Thyroid Hormone Synthesis

The thyroid is a small butterfly-shaped endocrine gland that is located in the front of a person’s neck. It is responsible for regulating the body’s metabolic rate by secreting the thyroid hormone, which is a combination of two hormones: thyroxine (T4) and triiodothyronine (T3). The thyroid gland generates these hormones through a process called thyroid hormone synthesis.

This article provides a detailed overview of the entire process, the disorders related to thyroid hormone synthesis, diagnostic methods, and treatment approaches. 

Thyroid Hormone Synthesis Process

The activity of the thyroid gland is controlled by a neuroendocrine system called the Hypothalamus–Pituitary–Thyroid (HPT) axis. This axis stimulates the hypothalamus to release thyroid-releasing hormone (TRH), which in turn triggers the anterior pituitary to secrete thyroid-stimulating hormone (TSH). 

After this, thyroid hormone synthesis takes place in the following steps:

• Thyroid hormone production is initiated through the absorption of iodine from the GI tract. Here, the iodine is broken down into iodide and released into the plasma. 
• These iodine ions are taken up from the bloodstream by the follicular epithelial cells through the sodium-iodide symporter (NIS).
• Then, a transporter protein called pendrin moves the iodide ions out of the thyroid follicular cells into the follicular lumen.
• Iodide is then oxidised by thyroperoxidase (TPO), forming active iodine. 
• Due to the action of an enzyme called iodinase, the active iodine binds to the thyroglobulin’s (TG) tyrosine residues to form two iodotyrosines, which are monoiodotyrosine (MIT) and diiodotyrosine (DIT).  
• These iodotyrosines undergo subsequent coupling reactions under the effect of TPO to form T4 and T3. They are stored in the form of colloids in the thyroid gland and are transported via the bloodstream to the target organs on thyroxine-binding prealbumin and thyroxine-binding globulin (TBG).     

Iodine and Thyroid Hormone Production

Iodine is the key element that helps the thyroid gland produce T3 and T4. The body gets iodine from the diet by absorbing it from the small intestine. Then, it converts it into iodide, binds it to plasma protein, and transports it to the thyroid gland for thyroid hormone synthesis. 

As a result, ensuring adequate iodine intake through food is crucial for maintaining the optimum production of thyroid hormones. To do so, one can consider including items like eggs, dairy products, seaweed (kelp, wakame, kombu, and nori), fish, and seafood in their diet.   

Thyroglobulin's Role in Hormone Production

Thyroglobulin is a large glycoprotein that is the matrix for thyroid hormone synthesis. It is discharged from the apical surface into the lumen during the synthesis process. The iodination required to form mature thyroglobulin only begins once it is released.

After the iodine is oxidised, it is organified by fusing into the tyrosyl residues of thyroglobulin. Eventually, as the T4 and T3 hormones are produced, they remain bound to the thyroglobulin in order to be stored in the thyroid gland.
Later, when the thyroid hormones need to be released into the body, the thyroglobulin is first engulfed by pinocytosis and then digested in lysosomes before being secreted into the bloodstream.     

Key Mechanisms in Hormone Release

Based on the level of thyroid hormones in the body, the pituitary gland secretes thyroid-stimulating hormone (TSH) to signal to the thyroid gland how much hormones it needs to generate.

For instance, if the thyroid hormone level in the blood is low, the pituitary gland will produce high amounts of TSH to indicate the thyroid gland to work harder. 

Alternatively, if the thyroid hormone level in the blood is high, the pituitary gland will produce little to no TSH. After adequate amounts of thyroid hormones are released into the bloodstream, almost 80% to 90% of the T4 is converted to T3 in the pituitary gland. 

Meanwhile, in the peripheral tissues, only around 30% to 50% of T4 is converted to active T3. The reason behind this is the inefficiency of Deiodinase Type I (D1) and the presence of Deiodinase Type III (D3) in tissues all over the body except for the pituitary gland. 

As a result, it competes with D1 and converts the T4 hormones to reverse T3.   

Regulation of Thyroid Hormone Levels

Thyroid hormone levels in the body are maintained by a feedback loop that involves the hypothalamus, pituitary gland, thyroid gland, and multiple hormones. 

The feedback loop starts with the hypothalamus releasing the Thyroid-Releasing Hormone (TRH), which stimulates the pituitary gland to release Thyroid-Stimulating Hormone (TSH). Consequently, the thyroid gland receives a signal to produce more T3 and T4. 

As the thyroid hormone levels in the blood increase, they prevent the further release of TRH and TSH. In case the T3 and T4 levels drop, the feedback loop starts again, ensuring that there is an optimum level of thyroid hormones in the bloodstream.  

Disorders Related to Thyroid Hormone Synthesis

• Hyperthyroidism

Hyperthyroidism is a condition in which the thyroid gland produces an excess amount of thyroid hormone, which speeds up the body’s metabolism. It is also known as an overactive thyroid and can lead to symptoms like unintended weight loss, rapid or irregular heartbeat, anxiety, hand tremors, increased appetite, and more.  

•   Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormones, thus reducing your body’s metabolic rate. It is also known as an underactive thyroid and can lead to symptoms like feeling tired all the time, unexpected weight gain, and brain fog, among others.  

Diagnostic Methods for Thyroid Function

• Thyroid Blood Tests

Some of the common thyroid blood tests are:

1. T3 and T4: These tests help measure the level of T3 and T4 hormones in a person’s body. 
2. TSH: Measures the amount of thyroid-stimulating hormone (TSH) in an individual’s body. 
3.  Thyroid Antibodies Test: This test measures specific thyroid antibodies in the blood in order to diagnose auto-immune thyroid diseases like Graves' disease or Hashimoto's thyroiditis. 

• Thyroid Imaging Tests

Thyroid imaging tests are prescribed by doctors to detect nodules (lumps) in a person’s neck and determine whether they are malignant (cancerous) or benign (non-cancerous). One such test is a thyroid scan in which small amounts of radioactive material are used to create a picture of the thyroid gland, showcasing its position, shape, and size. Similarly, a radioactive iodine uptake test helps check how well an individual’s thyroid is performing, along with finding the cause of hyperthyroidism.

Treatment Approaches for Thyroid Disorders

There are several treatment approaches for thyroid disorders and they are as follows:

Medical Approaches

In the case of hyperthyroidism, the treatment approaches include antithyroid drugs like methimazole and propylthiouracil apart from beta-blockers. Radioactive iodine therapy helps damage the thyroid cells to prevent them from secreting high levels of thyroid hormones.  In certain cases, healthcare providers can recommend surgically removing the thyroid to prevent it from producing hormones. 

For individuals having hypothyroidism, thyroid replacement medication is the only option. It involves synthetically adding thyroid hormones back into the person’s body. 

Lifestyle Changes

Some essential lifestyle changes needed to manage thyroid issues include:

• Quitting smoking
• Managing stress
• Prioritising sleep
• Staying active and exercising regularly
• Having a balanced diet and staying hydrated
• Limiting the intake of sugar and processed foods

Conclusion

Thyroid hormone synthesis takes place by absorbing iodine from a person’s diet to produce T3 and T4. These hormones help maintain the body’s metabolic rate and several other crucial processes. Thus, it is crucial that individuals maintain good thyroid health and seek medical assistance in case they notice any symptoms of thyroid-related disorders.