Invited critical review Thyroid function in childhood obesity and metabolic comorbidity ☆ , ☆☆ Lucia Pacifico a , Caterina Anania a , Flavia Ferraro a , Gian Marco Andreoli a , Claudio Chiesa b, ⁎ a Department of Pediatrics, Sapienza University of Rome, Rome, Italy b Institute of Translational Pharmacology, National Research Council, Rome, Italy abstract article info Article history: Received 7 September 2011 Received in revised form 10 November 2011 Accepted 15 November 2011 Available online 27 November 2011 Keywords: Thyroid hormones Obesity Metabolic syndrome Nonalcoholic fatty liver disease Children Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mech- anisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obe- sity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains con- troversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity- related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396 2. Thyroid function in obese children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397 3. Causes of thyroid hormonal change in obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400 3.1. Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400 3.2. Mutations in the TSH-R gene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400 3.3. Role of leptin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400 3.4. Thyroid hormone resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400 3.5. Mitochondrial dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 3.6. Adaptation process to increase energy expenditure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 4. Thyroid and metabolic syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 5. Thyroid and nonalcoholic fatty liver disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402 6. TSH and its relation to weight loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403 1. Introduction Childhood obesity is a worldwide health problem and its preva- lence is increasing steadily and dramatically all over the world [1]. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and im- paired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases [2]. Recently, there has been Clinica Chimica Acta 413 (2012) 396–405 ☆ Financial support: This work was supported by a grant of Sapienza University of Rome (Progetti di Ricerca Universitaria 2010). ☆☆ Conflict of interest: none declared. ⁎ Corresponding author at: Institute of Translational Pharmacology, National Research Council, Via del Fosso del Cavaliere, 100, I-00133 Rome, Italy. Tel.: + 39 06 49979215; fax: + 39 06 49979216. E-mail address: claudio.chiesa@ift.cnr.it (C. Chiesa). 403 403 0009-8981/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.cca.2011.11.013 Contents lists available at SciVerse ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim