Mortality and radioiodine treatment

TOPIC: Increased risk of cardiovascular & cancer deaths from radioiodine treatment for hyperthyroidism

Title: Increased cardiovascular and cancer mortality after radioiodine treatment of hyperthyroidism.

Authors: Metso S, Jaatinen P, Huhtala H, Auvinen A, Oksala H, & Salmi J.

Reference: Journal of Clinical Endocrinology & Metabolism 92: 2190-2196, 2007

Summary

Background

Although patients treated with radioiodine (RI) for hyperthyroidism are at increased risk for death, it is unclear if this is due to the disease itself or due to the treatment.

Purpose

To compare the mortality of hyperthyroid patients treated with RI with that of an age- and gender-matched controlled population.

Patients and Methods: A total of 2.793 hyperthyroid Finnish patients who received RI treatment between 1965 and 2002 were compared with 2.793 reference subjects, and followed for a median of 9 years.

Methods

Diagnosis, dates, and doses of RI treatment for 2.793 patients were retrospectively reviewed. The study included an age- and sex-matched control group of the same number of subjects using the Population Register Center.

Results

Patients and controls had a median age of 62 years at treatment or study; the median follow-up period was 9.8 & 10 years, for patients and controls, respectively. Overall, there was an increased all-cause mortality in the RI-treated patients versus controls. Mortality was increased due to cerebro-vascular disease (atrial fibrillation) as well as upper gastro-intestinal tumors.

Conclusions

Hyperthyroidism probably accounts for increased cerebrovascular mortality after radioiodine treatment. Results emphasize the need for careful, long-term follow-up of RI-treated hyperthyroid patients.

Commentary

Radioactive iodine ( 131- I, RI) has been used for over six decades to treat hyperthyroidism. It is considered an effective treatment for patients with diffuse toxic goiter (Graves- disease) or those with toxic nodular goiter (toxic adenoma or Plummer-s disease). Moreover, it is the most popular treatment modality and treatment of choice for hyperthyroid patients in the U.S., although not so in other countries such as Japan, Germany, or U.K.

The safety of RI and its long-term side effects have been subject of many reports through the years. It was reassuring that the U.S. Public Health Service Cooperative Thyrotoxicosis Therapy follow-up Study of 1946-1964 (Hoffman DA et al, 1982) reported no increased mortality after RI treatment. In a subsequent report from the same group, another study, including 35.593 patients, showed no increased risk of mortality or cancer after RAI treatment was found (Ron E et al, 1998). More recent data on this subject have HGH been conflicting, some suggesting an increased risk of death or of cancer after RI. For example, one U.K. study showed that the all-cause mortality was increased, whereas cancer mortality was in fact decreased (Franklyn J et al, 1998); the slightly increased mortality was caused by heart failure and arrhythmias. On the other hand, another U.K. group published a population-study and reported no increase in mortality after RAI treatment (Flynn RW et al, 2006).

In present study from Finland, Metso and colleagues report on the frequency of death and cancer after RI treatment for hyperthyroidism. The authors reviewed records of 2.793 hyperthyroid Finnish patients who had received RI treatment between 1965-2002, with a median age of 62 years and a median follow-up period of 9 years. The study included a similar number of controls, age- and gender-matched, followed for the same duration. Main results showed the following:

  • Increased all-cause mortality in treated patients.
  • Increased mortality appeared due to cerebro-vascular disease but not to coronary artery disease.
  • Patients treated with radioiodine had an increased rate of atrial fibrillation (AF).
  • Increased frequency of malignancies, especially upper GI cancer, particularly in elderly men.
  • Analysis showed that cancer risk increased with cumulative radioiodine doses.

The strengths of this report include the presence of a controlled population as well as the thoroughness and length of duration of both RI-treated and controlled groups. Although there was documented increased mortality in patients treated with radioiodine, it was not established that radioiodine was the cause of this observation. In fact, the authors state that -the present study of patients treated with RI for hyperthyroidism reports an increase cerebro-vascular mortality in patients treated with RI compared with age- and sex-matched control groups which is probably explained by hyperthyroidism. Furthermore, cancer mortality increased among the patients-. The authors recommend careful and continued follow-up of hyperthyroid patients treated with radioiodine. In conclusion, RI is still considered safe and effective, and it is likely that endocrinologists and large clinics will continue to use it to treat hyperthyroid patients, either with Graves- disease or with toxic nodular goiter. These patients should be followed for development of post-therapy hypothyroidism as well as for cerebrovascular events due to AF caused by hyperthyroidism. The small risk of cancer in elderly men, reported here, is of doubtful clinical significance. Summary and commentary prepared by Hossein Gharib (related to Chapters 11 & 17 of TDM)