Thyroid and Adrenal Connection
Who knows someone who has a thyroid condition ? It seems like thyroid conditions are everywhere. I personally have had TSH levels that were suboptimal for many years. It was not until my TSH reached 4.0 and antibodies showed up, my hair was falling out and I gained 10lbs that I realized it was time to address my thyroid!
As many people already know, untreated hypothyroidism can lead to increased body weight, cognitive dysfunction, fatigue, abnormal serum lipids, coronary heart disease, and for women recurrent miscarriage, infertility, and autoimmune disease. I find it interesting how the thyroid is influenced by stress and stress hormones in so many different ways. According to Meyers (n.d.), cortisol functions in a negative feedback loop with the hypothalamus and pituitary gland. Since the pituitary gland regulates thyroid hormone production, excess cortisol can affect thyroid function. In the context of excessive stress hormone, T3 is converted to the inactive rT3. In addition, stress produces inflammatory cytokines that can make thyroid receptors less sensitive to thyroid hormones, which is often seen when people who take thyroid medication no longer responding to them. In addition, excessive cortisol can influence sex hormones, like estrogen, to accumulate which can increase the levels of thyroid binding globulin (TBG), which binds up the circulating thyroid making them inactive and unavailable. Chronic stress can also suppress the immune system and promote inflammation, which can trigger the release of latent infections and start the cascade of autoimmune thyroid disease. Moreover, stress can also weaken the mucosal barrier system such as in the intestines and the brain, causing intestinal permeability and leaky blood brain barrier (BBB), which can set off the cascade of a dysfunctional gut-brain axis, autoimmune disease, inflammation, food allergies/intolerances, and subsequent nutritional deficiencies.
The thyroid stimulating hormone (TSH) secretion typically is maintained within relatively narrow limits via a sensitive negative feedback loop in which TSH stimulates the synthesis and release of thyroid hormones, that in turn negatively feed back to the hypothalamus and anterior pituitary to limit further TSH release (Walter et al., 2012). Traditionally hypothyroidism is diagnosed when there is an indication of TSH elevation as well as T4 and T3 levels out of range. However, recent attention has been given to “subclinical hypothyroidism”. In fact two large population based studies revealed that 4-8.5% of people without any diagnosed thyroid disease actually have subclinical hypothyroidism, as evidenced by hypothyroid symptoms (hair loss, fatigue, dry skin, weight gain) and mildly elevated TSH levels (Walter et al., 2012). What makes this more complicated is setting the proper upper limit of the healthy reference range for TSH. “In apparently healthy populations, the TSH distribution is skewed towards the lower end of the reference range, with the mean value typically being around 1.5 uIU/L, but with the range extending from 0.5–4.5 uIU/L” (Walter et al., 2012). Therefore, it is possible that “normal” individuals with thyroid symptoms and TSH levels trending on the higher end may actually be experiencing early thyroid gland failure and should be considered having subclinical hypothyroidism. This is even further supported when patients are showing TSH ranging in 3-4.5 UIU/L range and are positive for antithyroid antibodies (Walter et al., 2012).
I also found some interesting correlations in a journal article published in 2012 in regards to TSH and cortisol. Just like elevated stress hormones can create downstream thyroid dysfunction, thyroid dysfunction can also elevated cortisol levels. This is thought to be due to both decreased cortisol clearance and blunted negative feedback of cortisol on the HPA-axis. Another explanation, according to Walter et al (2012), is due to subtle metabolic stress. “Metabolic stress could be imposing an effect on the adrenocorticotropin hormone-adrenal axis leading to an increase in stress hormone (i.e., cortisol) release and production. This hypothesis should be confirmed through the measurement of other stress” (Walter et al., 2012). Chronic elevations in serum cortisol and hypothyroidism (including subclinical hypothyroidism) have been separately linked with increased rates of depression, anxiety, and poor cognitive functioning, which demonstrates a novel pathway of hypothyroidism and poor mental health. In fact, according to Walter et al (2012), hypothyroidism and an elevated cortisol could have a synergistic effect on mental health (Walter et al., 2012). What is interesting is that the although the subtle elevation in TSH are associated with higher basal cortisol levels, this relationship is not as apparent for FT3 or FT4 levels. “One plausible explanation for the lack of an association between FT3 or FT4 and cortisol is that changes in FT3 and FT4 are slow to reflect subclinical hypothyroidism in the circulation because of adjustments made at the end organ level in both synthesis and metabolism of thyroid hormones” (Walter et al., 2012).
One last point that should be mentioned is when cortisol levels are manipulated through pathological or physiological ranges (such as in stress or Cushing’s syndrome), the corticosteroids actually suppress TSH, while low cortisol can elevated TSH (Walter et al., 2012). These studies all taken together suggest a physiologic feedback loop where lower thyroid function increases cortisol, but cortisol feeds back to reduce TSH (Walter et al., 2012). This hypothesis is consistent with the observations that in the case of primary hypothyroidism (elevated TSH) cortisol is elevated, but in the setting of primarily elevated cortisol TSH is suppressed. “This hypothesis is consistent with the observations that in the case of primary hypothyroidism (elevated TSH) cortisol is elevated, but in the setting of primarily elevated cortisol TSH is suppressed. Clearly further clinical studies, for instance studies that incrementally administer TSH and evaluate cortisol levels, are needed in order to better understand the mechanisms involved in the TSH-cortisol relationship” (Walter et al., 2012).
Meyers, A. (n.d.) The Adrenal-Thyroid Connection. Retrieved (2018, October 25) from https://www.amymyersmd.com/2017/03/adrenal-thyroid-connection/
Walter, K. N., Corwin, E. J., Ulbrecht, J., Demers, L. M., Bennett, J. M., Whetzel, C. A., & Klein, L. C. (2012). Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women. Thyroid Res, 5(1), 13. doi:10.1186/1756-6614-5-13