Context Hyperthyroidism has been reported to cause excess all-cause and circulatory
mortality. Whether this can be reversed is unknown, as is the influence of
mild persisting thyroid dysfunction and treatment-induced hypothyroidism.
Objectives To determine whether radioiodine treatment is associated with increased
mortality and to determine the influences of mild thyroid dysfunction and
the development of overt hypothyroidism treated with thyroxine (T4).
Design, Setting, and Participants A population-based study of 2668 individuals aged 40 years or older
treated for overt hyperthyroidism with radioiodine in the West Midlands region
of England from 1984-2002.
Main Outcome Measures Cause of death compared with age- and period-specific mortality in England
and Wales and assessment of the influence of T4 therapy for radioiodine-induced
hypothyroidism and subclinical thyroid dysfunction on mortality.
Results In 15 968 person-years of follow-up, 554 died vs 487 expected deaths
(standardized mortality ratio [SMR], 1.14; 95% confidence interval [CI], 1.04-1.24, P=.002). Increased risks of all-cause and circulatory deaths
vs age- and period-specific mortality were observed in follow-up in those
not requiring, or prior to, T4 therapy. These increased risks were
not observed during follow-up on T4 therapy (circulatory disease
SMR prior to T4, 1.33; 95% CI, 1.14-1.53 vs SMR, 0.91; 95% CI,
0.70-1.17 during T4). Patients receiving T4 had decreased
risk of mortality vs risk in the period not requiring, or prior to, T4 therapy (all-cause mortality hazard ratio [HR], 0.65; 95% CI, 0.54-0.79;
circulatory mortality HR, 0.65; 95% CI, 0.48-0.87). Increased all-cause mortality
vs the background population was observed in the period prior to T4 therapy
in follow-up associated with low, normal, and high serum thyrotropin. The
SMR for ischemic heart disease increased slightly when analyzed by serum thyrotropin,
high serum thyrotropin being the highest SMR (low thyrotropin SMR, 1.06; 95%
CI, 0.75-1.45; normal thyrotropin SMR, 1.17; 95% CI, 0.76-1.71; high thyrotropin
SMR, 1.48; 95% CI, 0.86-2.37). Comparison within the cohort showed that mild
hypothyroidism prior to T4 therapy was associated with increased
risk of mortality from ischemic heart disease vs biochemical euthyroidism
(HR, 2.08; 95% CI, 1.04-4.19).
Conclusions Patients treated with radioiodine for hyperthyroidism had increased
mortality vs age- and period-specific mortality in England and Wales, a finding
no longer evident during T4 therapy. This supports treating hyperthyroidism
with doses of radioiodine sufficient to induce overt hypothyroidism. The association
within the cohort of mortality from ischemic heart disease with subclinical
hypothyroidism suggests T4 replacement should be considered should
this biochemical abnormality develop after radioiodine therapy.