title: Physiological and Metabolic Changes During the Transition from Hyperthyroidism to Euthyroidism in Graves' Disease.
abstract: 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.
  
  
  
  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 24 h 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.
  
  
  
  Twenty four Chinese women with an average age of 36.3 ± 8.6 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 ± 9.0 kg to 55.3 ± 9.4 kg; p < 0.001) and fat mass (14.3 ± 6.9 kg to 16.8 ± 6.5 kg; p = 0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 ± 4.0 kcal/kg to 21.5 ± 4.1 kcal/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.
  
  
  
  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.
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Chiaw-Ling
authors.initials: CL
authors.lastname: Chng
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Adoree Yi Ying
authors.initials: AY
authors.lastname: Lim
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Hong Chang
authors.initials: HC
authors.lastname: Tan
authors.affiliation: 2 Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School , Singapore .
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Kovalik
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Kwang Wei
authors.initials: KW
authors.lastname: Tham
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Yong Mong
authors.initials: YM
authors.lastname: Bee
authors.affiliation: 1 Department of Endocrinology, Singapore General Hospital , Singapore .
authors.forename: Weiying
authors.initials: W
authors.lastname: Lim
authors.affiliation: 3 Centre for Quantitative Medicine, Duke-NUS Graduate Medical School , Singapore .
authors.forename: Sanchalika
authors.initials: S
authors.lastname: Acharyya
authors.affiliation: 4 Department of Clinical Research, Singapore General Hospital , Singapore .
authors.forename: Oi Fah
authors.initials: OF
authors.lastname: Lai
authors.affiliation: 5 Singapore Institute for Clinical Sciences (SICS) , A*star, Brenner Centre for Molecular Medicine, Singapore .
authors.forename: Mary Foong-Fong
authors.initials: MF
authors.lastname: Chong
authors.affiliation: 2 Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School , Singapore .
authors.forename: Paul Michael
authors.initials: PM
authors.lastname: Yen
mesh_terms: D052242:Adiponectin / Q000819:agonists / Q000097:blood; D000328:Adult; D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D001481:Basal Metabolism / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002231:Carbimazole / Q000009:adverse effects / Q000627:therapeutic use; D002681:China; D002149:Energy Intake / Q000187:drug effects / Q000208:ethnology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000503:physiopathology; D006786:Hospitals, Urban; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology / Q000517:prevention & control*; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D010044:Outpatient Clinics, Hospital; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use; D013961:Thyroid Gland / Q000187:drug effects* / Q000503:physiopathology; D015430:Weight Gain / Q000187:drug effects / Q000208:ethnology; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D013956:Antithyroid Agents; D015415:Biomarkers; D011441:Propylthiouracil; D002231:Carbimazole