Obesity is a result of net energy intake greater than energy expenditure. How many times have we told this to our patients and had them respond that, despite a vigorous commitment to a low-calorie diet and an exercise program, their weight continues to increase? Patients and investigators have long considered whether alterations in the hypothalamic-pituitary-thyroid (HPT) axis contribute to the energy equation such that low thyroid hormone levels result in obesity. Although thyroid hormone levels are frequently measured in the search for the holy grail of the overweight, the incidence of overt or subclinical hypothyroidism in subjects with obesity is relatively low.1 However, several studies have demonstrated that thyroid hormone levels, even within the reference range for the population, may be associated with obesity. A study of 4082 euthyroid Danes demonstrated a positive correlation between body mass index and serum thyrotropin (TSH) concentrations,2 and a study of approximately 8000 euthyroid Norwegians confirmed this finding in nonsmokers but not in smokers.3 In 226 Turks, there was a significant positive correlation between serum TSH levels and body mass index.4 In this issue of the Archives, Fox et al,5 in a study of 2407 Americans, demonstrate that adjusted mean baseline weight from 64.5 to 85.6 kg correlated positively with increasing serum TSH concentrations, although all were within the reference range. Furthermore, an increase in TSH concentration after 3.5 years of follow-up was positively associated with weight gain in women and men. Although the range of thyroid hormone values may vary in these populations because of dietary iodine intake, the common finding in these 3 large studies2,3,5 is that TSH levels correlate with body weight. The important thing to remember about these studies is that they demonstrate changes in serum TSH levels across the reference range for the population. This finding lends credence to the idea that the set point of the HPT axis is precisely determined by a variety of factors that may influence obesity and/or be influenced by obesity.
Interplay between adipose tissue and the hypothalamic-pituitary-thyroid axis. Adipokines such as leptin and other factors associated with obesity may directly affect the sensitivity of the thyrotroph or the thyrocyte. D2R indicates dopamine receptor; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone; TSH, thyrotropin; plus signs, stimulatory action; minus signs, inhibitory action; and question marks, unknown effect.
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