“It’s not your thyroid”: Facts and fiction in the thyroid-obesity relationship. |
“Obesity, TSH and β-cell Function: An Intriguing Relationship” In this context, normal thyroid function is necessary to maintain body weight. This is a comment on "Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of. New studies on the relation between L-T3 therapy and weight control are .. Biondi B: Thyroid and obesity: an intriguing relationship. J Clin.
High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism.
There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients. The link has become more relevant in the context of an unprecedented rise in the prevalence of obesity worldwide.
Obesity is generally regarded by patients as being secondary to thyroid dysfunction. Recent data have also disclosed a relation between obesity and thyroid autoimmunity with the adipocyte hormone leptin appearing to be the key factor linking these two conditions.
In this article, we will review the intriguing relationship between obesity and hypothyroidism and the consequent clinical implications. Thyroid hormones regulate basal metabolism, thermogenesis and play an important role in lipid and glucose metabolism, food intake and fat oxidation.
Hypothyroidism is associated with decreased thermogenesis, decreased metabolic rate, and has also been shown to correlate with a higher body mass index BMI and a higher prevalence of obesity. It has been further noted that small variations in serum TSH caused by minimal changes in L-T4 dosage during replacement therapy are associated with significantly altered REE in hypothyroid patients.
An inverse correlation between free T4 fT4 and BMI, even when fT4 remains in the normal range has been reported;[ 3 ] fat accumulation has been associated with lower fT4 and higher TSH levels among slightly overweight euthyroid individuals, thereby resulting in a positive correlation between TSH and the progressive increase in weight with time.
In obese children, the most common abnormality clearly is hyperthyrotropinemia. Recently, it has also been shown that obese pediatric patients frequently have an ultrasound pattern of the thyroid which is highly suggestive of Hashimoto's thyroiditis.
The causes underlying these alterations in thyroid functions are not known. One theory suggests an increased deiodinase activity leading to a high conversion rate of T4 to T3. This is interpreted as a defense mechanism in obese subjects capable of counteracting the accumulation of fat by increasing energy expenditure.
The main action of leptin is to report centrally the amount of fat, leading to a decrease in appetite and food intake. Leptin also enhances the activity of deiodinases. The prevalence of AITD in obesity has been reported to be This study suggested that obesity is a risk factor for thyroid autoimmunity, thus establishing a link between the main cause of acquired thyroid failure and obesity. Hence, the presence of thermogenically active D2 BAT in an adult is clinically important.My Struggle w/ Hypothyroidism - Weight Loss , Symptoms , How I Live w/ it
In the recent years, the presence of BAT has been recognized as an important target for treating obesity. The energy homeostasis in the BAT has been found to be affected by a great extent by thyroid hormone signaling. Thyroid hormone signaling, particularly by inducing type II deiodinases, has a cardinal function in brown tissue adipogenesis. D2 increases expression of the gene Ppargc1a by enhancing thyroid hormone signaling, which coactivates thyroid hormone receptors, leading to increased expression of the gene Ucp1.
Dio2 is also upregulated by increased triiodothyronine T3 signaling.
Hypothyroidism and obesity: An intriguing link
These type II deiodinase D2-dependent pathways provide the mature brown adipocyte with its full thermogenic identity. TSH seems to be positively related to the degree of obesity A positive correlation has been identified between serum leptin and serum TSH levels in obese individuals 17which could reflect the positive association between TSH and BMI reported in some individuals 489 Leptin, adjusted for BMI, was found to correlate with TSH 17which suggests that the increase in TSH and leptin levels in severe obesity could result from the increased amount of fat.
Thyroid hormone levels have been reported to be normal, increased, and decreased in obese patients 4 ; this discrepancy among studies probably reflects the fact that patients were examined at different times during overeating or a hypocaloric diet and may differ in degree and type of obesity and in plasma insulin sensitivity.
