Background/Aims: Thyroid-stimulating hormone (TSH) is affected in obesity and might influence metabolic risk. It is unclear what mechanisms cause elevated TSH in obesity. We aimed to investigate TSH status within the normal range and the association of TSH with degree of obesity and metabolic parameters in children with obesity. Methods: A total of 3,459 children, aged 3.0–17.9 years, were identified in the Swedish Childhood Obesity Treatment Registry, BORIS. Age, gender, TSH, free triiodothyronine (fT3), free thyroxine (fT4), body mass index standard deviation scores (BMI SDS), as well as variables of lipid and glucose metabolism were examined. Results: Children with high-normal TSH (>3.0 mU/L) (28.8%) had higher BMI SDS compared to children with low-normal TSH (<3.0 mU/L) (p < 0.001). Multivariable regression analysis adjusted for age and gender showed that TSH levels were associated with BMI SDS (β: 0.21, 95% CI: 0.14–0.28, p < 0.001). Associations of thyroid hormones with markers of lipid and glucose metabolism were observed, where TSH was associated with fasting insulin, HOMA (homeostatic model assessment of insulin resistance), total cholesterol, and triglycerides. Conclusions: A positive association between TSH levels and BMI SDS was seen in children with obesity. Associations of TSH and free thyroid hormones with glucose metabolism indicated that TSH might be one of several factors acting to determine body weight and obesity co-morbidities, although the underlying mechanism remains unclear.

1.
Drvota V, Janson A, Norman C, Sylven C, Haggblad J, Bronnegard M, et al: Evidence for the presence of functional thyrotropin receptor in cardiac muscle. Biochem Biophys Res Commun 1995; 211: 426–431.
2.
Endo T, Kobayashi T: Thyroid-stimulating hormone receptor in brown adipose tissue is involved in the regulation of thermogenesis. Am J Physiol Endocrinol Metab 2008; 295:E514–E518.
3.
Tsai JA, Janson A, Bucht E, Kindmark H, Marcus C, Stark A, et al: Weak evidence of thyrotropin receptors in primary cultures of human osteoblast-like cells. Calcif Tissue Int 2004; 74: 486–491.
4.
Baron DN: Hypothyroidism: its aetiology and relation to hypometabolism, hypercholesterolaemia, and increase in body-weight. Lancet 1956; 271: 277–281.
5.
Rosenbaum M, Hirsch J, Murphy E, Leibel RL: Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr 2000; 71: 1421–1432.
6.
Ruhla S, Weickert MO, Arafat AM, Osterhoff M, Isken F, Spranger J, et al: A high normal TSH is associated with the metabolic syndrome. Clin Endocrinol 2010; 72: 696–701.
7.
Nyrnes A, Jorde R, Sundsfjord J: Serum TSH is positively associated with BMI. Int J Obes (Lond) 2006; 30: 100–105.
8.
Manji N, Boelaert K, Sheppard MC, Holder RL, Gough SC, Franklyn JA: Lack of association between serum TSH or free T4 and body mass index in euthyroid subjects. Clin Endocrinol 2006; 64: 125–128.
9.
Knudsen N, Laurberg P, Rasmussen LB, Bulow I, Perrild H, Ovesen L, et al: Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab 2005; 90: 4019–4024.
10.
Reinehr T, Isa A, de Sousa G, Dieffenbach R, Andler W: Thyroid hormones and their relation to weight status. Horm Res 2008; 70: 51–57.
11.
Bastemir M, Akin F, Alkis E, Kaptanoglu B: Obesity is associated with increased serum TSH level, independent of thyroid function. Swiss Med Wkly 2007; 137: 431–434.
12.
Danforth E Jr, Burger A: The role of thyroid hormones in the control of energy expenditure. Clin Endocrinol Metab 1984; 13: 581–595.
13.
Rotondi M, Magri F, Chiovato L: Thyroid and obesity: not a one-way interaction. J Clin Endocrinol Metab 2011; 96: 344–346.
14.
al-Adsani H, Hoffer LJ, Silva JE: Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab 1997; 82: 1118–1125.
15.
Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH: Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab 2007; 92: 491–496.
16.
Stichel H, l’Allemand D, Gruters A: Thyroid function and obesity in children and adolescents. Horm Res 2000; 54: 14–19.
17.
Grandone A, Santoro N, Coppola F, Calabro P, Perrone L, Del Giudice EM: Thyroid function derangement and childhood obesity: an Italian experience. BMC Endocr Disord 2010; 10: 8.
18.
Ozer S, Butun I, Sonmezgoz E, Yilmaz R, Demir O: Relationships among thyroid hormones and obesity severity, metabolic syndrome and its components in Turkish children with obesity. Nutr Hosp 2015; 32: 645–651.
19.
