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Ji Min Han, Tae Yong Kim, Min Ji Jeon, Ji Hye Yim, Won Gu Kim, Dong Eun Song, Suck Joon Hong, Sung Jin Bae, Hong-Kyu Kim, Myung-Hee Shin, Young Kee Shong and Won Bae Kim

Objective

Obesity is a well-known risk factor for many cancers, including those of the esophagus, colon, kidney, breast, and skin. However, there are few reports on the relationship between obesity and thyroid cancer. We conducted this study to determine whether obesity is a risk factor for thyroid cancer by systematically screening a selected population by ultrasonography.

Design and methods

We obtained data from 15 068 subjects that underwent a routine health checkup from 2007 to 2008 at the Health Screening and Promotion Center of Asan Medical Center. Thyroid ultrasonography was included in the checkup, and suspicious nodules were examined by ultrasonography-guided aspiration. Those with a history of thyroid disease or family history of thyroid cancer were excluded from this study.

Results

In total, 15 068 subjects, 8491 men and 6577 women, were screened by thyroid ultrasonography. Fine-needle aspiration cytology was performed in 1427 of these patients based on the predefined criteria and thyroid cancer was diagnosed in 267 patients. The prevalence of thyroid cancer in women was associated with a high BMI (per 5 kg/m2 increase) (odds ratios (OR)=1.63, 95% CI 1.24–2.10, P<0.001), after adjustment for age, smoking status, and TSH levels. There was no positive correlation between the prevalence of thyroid cancer in men and a high BMI (OR=1.16, 95% CI 0.85–1.57, P=0.336). There was no association between age, fasting serum insulin, or basal TSH levels and thyroid cancer in either gender.

Conclusions

Obesity was associated with a higher prevalence of thyroid cancer in women when evaluated in a routine health checkup setting. This association between risk factor and disease was unrelated to serum insulin and TSH levels. Additional studies are needed to understand the mechanism(s) behind the association of obesity with thyroid cancer risk.

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Hyemi Kwon, Min Ji Jeon, Won Gu Kim, Suyeon Park, Mijin Kim, Dong Eun Song, Tae-Yon Sung, Jong Ho Yoon, Suck Joon Hong, Tae Yong Kim, Young Kee Shong and Won Bae Kim

Objective

Papillary thyroid microcarcinoma (PTMC) accounts for most of the increase in thyroid cancer in recent decades. We compared clinical outcomes and surgical complications of lobectomy and total thyroidectomy (TT) in PTMC patients.

Design and methods

In this retrospective individual risk factor-matched cohort study, 2031 patients with PTMC were initially included. Patients who underwent lobectomy or TT were one-to-one matched according to individual risk factors, including age, sex, primary tumor size, extrathyroidal extension, multifocality and cervical lymph node (LN) metastasis.

Results

In total, 688 patients were assigned to each group. During the median 8.5 years of follow-up, 26 patients (3.8%) in the lobectomy group and 11 patients (1.6%) in the TT group had recurrences. The relative risk of recurrence was significantly less in the TT than that in the lobectomy group (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.21–0.81; P = 0.01). Most recurrences (84.6%) in the lobectomy group occurred in the contralateral lobe, and all patients were disease-free after completion of thyroidectomy. There were no significant differences in recurrence-free survival between the two groups after exclusion of contralateral lobe recurrences (HR, 2.75; 95% CI, 0.08–8.79; P = 0.08). There were significantly more patients with transient and permanent hypoparathyroidism in the TT than that in the lobectomy group (P < 0.001).

Conclusions

Lobectomy could be appropriate for most patients with PTMC when there is no evidence of extrathyroidal disease in the preoperative work-up. Preoperative and postoperative imaging studies are important for patients who undergo lobectomy for PTMC, because most recurrences are in the contralateral lobe.

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Min Ji Jeon, Won Gu Kim, Hyemi Kwon, Mijin Kim, Suyeon Park, Hye-Seon Oh, Minkyu Han, Tae-Yon Sung, Ki-Wook Chung, Suck Joon Hong, Tae Yong Kim, Young Kee Shong and Won Bae Kim

Objective

Active surveillance is an option for patients with papillary thyroid microcarcinoma (PTMC). However, the long-term clinical outcomes after delayed surgery remain unclear. We compared the long-term clinical outcomes of PTMC patients according to the time interval between initial diagnosis and surgery.

Design and methods

In this individual risk factor-matched cohort study, PTMC patients were classified into three groups according to the delay period: ≤6 months, 6–12 months and >12 months. Patients were matched by age, sex, extent of surgery, initial tumor size as measured by ultrasonography (US), and by the presence of extrathyroidal extension, multifocal tumors and central cervical lymph node metastasis. We compared the dynamic risk stratification (DRS) and the development of structural persistent/recurrent disease of patients.

