Seo Young Sohn

Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer.

Epidemiological studies have demonstrated that excess weight increases the risk of thyroid cancer. However, the associations between excess weight and prognostic factors for thyroid cancer are uncertain. We evaluated the relationships between body mass index (BMI) and clinico‐pathological features and outcomes of papillary thyroid cancer (PTC).

The Impact of Iodinated Contrast Agent Administered During Preoperative Computed Tomography Scan on Body Iodine Pool in Patients with Differentiated Thyroid Cancer Preparing for Radioactive Iodine Treatment

BACKGROUND Iodine in iodinated contrast agents (ICAs) interferes with radioactive iodine treatment (RAIT) and diagnostic scans in patients with differentiated thyroid carcinoma (DTC) because it can compete with ¹³¹I. Published guidelines recommend delaying RAIT for three to four months in patients who have been exposed to ICA. Spot urinary iodine concentration is a useful marker to reflect the body iodine pool. We investigated the impact of ICAs administered at preoperative computed tomography (CT) scan on the body iodine pool to determine the proper time interval between preoperative CT and RAIT in DTC patients. METHODS We performed a retrospective review of 1023 patients with DTC who underwent a preoperative CT scan with ICA, total thyroidectomy, and one week of low-iodine diet in preparation for RAIT. Urine iodine excretion (UIE) was measured in spot urine by inductively coupled plasma mass spectrometry and reported both in simple concentration (μg/L) and divided by gram creatinine (μg/gCr). Patients were divided into five groups by time interval in days between preoperative CT scan and spot urine iodine measurement (A, 31-60 [n=29]; B, 61-90 [n=155]; C, 91-120 [n=546]; D, 121-150 [n=226]; E, 151-180 [n=67]). RESULTS The median (interquartile range) of UIE (μg/gCr) in each group was 44.4 (27.7-73.2) in group A, 33.3 (22.8-64.7) in group B, 32.7 (20.8-63.0) in group C, 32.0 (20.6-67.0) in group D, and 30.4 (19.6-70.8) in group E. There was no significant difference between group A and the remaining groups (p>0.05) Also, the proportion of patients who achieved the appropriate UIE for RAIT according to our hospitals cutoff (≤66.2 μg/gCr) was not different between groups (A, 72.4%; B, 76.1%; C, 77.5%; D, 74.8%; E, 74.6%) (p=0.78). CONCLUSION This study shows that a UIE of one month after preoperative CT scan with ICA was not higher than that of six months after CT scan in patients who underwent total thyroidectomy for DTC. Thus, current guidelines that recommend delay of RAIT for three to four months after CT scan with ICA should be revisited and future studies to clarify the appropriate time interval between CT scan with ICA and RAIT are warranted.

Association between excessive urinary iodine excretion and failure of radioactive iodine thyroid ablation in patients with papillary thyroid cancer.

BACKGROUND A low-iodine diet (LID) is usually recommended for a week or two before radioactive iodine (RAI) ablation therapy in papillary thyroid cancer (PTC) patients after total thyroidectomy. However, it is still controversial whether an LID affects ablation outcomes. We therefore evaluated the association between urinary iodine excretion and the rate of successful ablation and investigated the determinants of successful RAI ablation outcomes. METHODS We retrospectively reviewed the records of 295 consecutive patients with PTC who received 1110 MBq RAI remnant ablation therapy with thyroid hormone withdrawal after total thyroidectomy. Successful ablation was defined as either no visible or faint uptake on a follow-up scan (definition 1), or no visible or faint uptake on a follow-up scan and a stimulated thyroglobulin level <2 ng/mL (definition 2). RESULTS The proportion of patients with appropriate LID status (defined as a urinary iodine concentration [UIC] <66.2 μg iodine/g creatinine [μg/gCr]) was significantly higher in the successfully ablated group (81% vs. 67%, p=0.03). Based on definition 1, 80.3% (237/295) of patients were successfully ablated. The ablation rate was significantly lower in patients who had a UIC >250 μg/gCr at the time of RAI ablation (p<0.05). In multivariate analysis, a UIC >250 μg/gCr was the only significant variable associated with ablation failure (p=0.002, odds ratio [OR] 4.74 [95% confidence interval (CI) 1.78-12.63]). Based on definition 2, 74.9% (221/295) of patients were successfully ablated. A UIC >250 μg/gCr at RAI administration showed a significant association with ablation failure (p<0.05). The OR of a UIC >250 μg/gCr for ablation failure was 3.88 [CI 1.42-10.57] (p=0.008). CONCLUSION Excessive iodine intake (UIC >250 μg/gCr) was associated with poor RAI ablation outcomes. Because this amount of iodine is very high, we propose that the level of strictness of the LID protocol should be modified according to the region that the patient is from and the food that the patient is accustomed to eating. Even in those areas where iodine intake is high, overly strict compliance with an LID protocol is not necessary and simple recommendations to avoid iodine-rich foods would be appropriate.

