Hypothyroidism is one of the most common chronic conditions caused by the deficiency of thyroid hormones – thyroxine (T4) and triiodothyronine (T3). Around 5% of the population is affected by hypothyroidism, and a further 5% are undiagnosed. 

Hypothyroidism or underactive thyroid is a disease condition with partial or complete loss of the function of the thyroid gland. 

The thyroid gland is a butterfly-shaped tissue present in the lower neck. It is responsible for producing and regulating thyroid hormones. These hormones are popularly known as triiodothyronine (T3) and thyroxine (T4). 

These hormones play a vital role in various functions of the body, including regulation of growth, maintaining brain development, regulating metabolism and body temperature.

If a first-degree family member (parent or sibling) experiences any thyroid disease, the likelihood of developing a thyroid condition increases. 

TSH is a hormone produced by the pituitary gland that stimulates the thyroid gland to produce T4 and T3 hormones. One study suggests that genetics play a vital role in determining thyroid hormones – thyroxine (T4) and triiodothyronine (T3) – and thyrotropin (TSH) hormones. 

Although there are several causes for hypothyroidism, such as environmental factors, iodine deficiency, autoimmunity etc., genetics stand out as one of the predominant causes of its development. 

So, let’s try to understand the science behind how genetics influence hypothyroidism. 

What is Hypothyroidism? 

Hypothyroidism, also known as underactive thyroid, is a medical condition in which your body doesn’t produce enough thyroid hormone for your body. This hormonal insufficiency leads to various symptoms, such as weight gain, fatigue, depression, and reduced cognitive function.

These hormones play a vital role in various bodily functions, like regulating growth, maintaining brain development, and regulating metabolism and body temperature.

What are the Causes of Hypothyroidism?

There are several causes of Hypothyroidism, including

• Genetic/family history 
• Iodine deficiency
• Autoimmune disease (Hashimoto’s thyroiditis)
• Surgical removal of the thyroid gland
• Radiation treatment
• Medications like Lithium, Bromocriptine, Glucocorticoids
• Thyroiditis
• A congenital condition
• Pituitary gland disorders

What are the Symptoms of Hypothyroidism?

The insufficient production of thyroid hormone levels causes several body processes to slow down. Many people may not notice any symptoms in the early stages of hypothyroidism. Symptoms vary depending on the severity of hypothyroidism. 

• Fatigue
• Weight gain
• Depression
• Dry skin and hair
• Cold intolerance
• Joint and muscle pain
• Infertility
• Irregular menstrual cycle 
• Constipation
• Heavy Menstrual Flow
• Hair Fall

Is Hypothyroidism Genetic?

This is a complex question. As researchers dig deeper into the role of genetics, it is evident that genetics play a significant part in hypothyroidism. However, environmental factors also influence the onset of the condition. 

Genes are like instructions passed from parents to children, and they affect how our bodies produce thyroid hormones. One study found that 64% of thyroid stimulating hormone (TSH) and 65% of thyroid hormones are genetically determined. This is especially true for those who have a family member with an autoimmune disease (e.g., Hashimoto’s thyroiditis). So, we can conclude that genetics do play a role in hypothyroidism, but that’s not the entire story – environmental factors are critical as well. 

Linking Genetics to Hypothyroidism

Many genes are identified to be associated with hypothyroidism. SLC5A5, SLC26A4, TG, TPO, DUOX2, DUOXA2 are related to hypothyroidism.

One of those identified genes is TPO (Thyroid Peroxidase). 

TPO is a crucial enzyme responsible for the production of thyroid hormone. However, any mutation to this enzyme (TPO) can hinder its function, leading to reduced thyroid hormone production. This, in turn, increases the risk of developing hypothyroidism.

Another hypothyroidism-associated gene named thyroglobulin protein (TG) is vital for the storage and secretion of thyroid hormones. Mutation of these genes can obstruct the production and release of thyroid hormones, leading to hypothyroidism.

Various studies have also found a genetic relationship between hypothyroidism and other genes. Genes like sodium-iodide symporter gen (SLC5A5) and deiodinase genes (DlO1, DIO2, and DIO3) play a crucial role in thyroid hormone uptake activation and deactivation.

Several inherited genes have been linked to Hashimoto’s disease, including immune regulatory genes HLA, CTLA4, and PTPN22 and thyroid-specific genes TG and TSHR.⁶ First-degree relatives (e.g., parents, siblings) of a person with Hashimoto’s are nine times more likely to develop the condition.⁷

Thyroid diseases are polygenetic, and while there are sufficient pathways affected by genetic changes, and there is, to our knowledge, no gene that has been found to be specifically causal, and the pathology has been the result of the interaction of many genetic variables such as polymorphisms or mutations.( refer to-  https://pubmed.ncbi.nlm.nih.gov/31301652/ )

Genetic Markers

Genetic markers are a unique alternative approach to studying the genetic component of hypothyroidism. They are nothing but variations in the DNA sequencing indicating an increased risk of a particular ailment or condition.

