of thyroid hormone activity[3].

The conversion process of T4 to T3 hormone in extrathyroidal tissues takes place in kidneys and the liver and it accounts for about 30% to 40% “of the extrathyroidal production of T3.” Production and metabolism of thyroid hormone is a complex process and the liver plays a huge role here.

“About 5% to 10% of plasma T4 is extracted by the liver during a single passage.” This particular value is significantly higher than it can be accounted for by free T4 level delivered to the liver. And according to Mendel et al, that means that a “substantial amount of protein-bound T4 is available for uptake[4].”

The liver has a role to synthesize various plasma proteins that go on and bind the lipophilic thyroid hormones. Basically, we can say that your liver takes part in a process that provides a large and exchangeable pool of circulating hormone.

Bianco et al found that plasma concentrations of free T4 and T3 are in the steady amounts in order to ensure tissues are exposed to the equal level of free thyroid hormones.

That being said, concentrations of free hormones “in different tissues vary depending on deiodinase activity within the specific tissues and transport”[5]; which again confirms the role of the liver (because it plays a crucial role in metabolism and transport of thyroid hormones).

Therefore, not only does thyroid status depend on the secretion of thyroxine, but other factors too. These factors include delivery of T3 to nuclear receptors, normal thyroid hormone metabolism, and function and distribution of receptors.

Bearing in mind that liver plays a crucial role in metabolism and transport of thyroid hormones, the health of the butterfly-shaped gland depends on the function of the liver and its ability to do this “job”.

Liver diseases and thyroid abnormalities

Liver participates in hundreds of functions whose purpose is to make sure you’re healthy. Since this organ or gland works hard all the time, it is prone to damage and many conditions and some of them are life-threatening.

As seen above, the liver is much-needed for thyroid hormone metabolism and function of this gland, but the relationship between the two goes deeper than that. Thyroid abnormalities could be linked to liver diseases. Here are some examples.

Cirrhosis

Cirrhosis is defined as a complication of liver disease that impairs the function of the organ due to long-term damage brought on by chronic alcoholism, hepatitis, and others. The liver has the ability to repair itself after damage but during the process scar forms. A multitude of scars makes it difficult to the liver to function properly[6]. Liver cirrhosis could be connected with thyroid dysfunction.

Joeimon et al carried out a study to analyze the prevalence of thyroid dysfunction in patients with liver cirrhosis. For this purpose, they enrolled 111 patients (80 men and 31 women) and measured their hormone levels. Results showed that 24 out of 111 subjects were hypothyroid and 64 had ethanol-related liver cirrhosis. Of the total liver cirrhosis patients (64), 16 of them or 25% had hypothyroidism. These findings led to a conclusion that thyroid abnormalities are present in this common liver disease, especially in cases when cirrhosis is alcohol-related[7].

In addition, Bianchi et al discovered that patients with liver cirrhosis exhibited 17% increase in thyroid glandular volume compared to healthy controls[8]. In other words, some people with cirrhosis also have changes in thyroid gland size. It’s also important to point out that a study from the European Journal of Medicine demonstrated patients with non-alcoholic cirrhosis are under a great risk of hepatic encephalopathy when their free T3 levels are low[9]. Hepatic encephalopathy is a decline in brain function that occurs as a result of the severe liver disease.

The most consistent thyroid hormone profile changes in cirrhosis patients are low total and free T3 and higher rT3. This could be a result of impaired function of the liver and its inability to do its job properly which also leads to an increase in rT3 to T3 ratio.

Low total and free T3 are considered “an adaptive hypothyroid state” whose primary purpose is to “decrease basal metabolic rate within hepatocytes (liver cells) and thus preserve liver function.”

Nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a term that refers to conditions affecting liver of persons who drink little to no alcohol. The primary characteristic of this disease is excessive fat stored in liver cells, hence the name. Figures show NAFLD is the most prevalent type of chronic liver disease affecting 80 to 100 million people[10].

The specific cause of excessive fat accumulation in the liver is unknown, but different factors play a role such as overweight/obesity, high levels of fats (particularly triglycerides) in blood, high blood sugar, and insulin resistance.

He W. et al carried out a study which evaluated the relationship between NAFLD and hypothyroidism. The idea for the study stems from the theory that hypothyroidism plays a role in the pathogenesis of this disease. Scientists searched databases such as PubMed, EMBASE, China Dissertation Database for observational studies on the subject.

