Leptin, rT3, and Weight Gain With Hypothyroidism

These hormones play a major role in weight regulation and metabolism

You may have difficulty losing weight if you have an underactive thyroid. Leptin and reverse T3 (rT3), two hormones believed to play a role in regulating weight and metabolism, are altered in level and function in hypothyroidism. While it is not completely clear how these hormones could be affected by or could affect thyroid disease, they may contribute to the weight problems that are commonly associated with this condition.

Because of the many hormonal changes that occur with thyroid disease, dieting and caloric restriction may not be enough to achieve optimal weight loss if you are hypothyroid. Understanding leptin and rT3 can help you gain a broader picture of the many factors involved in hypothyroidism.

treating leptin resistance and rT3

Verywell / Laura Porter


The hormone leptin has been found to be a major regulator of body weight and metabolism. Leptin is secreted by fat cells, and levels of leptin normally increase with the accumulation of fat.

The increased leptin secretion that occurs as a response to weight gain is usually a signal to the body that energy (fat) stores are adequate.

This results in a series of physiological responses that cause the body to burn fat rather than continue to store excess. It also causes thyroid-releasing hormone (TRH) to increase production of thyroid-stimulating hormone (TSH), which helps in using up excess calories.

Leptin Resistance

Hypothyroidism, diabetes, and obesity are the most common medical conditions associated with high levels of leptin, as well as with another condition described as leptin resistance.

Leptin resistance is a diminished response to leptin, even if there is enough of it circulating throughout the body. This resistance is based on a false message that the body is starving and, thus, multiple hormonal mechanisms are activated to increase fat stores, as the body tries to reverse the perceived state of starvation. Even with a moderate caloric intake, this is believed to increase the risk of weight gain or obesity.


Often, people who are chronically overweight have varying degrees of leptin resistance, in which leptin's ability to regulate metabolism is diminished.

The mechanisms that are activated by leptin resistance, all of which result in weight gain, include:

  • Diminished TSH secretion
  • Suppressed thyroxin (T4) to active triiodothyronine (T3) conversion
  • Increased reverse T3 production
  • Increased appetite
  • Increased insulin resistance
  • Inhibition of lipolysis (fat breakdown)

These mechanisms may be in part due to a down-regulation of leptin receptors that occurs after a prolonged exposure to excessive leptin. As a result, if you're overweight for an extended period of time, it becomes increasingly difficult to lose weight.


Thyroid disease, excess body fat, excess leptin, and leptin resistance all seem to exacerbate each other. While these interactions make treatment and weight loss challenging, modifying your diet and getting adequate thyroid treatment can help reverse some of the effects and normalize hormone levels.

There is not currently a medication that specifically treats leptin resistance. A healthy diet low in sugar and processed foods, regular exercise, and obtaining enough sleep have all been associated with an improved physical response to leptin.

Treatment of hypothyroidism with thyroid-replacement medications has also been shown to reduce leptin levels and reduce the effects of leptin resistance.

Reverse T3 (rT3)

Thyroxin (T4) and triiodothyronine (T3) are both produced by the thyroid gland. The thyroid gland produces more T4 than T3, but T4 is then activated to T3 in the tissues. It is the T3 form of the hormone that has a metabolic effect, increasing metabolism, producing energy, and stimulating weight loss.

There is some evidence that T3 may be low in people who suffer from chronic fatigue syndrome, and this has led some researchers to consider chronic fatigue syndrome a variant of thyroid disease.

T4 can also convert to reverse T3 (rT3), which is an inactive form of T3 that actually blocks the effects of T3. The balance of T3 and rT3 is based on your body's energy needs.

RT3 is produced in times of starvation to reduce metabolism and preserve the body's energy stores. RT3 can also be produced in times of stress or as a response to chronic dieting. Because rT3 it is a product of T4, it has been investigated in the context of thyroid disease, but with unclear results.

With less-than-optimal T4, hypothyroidism is usually characterized by low T3 and low rT3. Yet, sometimes, unexpectedly high rT3 can develop if you are hypothyroid. This can cause weight gain, and it may also be caused by weight gain.

rT3 Levels and Thyroid Disease

In hypothyroidism, you may not have enough T4 to begin with, and this often (but not always) results in lower levels of rT3. The significance of rT3 isn't well understood. The low levels can be a reflection of thyroid disease, but it is unclear if chronically low rT3 affects the body and, if so, what the effects are.

Nevertheless, it is high rT3 levels that seem to be problematic in thyroid disease. Sometimes, for unknown reasons, rT3 is actually elevated in hypothyroidism when T4 converts to rT3 instead of T3. This can lead to weight gain, which, interestingly, leads to higher levels of rT3, and a cycle ensues.


For most healthy people, rT3 is usually below 250 pg/ml, and the T3/rT3 ratio should be greater than 1.8, if free T3 is measured in ng/dl, or 0.018 if free T3 is measured in pg/ml. There is a great deal of controversy about the significance of rT3 and whether it should be measured or treated at all.

It has been suggested that low-carbohydrate diets may suppress thyroid function and increase rT3 more than comparable calorie reductions with adequate carbohydrates.

While a low-carbohydrate diet may result in weight loss if you don't have hypothyroidism, you may regain weight if you have the condition. This may be associated with overproduction of rT3, although it is currently unclear which is the cause and which is the effect.

Treatment for hypothyroidism can include T4 replacement or T4/T3 combinations. The rationale for combination treatment is that excess rT3 could counteract T3 activity or that T4-to-T3 conversion may be impaired, even with adequate T4 replacement.

While combination treatment can be a solution for some people who have hypothyroidism, there is no strong evidence that combination therapy is better than treatment with T4 alone. Another issue is that the correlation between treatment and normalization of rT3 level is weak.

A Word From Verywell

Thyroid hormone activity is complex, and hypothyroidism causes weight gain through a number of mechanisms. T4 and T3 levels are traditionally accepted as the most reliable indicators of thyroid disease. Leptin and rT3 have also been associated with thyroid disease, but there is still a lot to learn about the connection. The value of blood measurements of these hormones also remains unclear.

The key takeaway is that studies of leptin and rT3 in the context of weight gain in hypothyroidism suggest that diet and exercise alone may not be effective in achieving target weight: optimizing treatment for your hypothyroidism is also necessary to regulate metabolism.

7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Mary Shomon
Mary Shomon is a writer and hormonal health and thyroid advocate. She is the author of "The Thyroid Diet Revolution."