title: Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function.
abstract: BACKGROUND
  Hypothyroidism is a common endocrine disorder frequently accompanied by alterations in lipid metabolism, such as hypercholesterolemia and high circulating triglycerides, both risk factors for nonischemic cardiomyopathy. Rodent studies suggest that the hypothyroid state promotes cardiac lipid retention by increasing lipid uptake into cardiomyocytes while reducing fatty acid oxidation. Furthermore, increased cardiac lipid load has been linked to cardiac dysfunction.
  
  
  OBJECTIVE
  Dyslipidemia and hypothyroidism frequently coexist; thus, we hypothesized that overt hypothyroidism causes cardiac lipid deposition and ultimately cardiac dysfunction.
  
  
  METHODS
  An interventional prospective study with balanced within-subject comparison. PARTICIPANTS/SETTING/INTERVENTION: Ten patients recruited at an academic center, who underwent a thyroidectomy due to differentiated thyroid carcinoma, were examined 4 weeks postoperatively in the overtly hypothyroid state, right before radioiodine therapy, and 6-8 weeks after initiation of levothyroxine replacement.
  
  
  METHODS
  We measured cardiac lipid content and function in vivo before and after levothyroxine treatment using electrocardiogram-gated (1)H-magnetic resonance spectroscopy and imaging.
  
  
  RESULTS
  Levothyroxine therapy reduced cardiac lipid content in nine of the 10 patients (0.35 ± 0.09 vs 0.22 ± 0.06 % water signal; P = .008; n = 10) and improved cardiac index (2 ± 0.2 vs 2.4 ± 0.1 L/min/m(2); P = .047) when comparing the hypothyroid with the euthyroid state, independent of changes in liver fat content (7.5 ± 3.2 vs 7.1 ± 2.6% magnetic resonance spectroscopy signal; P = .60) or body weight.
  
  
  CONCLUSIONS
  Here we show that levothyroxine treatment reduces lipid accumulation in the heart and increases cardiac output in overtly hypothyroid patients. These results could in part explain the increased risk of death and heart failure in hypothyroid patients.
authors.affiliation: Department of Medicine III, Division of Endocrinology and Metabolism (T.S., P.W., Y.W., A.G., A.L., S.B.-P., M.Krš., M.Kre.); Department of Nuclear Medicine (H.D., M.H.); Department of Medical and Chemical Laboratory Diagnostics (E.E.); Department of Biomedical Imaging and Image Guided Therapy, High Field Magnetic Resonance Centre of Excellence (S.T., M.Krš.); and Department of Internal Medicine II, Division of Cardiology (A.N.), Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scherer
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Winhofer
authors.forename: Heying
authors.initials: H
authors.lastname: Duan
authors.forename: Elisa
authors.initials: E
authors.lastname: Einwallner
authors.forename: Alois
authors.initials: A
authors.lastname: Gessl
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Siegfried
authors.initials: S
authors.lastname: Trattnig
authors.forename: Martha
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Niessner
authors.forename: Sabina
authors.initials: S
authors.lastname: Baumgartner-Parzer
authors.forename: Martin
authors.initials: M
authors.lastname: Krššák
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000378:metabolism / Q000601:surgery; D000328:Adult; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000601:surgery; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D011446:Prospective Studies; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000601:surgery; D013974:Thyroxine / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D008055:Lipids; D013974:Thyroxine