Results

A total of 2863 patients were assigned to three groups. Their mean age was 50 years, 81% were female and 66% underwent lobectomy. The mean tumor size at the initial US was 0.63 cm. There were no significant differences in clinicopathological characteristics between groups after individual risk factor matching. Comparison of the DRS revealed no significant difference according to the delay period (P = 0.07). During the median 4.8 years of follow-up, there were no significant differences in the development of structural recurrent/persistent disease (P = 0.34) and disease-free survival (P = 0.25) between groups.

Conclusions

In PTMC patients, delayed surgery was not associated with higher risk of structural recurrent/persistent disease compared to immediate surgery. These findings support the notion that surgical treatment can be safely delayed in patients with PTMC under close monitoring.

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Eyun Song, Min Ji Jeon, Hye-Seon Oh, Minkyu Han, Yu-Mi Lee, Tae Yong Kim, Ki-Wook Chung, Won Bae Kim, Young Kee Shong, Dong Eun Song and Won Gu Kim

Objective

Evidence for unfavorable outcomes of each type of aggressive variant papillary thyroid carcinoma (AV-PTC) is not clear because most previous studies are focused on tall cell variant (TCV) and did not control for other major confounding factors contributing to clinical outcomes.

Design

Retrospective cohort study.

Methods

This study included 763 patients with classical PTC (cPTC) and 144 with AV-PTC, including TCV, columnar cell variant (CCV) and hobnail variants. Disease-free survival (DFS) and dynamic risk stratification (DRS) were compared after two-to-one propensity score matching by age, sex, tumor size, lymph node metastasis and extrathyroidal extension.

Results

The AV-PTC group had significantly lower DFS rates than its matched cPTC group (HR = 2.16, 95% CI: 1.12–4.16, P = 0.018). When TCV and CCV were evaluated separately, there was no significant differences in DFS and DRS between patients with TCV (n = 121) and matched cPTC. However, CCV group (n = 18) had significantly poorer DFS than matched cPTC group (HR = 12.19, 95% CI: 2.11–70.33, P = 0.005). In DRS, there were significantly more patients with structural incomplete responses in CCV group compared by matched cPTC group (P = 0.047). CCV was an independent risk factor for structural persistent/recurrent disease in multivariate analysis (HR = 4.28; 95% CI: 1.66–11.00, P = 0.001).

Conclusions

When other clinicopathological factors were similar, patients with TCV did not exhibit unfavorable clinical outcome, whereas those with CCV had significantly poorer clinical outcome. Individualized therapeutic approach might be necessary for each type of AV-PTCs.

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Min Ji Jeon, Won Gu Kim, Woo Ri Park, Ji Min Han, Tae Yong Kim, Dong Eun Song, Ki-Wook Chung, Jin-Sook Ryu, Suck Joon Hong, Young Kee Shong and Won Bae Kim

Objective

A new risk stratification system was proposed to estimate the risk of recurrence in patients with differentiated thyroid carcinoma (DTC) using the response to initial therapy. Here, we describe the modified dynamic risk stratification system, which takes into consideration the status of serum anti-Tg antibody (TgAb), and validate this system for assessing the risk of recurrence in patients with DTC.

Patients and methods

Patients who underwent total thyroidectomy with radioiodine remnant ablation due to DTC between 2000 and 2005 were included. We classified patients into four groups based on the response to the initial therapy (‘excellent’, ‘acceptable’, ‘biochemical incomplete’, and ‘structural incomplete’ response).

Results

The median follow-up period of 715 patients with DTC was 8 years. The response to initial therapy was an important risk predictor for recurrent/persistent DTC. The relative risks (95% CI) of recurrence were 16.5 (6.3–43.0) in the ‘acceptable response’ group, 41.3 (15.4–110.8) in the ‘biochemical incomplete response’ group, and 281.2 (112.9–700.5) in the ‘structural incomplete response’ group compared with the ‘excellent response’ group (P<0.001, P<0.001, and P<0.001 respectively). The disease-free survival rate of the ‘excellent response’ group to initial therapy was 98.3% whereas that of the ‘structural incomplete response’ group was only 6.8%.

Conclusions

Our study validates the usefulness of the modified dynamic risk stratification system including the status of serum TgAb for predicting recurrent/persistent disease in patients with DTC. Personalized risk assessment using the response to initial therapy could be useful for the follow-up and management of patients with DTC.

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Yun Mi Choi, Won Gu Kim, Hyemi Kwon, Min Ji Jeon, Jong Jin Lee, Jin-Sook Ryu, Eun-Gyoung Hong, Tae Yong Kim, Young Kee Shong and Won Bae Kim

Objective

Bone is the second most common site of distant metastases from differentiated thyroid cancer (DTC). Patients with bone metastases were associated with poor clinical outcomes; however, their clinical courses are heterogeneous. The aim of this study is to evaluate early prognostic factors of patients with bone metastases from DTC at the time of diagnosis of bone metastasis.

Methods

This retrospective study included 93 patients with bone metastases from DTC. We defined ‘Pre-RAIT group’ as patients whose bone metastases were detected before initial RAIT. The ‘post-RAIT group’ was defined as patients whose bone metastases were detected after initial RAIT or during the follow-up period.