For example, a recognized marker associated with autoimmune hypothyroidism is the HLA-DR gene. This gene is associated with the regulation of the immune system. It is found to be more prevalent in individuals with autoimmune diseases such as Hashimoto’s thyroiditis. It’s worth noting that while genetic markers can indicate an increased risk, they do not guarantee the development of the condition. 

Hashimoto’s thyroiditis is a condition where the body’s immune system attacks the thyroid tissue. This eventually leads to inflammation and decreased production of thyroid hormones.

Environmental Factors

Indeed, the genetic component in the case of hypothyroidism is surely convincing. However, it is also necessary to consider other non-genetic factors, such as the environment, which affects hypothyroidism  

• Iodine deficiency: Insufficient amount of iodine in the diet may lead to impairment of thyroid hormones. In regions with low iodine dietary habits, hypothyroidism is a prevalent issue, especially among individuals who are genetically more susceptible to it.
• Exposure to toxins: Substances like perchlorate, nitrates, and heavy metals play a crucial role in interfering with the normal functioning of the thyroid. These toxins disrupt the iodine uptake and also hinder thyroid gland functions, leading to hypothyroidism. 

Gene-Environment Interaction

Genetics majorly contributes to hypothyroidism occurrence but is often characterized by the interplay between genetic vulnerabilities and triggering environmental factors.

For example, an individual with a genetic predisposition may stay asymptomatic until triggered by an environmental factor. These environmental factors may induce or accelerate the onset of hypothyroidism, making it challenging to identify the exact reason for the occurrence of hypothyroidism.  

• In Hashimoto’s thyroiditis, the body’s immune system attacks the thyroid gland. The autoimmune response can be triggered by an environmental factor such as a viral infection or exposure to certain chemicals. This can lead to the development of conditions sometimes in a genetically susceptible individual. 
• Diet and Lifestyle: Dietary factors often act as triggers that lead to disease when combined with genetic factors. For example, a nutrient-poor diet high in processed foods can lead to hypothyroidism.
• Radiation Exposure: Genetic variations determine an individual’s vulnerability to radiation exposure. Those who are genetically more susceptible to radiation’s effects may develop hypothyroidism when exposed to radiation therapy, particularly to the neck or head area.
• Stress and Genetics: Chronic stress can impact the body’s hormonal balance, including thyroid function. An individual more susceptible to stress-induced hormonal imbalances due to genetic factors is at a higher risk of developing hypothyroidism during prolonged periods of stress.
• Gut Health and Autoimmunity: Gut health is increasingly linked to autoimmune diseases like Hashimoto’s thyroiditis. A diet high in gluten or low in probiotics may cause poor gut health. This, in turn, can trigger or exacerbate autoimmune responses in genetically predisposed individuals.

It is important to note that these environmental factors may lead to thyroid disorder, even if you are not genetically predisposed to it.

Genetic Testing and Hypothyroidism

Genetic testing is a technology that identifies individuals at higher risk of developing hypothyroidism. Early detection of mutation of specific genes, such as TPO or TPG genes, helps in early detection and preventive management. It can also help in timely intervention and personalized functional medicine program as per the requirements. 

Conventionally, genetic testing for thyroid conditions is not a typical healthcare diagnosis tool. It may be considered when there’s a strong family history or suspicion of a genetic component.

Conclusion

Hypothyroidism is a complex condition that results from a combination of genetic and environmental factors. While genetics play a significant role, environmental triggers, and lifestyle choices can either initiate or exacerbate this risk. Genetics interact with various environmental influences, such as iodine deficiency, autoimmune triggers, dietary choices, radiation exposure, and stress. 

Research suggests that about 65% of thyroid hormone production is determined by genetics. Therefore, individuals with a family history of thyroid conditions, especially Hashimoto’s thyroiditis, should consider early monitoring and genetic testing to assess their risk. 

By recognizing the interplay between genetics and the environment, functional medicine practitioners  can offer more personalized approaches to managing and preventing hypothyroidism, ultimately leading to better patient outcomes.

Frequently Asked Questions

1. Is hypothyroidism a genetic condition?

Answer. Yes, various pieces of evidence prove that there is a link between hypothyroidism and genetics. Research shows that a certain gene mutation increases the risk of hypothyroidism. However, a few environmental factors accompany the genetic condition in the occurrence of hypothyroidism.

2. Can hypothyroidism be passed from parents to children?

Answer. Yes, hypothyroidism can be transferred to children if one or both parents have an element of hypothyroidism. However, it’s uncertain as environmental factors also play a huge role in hypothyroidism occurrence.

3. How do genetics contribute to hypothyroidism?

Answer. Genetics plays a crucial role in the development of hypothyroidism. Certain mutations of a few special genes can easily hinder the functioning of the thyroid gland. Additionally, genetic factors influence the immune system, leading to an auto-immune thyroid condition such as Hashimoto’s thyroiditis.