Higher TSH Associated with Weight Gain

Here is a good review of a study showing that higher thyroid stimulating hormone (TSH, the most sensitive indicator of thyroid function) is associated with weight gain, and the increase is linear. Optimum TSH is < 2.5.

News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD

March 25, 2008 — Modest increases of thyroid-stimulating hormone (TSH) within the reference range may be associated with weight gain, according to the results of a large, community-based study reported in the March 24 issue of the Archives of Internal Medicine.

"Overt hypothyroidism and hyperthyroidism may be associated with weight gain and loss," write Caroline S. Fox, MD, MPH, from the National Heart, Lung, and Blood Institute's Framingham Heart Study in Framingham, Massachusetts, and colleagues. "We assessed whether variations in thyroid function within the reference (physiologic) range are associated with body weight."

This study included 2407 participants in the Framingham Offspring Study who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had baseline serum thyrotropin (TSH) concentrations of 0.5 to 5.0 mIU/L and follow-up concentrations of 0.5 to 10.0 mIU/L. During 3.5 years of follow-up, the relationship of baseline TSH concentrations with body weight and body weight change was determined.

From the lowest to highest TSH concentration quartiles at baseline, adjusted mean weight increased progressively from 64.5 to 70.2 kg in women (P < .001 for trend) and from 82.8 (lowest quartile) to 85.6 kg (highest quartile) in men (P = .007 for trend). Mean body weight increased by 1.5 ± 5.6 kg in women and 1.0 ± 5.0 kg in men during 3.5 years of follow-up.

Although baseline TSH concentrations were not associated with weight change during follow-up, an increase in TSH concentration at follow-up was positively associated with weight gain in women
(0.5 - 2.3 kg across increasing quartiles of TSH concentration change; P < .001 for trend) and men (0.4 - 1.3 kg across quartiles of TSH concentration change; P = .007 for trend).

"Thyroid function (as assessed by serum TSH concentration) within the reference range is associated with body weight in both sexes," the study authors write. "Our findings raise the possibility that modest increases in serum TSH concentrations within the reference range may be associated with weight gain."

Limitations of the study include observational design precluding determination of causality; lack of measurement of free thyroxine levels; sample nearly entirely white, with possible lack of generalizability to other ethnic groups; and inability to account for other covariates known to be associated with body weight and weight change, including diet and physical activity.

"The identification of change in thyroid function as a risk factor for weight gain might help guide research into the identification, prevention, and treatment of individuals at risk for the development of excess adiposity," the study authors write. "Confirmation of our findings in other samples is warranted, and in particular more longitudinal studies are warranted."

The National Heart, Lung, and Blood Institute's Framingham Heart Study supported this study. Two of the study authors have been supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases. The other study authors have disclosed no relevant financial relationships.

In an accompanying editorial, Roy E. Weiss, MD, PhD, and Rebecca L. Brown, MD, from the University of Chicago Medical Center in Chicago, Illinois, address potential mechanisms linking thyroid function and obesity.

"Assuming preservation of tissue responsiveness to thyroid hormone levels, the absence of reciprocal changes in T3 and T4 levels suggests a central modification of the HPT [hypothalamic-pituitary-thyroid] axis in obesity," Drs. Weiss and Brown write. "Elucidation of the mechanisms by which obesity alters the HPT axis may give clues to the other metabolic abnormalities seen in this condition. There is no evidence at this time to advocate lowering serum TSH concentrations to treat obesity."

Drs. Weiss and Brown have disclosed no relevant financial relationships.

Arch Intern Med. 2008;168:568-569, 587-592.

Clinical Context

In the United States, the prevalence of obesity is rising. Obesity is associated with the increased risk for diabetes, vascular disease, all-cause mortality, and cancer. Known predictors of obesity and weight gain include a low level of physical activity, increased energy intake, parity, smoking cessation, inflammation, depression, and genetic factors. It has been recognized that thyroid dysfunction is a cause of weight change. Studies have suggested that variation in thyroid function within the reference range may be related to weight change.

The aim of this study was to determine whether variations in thyroid function are associated with body weight.

Study Highlights

• From the Framingham Offspring Study, participants (n = 2407) who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had baseline serum TSH concentrations of 0.5 to 5.0 mIU/L and follow-up concentrations of 0.5 to 10.0 mIU/L were included in this study.
• The prevalence of obesity at baseline was 14.3%, and the mean baseline serum TSH concentration was 1.91 mIU/L in women and 1.70 mIU/L in men.
• Baseline TSH concentrations were related to body weight and change in body weight during 3.5 years of follow-up.
• Results revealed that at baseline, adjusted mean weight increased progressively from 64.5 to 70.2 kg in the lowest to the highest TSH concentration quartiles in women (P < .001 for trend) and from 82.8 (lowest quartile) to 85.6 kg (highest quartile) in men (P = .007 for trend).
• Baseline TSH concentrations were not associated with weight change during follow-up.
• During 3.5 years of follow-up, mean (SD) body weight increased by 1.5 (5.6) kg in women and 1.0 (5.0) kg in men.
• Weight increased by 1.9 kg per every 1-unit increase in log TSH concentration (P < .001) in women and by 1.0 kg per every 1-unit increase in log TSH concentration (P = .007) in men.
• An increase in TSH concentration at follow-up was positively associated with weight gain in women (0.5 - 2.3 kg across increasing quartiles of TSH concentration change; P < .001 for trend) and men (0.4 - 1.3 kg across quartiles of TSH concentration change; P = .007 for trend).
• Limitations to this study included the observational design of the study; lack of measurement of free thyroxine levels; sample nearly entirely white, with possible lack of generalizability to other ethnic groups; and inability to account for other covariates that may affect body weight, such as diet and physical activity.

Pearls for Practice

• Risk factors leading to obesity include low level of physical activity, increased energy intake, parity, smoking cessation, inflammation, depression, and genetic factors.
• Thyroid function within the reference range is associated with body weight in both sexes, suggesting that modest increases in serum TSH concentrations within the reference range may be associated with weight gain.