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Izkhakov et al. J Cancer Metastasis Treat 2021;7:24 https://dx.doi.org/10.20517/2394-4722.2021.24 Page 5 of 8

Association between I-131 therapy and cardiovascular/cerebrovascular morbidity
Lin et al. retrospectively evaluated the association between I-131 therapy for TC and stroke risk in 10,104
[34]
Taiwanese DTC survivors (mean age 49.4 years). The participants were classified into two groups that did
and did not receive I-131 therapy. The mean stroke latency after I-131 therapy was 6.6 years compared to
6.59 years without I-131 therapy. The risk of ischemic or hemorrhagic stroke was not greater in the group
who received I-131 therapy after a 10-year follow-up.

Kim et al. recently assessed the adverse effects of I-131 therapy on cardiovascular and cerebrovascular
[35]
diseases among 4845 TC patients aged 40-79 years. Overall, 2533 DTC patients (52.3%) received I-131
therapy and the median I-131 cumulative dosage was 103 mCi. After a median 5.5-year follow-up, no
significant difference was found in the risk of ischemic or hemorrhagic stroke, ischemic heart disease, or
heart failure among DTC survivors who received I-131 therapy and those who did not. In addition, the I-
131 accumulative dosage was not associated with cardiovascular morbidity among the TC survivors.

Metabolic, resting energy expenditure, and body composition changes
The major role of thyroid hormones in the regulation of rest energy expenditure (REE), body composition,
and body weight has been well documented . Several studies have found a positive association between
[36]
TSH and FT3 and metabolic parameters, obesity, and body mass index (BMI) in euthyroid adults [37,38] .

Izkhakov et al. assessed body composition, body weight, metabolic parameters, respiratory quotient (RQ),
[39]
and REE changes among 15 female DTC patients starting from the endogenous euthyroid state prior to total
thyroidectomy and continuing throughout the following year of an exogenous subclinical hyperthyroid
state. The major findings of that study were that the standard protocol of thyroidectomy and I-131 therapy
followed by TSH suppression with LT4 resulted in elevation of REE, while there were no meaningful
changes in BMI and lean body mass (LBM). Additionally, the following significant changes were found:
increases in heart rate, systolic and diastolic blood pressures, and FT4 levels, while RQs, TSH levels, and
TT3/FT4 ratios decreased in comparison to the endogenous euthyroid state at the beginning of the follow-
up. There was a subsequent negative relationship between the TT3/FT4 ratio and BMI, fasting blood
glucose, systolic blood pressure, android fat distribution, REE, and REE/LBM, while a positive relationship
between TT3/FT4 ratio and RQ was revealed.

An earlier investigation by Wolf et al. included 29 female and 12 male DTC survivors after thyroidectomy
[40]
and TSH suppressive LT4 therapy, and there were non-significant changes in REE and in body composition
in the DTC group compared to the matched control group.

CONCLUSION
Despite the excellent overall prognosis in TC, afflicted patients are at higher risk for unfavorable metabolic
changes, cardiovascular and cerebrovascular morbidity, and long-term cardiovascular and all-cause
mortality. Furthermore, this appears to be at least partially related to the unique state of post-thyroidectomy
and intentionally induced hyperthyroidism, with attempted suppression of circulating TSH. Collectively,
the data reviewed herein suggest that benefits in terms of TC treatment outcome should be weighed against
significant treatment-related cardiovascular risk. This highlights the need for personally tailored decisions
regarding both surgical and medical therapeutic strategies in TC.

The first question that arises regarding the therapeutic management of patients with TC concerns the extent
of thyroid removal, hemithyroidectomy, or total thyroidectomy. The choice of operation can radically affect
the patient’s future comorbidities. According to recently published American guidelines, patients at low risk