Liver And Thyroid Function - An Unusual Partnership

The interdependence between two different components makes the action of each component multifaceted due to the nature of their dependency. For example, in the field of information technology (IT), for a system to operate flawlessly different components are interconnected. Processors for processing information, databases for storing and retrieving, networks for passing on the information from one system to another and so forth. If any component of this structure goes missing, the entire system fails to function correctly.

Likewise, organs in the body are interdependent on each other. One such example is the relationship between thyroid and Liver Function Tests. The partnership might be unusual but is very important for the healthy living.

Thyroid hormone production and metabolism
Thyroid hormones are crucial for normal growth and development of all the tissues in the body and it does so by regulating the basal metabolic rate of the cells, including the hepatocytes. On the other hand, liver metabolizes thyroid hormones and regulates the endocrine effects of the thyroid. Normal serum levels of thyroid hormones are important for smooth liver functioning and bilirubin metabolism.

The thyroid gland produces two thyroid hormones (TH)- approximately 80% thyroxine (T4) and 20% triiodothyronine (T3). T4 is biologically inactive and requires conversion by deiodination to T3 to become active and exhibit its effect. The metabolism of thyroid hormones is controlled by an enzyme system, one of whose component is iodothyronine selenodeiodinase. This enzyme predominantly regulates the conversion of T4 to T3 and activation of thyroid hormones. Deiodinase is found in liver and kidney and is accountable for 30-40% of the T3 production excluding that which is produced by the thyroid gland. T3 although produced in meager amounts as compared to T4, is ten times greater in efficacy and in affinity for the nuclear receptors.

Liver and Thyroid - The Association
The health of this butterfly shaped thyroid gland depends on the functioning of the second largest organ of the body i.e liver and vice versa. Liver plays a principal role in thyroid hormones production, conversion, activation and inactivation of thyroid, hormones, as well as their transport and metabolism. The liver also synthesizes many plasma proteins that bind to the thyroid hormones and allow access to a large exchangeable pool of circulating hormones. Over 99% of thyroid hormones in plasma are bound to thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin. Thus, the liver secretes and degrades the carrier proteins to which the thyroid hormones attach, forming a complex found in circulating blood. In this manner, it plays a direct role in modifying the concentration of circulating T4(thyroxine) and T3 (triiodothyronine) hormones in the blood stream.

Liver Disease and Thyroid Abnormalities
Some of the thyroid abnormalities incidental in the liver diseases are explained below

Cirrhosis
It is a condition in which long term damage is caused to the liver as a result of chronic alcoholism, hepatitis and other factors. liver has the ability of self-repair after damage, but forms scars. Multitude of scar tissue affects proper functioning of liver, as these cells are not capable of carrying out functions of healthy liver cells. Most patients with liver cirrhosis have consistently shown low level of total and free T3, and increase in level of reverse T3. The reason associated with this may involve decreased activity of the enzyme system which is involved in the conversion of inactive T4 to active T3. In such conditions, the conversion of T4 to reverse T3 increases thus explaining the elevation in reverse T3 levels The decrease in total and free T3 level can be interpreted as the thyroid to be in hypothyroid state which manifests as decrease in the basal metabolic rate (BMR) in the liver, among other signs.

Acute Hepatitis and Acute Liver Failure
Mild or moderate severity cases of acute hepatitis exhibit elevation in the level of total T4 in the blood stream as a result of increased synthesis of thyroid-binding globulin. However, the level of free T3 in such incidences is normal. In extremely severe cases such as liver failure, there is reduction in synthesis of thyroid-binding globulin, reflecting low levels of total T4. Serum T3 levels are usually not stable, though the ratio of T3:14 can indicate the severity of the condition; lower the ratio of T3:14, higher is the severity of the liver disease. Lower T3 level might again arise due to reduced activity of deiodinase enzyme activity, decreasing the conversion of inactive T4 to T3.

