Every cell in the body has receptors for thyroid hormones. These hormones are responsible for the most basic aspects of body function, impacting all major systems of the body. Thyroid hormone directly acts on the brain, the G.I. tract, the cardiovascular system, bone metabolism, red blood cell metabolism, gall bladder and liver function, steroid hormone production, glucose metabolism, lipid and cholesterol metabolism, protein metabolism and body temperature regulation. Thyroid health is thus critical to consider in numerous disease states.
Sub-clinical hypothyroidism (SCH) is a common issue in chronic fatigue.
Subclinical thyroid disease (SCTD) is defined as serum free T4 and free T3 levels within their respective reference ranges in the presence of abnormal serum TSH levels.
However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems.
It has been concluded in research that “it seems reasonable to treat symptomatic patients, those with cardiovascular risk factors, pregnant women, patients with goiter and a positive thyroid antibody test, and subjects with ovulatory dysfunction and infertility because there is evidence of the potential reversibility of these dysfunctions associated with mild thyroid failure.”
The causes of SCH resemble the causes of hypothyroidism, where autoimmune thyroiditis is the most frequent cause
The below table lists other common causes of sub-clinical hypothyroidism:
A more Comprehensive Approach Is Needed
Evidence is mounting that levothyroxine monotherapy cannot assure a euthyroid state in all tissues simultaneously, and that normal serum TSH levels in patients receiving levothyroxine reflect pituitary euthyroidism alone.
Persistent symptoms might be explained by factors unrelated to thyroid disease, unrecognized autoimmune disease, or inability of levothyroxine to restore T3 levels in serum and all target tissues
Autoimmune thyroid disease is present in about 70% of hypothyroid individuals, and patients with autoimmune thyroid disease are at high risk of developing other autoimmune diseases
In fact, a few reports suggest the possibility that thyroid autoimmunity itself might give rise to nonspecific symptoms, independent of decreased thyroid function
These observations raise the question of whether normal serum TSH levels are a reliable marker of euthyroidism in nonpituitary tissues during levothyroxine replacement.
Low levels of serum sex-hormone-binding globulin (SHBG) in patients receiving levothyroxine who have normal TSH levels suggests the presence of tissue hypothyroidism in the liver.
The modern paradigm of thyroid hormone action also recognizes that thyroid hormone signaling in individual tissues can change even as serum hormone concentrations remain normal, thanks to local activation or inactivation of thyroid hormone. The underlying mechanism of these phenomena is deiodination
While dopamine and glucocorticoids play a suppressive role with respect to TSH, leptin administration leads to increases in serum TSH, T4, and T3 concentrations. Another pathway that could be involved in the suppression of TSH secretion is the NF-κB cascade (inflammation)
- Excess dietary iodine
- Naturally occurring goitrogens
- Dietary Fat
- Heavy metals: Heavy metals like cadmium and lead are known to affect thyroid function
Daily diet should include thyroid boosting foods like those rich in iodine, amino acid tyrosine, minerals like selenium, zinc, copper, iron, various vitamins including, B2, B3, B6, C and E.
The benefits of iodine repletion outweigh the risk of thyroid auto-immunity, hence global iodine sufficiency should be ensured. The amount of fat consumed and its composition definitely influences thyroid activity. The below table highlights some key nutrients that support various aspects of thyroid function/health.
Interpreting Lab Results
Testing TSH indicates only pituitary production
Accordingly, the same TSH value could be “normal” for one individual but pathological for another. This also holds for patients with subclinical dysfunction, in whom the relationship between FT4 and TSH shows elements both of normality and abnormality. Apart from the statistical requirement that a TSH value in the subclinical range must change by 30% to be confidently classified as change rather than variation or fluctuation, the true nature of TSH referencing is bivariate in relation to an appropriate individual TSH level when combined with a certain FT4 level. Pulsatility of TSH release adds to the intraindividual variation in TSH levels, which is higher than that of circulating FT4 concentrations.
Circadian and ultradian rhythms of TSH levels reduce diagnostic accuracy unless reference intervals are adapted or blood sampling is restricted to morning time.
TSH reference ranges may in fact be but a crude parameter for detecting disease in an individual patient and we should not be confusing a population reference range with an individual’s ‘normal range’.
The Plasticity Of The Thyroid
The persistence of a significant homeostatic deviation for a prolonged period of time, may, in turn, irrevocably alter the position of the set point, which then assumes a “normality” that is now vigorously defended anew. This potential plasticity of thyroid homeostasis is part of a broader concept of epigenetic influences where the bidirectional interchange between heredity and the environment plays a defining role
Antioxidants & Autoimmune Thyroiditis
Research demonstrates a substantial reduction in glutathione (the main antioxidant) status in hashimoto’s subjects
Mechanism(s) linking deterioration of cellular antioxidant defense to the pathogenesis of autoimmune thyroiditis is not fully clear. However, it has postulated that overproduction of ROS is main event leading to thyroid dysfunction
Selenium & Thyroid Health
Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation
The course and severity of autoimmune thyroid disease may be positively modulated by selenium supplementation via optimizing the endocrine–immune system interface
Chronic Stress & The Thyroid
- Chronic stress disrupts the HPA axis: Countless studies show that chronic adrenal stress depresses hypothalamic and pituitary function. And since these two organs direct thyroid hormone production, anything that disrupts the HPA axis will also suppress thyroid function.
- Chronic stress reduces conversion of T4 to T3
- Chronic stress promotes autoimmunity by weakening immune barriers
- Chronic stress causes thyroid hormone resistance
- Chronic stress causes hormonal imbalances: Cortisol is one of the hormones released by the adrenals during the stress response. Prolonged cortisol elevations, caused by chronic stress, decrease the liver’s ability to clear excess estrogens from the blood. Excess estrogen increases levels of thyroid binding globulin (TBG), the proteins that thyroid hormone is attached to as it’s transported through the body
The below visual is from ThyroidPharmicist.com.
A great way to think about thyroid function is using the acronym PTSD.
Production or synthesis of HPT axis hormones
- T4, T3, TSH, TRH
Transport/distribution/metabolism of hormones
- Conversion to T3 and/or RT3
Sensitivity at the cellular level of thyroid hormones
- Receptor sensitivity
Detoxification/metabolism of thyroid hormones
Let’s look at these in more detail.
We have already mentioned stress impacts on TSH and T4 production. It has also been shown that increased urinary cortisol metabolites have been associated with reduction in peripheral thyroid hormone metabolism and symptoms of functional hypothyroidism.
Inflammation (via elevated cytokines) blocks conversion of T4 to T3.
During caloric restriction serum T3 concentrations decrease as a consequence of its reduced production rate from peripheral deiodination of T4. Opposite, serum RT3 concentrations markedly increase as a result of its decreased metabolic clearance rate.
Factors that either produce vitamin A (retinol) insufficiency or prevent the conversion of vitamin A to retinoic acid may result in reduced thyroid nuclear signaling.
A study of older-aged individuals found that low T3- to-T4 ratio was related to impaired zinc and/or selenium status. Selenium and zinc both play a role in promoting proper thyroid function:
- Selenium through its deiodination and the activity of thyroid hormones
- Zinc by its role as a cofactor for the thyroid receptor
Medications that block conversion of T4 to T3:
- Beta blockers
- Birth control pills
- Estrogen replacement
Compromised liver or kidney function, Cd, Hg, Pb, herbicides, pesticides all compromise T4 to T3 conversion.
Signs Of Low Thyroid Function
- Dry skin, elbow keratosis, brittle nails
- Diffuse hair loss
- Puffy face, swollen eyelids; edema in legs, feet, hands
- Elevated cholesterol, generally seen as LDL increases
- Easy bruising
- Prolonged Achilles tendon reflex time
Symptoms of Low Thyroid Function
- Fatigue, usually persistent, especially on waking; less toward the evening
- Cold intolerance, with cold extremities
- Slow speech, movement, heart rate
- Morning stiffness, arthralgias, muscle pain/cramps particularly in calves, thighs, and upper arms
- Memory and concentration problems
- Constipation: hard bowel movements and decreased frequency
- Diffuse headache, migraines
- Depression; melancholia