Their search yielded 13 studies and the final analysis demonstrated that both overt and subclinical hypothyroidism were significantly related to NAFLD. Scientists concluded that hypothyroid patients are at a higher risk of getting the nonalcoholic fatty liver disease[11], thus providing more evidence about the relationship between liver and thyroid.

Acute hepatitis and liver failure

Patients with mild to moderate acute hepatitis have elevated total T4 levels[12] due to higher thyroid-binding globulin (TBG). Levels of free T4 remain normal. In severe cases of hepatitis with impending liver failure patients can experience low total T4[13] due to the decreased hepatocellular synthesis of TBG.

Regarding T3, Kano et al discovered that free T3:rT3 ratio negatively correlates with severity of the disease, thus showing a prognostic value. The concentration of T3 hormone improved in patients who survived severe hepatitis but didn’t improve in patients with fatal outcome[14].

Metabolism journal featured a study which found that some acute hepatitis patients have a goiter[15]. Fortunately, the problem resolved with the improvement of liver function. Just a little reminder, goiter is associated with thyroid dysfunction.

Liver and hypothyroidism

Bearing in mind that liver is crucial for transport and metabolism of thyroid hormones, it seems a logical function of the liver is also linked with common thyroid disorder hypothyroidism. The underactive thyroid gland directly affects the liver structure and function.

Van Steenbergen et al found that hypothyroidism is linked to cholestatic jaundice which is attributed to decreased bile extraction and reduced bilirubin[16]. The decline in bile flow could be a result of elevated cholesterol-phospholipid ratio and reduced membrane fluidity which affect numerous enzymes.

Furthermore, Inkinen et al found that effects of hypothyroidism such as reduced excretion of bilirubin, higher cholesterol levels, and hypotonia or reduced strength of gallbladder increase incidence of gallstones in patients[17].

Hypothyroidism can cause liver dysfunctions in different ways, but more studies are necessary to uncover all the effects.

Hepatic abnormalities associated with hypothyroidism are usually reversible and tend to improve with adherence to doctor-recommended treatment which usually involves intake of levothyroxine.

Liver and hyperthyroidism

Unlike hypothyroidism where production of thyroid hormones is decreased, hyperthyroidism is associated with excessive levels of T4 and T3.

Madani et al found that hyperthyroidism is often associated with abnormal hepatocellular enzymes, especially ALT (necessary for the breakdown of food to energy) and ALP (breaks down proteins), meaning it can be utilized as a diagnostic tool for identifying the presence of clinically significant hepatic changes in patients with this thyroid disorder[18].

Hyperthyroidism, especially Graves’ disease (an autoimmune condition), is strongly associated with liver dysfunctions. Boelaert et al found that almost 10% of patients with Graves’ disease also have a coexisting autoimmune condition[19]. For example, Graves’ disease is strongly related to primary biliary cirrhosis or autoimmune hepatitis[20].

To sum up, current evidence suggests that hyperthyroidism leads to excessive concentration of liver enzymes and is connected with autoimmune conditions affecting the liver.

Factors that affect liver health

The healthy and strong liver is crucial for metabolism of thyroid hormones.

When the liver doesn’t work properly, hormones don’t get to exhibit their effects properly.

Different factors affect liver function, including:

• Excessive alcohol intake – the primary cause of many conditions affecting liver
• Obesity – plays a role in NAFLD, cirrhosis, and liver failure
• Sugar-laden sodas – contribute to obesity
• Some medications – many over-the-counter and prescription drugs can harm the liver
• Heredity – family history of liver-related conditions significantly increases the risk of developing them as well
• Autoimmune diseases – such as Graves’ disease; the immune system doesn’t work properly and starts attacking healthy cells and tissues, including liver
• Smoking – the unhealthy habit increases the risk of cirrhosis and liver cancer because toxic chemicals in tobacco smoke cause inflammation

Tips to improve liver health

• Eat an anti-inflammatory diet
• Reduce or avoid alcohol intake
• Avoid soda and other sugar-laden beverages
• Manage stress
• Exercise regularly
• Limit intake of highly processed foods containing too many additives
• Avoid late-night snacks

Conclusion

The liver is important for our health and wellbeing. It participates in about 500 functions and metabolism of thyroid hormones is one of them.

Liver and thyroid are strongly connected to one another, but their relationship is still insufficiently explained.

This only emphasizes the importance of more studies on this subject to provide a deeper insight into how they affect one another.

Thyroid dysfunctions can cause liver abnormalities and vice versa.

References