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Background: Treatment for patients with radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC) is challenging. Recently, two tyrosine kinase inhibitors (sorafenib and lenvatinib) have been approved and showed benefits for progression-free survival with tolerable adverse events. Methods: This is an extension study of a previous multicenter, retrospective cohort study of real-world experience in treating 98 patients with progressive RAI-refractory DTC with sorafenib. The primary endpoint was overall survival (OS). The efficacy of lenvatinib as salvage therapy after disease progression on first-line sorafenib was evaluated by comparing outcomes in 32 patients who were treated with lenvatinib with 41 patients who were not and therefore served as a no salvage treatment group. Results: The median OS of all 98 patients treated with sorafenib was 41.5 months, and the median progression-free survival was 13.5 months. Patients without disease-related symptoms before sorafenib treatment had better OS than those with symptoms (hazard ratio [HR] = 0.56 [95% confidence interval, CI 0.31-0.99], p  = 0.048). Larger tumor size was associated with a minimally increased risk of death (HR = 1.02 [CI 1.00-1.03], p  = 0.049). Best tumor response was not associated with OS ( p  = 0.490). Lenvatinib salvage treatment significantly improved OS in patients receiving it compared with those who did not (HR = 0.28 [CI 0.15-0.53], p  < 0.001). The median OS from the time of disease progression after first-line sorafenib treatment was 4.9 months in no salvage treatment group, whereas it was not reached in the lenvatinib salvage group. Conclusions: The absence of disease-related symptoms and smaller tumor burden was associated with survival benefits of first-line sorafenib treatment in patients with progressive RAI-refractory DTC. Lenvatinib salvage therapy was effective in improving OS in patients with disease progression after first-line sorafenib.

Background: The lymphocyte-to-monocyte ratio (LMR), which reflects the tumor-infiltrating immune cell status and host immunity, has been reported as a prognostic marker in various cancers. The aim of the present study was to evaluate the role of the LMR as a prognostic marker in predicting the survival of patients with anaplastic thyroid carcinoma (ATC). Methods: This study retrospectively included 35 ATC patients with available complete blood cell count data. The primary outcome was the overall survival (OS) of patients with ATC. Results: There were no significant differences between the LMR of the baseline and that of the follow-up complete blood cell count data ( p  = 0.53). The patients were divided into two groups based on their baseline LMR: a low LMR group (<4; n  = 23, 66%) and a high LMR group (≥4; n  = 12, 34%). The proportion of cervical lymph node metastasis in the low LMR group was significantly higher than that in the high LMR group ( p  = 0.021). The OS curves were significantly different based on the LMR values, and the median OS of the low and high LMR groups were 3.0 and 9.5 months, respectively ( p  = 0.004). In multivariate analysis, a low LMR was also an independent risk factor for all-cause mortality in patients with ATC (hazard ratio = 2.55 [confidence interval 1.08-6.00], p  = 0.032) after adjusting for sex, tumor size, and distant metastasis. Conclusions: A low LMR is associated with poor survival in patients with ATC. The LMR could be a simple and stable prognostic biomarker reflecting host immunity in patients with ATC. Further studies are needed to confirm the prognostic role of the LMR in ATC.

Background: Tumor volume (TV) of papillary thyroid carcinoma (PTC) increases exponentially during active surveillance, and the growth rate differs for each patient. TV doubling time (TVDT) is considered a strong dynamic marker for the prediction of the growth rate and progression of the tumor. Methods: This cohort study analyzed 273 PTC patients who underwent active surveillance for more than one year rather than immediate thyroid surgery. TVDT was calculated in each patient, and patients were divided into two groups: rapid-growing (TVDT <5 years) and stable (TVDT ≥5 years). Clinical and initial ultrasonography (US) features between the two groups were compared. Results: The median patient age was 51.1 years (interquartile range [IQR] 42.2-61.0 years), and 76% of the patients were women. The initial TV of PTC was 62.1 mm 3 (IQR 28.1-122.8 mm 3 ). During a median of 42 months (IQR 29-61 months) of active surveillance, 10.3% of the patients had a TVDT of less than two years, 5.1% had a TVDT between two and three years, 6.2% had a TVDT between three and four years, 6.6% had a TVDT between four and five years, and 71.8% had a TVDT of five years or more. Patients in the rapid-growing group (77 patients; 28.2%) were significantly younger ( p  = 0.004) than those in the stable group (196 patients; 71.8%). Being younger than 50 years of age was significantly associated with rapid tumor growth of PTC (odds ratio = 2.31 [confidence interval 1.30-4.31], p  = 0.004) in multivariate analysis. In ultrasound findings, macrocalcification was independently associated with rapid tumor growing of PTCs (odds ratio = 4.98 [confidence interval 2.19-11.69], p  < 0.001). Conclusions: TVDT is a good indicator for presenting the growing velocity of PTCs during active surveillance. Younger age and macrocalcification in the initial US were associated with rapid-growing PTCs. Determination of TVDT during the early phase of active surveillance may be helpful for the prediction of rapidly progressing PTCs and deciding whether to adopt an early surgical approach.

