title: Excess Mortality in Treated and Untreated Hyperthyroidism Is Related to Cumulative Periods of Low Serum TSH.
abstract: Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of antithyroid treatment on mortality, especially in subclinical hyperthyroidism, remains unclarified. We investigated the association between hyperthyroidism and mortality in both treated and untreated hyperthyroid individuals.
  
  
  
  Register-based cohort study of 235,547 individuals who had at least one serum thyroid-stimulating hormone (TSH) measurement in the period 1995 to 2011 (7.3 years median follow-up). Hyperthyroidism was defined as at least two measurements of low serum TSH. Mortality rates for treated and untreated hyperthyroid subjects compared with euthyroid controls were calculated using multivariate Cox regression analyses, controlling for age, sex, and comorbidities. Cumulative periods of decreased serum TSH were analyzed as a time-dependent covariate.
  
  
  
  Hazard ratio (HR) for mortality was increased in untreated [1.23; 95% confidence interval (CI), 1.12 to 1.37; P < 0.001], but not in treated, hyperthyroid patients. When including cumulative periods of TSH in the Cox regression analyses, HR for mortality per every 6 months of decreased TSH was 1.11 (95% CI, 1.09 to 1.13; P < 0.0001) in untreated hyperthyroid patients (n = 1137) and 1.13 (95% CI, 1.11 to 1.15; P < 0.0001) in treated patients (n = 1656). This corresponds to a 184% and 239% increase in mortality after 5 years of decreased TSH in untreated and treated hyperthyroidism, respectively.
  
  
  
  Mortality is increased in hyperthyroidism. Cumulative periods of decreased TSH increased mortality in both treated and untreated hyperthyroidism, implying that excess mortality may not be driven by lack of therapy, but rather inability to keep patients euthyroid. Meticulous follow-up during treatment to maintain biochemical euthyroidism may be warranted.
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense, Denmark.|Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Lillevang-Johansen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.|Odense Patient Data Explorative Network OPEN, University of Southern Denmark, 5000 Odense, Denmark.|Department of Medicine, Holbæk Hospital, 4300 Holbæk, Denmark.
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg Hospital, 2400 Copenhagen, Denmark.
authors.forename: Henrik Løvendahl
authors.initials: HL
authors.lastname: Jørgensen
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense, Denmark.
authors.forename: Thomas Heiberg
authors.initials: TH
authors.lastname: Brix
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense, Denmark.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D013956:Antithyroid Agents / Q000627:therapeutic use; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012042:Registries; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood* / Q000172:deficiency; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine