The thyroid hormones (T3 & T4) stimulate energy metabolism, regulate immunity, support cognitive development, and more. Due to their complex metabolic roles, it’s essential for overall health to keep them in the normal range. Read on to learn the diverse functions of thyroid hormones, blood test reference values, and the consequences of high/low levels.
The thyroid gland is located in the base of your neck and is involved in secreting important hormones T4 (thyroxine) and T3 (triiodothyronine).
T3 contains 3 iodine atoms and is created from the breakdown of T4. The breakdown of T4 is encouraged by the thyroid-stimulating hormone.
T4 is synthesized from residues of the amino acid tyrosine, found in thyroglobulin (a protein created in the thyroid). It contains 4 iodine atoms and allows the body to better control the more active T3.
Reverse T3 (rT3) is the mirror image of T3. It competes with T3 and binds to the thyroid receptor but does not activate it.
T3 and T4 affect :
- Heart rate
- The nervous system
- Muscle strength
- Menstrual cycles
- Body temperature
- Cholesterol levels
- Growth and development
- Intestinal flow
T3 changes gene expression (cellular production of certain proteins and hormones) of multiple metabolism-related genes.
Therefore, mitochondrial dysfunction can result in symptoms of hypothyroidism, even in the presence of healthy levels of thyroid hormones.
Immune cells have receptors for T3, and the administration of T3 increases the size and growth of cells in the thymus .
TNF-alpha and interferons induce production of class I and II HLA antigens in human thyroid cells (thyrocytes), which cause autoimmunity, as patients with autoimmune thyroid disorders have increased HLA class I and II antigens. The thyroid cells themselves produce IL-1 and IL-6 .
Histamine decreases T3 and T4 for a short amount of time (15 to 30 minutes) .
TSH is lower during the daytime and increases at night around the time we go to sleep. Our biological clock (suprachiasmatic nucleus or SCN) communicates with cells that produce TRH in the hypothalamus. However, T3 and T4 fluctuate much less than TSH, perhaps because they take much longer to produce and degrade in the blood .
In depressed people, the nighttime TSH surge doesn’t happen. In addition, this fluctuation of TSH is abnormal in certain other diseases .
Thyroid hormones are essential for cognitive development and functions. People with sufficient levels generally perform better on cognitive tasks and process information more efficiently. The lack of thyroid hormones can result in a range of cognitive disorders, from mild impairments to severe developmental disorders .
Thyroid hormones regulate nervous system-related growth. In particular, the central nervous system (which consists of the brain and spinal cord) needs T3 and T4 to upkeep normal development. A drug, L-T4 (which consists of T4), when administered to rats, enhanced spatial memory .
Increased total T3 count was related to lower overall cognitive ability in people with mild cognitive impairment. Those with higher than average total T3 counts had trouble with remembering, visuospatial skills, planning, and emotional regulation .
Based on studies in rats, T3 along with electroconvulsive shock therapy may be a viable alternative to lithium with electroconvulsive shock therapy because the lithium treatment has shown cognitive damage in patients .
Incorrectly formed thyroid hormone receptors might lead to acute erythroleukemia (immature red and white blood cells crowd out the body) and sarcomas (connective or nonepithelial tissue cancers). Defects in the production of thyroid hormone receptors may correlate with a higher prevalence of breast, lung, and thyroid cancers .
T3 can make heart contractions harder and dilate the blood vessels .
Overt hyperthyroidism induces a state of a faster heart rate, especially atrial fibrillation (irregularly quick heart rate that causes poor circulation), whereas overt hypothyroidism is characterized by the opposite changes.
Subclinical hypothyroidism causes heart rate problems and an enhanced risk for atherosclerosis and myocardial infarction (heart attack). L-thyroxine (L-T4) or 3,5-diiodothyropropionic acid administered in a timely manner help prevent heart complications [26, 27, 28].
Thyroid hormones encourage protein breakdown and glucose exchange throughout cells and insulin .
T3 improved insulin production and blood glucose control in mice .
Hypothyroidism in children leads to delayed growth, while thyrotoxicosis makes bones mature so quickly that children’s bones fuse before the child is ready. T3 builds up bone mass but also can break down bones in adults to increase new bone growth [35, 36, 37].
T4 and T3 supplements can be used for hypothyroid children with inadequate bone development .
|Measurement||Full Name||Unit||Reference Range|
|fT3||Free T3||pg/ml||2.5 – 4.3|
|fT4||Free T4||ng/dL||0.9 – 1.7|
|T3||Triiodothyronine (free and bound)||ng/dL||75 – 200|
|T4||Tetraiodothyronine or Thyroxine (free T4)||ug/dL||6 – 12|
|TBG||Thyroxine Binding Globulin||mg/dL||1.1 – 2.1|
|TPO||Thyroid Peroxidase Antibody||IU/ml||<35|
|TRH||Thyrotropin Releasing Hormone||U/mL||5 – 25|
|TSH||Thyroid Stimulating Hormone||U/mL||0.27 – 4.2|
Iodine builds thyroid hormones, and it’s essential for their optimal functioning. Optimal iodine intake is a major factor of thyroid health, while both excessive and insufficient intake can contribute to different thyroid disorders .
|Birth to 6 months||110 mcg*||110 mcg*|
|7–12 months||130 mcg*||130 mcg*|
|1–3 years||90 mcg||90 mcg|
|4–8 years||90 mcg||90 mcg|
|9–13 years||120 mcg||120 mcg|
|14–18 years||150 mcg||150 mcg||220 mcg||290 mcg|
|19+ years||150 mcg||150 mcg||220 mcg||290 mcg|
- Adequate Intake (AI)
*mcg stands for micrograms.