Results

Median age was 55.4years, and 55 patients (59%) had papillary thyroid cancer. Patients in the pre-RAIT group (n=32) demonstrated significantly poorer overall survival (OS) (HR=1.86, P=0.04) than those in the post-RAIT group. There was no significant difference in the OS according to the initial RAI avidity among all patients (P=0.18). RAI-avid bone metastases had better OS only in the pre-RAIT group (HR=0.23, P=0.01) but not in the post-RAIT group. In the post-RAIT group, older age (>45years), elevated serum thyroglobulin (Tg) level (>250ng/mL), and the presence of skeletal-related events (SREs) were significantly associated with poor OS. RAI avidity was not a significant prognostic factor in the post-RAIT group (P=0.33).

Conclusions

Patients whose bone metastases were diagnosed before initial RAIT demonstrate a poorer prognosis. RAI avidity is an early prognostic indicator in the pre-RAIT group. Old age, higher serum Tg levels, and SRE are associated with poor survival outcomes in the post-RAIT group.

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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.

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Min Ji Jeon, Jong Ho Yoon, Ji Min Han, Ji Hye Yim, Suck Joon Hong, Dong Eun Song, Jin-Sook Ryu, Tae Yong Kim, Young Kee Shong and Won Bae Kim

Objective

The presence of central neck lymph node (LN) metastases (defined as pN1a according to Tumor Node Metastasis classification) in papillary thyroid cancer (PTC) is known as an independent risk factor for recurrence. Extent of LN metastasis and the completeness of removal of metastatic LN must have an impact on prognosis but they are not easy to measure. Moreover, the significance of the size of metastatic tumors in LNs has not been clarified. This study was to evaluate the impact of the extent of LN metastasis and size of metastatic tumors on the recurrence in pathological N1a PTC.

Design

This retrospective observational cohort study enrolled 292 PTC patients who underwent total thyroidectomy with central neck dissection from 1999 to 2005. LN ratio was defined as the number of metastatic LNs divided by the number of removed LNs, which was regarded as variable reflecting both extent of LN metastasis and completeness of resection, and LN size as the maximal diameter of tumor in metastatic LN.

Results

The significant risk factors for recurrence in univariate analysis were large primary tumor size (defined as larger than 2 cm), high LN ratio (defined as higher than 0.4), and presence of macrometastasis (defined as larger than 0.2 cm). Age, sex, clinical node status, and microscopic perithyroidal extension had no effect on recurrence. In multivariate analysis, high LN ratio and presence of macrometastasis were independent risk factors for recurrence.

Conclusion

LN ratio and size of metastatic nodes had a significant prognostic value in pathological N1a PTC. We suggest that risk stratification of pathological N1a PTC according to the pattern of LN metastasis such as LN ratio and size would give valuable information to clinicians.

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Jin Soon Hwang, Hae Sang Lee, Woo Yeong Chung, Heon-Seok Han, Dong-Kyu Jin, Ho-Seong Kim, Cheol-Woo Ko, Byung-Churl Lee, Dae-Yeol Lee, Kee-Hyoung Lee, Jeh-Hoon Shin, Byung-Kyu Suh, Han-Wook Yoo, Hyi-Jeong Ji, Jin-Hwa Lee, Yoon Ju Bae, Duk-Hee Kim and Sei Won Yang

Purpose

The purpose of this study was to investigate the efficacy and safety of LB03002, a sustained-release human GH (SR-hGH), compared with that of daily rhGH for 12 months in children with GH deficiency (GHD).

Methods

A total of 73 children with GHD were screened and 63 eligible subjects were randomized in a 1:1 ratio of LB03002 (SR-hGH) to daily rhGH treatment group. LB03002 was administered once weekly at a dose of 0.5 mg/kg while daily rhGH was administered for 6 consecutive days with equally divided doses to make a total of 0.21 mg/kg per week. Treatments were given for 12 months by s.c. injections. Injection site reactions and adverse events were investigated throughout the study period.

Results

The mean (s.d.) height velocity (HV) showed a clinically significant increase after the 6-month treatment: 3.00 (1.15) cm/year at screening to 9.78 (1.98) cm/year at 6 months in the LB03002 group; 2.39 (1.63) cm/year at screening to 10.56 (2.65) cm/year at 6 months in the daily rhGH group. The increased HV at 12 months was still maintained in both the groups: 9.06 (1.63) cm/year at 12 months in the LB03002 group; 9.72 (2.32) cm/year at 12 months in the daily rhGH group. Most of the adverse drug reactions were mild and tolerable. No subjects were withdrawn due to adverse events.

Conclusion

Weekly injection of LB03002 at a dose of 0.5 mg/kg per week was confirmed to have comparable efficacy to daily injection of rhGH at a dose of 0.21 mg/kg per week. Both formulations were well tolerated.