Non-Alcoholic Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) indicates accumulation of fat, largely triglycerides. NAFLD is observed to be associated with hypothyroidism. Individuals with poorly active thyroid gland suffer from weight gain and are mostly obese. In such patients, an elevation in level of serum thyroid stimulating hormone (TSH) may be observed, along with increase in antithyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels. A significant decrease in free T3 and free T4 levels might indicate the association of thyroid dysfunction and NAFLD.

Thyroid Disease and Liver Abnormalities
Hyperthyroidism
Hyperthyroidism is characterized by higher than normal range of T3 and T4 levels, and lower than normal range of TSH. Hyperthyroidism is generally incidental with abnormal liver enzymes such as alanine aminotranferase (ALT) and alkaline phosphatase (ALP), which are essential for breakdown of amino acids. Increased thyroid hormones incases of hepatic injuries may influence the liver Cirrhosis enzymes, as evinced by the increase in levels of ALT and aspartate aminotransferase (AST). Incidents associated with cholestatic injuries exhibit elevated level of serum ALP. Other abnormalities which may be reported in liver due to thyroid diseases include, decreased albumin and increased bilirubin and gamma-glutamyl transpeptidase.

Hypothyroidism
Poor activity of thyroid gland can affect the liver functioning directly. Decreased levels of T3 and T4 might have a negative impact on liver by causing decrease in activity of enzyme bilirubin UDP- glucuronosyltransferase. This results in reduced bilirubin production and bile excretion, causing cholestatic jaundice. In hypothyroidism, due to reduced bile excretion, incidences are characterized by hypercholesterolaemia and hypotonia of the gall bladder. As a result, these patients suffer from increased risk of gallstones.

Detection of Thyroid and Liver Abnormalities
A. Thyroid Profile
1. Thyroid Stimulating Hormone (TSH)
TSH is a pituitary hormone responsible for triggering the release of thyroid hormones 13 and 14 by the thyroid, gland. Measure of TSH in the blood stream indicates the health of thyroid. Lower TSH level reflect hyperthyroidism whereas elevated level indicate hypothyroidism.
2. Thyroxine (t4)
T4 is an inactive thyroid hormone produced by the thyroid, which controls the body's Metabolic rates when converted to its active form. Lower level of T4 indicates hypothyroidism and high level are associated with hyperthyroidism.
3. Triiodothyronine (T3)
Inactive T4 is converted to active T3 in kidney and liver. T3 helps in regulating body's metabolic rate, temperature, etc. Evaluating T3 helps to diagnose hyperthyroidism.

B. Liver Function Tests
1. Serum Albumin
Albumin is a liver protein which plays numerous important roles such as transporting hormones, Vitamins, drugs, calcium and other substances, nourishing the tissues, prevent leaking of fluids out of the blood vessels, etc. Lower serum albumin levels are indicative of loss of liver function associated with severe liver diseases.
2. Bilirubin
Bilirubin is found in bile in the liver and helps in digestion of food. A healthy liver will excrete most of bilirubin from the body. Thus, an increase in bilirubin level in the serum might be an indication of liver damage, because of which bilirubin may have leaked out of the liver into the circulating blood. High bilirubin levels are associated with jaundice.
3. Alanine Aminotransferase (ALT)
ALT is a liver enzyme detectable by serum glutamic pyruvic transaminase (SGPT test). ALT is generally found inside the liver cells, therefore increase in serum ALT may indicate liver damage.
4. Aspartate Aminotransferase (AST)
AST is an enzyme found mostly in liver but also throughout the body at lower levels. Liver injury may cause the leakage of AST into the bloodstream thu elevating its level. A ratio of APT/ALT is usually estimated to identify the type of liver injury.
Thyroid - A gland located below the Adam's apple in the base of the neck; liver- an organ located beneath the diaphgram of the upper-right side of the body. Two complex organs coordinating with each other for the smooth functioning of the body. This far complicated, connection is equally dependent on the healthy functioning of both these organs.