A benign goiter is the swelling of the thyroid gland which may occur due to inadequate iodine intake.
The hypothalamus, pituitary, and the thyroid gland (also called the hypothalamic/pituitary/thyroid or HPT axis) control thyroid hormone levels .
Thyrotropin-releasing hormone (TRH) made in the hypothalamus binds to the receptors in the pituitary, causing it to release thyroid-stimulating hormone (TSH), which then stimulates T4 production.
If there is too little of the thyroid hormones in the bloodstream, the hypothalamus signals the pituitary gland (via TRH) to produce TSH for the thyroid to release more T3 and T4.
Once there is enough of these hormones, the hypothalamus is signaled to stop the release of TRH and the cascade of actions to increase T3 and T4.
High free T4 and free T3 levels signal the pituitary to adjust TSH and TRH levels.
Low free T3 and free T4 increase TSH, so TSH is a valuable marker for diagnosing hypothyroidism.
Both T3 and T4 are produced in the thyroid gland, although T3 is much more potent than T4.
In the blood, T4 levels are around 45 fold higher (90 nM) than T3 (2 nM).
The total activity of the T3 thyroid hormone in the body depends on the enzyme that converts T4 to T3, which is found outside of the thyroid. This includes:
- Type 1 deiodinase, which generates T3 for circulation, is found in the liver and kidney.
- Type 2 deiodinase converts T4 to T3 within the cells of the brain, pituitary, and brown fat tissue.
- Type 3 deiodinase, found in the placenta, brain, and skin, leads to the generation of rT3
Carrier proteins bind to most thyroid hormones, leaving only a very small fraction available. These include thyroxine-binding globulin (TBG), albumin, and thyroid-binding prealbumin.
Thyroxine Binding Globulin is made by the liver .
- 99.97% of T4 is bound, and 0.03% is free.
- 99.7% of T3 is bound and 0.3% of T3 is free.
If you notice any of the signs and symptoms described low and suspect a thyroid disorder, make sure to seek medical attention. Adequate treatment can keep the symptoms under control and prevent dangerous complications.
Higher levels of thyroid hormones (hyperthyroidism) may cause the following symptoms:
- Faster heart rate
- Weight loss
- Irritability or moodiness
- Sweating or sensitivity to high temperatures
- Hand trembling
- Hair loss
- Missed or light menstrual periods
Low levels of thyroid hormones (hypothyroidism) may cause:
- Slower heart rate
- Weight gain
- Trouble sleeping
- Tiredness and fatigue
- Difficulty concentrating
- Dry skin and hair
- Sensitivity to cold temperature
- Frequent, heavy periods
- Joint and muscle pain
Hypothyroidism in adults causes mild anxiety in mice. T3 is suggested to lower the sensitivity of the part of the brain that makes hypothyroid test subjects anxious. More T4 in the body corresponds to less severe anxiety. More severe panic attacks were associated with higher TSH levels [42, 43].
Major depressive and anxious-depressive women showed lower T3, T4, and TSH levels than their non-depressive female counterparts. Furthermore, these depressive women showed less sensitivity to TSH .
Thyroid dysfunction is often one of the reasons behind chronic fatigue .
General fatigue and fatigue due to strain are associated with lower free T4. Physical fatigue was associated with lower T3 .
The immune system is weakened with stress, making the body more receptive of autoimmune (a condition where the immune system attacks itself) thyroid conditions (eg, Hashimoto’s thyroiditis) .
Too much physical stress can trigger severe thyroid problems in those with prior thyroid disorders, such as untreated hyperthyroidism or Graves’ disease .
A full day of no sleep caused a 1.5X increase of T4 to convert into T3 (levels of T4 stayed the same in the study) .
Half a typical dose of sleep deprivation led to higher levels of TSH in the blood; this elevation continued for another day .
When a mouse is infected, after food consumption, it will contain 75% less T3, T4, and liver nuclear T3 receptors when compared to uninfected mice .
Less thyroid hormone in the body translates to less extensive energy extraction from food molecules, which means there would be less energy wasted for the body. Regular TSH levels reboot after the infection [54, 55].
Thyroid Autoimmunity occurs when the body creates particles (called antibodies, etc) that, though normally is supposed to attack foreign substances, attacks the body’s own thyroid hormone .
An autoimmune disease (AD) against thyroid hormones will exhibit a rise in TSH (a hormone by the pituitary gland which triggers the release of T3 and T4 from the thyroid) levels in the blood .
In Graves’ Disease, there’s excessive production of thyroid hormones because the antibodies stimulate the thyroid by activating the TSH receptor .