Thyroxine (T4),Total

 (μg/dl or nmol/l)

The thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are tyrosine-based hormones produced by the thyroid gland that are primarily responsible for regulation of metabolism and growth. Production of T3 and T4 is regulated by TSH (thyroid-stimulating hormone) made by the pituitary gland [1,2].

Thyroid hormone affects virtually every organ system in the body, including the heart, CNS, autonomic nervous system, bone, GI, and metabolism. In general, when the thyroid hormone binds to its intranuclear receptor, it activates the genes for increasing metabolic rate and thermogenesis. Increasing metabolic rate involves increased oxygen and energy consumption [3].

Heart: thyroid hormones have a permissive effect on catecholamines. It increases the expression of beta-receptors to increase heart rate, stroke volume, cardiac output, and contractility

Lungs: thyroid hormones stimulate the respiratory centers and lead to increased oxygenation because of increased perfusion.

Skeletal muscles: thyroid hormones cause increased development of type II muscle fibers. These are fast-twitch muscle fibers capable of fast and powerful contractions.

Metabolism: thyroid hormone increases the basal metabolic rate. It increases the gene expression of Na+/K+ ATPase in different tissues leading to increased oxygen consumption, respiration rate, and body temperature. Depending on the metabolic status, it can induce lipolysis or lipid synthesis. Thyroid hormones stimulate the metabolism of carbohydrates and anabolism of proteins. Thyroid hormones can also induce catabolism of proteins in high doses. Thyroid hormones do not change the blood glucose level, but they can cause increased glucose reabsorption, gluconeogenesis, glycogen synthesis, and glucose oxidation.

Growth during childhood: In children, thyroid hormones act synergistically with growth hormone to stimulate bone growth. It induces chondrocytes, osteoblasts, and osteoclasts. Thyroid hormone also helps with brain maturation by axonal growth and the formation of the myelin sheath

Thyroxin (T4) exists in two forms: free and bonded (bonded to protein in the blood). Most of the T4 in the bloodstream is bonded. A total T4 test measures the T4 that’s bonded to protein along with any free T4.

Usually, it is analysed together with TSH and T3 (triiodothyronine) results.

Abnormalities. Disorders or diseases caused or related.

Iodine is necessary for the production of T3 and T4. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.

Elevated T4 levels indicate thyroid problems and some other health conditions, namely [1-4]:  

hyperthyroidism (occurs in conditions such as Graves’ disease, inflammation of the thyroid or a benign tumor)

thyroiditis

toxic multinodular goiter

high levels of protein in the blood

too much iodine

too much thyroid replacement medication

trophoblastic disease, a group of rare pregnancy related tumors

germ cell tumors

Too much iodine can raise your T4 levels. Because X-ray dyes can include iodine, a recent X-ray involving dye may also raise your T4 test results.

Abnormally low levels of T4 may indicate:^276-278

dietary issues, such as fasting, malnutrition

an iodine deficiency

medications that affect protein levels

hypothyroidism (may be due to autoimmune conditions, such as Hashimoto’s thyroiditis or certain medications or in pituitary dysfunction, such as pituitary tumors or inflammation)

illness

a pituitary problem

What are normal free T4 levels?

Normal levels of free T4 vary based on your age. In general, normal ranges of free T4 for healthy people include:

 

Children up to 5 years old: 0.8 – 2.8 nanograms per deciliter (ng/dL).

Children 6 to 15 years old: 0.8 – 2.1 ng/dL.

Adolescents assigned male at birth 16 to 17 years old: 0.8 – 2.8 ng/dL.

Adolescents assigned female at birth 16 to 17 years old: 0.8 – 1.5 ng/dL.

Adults over 18 years old: 0.9 – 1.7 ng/dL.

Normal value ranges for free T4 may vary slightly among different laboratories. Be sure to check your lab report’s reference range on your results. If you have any questions about your results, ask your healthcare provider.

What happens when T4 (thyroxine) levels are too high?

If you have higher-than-normal T4 or free T4 levels, it could indicate thyrotoxicosis. This can result from several situations and conditions, including hyperthyroidism (overactive thyroid), thyroid inflammation (thyroiditis) and taking excessive amounts of thyroid medication.

 

Thyrotoxicosis speeds up your metabolism, which can be dangerous to your health. Symptoms of thyrotoxicosis include:

Unexplained weight loss.

Increased bowel movements.

Rapid or irregular heartbeat (arrhythmia).

If you’re experiencing symptoms of thyrotoxicosis, it’s important to contact your healthcare provider.

 

Other conditions that could cause elevated total T4 levels with normal free T4 levels include pregnancy and estrogen-containing birth control pills. This is because estrogen levels are high in those two scenarios. Estrogen increases the proteins bound to T4 and causes the total T4 (which is free T4+ binding proteins) to be high.

What happens when T4 (thyroxine) levels are too low?

If you have lower-than-normal T4 levels, it usually indicates hypothyroidism (underactive thyroid). Hypothyroidism has several causes, including certain autoimmune diseases, poor iodine intake in your diet and the use of certain medications.

 

Hypothyroidism slows down your metabolism. Symptoms include:

 

Fatigue.

Intolerance of cold temperatures.

Low heart rate.

Weight gain.

If you’re experiencing symptoms of hypothyroidism, it’s important to talk to your healthcare provider.

 

1.        Thyroid Hormone Production and Function. Current as of: March 31, 2020. The University of Michigan Health. Healthwise. Medical Review: Kathleen Romito, MD - Family Medicine & Adam Husney, MD - Family Medicine. Available online https://www.uofmhealth.org/health-library/ug1836

2.        Thyroxine (T4) test. (2019). Available online: medlineplus.gov/lab-tests/thyroxine-t4-test/

3.        Thyroid hormones. The Hormone Health Network provided by the Endocrine Society, available online: https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/thyroid-hormones

4.        Muhammad A. Shahid, et al. Physiology, Thyroid Hormone. StatPearls Publishing; 2021 Jan. Last Update: May 12, 2021. https://www.ncbi.nlm.nih.gov/books/NBK500006/

5.        https://my.clevelandclinic.org/health/diagnostics/24235-thyroxine-t4-test