Aeberli I, Jung A, Murer SB, Wildhaber J, Wildhaber-Brooks J, Knopfli BH, et al: During rapid weight loss in obese children, reductions in TSH predict improvements in insulin sensitivity independent of changes in body weight or fat. J Clin Endocrinol Metab 2010; 95: 5412–5418.
20.
Shalitin S, Yackobovitch-Gavan M, Phillip M: Prevalence of thyroid dysfunction in obese children and adolescents before and after weight reduction and its relation to other metabolic parameters. Horm Res 2009; 71: 155–161.
21.
Witte T, Ittermann T, Thamm M, Riblet NB, Volzke H: Association between serum thyroid-stimulating hormone levels and serum lipids in children and adolescents: a population-based study of German youth. J Clin Endocrinol Metab 2015; 100: 2090–2097.
22.
Bougle D, Morello R, Brouard J: Thyroid function and metabolic risk factors in obese youth. Changes during follow-up: a preventive mechanism? Exp Clin Endocrinol Diabetes 2014; 122: 548–552.
23.
Santos MI, Limbert C, Marques FC, Rosario F, Lopes L: Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study. J Pediatr Endocrinol Metab 2015; 28: 557–562.
24.
Reinehr T, de Sousa G, Andler W: Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids. J Clin Endocrinol Metab 2006; 91: 3088–3091.
25.
Reinehr T: Obesity and thyroid function. Mol Cell Endocrinol 2010; 316: 165–171.
26.
Cole TJ, Lobstein T: Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes 2012; 7: 284–294.
27.
Marshall WA, Tanner JM: Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291–303.
28.
Radhakishun NN, van Vliet M, von Rosenstiel IA, Weijer O, Beijnen JH, Brandjes DP, et al: Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents. J Pediatr Endocrinol Metab 2013; 26: 531–537.
29.
Karavani G, Strich D, Edri S, Gillis D: Increases in thyrotropin within the near-normal range are associated with increased triiodothyronine but not increased thyroxine in the pediatric age group. J Clin Endocrinol Metab 2014; 99:E1471–E1475.
30.
Araujo RL, Andrade BM, Padron AS, Gaidhu MP, Perry RL, Carvalho DP, et al: High-fat diet increases thyrotropin and oxygen consumption without altering circulating 3,5,3′-triiodothyronine (T3) and thyroxine in rats: the role of iodothyronine deiodinases, reverse T3 production, and whole-body fat oxidation. Endocrinology 2010; 151: 3460–3469.
31.
Wolters B, Lass N, Reinehr T: TSH and free triiodothyronine concentrations are associated with weight loss in a lifestyle intervention and weight regain afterwards in obese children. Eur J Endocrinol 2013; 168: 323–329.
32.
Lartey LJ, Werneck-de-Castro JP, I OS, Unterman TG, Bianco AC: Coupling between nutrient availability and thyroid hormone activation. J Biol Chem 2015; 290: 30551–30561.
33.
Reinehr T, Andler W: Thyroid hormones before and after weight loss in obesity. Arch Dis Child 2002; 87: 320–323.
34.
Aziz Elgadi HZ, Marcus C, Norgren S: Tissue-specific knockout of TSHr in white adipose tissue increases adipocyte size and decreases TSH induced lipolysis. Biochem Biophys Res Commun 2010; 393: 526–530.
35.
Janson A, Rawet H, Perbeck L, Marcus C: Presence of thyrotropin receptor in infant adipocytes. Pediatr Res 1998; 43(4 Pt 1):555–558.
36.
Marcus C, Ehren H, Bolme P, Arner P: Regulation of lipolysis during the neonatal period. Importance of thyrotropin. J Clin Invest 1988; 82: 1793–1797.
37.
Lu M, Lin RY: TSH stimulates adipogenesis in mouse embryonic stem cells. J Endocrinol 2008; 196: 159–169.
38.
Menendez C, Baldelli R, Camina JP, Escudero B, Peino R, Dieguez C, et al: TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol 2003; 176: 7–12.
39.
Lu S, Guan Q, Liu Y, Wang H, Xu W, Li X, et al: Role of extrathyroidal TSHR expression in adipocyte differentiation and its association with obesity. Lipids Health Dis 2012; 11: 17.
40.
Nannipieri M, Cecchetti F, Anselmino M, Camastra S, Niccolini P, Lamacchia M, et al: Expression of thyrotropin and thyroid hormone receptors in adipose tissue of patients with morbid obesity and/or type 2 diabetes: effects of weight loss. Int J Obes (Lond) 2009; 33: 1001–1006.
41.
Kapelari K, Kirchlechner C, Hogler W, Schweitzer K, Virgolini I, Moncayo R: Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study. BMC Endocr Disord 2008; 8: 15.
42.
Wartofsky L, Dickey RA: The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab 2005; 90: 5483–5488.
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