Many patients question whether they might have a thyroid problem because they have been gaining weight, even when their thyroid tests show little or no abnormalities. Given the high prevalence of thyroid diseases and obesity, could an occult thyroid dysfunction contribute to weight gain in this type of patient?

Background: Thyroid hormone accelerates metabolism and the rate at which calories are burnt. Metabolism slows down by as much as half in patients with profound hypothyroidism whereas metabolism is accelerated well above the baseline, and could even double, in patients with hyperthyroidism. This happens as a result of changes in the turnover of ATP molecules, the body’s currency for energy. Each time an ATP molecule is produced or utilized, calories are burnt and heat is released. Thyroid hormone also stimulates the brown adipose tissue, a specialized heat-producing organ that burns calories and releases heat to warm up the body. Similar to the hood of a car’s engine, patients with hyperthyroidism are frequently hot and feel warm to the touch because their organs are rapidly burning calories.

Fact: Patients with hyperthyroidism generally lose weight and complain of heat intolerance whereas patients with hypothyroidism are sensitive to cold and tend to gain weight. However, contrary to the popular belief, not all patients with hypothyroidism gain weight. In addition, a substantial fraction of the weight gained is due to water retention, not all is due to fat accumulation.

Fiction: Obesity is a sign/symptom of hypothyroidism. Changes in body weight following thyroid diseases are not dramatic and, most of the time, are limited to plus/minus 20%. In fact, the vast majority of obese individuals have normal thyroid function. However, both diseases can overlap in the same patient because both conditions are so prevalent. But, for most of these individuals, obesity is not a direct consequence of the hypothyroidism, and weight loss after treatment of hypothyroidism is also due to water elimination.

Fact: Once hyperthyroid patients are treated they will almost immediately gain weight, and the amount of weight gained is not trivial. Here is why: (i) hyperthyroid patients have increased apetite because thyroid hormone acts in the brain stimulating food intake and (ii) patients with hyperthyroidism are used to eating large amounts of food without major consequences on body weight because their metabolism is accelerated. In other words, patients with hyperthyroidism eat more (increased appetite) but easily burn the excess of calories (faster metabolism). However, once hyperthyroidism is treated and the metabolic rate is lowered to normal levels, most patients continue to eat as much as they used to eat before treatment, thus the weight gain. To avoid gaining much weight hyperthyroid patients need to adjust down caloric intake as soon as treatment is initiated.

Fiction: Obesity can be treated with thyroid hormone supplementation to accelerate metabolism and force weight loss. Here is the rationale: To protect the body from running out of fuel, fasting slows down the thyroid gland and the circulating levels of thyroid hormones (especially T3) decrease markedly. The drop in blood levels of thyroid hormones slows down metabolism and reduces the rate at which calories are burnt. This is why fasting/caloric restriction alone have a limited effect in weight loss. To bypass this mechanism, some thought of combining caloric restriction with thyroid hormone supplementation as a more effective way to treat obesity. However, the results did not consistently show greater weight loss and many individuals developed mild forms of hyperthyroidism, which places them at a higher risk for a heart condition known as atrial fibrillation and/or osteoporosis (Kaptein et al, JCEM 2009). Furthermore, many patients taking weight loss supplements tainted with thyroid hormone suffered consequences of overt hyperthyroidism (Tang et al. Br J Clin Pharmacol 2009).

Fact: The metabolic effects of thyroid hormone can be harnessed to “safely” achieve weight loss. This was accomplished in preclinical studies via pharmacologic stimulation of the type 2 deiodinase or through the use of thyroid hormone analogues, molecules similar in structure to thyroid hormone. Both approaches can accelerate metabolism while sparing the heart and skeleton from potential side effects. Both D2 stimulation and thyroid hormone analogues enhance thyroid hormone action in brown adipose tissue. In addition, analogues act in the liver and have the ability to lower circulating levels of cholesterol. While studies with analogues in rodents, monkeys, and humans have validated their clinical utilization, dogs that were placed on one specific analogue developed serious side effects. Despite this set back, the strategy proved to be successful and future developments in this area should be expected, including clinical trials.

In conclusion, thyroid hormone accelerates the metabolic rate and stimulates appetite. Uncoupling between these two effects places hyperthyroid patients at a higher risk of substantial weight gain upon initiation of therapy. Hypothyroidism does not cause morbid obesity and thyroid hormone should not be offered as a treatment for obesity in individuals with a normal thyroid function. Thyroid hormone signaling can be harnessed via deiodinase stimulation or usage of thyroid hormone analogues and could constitute promising pharmacological targets for treatment of obesity.

Contributed by Elizabeth McAninch MD and Antonio C. Bianco MD, PhD.