Many obese patients hold out hope that a sluggish thyroid might explain their expanding girth. Could the association actually go the other way?
Cari Kitahara, PhD, MHS, an epidemiologist at the National Cancer Institute (NCI) made a case for the relationship between thyroid function, body weight, and thyroid cancer--Adiposity, Weight Gain, and Thyroid Disease--at the 86th annual meeting of the American Thyroid Association. Her initial response to the question--possibly.1
“Understanding the directionality of the link is crucial,” Dr. Kitahara said, as ''obesity raises the risk of many diseases, including thyroid cancer."1
In a recent metaanalysis, Dr. Kitahara and her team conducted a pooled analysis of 22 studies that included more than 830,000 men and 1.2 million women, using NCI Cohort Consortium data.2
“Higher BMIs were linked to greater thyroid cancer risk, with a stronger association in men,” said Dr. Kitahara. During the analysis, 2996 incident thyroid cancers and 104 thyroid cancer deaths were noted.2 In fact, the researchers found a correlation with all anthropometric factors showing a positive association with thyroid cancer incidence: Hazard ratios for height (per 5 cm) were 1.07 [1.04-1.10 CI], BMI (per 5 kg/m2), was 1.06 [1.02-1.10), waist circumference (per 5 cm) is 1.03 [CI of 1.01-1.05], young-adult BMI (per 5 kg/m2) was 1.13 [CI of 1.02-1.25] and adult BMI gain (per 5kg/m2) was 1.07 [1.00-1.15 CI].2
Dr. Kitahara said, “higher adiposity throughout adulthood is linked with higher incidence of most major thyroid cancer types as well as higher cancer mortality."3 Potential underlying biological mechanisms should be explored in future studies."1
“As such, in overt hypothyroidism, with a high TSH, low fT3 and low fT4, there is a link to weight gain,” she said, while the reverse is true. In “overt hyperthyroidism, with low TSH, high fT3 and fT4, weight loss may be expected.
Treatment typically reverses the weight change effects.”1
“Research on euthyroid individuals,” she continued “has produced conflicting results, which suggests a bidirectionality."4
It appears that the association between adiposity and thyroid function is seen in small variations in a person who is euthyroid [due to the effects of thyroid hormones on metabolism],'' Dr. Kitahara told EndocrineWeb, "and conversely, slight changes in weight can also influence TSH and thyroid hormone levels."
"In euthyroid patients, weight loss lowers TSH and fT3, while weight gain raises TSH and fT3,” she said.There is limited evidence that thyroid hormone treatment lead to weight loss, or other benefits, in obese, euthyroid patients.1,4
“For obese, euthyroid individuals, elevated TSH may be a consequence [not a cause] of excess weight,” concluded Dr. Kitahara. As such, "thyroid dysfunction may not be the primary explanation for higher TSH and fT3."
"Weight loss may be the most appropriate intervention to reduce the risk of elevated TSH,'' she said.
More compelling, “TSH may have a role in mediating the obesity-thyroid cancer link,” Dr. Kitahara said. TSH influences the growth and differentiation of thyroid cells, and TSH levels tend to be elevated in people with thyroid cancer.3,4 There is growing evidence to support a role for TSH as a mediator [in thyroid cancer], said Dr. Kitahara, "given its known influence on the growth and differentiation of thyroid cells." Its common for TSH levels to be higher in patients with more aggressive tumors, suggesting a possible role in the progression of differentiated thyroid cancer.2,4
Going forward, longitudinal and experimental studies remain crucial to assess the temporality of association in euthyroid individuals, and to aid in treatment-making decisions, according to Dr. Kitahara.1
“The research findings may seem counterintuitive,” said Arthur Schneider, MD, PhD, professor emeritus at the University of Illinois College of Medicine at Chicago, who commented on the findings after the session. "However," he said, the practical implication, in his opinion, is that endocrinologists ''consider the possibility that some subtle changes in thyroid [function] may be the result of obesity, not the cause of it.”
EndocrineWeb asked Dr. Kitahara to sum up the state of the research and practical implications for endocrinologists.
"Obese patients with elevated TSH may not necessarily have an underlying thyroid disorder (e.g. overt or subclinical hypothyroidism)," she said, "rather, it may just be a normal, adaptive response to recent weight gain."
“In these cases, thyroid hormone treatment may be inappropriate without doing additional tests to determine that thyroid dysfunction or thyroid autoimmunity is responsible for the elevated TSH,” Dr. Kitahara told EndocrineWeb. "Weight loss may be a better course of action for these patients with elevated TSH but with no other evidence of an underlying thyroid disorder."
She commented that weight loss in obese, euthyroid patients ''has been shown to reduce both TSH and fT3 levels and can provide a number of additional health benefits."