Altered Thyroid Function and Structure in Children and Adolescents Who Are Overweight and Obese

Reversal After Weight Loss

Maria Rosaria Licenziati; Giuliana Valerio; Ilaria Vetrani; Gaetano De Maria; Fabrizia Liotta; Giorgio Radetti

Disclosures

J Clin Endocrinol Metab. 2019;104(7):2757-2765. 

In This Article

Abstract and Introduction

Abstract

Context: Obesity is associated with hypothyroidism and goiter.

Objective: The aim of the study was to verify whether thyroid structure and function would improve after weight loss.

Design and Patients: We evaluated 96 children who were overweight/obese who showed an altered parenchymal pattern at thyroid ultrasound without circulating antithyroid antibodies. At phase 1, body mass index (BMI), SD score (SDS), body composition, free T4 (fT4), TSH, high-sensitivity C reactive protein (CRPhs), white blood cells, metabolic profile, and a thyroid ultrasound were assessed. Thyroid volume was expressed as SDS on the basis of the references values for age. Alterations in echogenicity and homogeneity were graded from 0 to 5 (thyroid score). The same parameters were re-examined after a weight loss program (phase 2).

Results: After a mean period of treatment of 0.8 ± 0.3 years, there was a significant decrease of BMI SDS, percentage fat mass, CRPhs, TSH, and thyroid volume SDS (all P < 0.0001), whereas fT4 remained unchanged. The thyroid score significantly improved (z = −9088; P < 0.0001) [i.e., it decreased in 82 individuals, was tied in 12, and worsened only in two subjects; the score completely normalized in 48 (50%) individuals]. BMI SDS reduction was a unique predictor of the decrease of TSH, thyroid volume, and structure, whereas CRPhs reduction was an independent predictor only for the TSH change. Moreover, CRPhs variations mediated the association between BMI SDS and TSH.

Conclusion: The alterations of thyroid function and structure in children with obesity are reversible after weight loss.

Introduction

Patients who are obese frequently show an altered thyroid function[1–8] and structure resembling Hashimoto thyroiditis[8,9] in the absence of thyroid disease. No definite etiology has been established for these modifications; however, it has been suggested that they might be ascribed to the accompanying inflammatory status. In fact, individuals who are obese secrete a large number of inflammatory cytokines,[10,11] which have been shown to impair sodium/iodide symporter function,[12–14] leading to a compensatory TSH elevation. Similarly, the increased cytokine production might underpin the parenchymal changes. Inflammatory cytokines may induce vasodilatation and increase the permeability of the thyroid vessels, with plasma exudation[15] and possible parenchyma imbibition, which might explain the abnormal ultrasound findings.

Weight loss, obtained with diet or bariatric surgery, normalizes thyroid function,[1,6,16–19] suggesting that the described alterations are functional. It is unknown whether the same holds true for impairment of thyroid structure. Radetti et al.[20] tried to verify this hypothesis; however, their attempt was hampered by unsatisfactory weight loss. In fact, despite a significant decrease of TSH and fT3 after intervention, thyroid structure showed only a slight improvement, probably due to increased physical activity and fat loss. Increased physical activity and improved physical fitness may reduce the inflammatory status, supporting the role of inflammation in thyroid structural changes.[21]

To fill the gap in the literature, the aim of this study was to assess whether the alterations of thyroid structure, along with thyroid function and volume, improve or disappear after weight loss in a clinical sample of children and adolescents who were obese enrolled in a multidisciplinary treatment based on diet, physical activity, and behavioral strategies. As a secondary endpoint, we investigated the role played by weight loss and inflammatory status in influencing the outcome, hypothesizing a mediating role of inflammatory status.

Patients and Methods

Patients. Between January and December 2016, 239 children and adolescentswhowere overweight or obese (124 boys, age 4 to 18 years) referred to the Obesity Center of the Santobono Pausilipon Children's Hospital of Naples, Italy, underwent an ultrasound thyroid assessment to be enrolled in a prospective study on thyroid structure and function changes with weight loss. The inclusion criteria to be enrolled in the study were overweight or simple obesity, evidence of alterations of the thyroid structure at ultrasound scan, absence of circulating antithyroid antibodies, full-term birth, and willingness to participate in a multidisciplinary treatment of weight loss. The exclusion criteria were genetic, endocrine, and pharmacological causes of overweight/obesity or recent history of acute infectious or noninfectious inflammatory disorders. A total of 116 youth (57 boys, 59 girls; 48.5% of the entire sample) fulfilled the inclusion criteria; 12 individuals (5% of the entire sample) were excluded for positivity of antithyroid antibodies, and eight individuals were lost at follow-up. Therefore, there were 96 patients in the final sample (49 boys).

Study protocol. Children and adolescents were enrolled in a multidisciplinary treatment based on diet, physical activity, and behavioral strategies. At phase 1, all children met a pediatric endocrinologist and a trained dietician and were fully instructed on having regular physical activity by a sports medicine physician. Thereafter they were followed regularly as outpatients. The compliance with dietary recommendations and physical activity was verified by a diary. All children also met a trained psychologist who evaluated the behavioral changes. Children were examined at the first encounter at the age of 11.1 ± 2.4 years (phase 1) and subsequently at the age of 11.9 ± 2.4 years (phase 2) after a mean period of 0.8 ± 0.3 years. The institutional review board approved the clinical protocol, and written informed consent for all procedures was obtained from all the youth and/or their parents or legal guardians before the enrolment.

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