title: Cohort study on radioactive iodine-induced hypothyroidism: implications for Graves' ophthalmopathy and optimal timing for thyroid hormone assessment.
abstract: BACKGROUND
  Graves' ophthalmopathy (GO) develops or worsens in up to one-third of patients treated with radioactive iodine (RAI) for Graves' hyperthyroidism. We sought to identify the prevalence of development or worsening of GO in patients treated with RAI for Graves' hyperthyroidism and to identify the risk factors associated with that outcome.
  
  
  METHODS
  We identified a retrospective cohort of consecutive patients treated with RAI at Mayo Clinic (Rochester, MN) between 2005 and 2006. We assessed their medical records for evidence of hypothyroidism and development or worsening of GO in the year after therapy. Hypothyroidism was defined as thyrotropin >3.0 mIU/L or free thyroxine <0.8 ng/dL.
  
  
  RESULTS
  We identified 291 consecutive patients who received RAI therapy during the study period, with 195 out of 291 having complete follow-up data for a one-year period. GO was present in 46 out of 195 patients (23.6%) at baseline. After RAI treatment, GO developed or worsened in 25 out of 195 patients (12.8%) and it was associated with hypothyroidism at first follow-up (p=0.011) with an odds ratio (OR) of 3.3 [95% confidence interval (CI) 1.3-8.7]. More smokers than nonsmokers developed new or worse GO (17.7% vs. 11.8%), but that difference did not reach statistical significance (p=0.35). Preexisting GO (24% of patients) was associated with a higher risk for negative GO outcome compared with patients who had no GO at baseline (11%; p=0.021). Both development of hypothyroidism by the first visit after RAI therapy (OR 3.6) and preexistent GO (OR 2.8) remained significant in a multivariate analysis. Development of hypothyroidism was more likely in patients with longer duration to first follow-up (p<0.001). By 6-8 weeks after RAI treatment, the prevalence of hypothyroidism was ∼40%, while that of hyperthyroidism was only 20%.
  
  
  CONCLUSIONS
  The presence of hypothyroidism at the first assessment of thyroid function after RAI administration is a strong predictor for adverse GO outcome. This risk is highest in patients with preexisting GO. We suggest that in order to prevent clinical hypothyroidism and the associated risk for GO, the optimal time for first measurement of fT4 is before 6 weeks after RAI therapy.
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic , Rochester, MN 55905, USA. stan.marius@mayo.edu
authors.forename: Marius N
authors.initials: MN
authors.lastname: Stan
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Durski
authors.forename: Juan P
authors.initials: JP
authors.lastname: Brito
authors.forename: Sumit
authors.initials: S
authors.lastname: Bhagra
authors.forename: Prabin
authors.initials: P
authors.lastname: Thapa
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Bahn
mesh_terms: D000328:Adult; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D049970:Graves Ophthalmopathy / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control; D020249:Hormone Replacement Therapy; D006801:Humans; D006980:Hyperthyroidism / Q000209:etiology / Q000532:radiotherapy*; D007037:Hypothyroidism / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D007457:Iodine Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D015995:Prevalence; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013961:Thyroid Gland / Q000378:metabolism / Q000528:radiation effects*; D013963:Thyroid Hormones / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013963:Thyroid Hormones