Highly Concordant Key Genetic Alterations in Primary Tumors and Matched Distant Metastases in Differentiated Thyroid Cancer.

BACKGROUND Distant metastases uncommonly occur in differentiated thyroid carcinoma (DTC), but they are a frequent cause of thyroid cancer-related death. Genomic alterations in metastatic tumors, and the relationship with their corresponding primary tumors in DTC, are poorly understood. The objective of this study was to investigate whether genetic alterations in primary tumors are concordant with distant metastases in DTC patients. METHODS Surgical samples from primary and matched distant metastatic tumor pairs from 17 DTC patients, and three additional unpaired metastatic tumors from two patients, were analyzed using targeted next-generation sequencing (Ion Torrent Ampliseq cancer panel) with a focus on known recurrent somatic mutations in thyroid cancer. Additionally, TERT promoter mutations were assessed by direct sequencing. RESULTS BRAF mutations were found in 8/10 patients with papillary thyroid carcinoma (PTC). A NRAS mutation was detected in one patient with follicular variant PTC. TERT promoter mutations were detected in 8/10 patients with PTC, and most were coexistent with a BRAF mutation (7/8 BRAF-positive PTC patients, and one BRAF-negative PTC patient). In follicular thyroid carcinoma, NRAS was the most frequently observed mutation (4/9 patients), followed by HRAS (two patients) and KRAS (one patient). TERT promoter mutations were found in 6/7 RAS-positive follicular thyroid carcinoma patients. Key somatic alterations such as BRAF and RAS mutations were highly concordant between primary and matched metastatic tumors without discrepancies. The BRAF or RAS mutant allelic frequency was higher in matched metastatic tumors than in the corresponding primary tumors (35% vs. 25% for BRAF mutation, p = 0.04; and 40% vs. 34% for RAS mutation, p = 0.002). TERT promoter mutations were also mostly concordant in matched tumors (concordance rate 93%). CONCLUSIONS BRAF, RAS, and TERT mutations are highly prevalent in metastatic DTC, and are concordant between primary and metastatic DTC. This high concordance suggests that primary tumors may reflect the key somatic alterations in matched metastatic DTC. Frequent coexistent TERT promoter and BRAF or RAS mutations in metastatic DTC also suggests its important role in the progression of DTC.

Effect of Iodine Restriction on Thyroid Function in Subclinical Hypothyroid Patients in an Iodine-Replete Area: A Long Period Observation in a Large-Scale Cohort

BACKGROUND Excessive iodine intake is related to a higher prevalence of hypothyroidism, including subclinical hypothyroidism (SCH), in iodine-replete areas. This study aimed to evaluate the effect of iodine restriction on thyroid function in SCH patients in an iodine-replete area and analyze the relationship between serum thyrotropin (TSH) levels and iodine intake. METHODS The study consisted of 146 consecutive patients who were diagnosed with SCH at the Samsung Medical Center between 2010 and 2012. Urinary iodine concentration (UIC) was measured in 82 patients. Of these, 20 patients with UIC < 300 μg/L were excluded, and 62 patients with UIC ≥ 300 μg/L were educated about the restriction of iodine-rich foods. Following the first follow-up visit, these patients were divided into two groups based on the UIC level: group A (well-controlled iodine intake, UIC < 300 μg/L, n = 40), and group B (poorly controlled iodine intake, UIC ≥ 300 μg/L, n = 22). The remaining 64 patients did not restrict iodine rich foods (group C). The 82 patients with measured UICs were reevaluated every 3-6 months, and the median follow-up was 13 months (range 3-32 months). Thyroid function and UIC were measured at each visit. The correlation between serum TSH level and UIC was determined for the 82 patients in whom UIC was measured. RESULTS Following 3-6 months of iodine restriction, the serum TSH levels significantly decreased in group A (from 9.0 mU/L to 4.7 mU/L; p < 0.01). In addition, the serum free thyroxine (T4) levels in group A significantly increased (from 1.11 ± 0.23 ng/dL to 1.18 ± 0.17 ng/dL; p < 0.05). However, there were no significant changes in serum TSH or free T4 levels in groups B and C. Serum TSH levels significantly correlated with UIC (r = 0.33, p < 0.01). CONCLUSION Iodine restriction may normalize or, at the very least, decrease serum TSH levels in SCH patients, and serum TSH levels are strongly correlated with UIC. Therefore, restriction of iodine intake could be a primary treatment option in SCH patients in an iodine-replete area.

