Thyroid hormone

Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are primarily responsible for regulation of metabolism, and thus act on nearly every cell in the body.

Thyroid hormones are partially comprised of iodine and a deficiency of iodine in the diet can lead to decreased production of these hormones. If left uncorrected the thyroid tissue can enlarge, resulting in a pronounced swelling in the neck, called a 'simple goitre.'

Over production of thyroid hormones (hyperthyroidism) can accelerate your body's metabolism causing sudden weight loss, a rapid or irregular heartbeat, sweating, nervousness or irritability, and other symptoms. Under production of thyroid hormones (hypothyroidism) can lower your body's metabolism causing obesity, fatigue, muscle weakness, thinning hair, slowed heart rate, depression and other symptoms.

Thyroxine (T4)
Thyroxine (abbreviated as T4) accounts for 90% of the hormone produced by the thyroid gland. It is physiological inactive and must be converted to T3 in the liver and kidneys.

Triiodothyronine (T3)
Triiodothyronine (abbreviated as T3) is the active form of the hormone, and is converted from T4 within the cell by deiodinases, which are selenium-dependent enzymes. Selenium sufficiency is therefore important for the proper conversion of T4 to T3.

Diiodothyronine (T2)
The physiological functions of diiodothyronine (T2), including 3,5-diiodo-L-thyronine, are less well-understood.

Metabolism of thyroid hormones
Thyroid binding globulin

Individual variation in the ability to convert T4 to T3 after total thyroidectomy appears to be genetic. A gene called DIO2  encodes for Type 2 deiodinase enzyme, which converts T4 to T3. A study of 102 patients pre- and post- total thyroidectomy showed that after receiving T4-only hormone replacement, 34% of patients had lower reduced Free T3 levels (FT3) than they had pre-surgery. Those with the Thr92Ala polymorphism had lower levels of Free T3 hormone than wild type patients. The percentage of reduced post-surgery FT3 levels was directly correlated with the presence and severity of the polymorphism: 58.3% in homozygous (Ala/Ala) patients vs 36.5% in heterozygous (Thr/Ala) subjects.

Mitochondrial function
T3 plays an important role in the regulation of mitchondrial function as well as in mitochondrial biogenesis. T3 rapidly stimulates an increase in cellular respiration within minutes to hours after hormone treatment. One to several days after hormone treatment, changes in gene expression as well as direct binding of hormone to receptors induces mitochondrial biogenesis and changes to mitochondrial mass. T3 stimulates the expression of an inner membrane mitochondrial protein called uncoupling protein, resulting in increased inner membrane proton leak. It also induces changes in phospholipid turnover. ATP synthesis and turnover reactions are also affected.

Uncoupling protein is responsible for thermogenesis, which is why hyperthyroidism results in excess heat while hypothyroidism results in cold intolerance.

T2 also plays a role in regulating energy metabolism, although its role is less studied. 3,5-diiodo-L-thyronine influences resting metabolic rate.

Hormone replacement
Patients with hypothyrodism may need hormone replacement. The standard replacement therapy is Levothyroxine, a synthetic form of T4. However, some patients on Levothyroxine report continuing symptoms of hypothyrodism despite normal laboratory results, owing to poor conversion of T4 to T3. In these cases, patients may add a T3 replacement hormone drug, such as Cytomel, or Armour thyroid, which is whole desiccated thyroid glandular from pigs.

Role in Chronic Fatigue Syndrome
A study of 99 patients with a diagnosis of Chronic Fatigue Syndrome found similar levels of TSH to healthy controls but lower free triiodothyronine (FT3), total thyroxine (TT4), total triiodothyronine (TT3), %TT3 (4.7%), deiodinase activity, secretory capacity of the thyroid gland, lower 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3). "Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state."

Notable studies

 * 2018, Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study Full Text)

Learn more

 * American Thyroid Association webpage