Background: The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response., Methods: This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients)., Results: With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis., Conclusions: The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

Background: The recently published eighth edition of the American Joint Committee on Cancer (AJCC) staging system has emphasized the importance of gross extrathyroidal extension (gETE) while classifying the tumor (T) stage in differentiated thyroid carcinoma (DTC). However, the clinical impact of gETE invading only the strap muscles or the recurrent laryngeal nerve (RLN) remains unclear due to scarce and conflicting data., Methods: A retrospective cohort study was carried out in patients with DTC who underwent thyroid surgery from 1996 to 2005. In total, 3104 patients were included, and disease-specific survival (DSS) was compared according to the degree of gETE, with a median follow-up duration of 10 years., Results: Patients with gETE invading only the strap muscles and with a tumor size ≤4 cm (T3b [≤4 cm]) showed no difference in DSS compared to patients with T2 stage disease (hazard ratio [HR] = 0.81 [confidence interval (CI) 0.24-2.77]; p = 0.737) but rather showed a better DSS than patients with T3a disease (HR = 0.19 [CI 0.05-0.72]; p = 0.014). Conversely, patients with gETE invading to the posterior direction showed significantly poorer DSS than patients with T3 stage disease, even when only the RLN was invaded (HR = 7.78 [CI 3.41-17.75]; p < 0.001). However, there was no difference in DSS between gETE invading only the RLN and that invading other posterior organs beyond the RLN (p = 0.563). A modified T classification was suggested to downgrade patients with T3b (≤4 cm) disease to the T2 stage, which revealed higher predictability of survival than the T classification according to the eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (proportion of variation explained: 3.6% vs. 2.65%)., Conclusions: gETE invading only the strap muscles did not significantly affect DSS, while that invading the posterior organs significantly affected DSS, even when only the RLN was invaded. The data support the applicability of downgrading patients with T3b (≤4 cm) disease to the T2 stage for a better predictability of survival.

Background: Current guidelines allow lobectomy as treatment for 1-4 cm papillary thyroid carcinomas (PTCs), as previous studies reported no clear survival advantages for total thyroidectomy (TT). However, data on recurrence based on surgical extent are limited., Methods: This study enrolled 2345 patients with 1-4 cm PTC. Those with lateral cervical lymph node metastasis or initial distant metastasis were excluded. Disease-free survival (DFS) was compared after 1:1 propensity score matching by age, sex, tumor size, extrathyroidal extension, multifocality, and cervical lymph node metastasis., Results: Lobectomy was performed in 383 (16.3%) and TT in 1962 (83.7%) patients. In the matched-pair analysis (381 patients in each group), no significant difference in DFS was observed during the median follow-up of 9.8 years (hazard ratio [HR] = 1.35 [confidence interval (CI) 0.40-1.36], p = 0.33). When stratified by tumor size, DFS did not differ between the group with 1-2 cm tumors and that with 2-4 cm tumors (HR = 1.57 [CI 0.75-3.25], p = 0.228; HR = 0.93 [CI 0.30-2.89], p = 0.902, respectively). Multivariate analysis showed that the surgical extent did not play an independent role in structural persistent/recurrent disease development (HR = 1.43 [CI 0.72-2.83], p = 0.306)., Conclusion: Patients with 1-4 cm PTCs who underwent lobectomy exhibited DFS rates similar to those who underwent TT after controlling for major prognostic factors. This supports the feasibility of lobectomy as initial surgical approach for these patients and emphasizes that tumor size should not be an absolute indication for TT.

