During Rapid Weight Loss in Obese Children, Reductions in TSH Predict Improvements in Insulin Sensitivity Independent of Changes in Body Weight or Fat

Background: Although serum TSH is often elevated in obesity and may be linked to disorders of lipid and glucose metabolism, the clinical relevance of these relationships remains unclear. Subjects: Subjects were obese children and adolescents (n = 206; mean age 14 yr) undergoing rapid weight and fat loss in a standardized, multidisciplinary, 2-month, in-patient weight loss program. Design: This was a prospective study that determined thyroid function, glucose and lipid parameters, leptin, anthropometric measures, and body composition measured by dual-energy x-ray absorption at baseline and at the end of the intervention. Results: At baseline, 52% of children had TSH concentrations in the high normal range (> 2.5 mU/liter), but TSH was not correlated with body weight, body mass index SD scores, lean body mass, or body fat percentage. At baseline, independent of adiposity, TSH significantly correlated with total cholesterol (P = 0.008), low-density lipoprotein cholesterol (P = 0.013), fasting insulin (P = 0.010), homeostatic model assessment (HOMA) (P = 0.004), and leptin (P = 0.006). During the intervention, mean body fat, TSH, HOMA, and fasting insulin decreased by 21, 11, 53, and 54%, respectively. Change (Delta) in TSH did not correlate with Delta body weight or Delta body composition, but Delta TSH significantly correlated with, Delta fasting insulin and Delta HOMA, independent of Delta body weight or Delta body composition (P <0.05). Conclusion: TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat. During weight loss, independent of changes in body weight or composition, decreases in elevated serum TSH predict decreases in fasting insulin and HOMA. These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity. (J Clin Endocrinol Metab 95: 5412-5418, 2010