When people think of cardiovascular symptoms and thyroid hormones, they usually think first about hyperthyroidism (EXCESS T3 thyroid hormone).
However, hypothyroidism (DEFICIENT T3 thyroid hormone) has an equally powerful effect on the heart and blood vessels. It can just be slower, more long-term, and less dramatic.
Did you know?
- Heart failure occurs in hypothyroidism. (See below)
- Chest pain or angina can occur in hypothyroidism. (Ellyin et al, 1986) (Strachan et al, 2000) (Lee et al, 2015). In some patients, this is microvascular angina.
- Ventricular fibrillation (Marrakchi et al, 2015) and atrial fibrillation (Wang et al, 2015 ; Zhang et al, 2013) also occur in hypothyroidism.
- Myocardial infarction and coronary artery lesions can occur in hypothyroidism and low T3 syndrome (Bai et al, 2014).
Let’s examine the research to see what the T3 thyroid hormone does to the heart and blood vessels.
The T3 hormone vs. T4 hormone
For several decades, Irwin Klein and Sara Danzi have researched the connection between thyroid hormones and the heart.
In a recent article (Klein & Danzi, 2016), they mention both T4 and T3.
However, T4 is important only insofar as it provides a supply from which the body can, potentially, create T3.
Early in their article, “T3” becomes synonymous with “thyroid hormone” because, as they explain,
“Thyroid hormone affects almost every cell and organ system in the body. T3 is the biologically active form of the hormone and T4 acts mostly as a prohormone requiring deiodination to become active.” (Figure 2)
Not every organ can use T4 from bloodstream efficiently. Some organs and systems rely on Free T3 in blood.
This is the case for the heart. Studies have found that the cardiac myocyte depends largely on Free T3 in bloodstream (Wang et al, 2016).
Both forms of thyroid hormone transporters to heart cells, MCT10 and MCT8, prefer to transport T3 rather than T4. Therefore, Low T3 status can be locally induced within heart muscle in patients who have genetic polymorphisms in thyroid hormone transporter MCT10.
Finally, Klein and Danzi note that only the binding of T3 to the thyroid hormone receptor can activate it.
- Activation of the receptor by T3 hormone causes the transcription of multiple positively regulated genes.
- An appropriate degree of activation vs. inactivation by T3 is required for an organ or tissue to function properly.
The level of T3 available also influences the sensitivity of thyroid hormone receptors in the heart. The T3 hormone receptors become more sensitive when T3 is lacking. However, an increased level of genetic expression in the thyroid receptor cannot compensate for Free T3 hormone levels that are too low.
Molecular effects of T3 hormone on the heart
In a more recent journal article, Razvi, et al, 2018 describe the effects known to date.
- Appropriate T3 levels protect the heart in case of injury or stress.
- It plays many roles in “stimulation of cell growth, neo-angiogenesis, and metabolic adaptation” and protects mitochondria (p. 1782).
- Proper T3 levels prevent cardiac myocyte death and reduce interstitial fibrosis. This results in a delay or prevention of heart failure after ischemia.
- The presence and/or activity of T3 shifts multiple cardiac genes in relation to each other. Sufficient or excess T3 positively regulates some genes, while negatively regulating others. Insufficient T3 may either dampen these effects or invert them:
- +T3 causes ↑ Alpha-MHC [a-MHC] / ↓ Beta-MHC [b-MHC]
- +T3 causes ↑ Voltage-gated potassium (K+) channels / ↓ Na+/Ca2+ echganger (NCX1),
- +T3 causes ↑ SERCA2, / ↓ Phospholamban
- +T3 causes ↑ sodium/potassium (Na+/K+) ATPase, / ↓ Adenylyl cyclase types V and VI
- +T3 causes ↑ beta1-andrenergic receptor ANT1 / ↓ Thyroid hormone receptor alpha-1.
Specific Low-T3 effects on cardiovascular disease
- Low T3 reduces overall basal heart rate. This occurs even before T3 enters the thyroid hormone receptor, through a direct “nongenomic” effect on ion transport at the blood plasma membrane.
- Low T3 directly reduces heart muscle contraction via shifting the emphasis between a-MHC and b-MHC in the cardiac myocyte.
- Low T3 directly affects the ability to pump calcium ions (Ca2+) into the heart’s sarcoplasmic reticulum during the relaxation phase. Optimal calcium flow is necessary for relaxation and contraction.
- Low T3 impairs diastolic function (when measuring blood pressure, the diastolic number is the second number: systolic/diastolic = 120/90. It causes “diastolic hypertension” (p. 1786). (This is distinct from low or high blood pressure in general.)
- Low T3 directly changes blood vessel properties, causing “endothelial dysfunction” (by influencing their production of nitric oxide).
- While excess T3 dilates blood vessels, low T3 does the opposite.
- Low T3 may lead to “impaired vasodilation” and “arterial stiffness.”
- Pulmonary (lung) vasculature is not affected as immediately as systemic vasculature.
- Low T3 contributes to heart failure, specifically, Left Ventricular dysfunction.
- Both systolic and diastolic dysfunction may occur at rest and during exercise.
- This type of heart failure occurs not only through the changes in the myocardium (described above), but through Low T3’s effect on increased “peripheral vascular resistance, plasma noradrenaline concentrations, and plasma renin activity,” and decreased erythropoietin (Figure 2, p 1785; Table 2, p. 1786).
- Low T3 in serum is associated with “cardiac fibrosis in patients with idiopathic dilated cardiomyopathy” (p. 1786).
These phenomena help to explain the wide variety cardiovascular symptoms that low T3 thyroid patients have reported. Low T3 thyroid patients have experienced palpitations and episodes of tachycardia despite basal low heart rate, microvascular angina (chest pain) and peripheral vasoconstriction. This can happen even while on therapy, while TSH and T4 are in normal range, if T3 is nearer the lower end of “normal” reference, or lower.
The T3 hormone is central, not TSH or T4
As we see above, the main mechanisms of cardiovascular harm is mainly from low or high T3 hormone levels, not TSH or T4.
Studies that compare T4, TSH and T3 often find that T3 has a more significant effect on cardiac markers such as left ventricular function (Roef et al, 2013). TSH and T4 may perform more minor roles. For example, TSH modulates cardiac electrical activity (Alonso, 2015).
When you define hypothyroidism from the perspective of the cardiovascular system as well as all other organs and tissues in the human body, hypothyroidism is largely defined as insufficient T3.
Make Free T3 levels a target in thyroid therapy
In a study of over 15,000 hypothyroid patients under L-T4 therapy in the UK, it was discovered that
despite treatment for primary hypothyroidism with T4, patients are at increased risk of morbidity associated with circulatory diseases, ischemic heart disease, dysrhythmias, and cerebrovascular disease. …
We also showed ongoing risk beyond the initial years of treatment. …[A] possibility is that hypothyroidism is not being treated optimally, either as a failure to reach target, i.e. normalization of TSH concentrations, or possibly because those targets may be inappropriate. (Flynn et al, 2006)
In response to Flynn, we can confidently say that no, TSH is insufficient as a target for thyroid therapy.
Utiger, the developer of the TSH test, explained long ago that TSH is not sensitive to bloodstream T3 levels that arise from T4-T3 conversion (Utiger, 1982).
This means that for thyroid patients, normalizing the TSH won’t necessarily optimize T3.
If only TSH is being monitored, a thyroid patient’s chronically lower T3 levels may remain undetected for years. Theoretically, in the long term this low T3 can harm their cardiovascular health. This is why we are advocating for Free T3 testing for thyroid patients.
The Canadian Cardiovascular Society agrees, but they recommend testing T3 only after a patient already has a cardiovascular diagnosis:
assessing thyroid function (by measuring thyroid-stimulating hormone, T4 and T3 levels) in a patient with undifferentiated left ventricular dysfunction is essential and recommended by the Canadian Cardiovascular Society’s consensus statement on the diagnosis and management of heart failure. (Hayley et al, 2014)
But why delay T3 testing until the patient already has damage and heart problems?
Razvi, et al, 2018 state that even “minor” changes in T3 levels make a difference:
“Minor changes in TH [Thyroid hormone] concentration may have an adverse impact on the CV [Cardiovascular] system, and subclinical thyroid dysfunction has been associated with 20% to 80% increase in vascular morbidity and mortality risk” (p. 1781)
“Subclinical thyroid dysfunction” means that T3 and T4 levels could be within the “normal” reference range but still be inappropriate for cardiovascular health.
Insufficient T3 can occur even within the “normal” reference range for T3.
Sufficiency is not determined by population-wide statistics, but by biological need from the perspective of the individual organism. The heart does not check the laboratory reference ranges in order to decide whether it has enough T3.
What happens to the chronically low-T3 thyroid patient if they have an accident that damages their heart and they end up in hospital?
If T3 is already rather low, we know myocardial injury could lower their T3 levels further.
Science teaches that the response of a healthy thyroid gland is essential to the recovery from “Low T3 syndrome.” But if patients have little ability to secrete T3 from their thyroid gland and receive no T3 supplementation, it is unknown whether they can recover as easily or quickly from chronic Low T3 (associated with chronic heart failure) or the acute Low T3 state induced by acute cardiovascular events.
Why is it unknown? Because thyroid patients have been excluded from research on Low T3 syndrome.
The promise of T3 therapy
T3-based thyroid therapy may be able to reduce Low-T3 cardiovascular risk factors and in assisting patients with Low T3 and cardiovascular disorders.
Some recent studies have examined T3 therapy in relation to Low T3 syndrome in heart failure and other cardiac conditions.
- Holmager, P., Schmidt, U., Mark, P., & Andersen, U. (2015). Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients: a randomised, double-blind, cross-over, placebo-controlled intervention study. Clinical Endocrinology, 83(6), 931.
- Pingitore, A., Galli, E., Barison, A., & Iervasi, A. (2008). Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. The Journal of Clinical Endocrinology and Metabolism, 93(4), 1351.
- Amin, A., Chitsazan, M., Taghavi, S., & Ardeshiri, M. (2015). Effects of triiodothyronine replacement therapy in patients with chronic stable heart failure and low‐triiodothyronine syndrome: a randomized, double‐blind, placebo‐controlled study. ESC Heart Failure, 2(1), 5–11. https://doi.org/10.1002/ehf2.12025
- Weltman, N. Y., Ojamaa, K., Schlenker, E. H., & Chen, Y.-F. (2014). Low-dose T₃ replacement restores depressed cardiac T₃ levels, preserves coronary microvasculature and attenuates cardiac dysfunction in experimental diabetes mellitus. Molecular Medicine (Cambridge, Mass.), 20, 302.
Several of these studies have shown promising results, and the best result is that no harm was done.
However, thyroid patients have been excluded from these trials of T3 therapy in heart disease.