Review
Obesity and thyroid function

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Abstract

A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels. Elevated thyroid hormone concentrations increase the resting energy expenditure (REE). The underlying pathways are not fully understood. As a consequence of the increased REE, the availability of accumulated energy for conversion into fat is diminished. In conclusion, the alterations of thyroid hormones in obesity suggest an adaptation process. Since rapid weight loss is associated with a decrease of TSH and T3, the resulting decrease in REE may contribute towards the difficulties maintaining weight loss. Leptin seems to be a promising link between obesity and alterations of thyroid hormones since leptin concentrations influence TSH release.

Introduction

Since the birth of civilization, humans have faced various periods of famine and scarcity. People who survived those conditions most probably had a greater capacity for storing energy whenever food was available and refilling the consumed stores as soon as supplies became available again. However, the same properties that once constituted an evolutionary advantage can nowadays make individuals more susceptible to become obese during times of abundance. Indeed, this thrifty genotype exposed to modern and industrialized societies, characterized by food security and reduced physical activity levels, recently culminated in an obesity epidemic of gigantic proportions (Ogden et al., 2007, Levin, 2006). Even more alarming than the figures regarding adult obesity (Ogden et al., 2006) is the increasing rate of obese children (Ogden et al., 2002). The ascending epidemiological curves of obesity, particularly in children, and the associated metabolic burden, brought about an estimation of decreased life expectancy at birth in the United States during the first half of this century (Olshansky et al., 2005).

While the prevalence of obesity increases worldwide, the understanding of its pathogenesis and metabolic consequences markedly advances. The white adipose tissue, previously considered to be the largest, although inert, energy store in the body, actively produces various hormones, cytokines, and chemokines, which together exert important roles in homeostasis and in thyroid hormone regulation (Rosen and Spiegelman, 2006, Ahima and Flier, 2000). In the recent years, there has been an increasing focus on the relationship between thyroid function and weight status. While it is well known that hyperthyroidism leads to weight loss and hypothyroidism is associated with weight gain, the changes of thyroid function are discussed controversially in obesity.

Section snippets

Impact of thyroid hormones on weight status

Weight status is a consequence of the relationship between energy intake and energy consumption. Energy consumption is determined by physical activity and mainly by resting energy expenditure (REE).

While it is clear that thyroid hormones can modulate numerous cellular processes that are relevant for REE (Danforth and Burger, 1984, Onur et al., 2005), the exact mechanisms that underlie this effect in humans remain unclear (Kim et al., 2000). Thyroid hormones have been demonstrated to modulate

The relationship between thyroid hormones and obesity

Since thyroid hormones upregulate many metabolic pathways relevant for REE, it is not surprising that patients with thyroid diseases usually exhibit changes in body weight, thermogenesis, and lipolysis in adipose tissue. Hypothyroidism is usually associated with a modest weight gain, decreased thermogenesis and metabolic rate, whereas hyperthyroidism is related with weight loss despite increased appetite and elevated metabolic rate.

Although thyroid function is usually normal in obese subjects,

Causes of increased TSH levels in obesity

Several causes of increased TSH levels in obesity have been suggested (see Table 1). In large cohorts of obese children and adults only a minority suffered from autoimmune thyroiditis, while most obese humans demonstrated moderately increased TSH levels without detecting any thyroid disease (Reinehr et al., 2007, Rotondi et al., 2009). The increase in TSH serum levels was not accounted for by iodine deficiency or autoimmune thyroiditis in several further studies (Stichel et al., 2000, Reinehr

Consequences of moderately elevated thyroid hormone levels in obesity

The moderate increase of TSH levels is usually not associated with changes in free and total T4 in obesity: FT4 and total T4 levels are comparable in normal weight and obese humans (Reinehr and Andler, 2002, Reinehr et al., 2006, Reinehr et al., 2008, Moulin de Moraes et al., 2005, Kok et al., 2005, Kozlowska and Rosolowska-Huszcz, 2004, Sari et al., 2003, Kiortis et al., 1999) ruling out significant hypothyroidism even if TSH is slightly increased in obesity. Furthermore, fasting and

Thyroid hormone levels in anorexia nervosa as the opposite of obesity

In concordance with the hypothesis of increased thyroid hormone levels in obesity, and as the opposite of obesity, anorexia nervosa (AN) is associated with low TSH levels and low fT3 concentrations, which increase in weight regain (Reinehr et al., 2008, Haas et al., 2005, Onur et al., 2005, Van Wymelbeke et al., 2004). Low T3 concentrations in patients with AN may be due to impaired peripheral conversion of T4 to T3 associated with the altered nutritional state. The REE is decreased in patients

Adipocytokines as a link between thyroid hormones and obesity

While increasing evidence suggests that obesity is associated with moderately increased TSH levels, fT3 levels, and consequently increased REE, the physiological pathways connecting obesity with increased thyroid hormone status are less clear. Leptin may be a promising link between weight status and thyroid hormones.

Leptin is a 16 kDa hormone predominantly released by adipocytes and circulates at levels proportional to the body's adiposity. More than a decade ago, research showed that the ob

Thyroid hormones and insulin resistance

An association between thyroid function and insulin resistance has been suggested in obesity (Galofré et al., 2008, Iacobellis et al., 2005): significant relationships between TSH and clinical features of insulin resistance such as increased blood pressure, dyslipidemia, hyperinsulinemia, and type 2 diabetes mellitus have been reported (Galofré et al., 2008, Iacobellis et al., 2005, Bastemir et al., 2007b, Saltiki et al., 2008, Kim et al., 2009). Moreover, improvements in insulin sensitivity

Conclusions and clinical implications

It is important for clinicians to know the alterations of thyroid hormones in obesity. In obese humans with slightly increased TSH levels, hypothyroidism has to be excluded which can easily be performed by measuring peripheral thyroid hormones (especially T4). A moderate increase of TSH, which is associated with normal T4 values and T3 values in or slightly above the upper normal range, should not be treated with thyroxine under the “diagnosis” of subclinical hypothyroidisms since these

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