Interestingly, a moderate increase in total T3 or free T3 FT3 levels has been reported in obese subjects 19 — Progressive fat accumulation was associated with a parallel increase in TSH and FT3 levels irrespective of insulin sensitivity and metabolic parameters 20and a positive association has been reported between the FT3 to FT4 ratio and both waist circumference and BMI in obese patients This finding suggests a high conversion of T4 to T3 in patients with central fat obesity due to increased deiodinase activity as a compensatory mechanism for fat accumulation to improve energy expenditure This reduced TSH receptor expression might induce down-regulation of thyroid hormone receptors and thyroid hormone action, thereby further increasing plasma TSH and FT3 concentrations and constituting a condition of peripheral thyroid hormone resistance This sequence of events would be reversed by weight loss, which restores the size and function of mature adipocytes Aberrant thyroid function and TSH level usually normalize after weight loss whether consequent to diet or to bariatric surgery 1920 — The decrease in T3 levels during weight loss with continued caloric deprivation reduces energy expenditure.
Therefore, decreased T3 levels may be responsible for difficulties in maintaining or further decreasing weight loss The finding that TSH, FT3, and leptin levels are increased in obese subjects and that weight loss leads to decreased serum TSH, FT3, and leptin levels supports the hypothesis that the alteration in thyroid function observed in obese subjects is reversible by losing weight Whatever the mechanism underlying elevated TSH in obesity, it is difficult to identify obese subjects who are affected by mild thyroid hormone deficiency.
It seems reasonable to suggest that hypothyroidism should be suspected in obese subjects with slightly increased TSH levels only after measuring plasma levels of thyroid hormones and thyroid autoantibodies, and after having detected evidence of impaired thyroid hormone activity at a tissue level.
Thyroid hormone deficiency can be excluded in obese subjects with high serum TSH in the case of FT3 levels that are at the upper limit of the normal range or slightly higher, especially in the presence of normal peripheral parameters of thyroid hormone action e. Furthermore, in this condition, the association with normal thyroid autoantibodies may help exclude even further the presence of mild thyroid dysfunction and its potential progression to overt disease.
The evaluation of the thyroid structure by ultrasound does not help to diagnose hypothyroidism in obese patients 18 In fact, in obese children and adults, the moderate increase in TSH is frequently associated with an increase in thyroid volume and hypoechogeneity with an ultrasound pattern suggestive of Hashimoto thyroiditis, even in the absence of thyroid autoantibodies 18 The increased hypoechogenicity in obese subjects has been linked to cytokines and other inflammatory markers produced by adipose tissue.
These cytokines can increase TSH levels thereby increasing thyroid size and can induce vasodilatation and increase permeability of thyroid vessels with increased parenchymal inhibition via imbibition of the thyroid gland that might be responsible for the hypoechogenicity at ultrasound There is some debate about the link between obesity and the risk of autoimmune thyroid dysfunction AITDwhich is the main cause of hypothyroidism in adults.
Hypothyroidism and obesity: An intriguing link
The prevalence of AITD in obesity has been reported to be This discrepancy may be due to such factors as sex, age, menopausal status, smoking habit, environmental factors, iodine intake, and degree of obesity. They estimated the prevalence and characteristics of thyroid autoimmunity in a population of obese men and premenopausal obese women and found that leptin increases susceptibility to AITD by regulating immune processes.
Multiple logistic regression analysis in pooled groups identified female sex and leptin as significant predictors of AITD Based on these data, one may envisage a link between obesity, TSH increase, leptin increase, autoimmunity, alterations in thyroid morphology and structure, and development of subclinical and overt hypothyroidism.
The onset of thyroid hormone deficiency, especially the subclinical form, may go undiagnosed in obese patients. Recent studies suggest that a higher BMI is associated with an increased risk of thyroid cancer Moreover, a serum TSH in the upper half of the normal range is considered as an independent predictor for the presence of thyroid cancer in thyroid nodules 30 Both of these findings together suggest that the higher serum TSH levels could be responsible for the development of thyroid malignancy in obese patients.