Background: Active surveillance has been introduced as a management option for low-risk papillary thyroid microcarcinoma (PTMC) due to its mostly indolent course., Methods: This was a multicenter study of 370 PTMC patients who underwent active surveillance more than one year. The changes in volume and maximum diameter between initial and last ultrasonography were evaluated to identify the natural course of PTMC during active surveillance., Results: Patients' age at diagnosis was 51 ± 12 years, and 110 (30%) patients were <45 years of age. The initial maximum diameter and volume of PTMCs were 5.9 ± 1.7 mm and 81.0 ± 77.7 mm 3 , respectively. During the median 32.5 months of follow-up, 86 (23.2%) patients were found to have an increase in tumor volume, and 13 (3.5%) patients showed an increase in the maximal diameter of the tumor. The cumulative incidence of volume increase gradually rose with time (6.9%, 17.3%, 28.2%, and 36.2% after two, three, four, and five years, respectively). The risk of volume increase in patients <45 years of age was twice as high as in older patients (p = 0.002). There was no significant difference in tumor size change according to sex, levothyroxine treatment, or presence of Hashimoto's thyroiditis. During the period, 58 (15.7%) patients underwent delayed thyroid surgery due to anxiety (37.9%), tumor size increase (32.8%), or appearance of cervical lymph node metastasis (8.6%). Lymph node metastasis was found in 29.3% of patients on pathological examination., Conclusions: A significant number of PTMCs grow during active surveillance, and tumor volume change is a more sensitive means of evaluating tumor growth. Active surveillance can be carefully applied for selected patients. Although it is not contraindicated, it should be applied more cautiously for younger patients.

Background: Low-risk patients with differentiated thyroid cancer can be treated with thyroid lobectomy. Serial measurements of serum thyroglobulin (Tg) are recommended for surveillance, but the cutoff values indicating recurrence are not known. This study documented the natural course of serum Tg levels during follow-up after lobectomy for low-risk papillary thyroid carcinoma (PTC) and evaluated whether changes in serum Tg levels predict disease recurrence., Methods: This historical cohort study included 208 patients with low-risk PTC who underwent lobectomy but did not require hormone replacement. Postoperative serum Tg levels and Tg/thyrotropin (TSH) ratios and neck ultrasound were evaluated during a follow-up period with a median of 6.9 years., Results: The serum Tg levels increased gradually, and the proportion of patients with levels >10 ng/dL increased annually by 13.9%, 18.8%, 22.1%, 21.9%, 28.4%, and 28.9% during the six-year follow-up period (β = 0.574, p = 0.027). The relative serum Tg levels increased by 10% annually (β = 0.105, p < 0.001), and the levels of Tg and Tg/TSH ratios in 19 patients with recurrent disease did not differ significantly (β = 0.150, p = 0.090). Patients without recurrent disease were more likely to have serum Tg levels increased by >20% (p = 0.022). There were no significant differences in the proportions of patients with serum Tg levels increased by ≥50% or ≥100% in terms of the disease recurrence., Conclusions: Serum Tg levels and the Tg/TSH ratio increased gradually after lobectomy in patients with and without recurrences, without any significant differences. Periodic measurements of serum Tg levels seem to have limited value in predicting recurrent PTCs after lobectomy.

Background: Lipid profiles of men and women change differently during the aging process. Guidelines recommend that dyslipidemia patients should consider screening for hypothyroidism without consideration of age or sex., Methods: Data from the sixth Korean National Health and Nutrition Examination Survey were used. A total of 4275 participants without thyroid disease and without a past history of dyslipidemia or dyslipidemia medication were evaluated. The association between thyroid dysfunction and lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDLC], and triglycerides [TG]) was analyzed by age and sex., Results: The prevalence of thyroid dysfunction was significantly different according to TC and LDLC levels (p = 0.003 and p = 0.021, respectively). In women, the weighted prevalence of thyroid dysfunction was significantly different according to levels of TC, LDLC, and TG (p = 0.007, p = 0.016, and p = 0.044, respectively). However, in men, no association was found in any of the lipid profiles. Female participants were divided into two groups using a cutoff age of 55 years. In younger women, the weighted prevalence of thyroid dysfunction was different according to the levels of TC, LDLC, and TG (p = 0.013, p = 0.007, and p = 0.007, respectively). However, in older women, no association was found for any of the lipid profiles., Conclusions: The prevalence of thyroid dysfunction was significantly different according to lipid profiles, and this association differed by age and sex.

