Radioactive Iodine-131 Therapy Reduced the Risk of MACEs and All-Cause Mortality in Elderly with Hyperthyroidism Combined with Type 2 Diabetes

Abstract

Aim: This study aimed to assess the efficacy of antithyroid drugs (ATDs) and radioactive iodine-131 (RAI) therapies in reducing the risk of major adverse cardiovascular events (MACEs) and all-cause mortality in patients with hyperthyroidism complicated with type 2 diabetes mellitus (T2DM).

Methods: Between January 2013 and December 2021, 540 subjects were included in the analysis. All participants were followed up for 9 years, with a median of 54 months (2451 person-years). The subjects were categorized into two groups: the ATDs group (n = 414) and the RAI group (n = 126). According to the free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped as follows: low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70-12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42). The efficacy of ATDs and RAI therapies in reducing the risk of MACEs and all-cause mortality was assessed.

Results: Of the 540 participants, 163 experienced MACEs (30.19%), 25 (15.34%) of whom died. Multivariate Cox regression analyses revealed that RAI was associated with a 38.5% lower risk of MACEs (P = 0.016) and a 77.1% lower risk of all-cause mortality (P = 0.046). Stratified analyses indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (P = 0.001, P for interaction = 0.031) and patients with a duration of diabetes mellitus ≥ 6 years (P = 0.013, P for interaction = 0.002). Kaplan‒Meier analysis revealed a lower cumulative incidence of MACEs and all-cause mortality in the RAI group (log-rank, all P < 0.05). Moreover, the ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001).

Conclusion: Our findings suggested that RAI therapy effectively reduced the risk of MACEs and all-cause mortality in elderly patients with hyperthyroidism combined with T2DM.

Keywords: all-cause mortality; hyperthyroidism; major adverse cardiovascular events; radioactive iodine-131; type 2 diabetes mellitus.

Figure 1

Flow chart for selecting participants. Data on all 832 patients with hyperthyroidism combined with diabetes between January 2013 and December 2021 were retrieved from the Heping Hospital Affiliated with Changzhi Medical College and the People’s Hospital of Guangxi Zhuang Autonomous Region. Finally, a total of 540 participants with hyperthyroidism combined with T2DM were analyzed over a median follow-up of 54 months (2451 person-years). The subjects were categorized into two groups: ATDs (n = 414) and RAI (n = 126). According to free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped into low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70–12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42) groups.

Figure 2

Forest plots for stratification analyses in subgroups. Stratified analysis indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (HR = 0.445, 95% CI = 0.272–0.730, P = 0.001, P for interaction = 0.031), patients with a duration of diabetes mellitus ≥ 6 years (HR = 0.493, 95% CI = 0.283–0.861, P = 0.013, P for interaction = 0.002), and patients with hyperthyroidism status, including FT3 levels (P for interaction = 0.006) and duration of hyperthyroidism (P for interaction = 0.005).

Figure 3

Survival analysis for the cumulative incidence of MACEs by ATDs and RAI. Kaplan-Meier survival analysis revealed that compared with the ATDs group, the RAI group had a lower cumulative incidence of MACEs (log-rank, P = 0.015).

Figure 4

Survival analysis for the cumulative incidence of all-cause mortality by ATDs and RAI. Kaplan-Meier survival analysis indicated that compared with ATDs, the RAI had a lower cumulative incidence of all-cause mortality (log-rank, P = 0.028).

Figure 5

Survival analysis for the cumulative incidence of MACE by FT3 level. In patients receiving RAI, the Kaplan‒Meier survival curve showed that the greater the FT3 concentration was, the lower the cumulative incidence of MACE (log-rank, P = 0.021).

Figure 6

ROC analysis evaluating the predictive value of FT3 for MACEs in the RAI group. The ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001) (the red dot position), with an area under the curve (AUC) of 0.7, a sensitivity of 71.0%, and a specificity of 65.3%, respectively.