Clinical Laboratory Strategies: May 8, 2008
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Relating Thyroid Function to Body Weight
TSH Changes in Reference Range Associated with Weight Gain
By Phil Kibak


Research has shown that weight gain is common among patients with hypothyroidism, while on the other hand, individuals receiving thyroid hormone therapy experience modest weight loss. But few studies have explored the association between thyroid function and body weight in individuals with normal thyroid function. This issue of Strategies examines a recent study that investigated TSH variation within the reference range and weight changes over time.

Understanding the factors that influence weight gain has become a focus of research, as obesity is associated with an increased risk for diabetes, vascular disease, all-cause mortality, and various forms of cancer. Now, new data published in the Archives of Internal Medicine raise the possibility that modest increases in serum TSH concentrations within the reference range are associated with weight gain in men and women (Arch Intern Med 2008; 168:587–592).

Increasing “Normal” TSH Levels Tied to Weight Gain

“Clinical observations have noted associations between hypothyroidism and weight gain, as well as hyperthyroidism and weight loss,” noted lead author Caroline S. Fox, MD, MPH, medical officer with the National Heart, Lung, and Blood Institute’s Framingham Heart Study. “So, we wondered whether variations of TSH within the normal range also were associated with body weight and body weight change. Our results show that thyroid function as assessed by TSH levels within the reference range is associated in a linear fashion with body weight in both men and women.”

Fox and her colleagues analyzed data from 2,407 men and women with a mean baseline age of 48 who were not receiving thyroid hormone therapy. Women weighed an average of 147 lbs at baseline and 150 lbs at follow-up, while men weighed an average of 185 lbs at baseline and 187 lbs at follow-up. Baseline serum concentrations of TSH ranged from 0.5 to 5.0  mIU/L, and the mean baseline serum concentration was 1.91 mIU/L in women and 1.7 mIU/L in men. The average interval between baseline and follow-up examination was 3.5 years.

The researchers divided the patients into quartiles based on TSH levels. They found weight at baseline was positively associated with rising TSH among both sexes. Increases in TSH concentrations at follow-up also were positively associated with weight gain in women (1.1 lbs–5.1 lbs across increasing quartiles of TSH concentration change) and men (0.9 lbs–2.9 lbs across quartile of TSH concentration change ).

“We can’t speak to the clinical relevance of our findings, as this was a mechanistic observation that did not address causality,” cautioned Fox. “However, the associations between TSH and body weight were much stronger than what I had expected.

Individual Versus Population 

“The important thing to remember about this study is that it demonstrates changes in serum TSH levels across the reference range for a population,” said Roy E. Weiss, MD, PhD, Professor of Medicine and Chief of the Section of Adult and Pediatric Endocrinology at the University of Chicago Medical Center. “And we need to remember that every individual is probably uniquely programmed as to what his or her TSH level is, and that the range for this value varies by a factor of ten.”

Weiss, who co-authored an editorial that accompanied Fox’s article in the journal, also noted that the study showed no correlation between follow-up period weight gain and T4 (Arch Intern Med 2008; 168: 568–569). “The entire neuroendocrine system, of which TSH is a part, is involved in weight gain, but we don’t know which comes first—do people become heavy and as a result have higher TSH levels, or do increases in TSH levels cause the person to gain weight? Previous studies suggest that there is a lot of cross-talk going on among all the factors related to obesity and weight gain but we don’t know enough about the specifics at this time.”

Other data have shown direct effects of thyroid hormone levels on adipokine release, and researchers have come up with several proposed pathways by which adipose tissue might directly influence the HPT axis.

The bottom line, at this point, said Weiss, is that “We know for a population what the normal serum concentration of TSH is, but we don’t know what that level is for every person within that population. The findings show that if someone has a higher TSH level within the normal range, that person is more likely to gain weight over time. But it doesn’t mean that the TSH level manifested in that person is necessarily normal for that individual.”

Additional Studies

One limitation of the study was that the sampled population was almost entirely Caucasian. Therefore, remarked Fox, the findings should be validated in different races and ethnicities. Also, because the study was designed to be observational, the scientists could not infer causality. “Indeed, one might question whether weight gain may cause increases in TSH concentrations,” they wrote, although the scientists  admitted that the increases in serum TSH concentrations they observed were due to weight gain alone.

Weight gain and its interaction with the thyroid also have to be better understood, said Weiss. “We have no evidence at this time to advocate lowering serum TSH to treat obesity. But future research in this area will help us to know whether the thyroid is causing changes that result in weight gain and obesity, or if it’s being affected by the underlying adiposity.” 


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