title: Thyroxine in acute myocardial infarction (ThyrAMI) - levothyroxine in subclinical hypothyroidism post-acute myocardial infarction: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Cardiac disease is the most common cause of morbidity and mortality in the United Kingdom. Even minor changes in thyroid hormone concentration may impact adversely on the cardiovascular system. Subclinical hypothyroidism (SCH) after admission for an acute cardiac problem has been associated with an increase in cardiac mortality and overall death. We have designed protocols for a prospective observational study to assess the association of thyroid function at the time of acute myocardial infarction (AMI) with cardiovascular outcomes, and a double-blinded randomised placebo-controlled trial of levothyroxine to evaluate its effect on LV function and vascular health.
  
  
  METHODS
  ThyrAMI 1: This will be a prospective longitudinal observational study of patients with AMI that will be followed for 24 months to study the association between thyroid status at the time of AMI (within 24 hours of diagnosis) with vascular outcomes. ThyrAMI 2: This will be a prospective double-blinded randomised placebo-controlled trial of levothyroxine of 12 months duration in patients with AMI and SCH.
  
  
  METHODS
  Patients will be recruited from five hospitals in the North East of England.
  
  
  METHODS
  One hundred patients with thyroid function tests within the subclinical hypothyroid range upon admission with an AMI and no previous history of thyroid disease.
  
  
  METHODS
  Levothyroxine will be administered at a starting dose of 25 mcg once daily, which will be increased at intervals if needed to maintain a TSH level between 0.4 to 2.5 mU/L, versus a placebo.
  
  
  METHODS
  Participants will be randomized with a computerised randomisation algorithm, stratified by type of MI (NSTEMI versus STEMI), in a 1:1 ratio to levothyroxine therapy or placebo (as container or bottle numbers), starting within 21 (+/- 7) days of AMI.
  
  
  METHODS
  Assignment to either the LT4 or placebo arm will be double-blinded.
  
  
  RESULTS
  The outcome will be the effect of levothyroxine on ventricular function, endothelial function and blood coagulability and rheology.
  
  
  CONCLUSIONS
  There is evidence to suggest that treatment of SCH can improve cardiovascular parameters. Therefore, ThyrAMI 1 and ThyrAMI 2 will be the first trials investigating SCH in AMI to give a better insight into whether thyroid hormone levels are a key target for improving cardiovascular outcomes.
  
  
  BACKGROUND
  ISRCTN number: ISRCTN52505169 . Date of registration: 09/01/2015.
authors: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. avais.jabbar@ncl.ac.uk.
authors: Avais
authors: A
authors: Jabbar
authors: Department of Endocrinology, Gateshead Health NHS Foundation trust, Sheriff Hill, Gateshead, NE9 6SX, UK. lorna.ingoe@ghnt.nhs.uk.
authors: Lorna
authors: L
authors: Ingoe
authors: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. simon.pearce@newcastle.ac.uk.|Endocrine Unit, Newcastle upon Tyne Hospitals NHS foundation trust, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK. simon.pearce@newcastle.ac.uk.
authors: Simon
authors: S
authors: Pearce
authors: Department of Cardiology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Road, NE7 7DN, Newcastle upon Tyne, UK. azfar.zaman@nuth.nhs.uk.|Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. azfar.zaman@nuth.nhs.uk.
authors: Azfar
authors: A
authors: Zaman
authors: Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. salman.razvi@ncl.ac.uk.|Department of Endocrinology, Gateshead Health NHS Foundation trust, Sheriff Hill, Gateshead, NE9 6SX, UK. salman.razvi@ncl.ac.uk.|Newcastle University, Queen Elizabeth Hospital, Sheriff Hill, Gateshead, NE9 6SX, UK. salman.razvi@ncl.ac.uk.
authors: Salman
authors: S
authors: Razvi
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004739:England; D007037:Hypothyroidism / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D008137:Longitudinal Studies; D009203:Myocardial Infarction / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D011446:Prospective Studies; D012107:Research Design; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D016032:Randomized Controlled Trials as Topic
chemical_list: D015415:Biomarkers; D013972:Thyrotropin; D013974:Thyroxine