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Hye Jeong Kim, Ji Cheol Bae, Hyeong Kyu Park, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Jee Jae Hwan, Jae Hyeon Kim, Yong-Ki Min, Sun Wook Kim, and Jae Hoon Chung

Background

Several cross-sectional studies have reported that thyroid hormone levels are associated with cardiovascular risk markers and metabolic syndrome (MetS) even in euthyroid subjects. However, the prognostic role of serum thyroid hormone levels in the risk of incident MetS has not been elucidated.

Aim

We aimed to investigate the associations of baseline serum thyroid hormone levels with the development of MetS in healthy subjects.

Methods

This 6-year, cross-sectional, longitudinal and follow-up study was conducted in 12 037 euthyroid middle-aged subjects without MetS subjected to comprehensive health examinations. Subjects were grouped according to total triiodothyronine (T3) quartiles. The hazard ratio (HR) for the development of MetS according to T3 quartiles was estimated using Cox proportional hazards model.

Results

During the 6-year period, 3544 incident cases of MetS (29%) were identified. The proportion of subjects with incident MetS increased across the T3 quartiles (P for trend <0.001). The HR and 95% confidence interval (CI) for the development of MetS were significantly higher in the highest T3 quartile compared with the lowest T3 quartile even after adjusting for confounding variables including gender, age and smoking (HR: 1.238, 95% CI: 1.128–1.358, P < 0.001).

Conclusion

In euthyroid middle-aged subjects, serum T3 levels are associated with increased risk for future development of MetS.

Free access

Young Shin Song, Jung Ah Lim, Hye Sook Min, Min Joo Kim, Hoon Sung Choi, Sun Wook Cho, Jae Hoon Moon, Ka Hee Yi, Do Joon Park, Bo Youn Cho, and Young Joo Park

Objective

Changes in the clinicopathological characteristics and genetic alterations of follicular thyroid cancer (FTC) over time have not been reported. Moreover, the prognostic effects of RAS and TERT promoter mutations in FTC have not been clearly elucidated. We investigated changes in the clinicopathological characteristics of patients with FTC over four decades, as well as the clinical significance of genetic mutations of FTC.

Design and methods

This retrospective study included 690 patients with FTC who underwent thyroidectomy between 1973 and 2015 at the Seoul National University Hospital. In 134 samples, genetic tests for N/H/KRAS and TERT promoter mutations and PAX8/PPARγ rearrangement were performed.

Results

The age at diagnosis has increased (P < 0.001) in recent decades and extrathyroidal extension of the tumor has become less common (P = 0.033). Other clinicopathological characteristics and prognosis of FTC have not significantly changed. The prevalence of RAS mutations decreased (P = 0.042) over time, whereas that of TERT promoter mutations remained stable. RAS mutations were associated with distant metastasis and persistent disease, and TERT promoter mutations were associated with distant metastasis, advanced TNM stage, recurrence and disease-specific mortality. FTC patients with coexistent RAS and TERT promoter mutations showed a higher recurrence risk than those with only one mutation.

Conclusions

The age at diagnosis of FTC and the frequency of extrathyroidal extension have changed over four decades. Moreover, the prevalence of RAS mutations decreased. RAS and TERT promoter mutations may be associated with poor clinical outcomes in FTC, especially when the two mutations coexist.

Free access

Hoonsung Choi, Jung Ah Lim, Hwa Young Ahn, Sun Wook Cho, Kyu Eun Lee, Kyung Won Kim, Ka Hee Yi, Myung-Whun Sung, Yeo-Kyu Youn, June-Key Chung, Young Joo Park, Do Joon Park, and Bo Youn Cho

Objective

With the recent increasing rates of screening for thyroid cancer, the cancers now tend to be smaller and less aggressive than those that are diagnosed when presented with symptoms, suggesting changes in the clinical validity of conventional prognostic factors for outcomes. We performed the retrospective study to identify the secular trends in the prognostic factors of thyroid cancer.

Methods

We used medical records of 3147 patients diagnosed with papillary thyroid cancer (PTC) at the Seoul National University Hospital Thyroid Cancer Clinic between 1962 and 2009.

Results

During the median 5.1-year follow-up, the overall recurrence rate was 13.3%, and male sex, tumor size, lymph node (LN) involvement, and extrathyroidal extension (ETE) were the significant prognostic factors for recurrence. Thyroid cancer-specific mortality was 1.4%, and the associated prognostic factors were older age, male sex, and LN involvement. For tumor recurrence, the hazard ratio (HR) for male sex decreased from 2.809 (95% CI, 1.497–5.269) in the pre-1989 period to 1.142 (95% CI, 0.736–1.772) in the post-1999 period. The pathologic characteristics, such as tumor size, LN involvement, and ETE, showed similar or increasing HRs over the time periods. For cancer-specific mortality, the HR for male sex decreased from 6.460 (95% CI, 1.714–24.348) in the pre-1990 period to 0.781 (95% CI, 0.083–7.379) in the post-1999 period.

Conclusion

The risk for poor outcomes in PTC associated with male sex decreased over time; in contrast, the risk associated with pathologic characteristics remained the same or increased over time. These trends might be associated with recent changes in the characteristics of patients with thyroid cancer.

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Jun Park, Hyun Ae Jung, Joon Ho Shim, Woong-Yang Park, Tae Hyuk Kim, Se-Hoon Lee, Sun Wook Kim, Myung-Ju Ahn, Keunchil Park, and Jae Hoon Chung

Background

Anaplastic thyroid cancer (ATC) has dismal prognosis and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real-world clinic and to suggest the most effective treatment modality according to the combination of treatments.

Methods

This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center.

Results

A total of 120 patients received anti-cancer treatment for ATC. Seventy-seven (64.2%) patients underwent surgery, 64 (53.3%) received radiotherapy, 29 (24.2%) received cytotoxic chemotherapy, and 19 (15.8%) received TKI therapy. In the TKI therapy group, eight achieved partial response (three with lenvatinib and five with dabrafenib plus trametinib), and two patients with lenvatinib showed stable disease. Median progression-free survival (PFS) of the TKI therapy group was 2.7 months (range: 0.1–12.7) and their median overall survival (OS) was 12.4 months (range: 1.7–47.7). Patients who received surgery or radiotherapy for local control showed superior OS than those who did not. In a multivariate analysis, surgery, TKI therapy, younger age, and no distant metastasis were associated with favorable OS. The combination of surgery, radiotherapy, and TKI therapy (median OS: 34.3 months, 6-month survival rates: 77.8%) was the most effective. Compared to the era without TKI therapy, distant metastasis has recently become the major cause of death in ATC over airway problems.

Conclusions

Multimodality treatment including TKI therapy demonstrated prolonged survival with dabrafenib plus trametinib as the most effective therapeutic option demonstrated for BRAF mutant ATC patients.