ReviewObesity and thyroid function
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.
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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
References (105)
- et al.
Adipose tissue as an endocrine organ
Trends Endocrinol. Metab.
(2000) - et al.
Effect of l-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein (a)
Metabolism
(1995) - et al.
Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight
Trends Endocrinol. Metab.
(2004) - et al.
The role of thyroid hormones in the control of energy expenditure
Clin. Endocrinol. Metab.
(1984) - et al.
Basal metabolism of weight stable chronically undernourished men and women: lack of metabolic adaptation and ethnic differences
Am. J. Clin. Nutr.
(1997) - et al.
Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery
Am. J. Clin. Nutr.
(2005) - et al.
Effects of exercise and food restriction on body composition and metabolic rate in obese women
Am. J. Clin. Nutr.
(1987) - et al.
Changes in resting energy expenditure and body composition in anorexia nervosa patients during refeeding
J. Am. Diet. Assoc.
(1993) - et al.
The epidemiology of obesity
Gastroenterology
(2007) - et al.
Changes in adenyl cyclase isoforms as a mechanism for thyroid hormone modulation of cardiac beta-adrenergic receptor responsiveness
Metabolism
(2000)
Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations
Am. J. Clin. Nutr.
Twenty-four-hour energy expenditure and resting metabolic rate in obese, moderately obese, and control subjects
Am. J. Clin. Nutr.
Regulation of in vivo TSH secretion by leptin
Regul. Pept.
Impact of regional and total body composition and hormones on resting energy expenditure in overweight postmenopausal women
Metabolism
Factors associated with the increase in resting energy expenditure during refeeding in malnourished anorexia nervosa patients
Am. J. Clin. Nutr.
Role of leptin in the neuroendocrine response to fasting
Nature
Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement
J. Clin. Endocrinol. Metab.
Improvements in insulin sensitivity are blunted by subclinical hypothyroidism
Med. Sci. Sports Exerc.
The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women
J. Clin. Endocrinol. Metab.
Obesity is associated with increased serum TSH level, independent of thyroid function
Swiss Med. Wkly.
Impact of insulin sensitivity in relationship with prolactin and thyroid stimulating hormone
Exp. Clin. Endocrinol. Diab.
Adaptive activation of thyroid hormone and energy expenditure
Biosci. Rep.
Nuclear 3,5,3-triiodothyronine (T3) in brown adipose tissue: receptor occupancy and sources of T3 as determined by in vivo techniques
Endocrinology
Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells
J. Clin. Endocrinol. Metab.
Influences of obesity and weight loss on thyroid hormones. A 3-year follow-up study on obese subjects with surgical biliopancreatic by-pass
J. Endocrinol. Invest.
Leptin acute modulation of the 5-deiodinase activities in hypothalamus, pituitary and brown adipose tissue of fed rats
Horm. Metab. Res.
Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean
Nature
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Nature
In vivo regulation of human skeletal muscle gene expression by thyroid hormone
Genome Res.
Thyroid hormones modulate the endocrine and autocrine/paracrine actions of leptin on thyrotropin secretion
J. Endocrinol.
Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature
J. Clin. Endocrinol. Metab.
Dietary-induced alterations in thyroid hormone metabolism during overnutrition
J. Clin. Invest.
Effect of carbohydrate and noncarbohydrate sources of calories on plasma 3,5,3H-triiodothyronine concentrations in man
J. Clin. Endocrinol. Metab.
The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue
J. Clin. Invest.
Effect of starvation on the production and peripheral metabolism of 3,3H,5H-triiodothyronine in euthyroid obese subjects
J. Clin. Endocrinol. Metab.
Thyroid hormones influence serum leptin concentrations in the rat
Endocrinology
Effects of thyroid hormones on contractility and cation transport in skeletal muscle
Acta Physiol. Scand.
Expression of leptin and beta 3-adrenergic receptors in rat adipose tissue in altered thyroid states
Biochem. J.
Alpha-melanocyte-stimulating hormone is contained in nerve terminals innervating thyrotropin-releasing hormone-synthesizing neurons in the hypothalamic paraventricular nucleus and prevents fasting-induced suppression of prothyrotropin-releasing hormone gene expression
J. Neurosci.
Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring
J. Clin. Invest.
Relationship between thyroid-stimulating hormone and insulin in euthyroid obese men
Ann. Nutr. Metab.
Interactions of leptin and thyrotropin 24-hour secretory profiles in short normal children
J. Clin. Endocrinol. Metab.
Leptin signaling targets the thyrotropin-releasing hormone gene promoter in vivo
Endocrinology
Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration
Mol. Psychiatry
Thyroid hormone deiodination in healthy man
Towards comprehension of the physiological role of UCP3
Horm. Metab. Res.
Relationship of thyroid function with body mass index, leptin, insulin sensitivity and adiponectin in euthyroid obese women
Clin. Endocrinol. (Oxf.)
Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism
J. Clin. Endocrinol. Metab.
The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effects of leptin
J. Clin. Invest.
Relationship between serum free T4 (FT4) levels and metabolic syndrome (MS) and its components in healthy euthyroid subjects
Clin. Endocrinol. (Oxf.)
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