Physiological and Metabolic Changes During the Transition from Hyperthyroidism to Euthyroidism in Graves' Disease

Background: The serum metabolomic profile and its relationship to physiological changes during hyperthyroidism and restoration to euthyroidism are not known. This study aimed to examine the physiological, adipokine, and metabolomic changes that occur when subjects with Graves' disease transition from hyperthyroidism to euthyroidism with medical treatment. Methods: Chinese women between 21 and 50 years of age and with newly diagnosed Graves' disease attending the endocrine outpatient clinics in a single institution were recruited between July 2012 and September 2014. All subjects were treated with thioamides to achieve euthyroidism. Clinical parameters (body weight, body composition via bioelectrical impedance analysis, resting energy expenditure and respiratory quotient via indirect calorimetry, and reported total energy intake via 24h food diary), biochemical parameters (thyroid hormones, lipid profile, fasting insulin and glucose levels), serum leptin, adiponectin, and metabolomics profiles were measured during hyperthyroidism and repeated in early euthyroidism. Results: Twenty four Chinese women with an average age of 36.38.6 years were included in the study. The average duration of treatment that was required to reach euthyroidism for these subjects was 38 +/- 16.3 weeks. There was a significant increase in body weight (52.6 +/- 9.0kg to 55.3 +/- 9.4kg; p<0.001) and fat mass (14.3 +/- 6.9kg to 16.8 +/- 6.5kg; p=0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 +/- 4.0kcal/kg to 21.5 +/- 4.1kcal/kg; p<0.001) and an increase in respiratory quotient (0.76 to 0.81; p=0.037). Resting energy expenditure increased significantly with increasing free triiodothyronine levels (p=0.007). Significant increases in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were noted. There was no significant change in leptin levels, but adiponectin levels increased significantly (p=0.018). Significant reductions in fasting C2, medium-chain, long-chain, and total acylcarnitines were observed, but no changes in the fat-free mass, branched chain amino acid levels, or insulin sensitivity during recovery from hyperthyroidism were noted. Conclusions: Serum metabolomics profile changes complemented the physiological changes observed during the transition from hyperthyroidism to euthyroidism. This study provides a comprehensive and integrated view of the changes in fuel metabolism and energy balance that occur following the treatment of hyperthyroidism.