含碘顯影劑的暴露和甲狀腺功能異常之研究

The Association Between Iodinated Contrast media Exposure and Thyroid Dysfunction

王威傑(Edy Kornelius)

指導教授 ： 黃建寧 ； 梁亞文 ； 李采娟

中山醫學大學/醫學院/醫學研究所/博士(2018年)

摘要

研究目的
臨床上常被使用的含碘顯影劑成分有含高劑量的碘，有暴露於含碘顯影劑之後是否會增加甲狀腺功能異常的風險仍未知，尤其是亞洲人。因此，本研究主要探討病患暴露於含碘顯影劑之後是否增加甲狀腺功能異常的風險。

研究方法與設計
我們採取了兩個不同的架構來進行分析;架構一主要針對過去沒有甲狀腺病史的患者經由顯影劑暴露後是否會增加甲狀腺功能異常的風險。以全民健康保險研究資料庫之2005年抽樣歸人檔，串聯該100百萬人2004年至2010年間的承保資料來進行回溯性研究;研究對象為自2005至2006年之間有暴露於含碘顯影劑的患者被選為試驗組，而從來未暴露者皆是對照組。經過七年的觀察，我們使用了SPSS for windows, ver 18，來分析有暴露於顯影劑的患者是否會增加甲狀腺功能異常的風險。

架構二則主要探討具有甲狀腺結節病史的患者經過顯影劑暴露後是否會增加甲狀腺功能異常的風險。研究架構二的流程則先篩選有暴露於顯影劑的病人再來分是否具有甲狀腺結節。有結節者被選為試驗組、沒有結節者則是對照組。我們更進一步分析有甲狀腺結節的患者經由顯影劑暴露後是否會增加甲狀腺功能異常的風險。

研究結果
研究架構一總共觀察到19,642位患者有含碘顯影劑暴露史與78,568位從來沒有顯影劑暴露史的患者。對於顯影劑暴露病患和未暴露者的平均年齡為 53.9歲和 53.6歲，平均追蹤時間為 4.1 和 5.6 年。本研究發現有暴露於含碘顯影劑的患者相較於未暴露者會有比較高的風險罹患甲狀腺功能異常(HR 1.46, 95% CI 1.29-1.66)。另外，次分析顯示有顯影劑暴露的患者發生甲狀腺機能亢進的風險為 HR 1.22(95% CI 1.04-1.44)，而發生甲狀腺功能低下的風險為HR 2.00(95% CI 1.65-2.44)。

對於具有甲狀腺結節病史的架構二來說，發生甲狀腺功能異常的風險更是顯著(HR 5.43, 95% CI 3.01-9.80)，包括甲狀腺機能亢進(HR 5.77, 95% CI 2.64-12.62)以及甲狀腺功能低下症(HR 4.95, 95% CI 2.15-11.40)。

結論
有含碘顯影劑暴露史的患者有較高的風險罹患甲狀腺功能異常，包括甲狀腺機能亢進及甲狀腺功能低下。有甲狀腺結節者則會有更顯著的風險。

關鍵字

顯影劑 ； 甲狀腺機能亢進 ； 及甲狀腺功能低下 ； 甲狀腺結節

並列摘要

Objective:
The risks of thyroid dysfunction after iodinated contrast media (ICM) exposure are largely unknown, especially in Asian populations. Therefore, we used Taiwan’s nationwide population-based study to determine whether ICM exposure would increase the risk of thyroid dysfunction, including hyperthyroidism or hypothyroidism in general population and patient with history of thyroid nodule.

Methods and Material:
We used two different study design to evaluate the risk of thyroid dysfunction. The first design was primarily designated to general population, i.e. patients without prior thyroid disease. This retrospective cohort study included a random selection of 1 million people in 2005 in Taiwan. Patients with ICM exposure between 2005 and 2006 were identified as cases, while patients without any ICM exposure were selected as controls. The primary endpoint was the composite risk of thyroid dysfunction associated with ICM exposure.

For the second study design, patients with ICM exposure were recruited and we selected patient with history of thyroid nodule as cases, while patient without history of thyroid nodule as control. We further evaluate whether patients with history of thyroid nodule have higher risk of thyroid dysfunction after ICM exposure compared with patients without thyroid nodule. Hazard ratio (HR) and Cox proportional hazards model with 95% confidence interval (CI) were used to analyze the data and to determine the risk of thyroid dysfunction. All statistical analyses were performed using the SPSS Statistical Package, version 18 (SPSS Inc).

Results:
For the first study design, a total of 19,642 cases and 78,568 matched controls were recruited in this study. The mean age of ICM exposure and non-exposure were 53.9 and 53.6 years old, and mean follow-up durations were 4.1 and 5.6 years, respectively. After adjustment, patients with ICM exposure had a significantly higher risk of thyroid dysfunction (HR 1.46, 95% CI 1.29-1.66). In the subgroup analysis, the adjusted hazard ratios of hyperthyroidism, and hypothyroidism compared with controls were 1.22 (95% CI 1.04-1.44), and 2.00 (95% CI 1.65-2.44), respectively.

For the second study design, the risk of thyroid dysfunction was more obvious in patients with thyroid nodule after ICM exposure with HR of 5.43, 95% CI 3.01-9.80, including hyperthyroidism (HR 5.77, 95% CI 2.64-12.62) and hypothyroidism (HR 4.95, 95% CI 2.15-11.40).

Conclusions:
ICM exposure was associated with higher risk of thyroid dysfunction, including hyperthyroidism and hypothyroidism. The risk was more obvious in the patients with history of thyroid nodule.

並列關鍵字

Iodinated contrast media ； hyperthyroidism ； hypothyroidism ； thyroid nodule

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