Stress & the Thyroid

Stress & the Thyroid

Stress manifests in different ways with many reporting symptoms of insomnia, depression, fatigue, headache, upset stomach, digestive disturbances and irritability, amongst others. These symptoms can also present in a thyroid condition and so it is vital that we investigate the health of the thyroid when these symptoms of stress present themselves.  

Stress is perceived as emotional, physical and environmental, with the latter triggered by toxins, pesticides, lack of sleep, elevated blood sugar and medications. All forms of stress send a message through the body which throws cortisol and adrenaline levels out of balance which can subsequently cause your thyroid to under-perform.

The HPA Axis

During stress we activate the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal glands are part of the endocrine system, just like the thyroid, and these sit on top of the kidneys. Stimulating the HPA axis causes the adrenal glands to release glucocorticoids (e.g. cortisol) and catecholamines (e.g. adrenaline). In ‘Fight or flight’, or what we call the sympathetic nervous system mode, adrenaline and cortisol are released in response to the threat in acute situations. Think about the threat of an attack from a bear when we were cave dwellers. The mechanism is there for our survival. Cortisol is also released and continues to be released during a long-term stress response. These days, often underlying this is the incessant boss or the unhappy marriage or the to do list that never ends. This chronic stress can disrupt thyroid function in the long-term.

The HPT Axis

Like the HPA axis, we rely on the pituitary gland in our brain to send signals to our thyroid in the hypothalamic-pituitary-thyroid (HPT) axis. When the HPA axis is disrupted it suppresses the HPT axis and thyroid function is directly affected. Production of thyroid hormone is suppressed, as well as the conversion of thyroxine (T4) to triiodothyronine (T3).

Immunity

The interplay between stress hormones and thyroid hormones has an effect on all systems of the body, with the immune system being no exception.  Stress hormones act on antigen presenting immune cells which may influence the differentiation of T Helper (TH) cells. Differentiation of TH cells away from TH1 and towards a TH2 phenotype occurs which leads to a suppression of cell mediated immunity and potentiation of humoral immunity. In other words, there is a shift in the immune system so that the arm that deals with antibodies is stimulated. Thyroid autoimmunity presents itself as Graves’ Disease – hyperthyroidism - or Hashimoto’s thyroiditis – hypothyroidism – and these are diagnosed when antibodies - thyroglobulin (TG) or thyroid peroxidase (TPO) – are raised, and this is what is meant by the humoral response or TH2 arm of the immune system.

Some of us are more susceptible to autoimmune diseases because of our genetic makeup but it is important to remember that our gene expression changes depending on the environment. So even if we are more susceptible, if we bathe our genes in a favourable environment - good nutrition and lifestyle factors - then autoimmunity may be kept at bay. As stress can be one of the environmental factors causing thyroid autoimmunity, it is important to engage in stress management techniques and recognise the signs of stress.

Insulin Resistance

A high production of cortisol increases our blood sugar. When blood sugar is high, insulin production increases in an attempt to remove the glucose from the blood and transfer it to the body’s cells. If chronic stress is left unchecked, insulin resistance occurs whereby the cells stop responding to insulin which means that glucose cannot get into the cell and instead remains in the blood. This raises blood sugar consistently which causes damage to blood vessels contributing to cardio-vascular disease. Furthermore, as the glucose is unable to reach inside the cell, the body cannot use it to make energy and so we feel those familiar symptoms of thyroid disease: tiredness and fatigue.

This insulin resistance will also impair uptake of T3 into the cell. This can often go unnoticed as TSH, T3 and T4 on bloodwork can show thyroid function as ‘normal’ when in fact there is thyroid hormone resistance occurring at the cellular level. In this instance hypothyroid symptoms can be attributed to high/chronic stress.

Intestinal Permeability/Leaky Gut

With Hashimoto’s thyroiditis or indeed any autoimmune condition we have weakened immune barriers. 70% of our immune system lies in the gut. The gastrointestinal tract, the lungs and the blood brain barrier are primary immune components of the body.  

In the gastrointestinal tract, there are little holes that can occur – triggered by toxins, gluten and stress. Adrenal stress weakens the barriers and weakens the immune system. In the gut-thyroid connection, when the barriers are breached the large antigens enter the bloodstream through the intestinal lining and create this systemic inflammatory response. When this happens over and over the immune system becomes overwhelmed and we become susceptible to other autoimmune disease.

So, as stress can turn on the gene where autoimmunity can express itself, it can also break down immune barriers and create an autoimmune flare.

Inflammation

The deiodinase family of enzymes mediates the activation and inactivation of thyroid hormone. The role of these enzymes in the regulation of thyroid hormone concentrations throughout the body is well established. They are made up of deiodinase 1 (D1), deiodinase 2 (D2) and deiodinase 3 (D3).

When we perceive stress, an influx of inflammatory cytokines occurs, and it is this cascade of chemicals – Interleukin 1, Interleukin 6, C-reactive protein (CRP) and Tumour necrosis factor alpha (TNFa) - which interferes with deiodinase activity.

