The evidence clearly demonstrates that there is functional crosstalk between the immune system and the thyroid. Thyroid hormones are not only used to support immune cells basic metabolic rate, but they also exhibit influences on cellular messenger systems that promote modulation of T and B-cell activity, cellular apoptosis, cytokine release and other immunokine responses. Therefore, thyroid hormones are classified as immune system modulators and thyroid function should be considered in cases of immune dysregulation or immune challenges.
Additionally, immune signaling mediators such as cytokines and adjuvants have been found to disrupt all aspects of the HPT (hypothalamic-pituitary-thyroid) axis, peripheral metabolism, and thyroid receptor site transcriptional expressions. Immune disorders have great potential to disrupt thyroid physiology and promote concomitant dysfunction in cellular metabolism.
Cytokines and the HPT Axis
Any type of AI disease causes increased cytokine activity. In any type of autoimmunity, there is dominance in either the TH1 or TH2 cytokine system. But the fact is that there is increased cytokine activity on either side. These cytokine are messenger proteins that have signaling effects. In either the TH1 or TH2 types of dominance, there is increased cytokine load which make the thyroid receptor sites less efficient. Any type of increased cytokine activity causes decreased receptor site response. This can result from any type of cytokine shift, including chronic infection. Anyone with chronic inflammation will have elevated cytokines. Any type of chronic inflammation will suppress the HPT axis.
Cytokines have been shown to downregulate the HPT axis by suppressing TSH output. If cytokines are suppressing TSH output, TSH and T4 will be low. When you see this pattern, you need to rule out systemic inflammation or autoimmunity. Autoimmune reactions will cause suppression of TSH and T4.
Cytokines and Peripheral Thyroid Hormone Conversion
Cytokines also have the potential to disrupt peripheral conversion of inactive T4 into active T3 hormone. Both TH1 and TH2 cytokines have demonstrated the ability to downregulate thyroid conversion potentials of T3. Chronic inflammation will cause decreased conversion of T4 to T3.
How will this look on a lab test?
- TSH is normal
- T4 is normal
- T3 is low
- RT3 is high
If we see this, we suspect inflammation. Most AI patients have T4 to T3 conversion issues. These patients do better with Armor or bioidentical hormone because all bioidentical hormone contains T3.
Any type of chronic inflammatory mechanism will shut down both receptor site responses and cause conversion issues
Lipopolysaccarides and Thyroid Metabolism
We also know chronic gut issues will impact thyroid conversion. These will cause T4 to T3 conversion issues. Gastrointestinal microorganisms which release compounds such as lipopolysaccharides (LPS) are adjuvants that impact thyroid physiology. LPS released from gram-negative bacteria are considerd endotoxins that may be used as adjuvants in the immune response.
Adjuvants are agents that cannot potentiate an immune response alone, but with the orchestration of other cellular agents, can influence physiological responses. LPS has the potential to influence the thyroid at all levels of function, including reducing thyroid hormone levels, diminishing the expression of the thyroid receptor sites, increasing inactive RT3 levels, decreasing TSH and promoting AI thyroid conditions.
A study of 24 healthy subjects who underwent IV injection of an LPS endotoxin demonstrated diminished levels of serum T4, serum free T3 and serum TSH and inactive RT3 was elevated when compared with controls. A similar study was conducted with 18 healthy subjects who underwent intravenous injections with an LPS endotoxin from E. coli. The LPS-challenged subjects demonstrated decreased levels of serum T4, serum free T4, T3, TSH, and a rise in inactive RT3.
These studies suggest that an immune challenge and abnormal gastrointestinal microorganism environments may promote abnormal central pituitary release of TSH as well as potential peripheral thyroid hormone production.
LPS has been shown to contribute to the pathogenesis of non-thyroidal illness (NTI) of the central part of the HPT axis. When the gut or lung epithelium is activated by infection, instead of just releasing cytokines, there is a LPS response which can shut down T4 to T3 conversion.
When we see a T4 to T3 conversion issue, we have to consider intestinal and lung epithelial infections or chronic inflammation. We need to do labwork to see what mechanisms are involved.
Cytokines and Thyroid Receptor Site Expression
Inflammatory cytokines alter thyroid function and thyroid receptor site proteomic responses. This is why many people taking thyroid hormones do not necessarily feel that much better. Proinflammatory cytokines have been associated with non-thyroid illness in view of their capability to decrease D1 and thyroid hormone receptor (TR) beta1 mRNA expression.
Active immune-related patterns may hinder thyroid metabolism and a careful evaluation of immune-related disorders must be provided to all individuals who present with thyroid symptomology. An example of this is the AI thyroid patient or a patient with an inflammatory disease who is taking replacement hormones but is still suffering from thyroid symptoms. In these scenarios, the elevations in inflammatory cytokines are depressing thyroid receptor site responsiveness while the hormones create a normal appearance of thyroid markers (TSH, T4, T3).
Many AI patients will not notice any difference even when taking thyroid hormone b/c of decreased receptor site sensitivity and decreased conversion of T4 to T3. What would happen to an autoimmune thyroid patient who has cytokine elevations and is given T4 thyroid hormone? They can’t convert T4 into T3 and they have decreased receptor site responsiveness. Many of them feel better with Armor, but some of them don’t because they have lost receptor site sensitivity.
The other we see with these patients is the have relapsing autoimmune responses. They flare up for a few days and calm down, flare up again and then calm down. When they flare up, there is destruction of the thyroid releasing more thyroid hormones and if they are taking T3, this is too much and they get nervousness, palpitations and insomnia. Many of them will not be able to tolerate bioidentical thyroid hormone at all because all the bioidenticals contain T3.
Summary of Immune Activity on Thyroid
Cytokine activity causes suppression of:
- HPT coordination
- TRH release
- T4 conversion into T3
- Post-transcriptional receptor site activity
- Thyroid hormone uptake
LPS or adjuvant causes suppression of:
- HPT coordination
- TSH production
- Thyroid hormone secretion
- Thyroid receptor site expression
- Active T3
LPS or adjuvant causes promotion of:
- RT3 production
- Autoimmune thyroid response
Content provided by Datis Kharrazian, D.C., Mastering the Thyroid, Nov. 12, 2010