title: Comparison of mortality in hyperthyroidism during periods of treatment with thionamides and after radioiodine.
abstract: BACKGROUND
  Hyperthyroidism is common, but opinions regarding optimal therapy with antithyroid drugs or radioiodine (131-I) differ. There are no randomized trials comparing these options in terms of mortality.
  
  
  OBJECTIVE
  The aim of the study was to determine whether mortality associated with hyperthyroidism varies with treatment administered or other factors.
  
  
  METHODS
  We conducted a prospective observational population-based study of 1036 subjects aged ≥ 40 years presenting to a single specialist clinic from 1989-2003 with a first episode of hyperthyroidism who were followed until June 2012.
  
  
  METHODS
  Antithyroid drugs or radioiodine (131-I) were administered.
  
  
  METHODS
  We compared causes of death with age-, sex-, and period-specific mortality in England and Wales and used within-cohort analysis of influence of treatment modality, outcome, disease etiology, severity and control, and comorbidities.
  
  
  RESULTS
  In 12 868 person-years of follow-up, 334 died vs 290.6 expected (standardized mortality ratio [SMR], 1.15 [95% confidence interval (CI),1.03-1.28]; P = .01). Increased all-cause mortality largely reflected increased circulatory deaths (SMR, 1.20 [95% CI, 1.01-1.43]; P = .04). All-cause mortality was increased for the person-years accumulated during thionamide treatment (SMR, 1.30 [95% CI, 1.05-1.61]; P = .02) and after 131-I not associated with hypothyroidism (SMR, 1.24 [95% CI, 1.04-1.46]; P = .01) but not during T₄ replacement for 131-I-induced hypothyroidism (SMR, 0.98 [95% CI, 0.82-1.18]; P = .85). Within-cohort analysis comparing mortality during thionamide treatment showed a similar hazard ratio (HR) for all-cause mortality when 131-I did not result in hypothyroidism (HR, 0.95 [95% CI, 0.70-1.29]), but reduced mortality with 131-I-induced hypothyroidism (HR, 0.70 [95% CI, 0.51-0.96]). Reduced mortality associated with hypothyroidism was seen only in those without significant comorbidities and not in those with other serious diseases. Atrial fibrillation at presentation (P = .02) and an increment of 10 pmol/L in serial free T₄ concentration during follow-up (P = .009) were independently associated with mortality.
  
  
  CONCLUSIONS
  Among hyperthyroid subjects aged 40 years or older, mortality was increased during periods of thionamide treatment and after radioiodine not resulting in hypothyroidism, but not during follow-up after radioiodine-induced hypothyroidism. Independent associations of mortality with atrial fibrillation and incomplete biochemical control during treatment indicate potential causative links with poor outcome.
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom. k.boelaert@bham.ac.uk
authors.forename: Kristien
authors.initials: K
authors.lastname: Boelaert
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Barbara
authors.initials: B
authors.lastname: Torlinska
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Franklyn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D015331:Cohort Studies; D015897:Comorbidity; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D006980:Hyperthyroidism / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D007037:Hypothyroidism / Q000139:chemically induced / Q000188:drug therapy; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013854:Thioamides / Q000009:adverse effects / Q000627:therapeutic use*; D013961:Thyroid Gland / Q000187:drug effects / Q000528:radiation effects; D014852:Wales / Q000453:epidemiology
chemical_list: D013956:Antithyroid Agents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013854:Thioamides