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Failure of radioactive iodine in the treatment of hyperthyroidism.

ABSTRACT: Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism.We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p < 0.05) variables from the univariate analysis.Of the 325 patients analyzed, 74 patients (22.8 %) failed initial RAI treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses <12.5 mCi were associated with failure while initial T3 and free T4 levels of at least 4.5 pg/mL and 2.3 ng/dL, respectively, were associated with failure. In the final multivariate analysis, higher T4 (hazard ratio [HR] 1.13; 95 % confidence interval [CI] 1.02-1.26; p = 0.02) and methimazole treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure.Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

SUBMITTER: Schneider DF

PROVIDER: S-EPMC4330099 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Failure of radioactive iodine in the treatment of hyperthyroidism.

Schneider David F DF Sonderman Philip E PE Jones Michaela F MF Ojomo Kristin A KA Chen Herbert H Jaume Juan C JC Elson Diane F DF Perlman Scott B SB Sippel Rebecca S RS

Annals of surgical oncology 20140708 13

<h4>Background</h4>Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism.<h4>Methods</h4>We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidecto ...[more]

PMID: 25001092

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Project description:Importance:Radioactive iodine (RAI) has been used extensively to treat hyperthyroidism since the 1940s. Although widely considered a safe and effective therapy, RAI has been associated with elevated risks of total and site-specific cancer death among patients with hypothyroidism. Objective:To determine whether greater organ- or tissue-absorbed doses from RAI treatment are associated with overall and site-specific cancer mortality in patients with hyperthyroidism. Design, Setting, and Participants:This cohort study is a 24-year extension of the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, which has followed up US and UK patients diagnosed and treated for hyperthyroidism for nearly 7 decades, beginning in 1946. Patients were traced using records from the National Death Index, Social Security Administration, and other resources. After exclusions, 18?805 patients who were treated with RAI and had no history of cancer at the time of the first treatment were eligible for the current analysis. Excess relative risks (ERRs) per 100-mGy dose to the organ or tissue were calculated using multivariable-adjusted linear dose-response models and were converted to relative risks (RR?=?1 + ERR). The current analyses were conducted from April 28, 2017, to January 30, 2019. Exposures:Mean total administered activity of sodium iodide I 131 was 375 MBq for patients with Graves disease and 653 MBq for patients with toxic nodular goiter. Mean organ or tissue dose estimates ranged from 20 to 99 mGy (colon or rectum, ovary, uterus, prostate, bladder, and brain/central nervous system), to 100 to 400 mGy (pancreas, kidney, liver, stomach, female breast, lung, oral mucosa, and marrow), to 1.6 Gy (esophagus), and to 130 Gy (thyroid gland). Main Outcomes and Measures:Site-specific and all solid-cancer mortality. Results:A total of 18?805 patients were included in the study cohort, and the mean (SD) entry age was 49 (14) years. Most patients were women (14?671 [78.0%]), and most had a Graves disease diagnosis (17?615 [93.7%]). Statistically significant positive associations were observed for all solid cancer mortality (n?=?1984; RR at 100-mGy dose to the stomach?=?1.06; 95% CI, 1.02-1.10; P?=?.002), including female breast cancer (n?=?291; RR at 100-mGy dose to the breast?=?1.12; 95% CI, 1.003-1.32; P?=?.04) and all other solid cancers combined (n?=?1693; RR at 100-mGy dose to the stomach?=?1.05; 95% CI, 1.01-1.10; P?=?.01). The 100-mGy dose to the stomach and breast corresponded to a mean (SD) administered activity of 243 (35) MBq and 266 (58) MBq in patients with Graves disease. For every 1000 patients with hyperthyroidism receiving typical doses to the stomach (150 to 250 mGy), an estimated lifetime excess of 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer deaths could occur. Conclusions and Relevance:In RAI-treated patients with hyperthyroidism, greater organ-absorbed doses appeared to be modestly positively associated with risk of death from solid cancer, including breast cancer. Additional studies are needed of the risks and advantages of all major treatment options available to patients with hyperthyroidism.

Project description:ImportanceWhether radioactive iodine (RAI) therapy for hyperthyroidism can increase cancer risk remains a controversial issue in medicine and public health.ObjectivesTo examine site-specific cancer incidence and mortality and to evaluate the radiation dose-response association after RAI treatment for hyperthyroidism.Data sourcesThe Medline and Cochrane Library electronic databases, using the Medical Subject Headings terms and text keywords, and Embase, using Emtree, were screened up to October 2020.Study selectionStudy inclusion criteria were as follows: (1) inclusion of patients treated for hyperthyroidism with RAI and followed up until cancer diagnosis or death, (2) inclusion of at least 1 comparison group composed of individuals unexposed to RAI treatment (eg, the general population or patients treated for hyperthyroidism with thyroidectomy or antithyroid drugs) or those exposed to different administered doses of RAI, and (3) inclusion of effect size measures (ie, standardized incidence ratio [SIR], standardized mortality ratio [SMR], hazard ratio [HR], or risk ratio [RR]).Data extraction and synthesisTwo independent investigators extracted data according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Overall quality assessment followed the recommendations of United Nations Scientific Committee on the Effects of Atomic Radiation. The SIR and SMRs and the RRs and HRs were pooled using random-effects meta-analysis.Main outcomes and measuresCancer incidence and mortality for exposure vs nonexposure to RAI therapy and by level of RAI administered activity.ResultsBased on data from 12 studies including 479 452 participants, the overall pooled cancer incidence ratio was 1.02 (95% CI, 0.95-1.09) and the pooled cancer mortality ratio was 0.98 (95% CI, 0.92-1.04) for exposure vs nonexposure to RAI therapy. No statistically significant elevations in risk were observed for specific cancers except thyroid cancer incidence (SIR, 1.86; 95% CI, 1.19-2.92) and mortality (SMR, 2.22; 95% CI, 1.37-3.59). However, inability to control for confounding by indication and other sources of bias were important limitations of studies comparing RAI exposure with nonexposure. In dose-response analysis, RAI was significantly associated with breast and solid cancer mortality (breast cancer mortality, per 370 MBq: 1.35; P = .03; solid cancer mortality, per 370 MBq: 1.14; P = .01), based on 2 studies.Conclusions and relevanceIn this meta-analysis, the overall pooled cancer risk after exposure to RAI therapy vs nonexposure was not significant, whereas a linear dose-response association between RAI therapy and solid cancer mortality was observed. These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose.

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Failure of radioactive iodine in the treatment of hyperthyroidism.

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Failure of radioactive iodine in the treatment of hyperthyroidism.

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