Background: Regional lymph node metastases (LNM) have prognostic significance in differentiated thyroid cancer (DTC). However, there was no distinction between N1a and N1b in the final staging classification in the eighth edition of the tumor-node-metastasis (TNM) staging system. This study aimed to evaluate the prognostic implication of N1b classification for predicting disease-specific survival (DSS) in DTC patients with stage I/II disease., Methods: A total of 3089 patients with stage I/II DTC who underwent thyroid surgery between 1996 and 2005 were included. DSS was evaluated according to N classification and number of LNM. A modification of the TNM was assessed that classified N1b cases in patients aged ≥55 years as stage IIB and the remaining cases as stage IIA., Results: The mean patient age was 45.6 years, and the median follow-up period was 10.0 years. In patients aged ≥55 years, patients with N1b had significantly poorer DSS compared to those with N0 (hazard ratio [HR] = 11.0; p < 0.001) and N1a (HR = 4.2; p = 0.013). The large-volume LNM group had significantly poorer DSS compared to the N0 (HR = 10.1; p < 0.001) and small-volume LNM (HR = 3.9; p = 0.019) groups. When patients were reclassified using the modified TNM staging system, DSS was significantly poorer in stage IIB patients than in stage IIA patients (HR = 2.9; p = 0.030)., Conclusions: N1b classification has a significant prognostic implication in patients with stage I/II DTC, especially in older patients. Modified TNM staging employing N1b classification could be more useful for the prediction of DSS.

Background: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor previously known as noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The absence of BRAF V600E mutations has been considered characteristic of NIFTPs. However, a recent study from Korea found that 28.6% of NIFTPs harbored a BRAF mutation. This study evaluated BRAF and RAS mutations in NIFTPs and invasive subtype of EFVPTCs., Methods: This study enrolled 32 patients with NIFTP and 48 with invasive EFVPTC. BRAF, NRAS, HRAS, and KRAS mutations were evaluated by direct sequencing using DNA from fresh-frozen tissues and formalin-fixed, paraffin-embedded tissue samples., Results: The primary tumor size of NIFTP was smaller than that of invasive EFVPTC (median 2.8 cm vs. 3.2 cm; p = 0.03). Cervical lymph node metastases were found in only four (8%) patients with invasive EFVPTC. There was no BRAF mutation in NIFTPs, whereas invasive EFVPTCs had three (6%) BRAF V600E mutations and one (2%) BRAF K601E mutation. RAS mutations were detected in 15 (47%) NIFTPs and 22 (46%) invasive EFVPTCs. NRAS mutations in codon 61 were the most common mutations in NIFTPs (34%) and invasive EFVPTCs (27%). There was no significant difference in the frequency of RAS mutations between the two groups., Conclusions: There was no BRAF mutation in any of the NIFTPs. RAS mutations, particularly mutations in codon 61 of NRAS, were the most common mutations in both NIFTPs and invasive EFVPTCs. The presence of a RAS mutation is not helpful for preoperative differentiation between NIFTPs and invasive EFVPTCs.