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

Background There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). Methods We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. Results Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. Conclusion Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective

Background Previous studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective. Methods This economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets. Results The additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY. Conclusion The use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea.

Validation of dynamic risk stratification in pediatric differentiated thyroid cancer

PurposeThere has been increasing interest in a risk-adopted management strategy known as dynamic risk stratification following the revised American Thyroid Association guidelines for differentiated thyroid cancer. We aimed to evaluate the usefulness of dynamic risk stratification for predicting structural disease in pediatric differentiated thyroid cancer patients.MethodsWe retrospectively reviewed 130 pediatric differentiated thyroid cancer patients (≤19 years) who were treated between 1996 and 2015 at Samsung Medical Center. Patients were stratified according to three American Thyroid Association initial risk group (low, intermediate, or high risk) and four dynamic risk stratification group (excellent, indeterminate, biochemical incomplete, or structural incomplete).ResultsBased on dynamic risk stratification strategy, structural disease was identified 3.9% in the excellent group, 9.7% in the indeterminate group, 76.9% in the biochemical incomplete group, and 100% in the structural incomplete group. The hazard ratios of the structural disease were 18.10 (P < 0.001) in the biochemical incomplete group, and 19.583 (P < 0.001) in the structural incomplete group compared to the excellent group. The prevalence of structural disease also increased as American Thyroid Association initial risk classification increased (5.9% in the low-risk group, 13.6% in the intermediate-risk group, and 45% in the high-risk group). The hazard ratios of structural disease in the high-risk group was 10.296 (P < 0.001) in compared to the low-risk group.ConclusionDynamic risk stratification based on patient responses to initial therapy was able to effectively predict the risk of structural disease in a pediatric population, and as a follow-up strategy, may work as well in pediatric differentiated thyroid cancer patients as it does in adult differentiated thyroid cancer patients.

Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in Korean Patients With Differentiated Thyroid Carcinoma: The First Report in Nonwestern Countries

Objective:The aim of this study was to confirm the equivalent efficacy of recombinant human TSH (rhTSH) and thyroid hormone withdrawal (THW) as used in the preparation for low-dose and high-dose radioactive iodine (RAI) ablation in Korean patients with differentiated thyroid carcinoma. Subjects and Methods:This retrospective study was designed to compare the efficacy of rhTSH and THW when used before ablation with low-dose (30 mCi) and high-dose (100 mCi) RAI, respectively. The study group included 570 patients with DTC with tumors staged T1 to T3, N0 to N1, and M0. Before RAI ablation, 190 patients used rhTSH and 380 patients matched by age, sex, T-stage, and N-stage used THW. The success of ablation was evaluated in each group based on 4 criteria: (1) stimulated thyroglobulin (sTg) <2 ng/mL, (2) sTg<2 ng/mL and negative diagnostic whole-body scan (DxWBS), (3) sTg<1 ng/mL, and (4) sTg<1 ng/mL and negative DxWBS. Results:When both sTg<2 ng/mL and negative DxWBS were selected as criteria for success in patients treated with low-dose RAI, the success rates were 80.5% and 77.0% with rhTSH and THW, respectively (95% confidence interval, 5.9-12.8). Using both sTg<1 ng/mL and negative DxWBS as criteria, success rates were 78.2% and 71.8% with rhTSH and THW, respectively (95% confidence interval, 3.6-16.2). Using any criteria for success, low-dose RAI ablation with rhTSH was as effective as THW. Similar results were found for high-dose RAI ablation in patients using either rhTSH or THW. Conclusions:Low-dose and high-dose RAI ablation were equally effective using either rhTSH or THW before ablation in Korean patients with DTC, respectively.