If you have thyroid disease, you may have encountered contradictory or confusing information about reverse T3 (rT3), also known as reverse triiodothyronine.

The blood test for this thyroid hormone is controversial: While most research does not point to a reliable way to interpret or treat abnormal results, some interest has been expressed in determining whether rT3 levels could be useful in understanding thyroid disease or severe medical illnesses.

Reverse T3 is a blood test that is not commonly ordered. However, if your healthcare provider has tested you for it and you are interested in understanding what your results mean, it’s worth exploring the debate surrounding it.

This article explores thyroid hormones, how rT3 is produced, and its significance. It also covers health conditions that can affect it.

An Overview of Thyroid Hormones

There are several thyroid hormones. The most commonly measured ones are thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyronine (T3), and free T3.

TSH: TSH is released from the pituitary gland in the brain. It stimulates the thyroid gland to make thyroid hormones.
T3 and T4: The thyroid gland makes and releases T4 and some T3. Total T3 and T4 levels include some T3 and T4 that are bound to protein, and some T3 and T4 not bound to protein. T3 and T4 not bound to protein are known as free T3 and free T4.
T4 conversion to T3 and rT3: After its release from the thyroid gland, T4 is converted to T3, which is an active thyroid hormone, or to rT3, which is considered an inactive form. The rate and ratio of T4 conversion to either T3 or rT3 depend on the body’s metabolic needs.

You can have hyperthyroidism or hypothyroidism due to a problem with any step in the process of thyroid hormone stimulation, production, activation, or protein binding. Your healthcare providers look at these tests to determine which step or steps are responsible for your symptoms.

factors affecting reverse t3 thyroid hormone levels — Laura Porter / Verywell

Production of rT3

Reverse T3 is a metabolite (byproduct) of T4. Typically, when T4 loses an atom of iodine—a process known as monodeiodination—it becomes (T3), the active thyroid hormone.

The body also converts T4 into rT3, which is 3,3',5'-triiodothyronine, an inactive form of T3 that is incapable of the metabolic activity normally carried out by T3.

Researchers believe the body produces rT3 in times of severe illness or starvation as a mechanism for preserving energy.

Measuring rT3

Reverse T3 can be measured by a blood test. A level below 250 pg/ml (10 ng/dL to 24 ng/dL) is considered normal.

Functions of rT3

Some understanding of rT3's relevance exists, but its significance and functions are not yet well understood.

Just like T3, rT3 can bind to cells in the same way. When T3 binds to cells, it interacts with thyroid hormone receptors. This, in turn, affects a person's metabolism, heart rate, and pulse and leads to growth and development in children.

However, when rT3 binds to a cell, no known physiological effects exist.

Reverse T3 and Health Conditions

It appears that rT3 can be elevated when the body is undergoing a crisis. Among people hospitalized for illness or injuries, those with a low rT3 level are more likely to have a poor prognosis, although researchers are not quite sure why.

Evidence from some animal studies also points to a possible reparative effect of rT3 on the body after stroke, but it’s unclear whether these effects transfer to humans.

Nonthyroidal Illness Syndrome

In some instances, people who are seriously ill, often in the intensive care unit of a hospital, may have a low or normal TSH with low T3 and possibly a low T4 level as a result of critical illness, even without having thyroid disease.

Nonthyroidal illness, also known as euthyroid-sick syndrome, refers to a reduced level of thyroid function blood tests found in the setting of severe illness in a person without preexisting thyroid dysfunction.

After recovery from the severe illness, the thyroid function test results should normalize.

Nonthyroidal Illness

People with hypothyroidism may have a low rT3, while people who are critically ill can have a high rT3. However, these changes do not always occur, so most critical care experts do not rely on rT3 to help distinguish thyroid disease from other causes of significant illness.

Furthermore, since thyroid hormone reduction is considered a potentially protective mechanism in nonthyroidal illness, healthcare providers do not generally recommend treatment based on rT3 alone. Instead, a number of well-understood physical signs and laboratory tests guide these decisions.

Other Health Conditions

Other health conditions that may trigger changes in thyroid test results, including rT3, without thyroid disease include:

Starvation
Surgery
Bone marrow transplantation
Heart attack
Kidney disease
HIV
Coronary artery bypass grafting

Reverse T3 and Dieting

Some people wonder whether increased rT3 can cause weight gain. No recent research suggests this is the case. However, studies do suggest that an extended period of calorie deprivation can raise rT3 levels. Thyroid hormones affect body weight by regulating how much energy is expended during activities and appetite. Researchers are still learning more about the exact role of rT3 in weight management.

Summary

The precise meaning and significance of rT3 are still being determined. Currently, no standardized guidelines exist concerning interpretation or treatment planning based on rT3 alone. However, TSH, T4, free T4, T3, and free T3 levels are adequate indicators of thyroid disease severity and management.

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