Inflammatory cytokines will decrease D1 activity as well as reduce tissue T3 levels and the conversion rate of T4 to T3. As T4 is the inactive thyroid hormone and T3 is the active hormone, maintaining conversion of T4 to T3 is essential in proper thyroid function.

The inflammatory cytokines will increase the activity of D2 and suppress TSH despite reduced peripheral T3 levels, interfering with the body’s negative feedback mechanism.

Inflammation will stimulate D3, producing more reverse T3, further causing cellular hypothyroidism by suppressing intracellular T4 to T3 conversion and blocking the T3 receptor inside the cell.

Oestrogen Dominance

Adrenal stress can also cause hormone imbalances. Prolonged cortisol elevations caused by chronic stress decreases the liver’s ability to clear excess oestrogens from the body.

Excess oestrogens increase the level of thyroid binding globulin (TBG), the protein thyroid hormone is attached to as it is transported through the body. When thyroid hormone is bound to TBG it is inactive and has to be cleaved to be of use to the body. Free T3 and free T4 levels in bloodwork tell us the amount that is unbound to TBG and available to exert its effect.

So when stress is high, we have high cortisol and excess oestrogen leading to reduced thyroid activity. This will show up in bloodwork as low T3 uptake and low FT3 and FT4. Women who take contraception containing oestrogen can contribute to oestrogen dominance which can, in turn, affect the thyroid.

To help with this excess oestrogen we can increase our cruciferous vegetables and fibre amongst other things in order to improve metabolism of oestrogen but we also need to address the source which in a lot of cases is stress.

Oxidative Stress

Both hyperthyroidism and hypothyroidism have been shown to be associated with oxidative stress (OS). Oxidative stress is an imbalance between the production of pro-oxidant substances, which can damage cells, and anti-oxidant defences. The thyroid gland is a unique endocrine organ that requires one of these pro-oxidant compounds, hydrogen peroxide (H2O2), for thyroid hormone formation. Because of this, thyroid cells contain antioxidants to protect themselves from the H2O2-mediated oxidative damage. Loss of this balance may result in thyroid cell dysfunction and thyroid diseases.

What Can We Do?

Through management of diet and lifestyle we can improve our stress levels and directly affect the way our body functions.

Nutritional factors

-         Balancing our blood sugar levels is key to improving our energy levels and regulating our stress hormones.

-         Ensuring sufficient intake of nutrients is vital if we expect our thyroid to function properly. For example, the amino acid tyrosine is a critical precursor of T4 and T3. Tyrosine is also required in the production of adrenaline so when we are stressed, it is adrenaline which takes priority which means less tyrosine is available to make thyroid hormone. Zinc, selenium, copper, vitamin D, and magnesium are also required for proper thyroid function and must be consumed on a daily basis.

-         We must remove any triggers that may be irritating the thyroid and causing it to send out a stress signal. For example, toxins can cause thyroid inflammation as a result of oxidative damage, triggering the thyroid to send out a stress response to the immune system.

-         We must also repair any damage to the gut lining, often caused by gluten and other food intolerances, to reduce reaction of the immune system which can lead to autoimmunity.

-         Balancing of our adrenal glands, immune system and optimisation of our detoxification capabilities are all vital processes which must be addressed.

Lifestyle Factors

Amongst the stress management techniques that have been shown to work over and over again are: yoga, deep breathing, meditation and walking in nature. By engaging in these activities we are engaging our parasympathetic nervous system and reducing levels of cortisol. The key is finding something that suits you and carving out time in your day to put it into practice.

Education

Knowing the mechanism of action helps you to pay attention to your own body. If you have any of the symptoms mentioned above, then stress could be affecting your HPA axis, having a knock-on effect on your thyroid function and creating a hormone imbalance. Interventions to help with stress must be undertaken in order to prevent exacerbation of symptoms and the consequent onset of disease.  

References

Engler, D. Burger, A. (1984). ‘The deiodination of the iodothyronines and of their derivatives in man’, Endocrinology Review, 5 (2) pp.151-84.

Freitas, J. (2012). ‘Development and validation of in vitro bioassays for thyroid hormone receptor mediated endocrine disruption’.

Holtorf, K. (2014) ‘Peripheral thyroid hormone conversion and its impact on TSH and metabolic activity’, Journal of Restorative Medicine, pp.3-30.

Lechan, R. & Fekete, C. (2005). ‘Role of thyroid hormone deiodination in the hypothalamus’, Thyroid, 15 (8) pp.883–897. 

Ohye, H. Sugawara, M. (2010). ‘Dual oxidase, hydrogen peroxide and thyroid diseases’, Exp Biol Med, 235 (4) pp.424-33.

Mancini, A. Di Segni, C. Raimondo, S. et al. (2016). ‘Thyroid hormones, oxidative stress and inflammation’, Mediators of Inflammation.

Mizokami, T. Wu Li, A. E-Kaissi, S. et al. (2005). ‘Stress and thyroid autoimmunity’, Thyroid, 14 (12).