Background: Total thyroidectomy and cervical lymph node (LN) dissection is generally recommended in patients with medullary thyroid carcinoma (MTC). However, there is no clear evidence for whom to perform prophylactic lateral neck dissection in MTC patients without evident lateral cervical lymph node (LCLN) metastasis in preoperative images. This study evaluated the preoperative features for predicting the LCLN metastasis of MTC., Methods: The study included 26 MTC patients with LCLN metastasis at initial surgery (N1b group) and 47 MTC patients without any LN metastasis or recurrence of disease (N0-NED group). The association between LCLN metastasis and preoperative clinical and sonographic characteristics (size, location, solid component, shape, margin, echogenicity, calcification, and subcapsular location of the tumor) were evaluated., Results: There were no significant differences in age and sex between the N1b and N0-NED groups. Preoperative serum levels of calcitonin >65 pg/mL were associated with LCLN metastasis (p < 0.001). In preoperative neck ultrasonography (US), patients in the N1b group were more commonly found with a larger tumor (>1.5 cm) of irregular shape with a spiculated margin and a subcapsular location than those in the N0-NED group (p = 0.029, p < 0.001, p < 0.001, and p < 0.001, respectively). Increases in the number of these LCLN metastasis-related features were significantly associated with higher risk for LCLN metastasis (p < 0.001). The presence of two or more predictors was an appropriate cutoff point for predicting LCLN metastasis of MTC with 73.1% sensitivity and 91.5% specificity., Conclusions: MTC tumors with high preoperative calcitonin levels (>65 pg/mL), larger size (>1.5 cm), irregular shape, spiculated margins, and subcapsular locations in the neck US are at higher risk for LCLN metastasis. MTC patents with fewer than two predictors might be suitable for treatment without prophylactic LCLN dissection.

Background: The risk of recurrence in patients with differentiated thyroid cancer (DTC) can be estimated based on their response to initial therapy. The aim of this study was to evaluate an adequate follow-up strategy for DTC patients with an excellent response by assessing the characteristics of structural recurrence., Methods: This historical cohort study included 1359 DTC patients who had excellent response to total thyroidectomy with radioactive iodine remnant ablation., Results: Among 1359 patients, 703 (54%) patients were classified as stage I according to the seventh tumor node metastasis staging system, and 987 (73%) patients were classified as intermediate risk according to the American Thyroid Association's risk stratification after initial therapy. During a median of 8.7 years of follow-up, only 13 (1%) patients were confirmed to have structural recurrence. All of the recurrences were locoregional disease, and there were no distant metastases. Recurrences were detected late at a median of 5.5 years after the initial surgery (range 3.6-10.7 years). All structural recurrences were detected on neck ultrasonography. Non-stimulated serum thyroglobulin (Tg) was detectable (≥0.2 ng/mL) in four (31%) patients, and serum anti-Tg antibodies were positive in one (8%) patient. However, non-stimulated serum Tg levels were stably low (<0.2 ng/mL) in eight (62%) patients when recurrences were detected. In addition to these 13 patients, 14 patients also presented with biochemical persistent disease at the end of follow-up., Conclusions: Recurrences of DTC in patients with an excellent response to initial therapy were detected relatively late. The intensity and frequency of follow-up of neck ultrasonography as well as serum Tg and anti-Tg antibody measurements should be reduced, especially within five years of the initial therapy, in DTC patients who have an excellent response.

Background: Large-volume lymph node metastasis (LNM) is associated with poor clinical outcomes in papillary thyroid microcarcinoma (PTMC) patients. However, sensitivity in the detection of central neck LNM on preoperative neck ultrasonography (US) is believed to be low. The aim of this study is to investigate the preoperative clinical factors associated with large-volume LNM in clinical N0 PTMC patients., Methods: In all, 2329 clinical N0 PTMC patients who underwent total thyroidectomy with prophylactic central lymph node (LN) dissection were evaluated. The LNM status of these patients was divided into three groups by the number of metastatic nodes: no LNM, small-volume LNM (≤5 metastatic LNs), and large-volume LNM (>5 metastatic LNs). The correlations between age, sex, and other clinical factors and large-volume LNM were evaluated., Results: Large-volume LNM was found in 94 (4.0%) patients. Young (<40 years old) and male patients tended to have large-volume LNM (p for trend <0.001). Young age (odds ratio [OR] = 2.69 [confidence interval (CI) 1.64-4.32], p < 0.001) and male sex (OR = 5.79 [CI 3.67-9.10], p < 0.001) were independent risk factors for large-volume LNM in multivariate analyses. The prevalence of large-volume LNM ranged from 24% in male patients <40 years of age to only 2% in female patients aged ≥40 years. Multifocal tumors and presence of extrathyroidal extension were also considered risk factors for large-volume LNM., Conclusions: Large-volume LNM was more frequently found in young (<40 years) and male patients. These findings support the notion that surgery rather than observation may be favored in young and male clinically LN negative PTMC patients as a primary therapeutic option.

Objective: To evaluate the efficacy and prognostic validity for disease-specific survival (DSS) of the eighth edition American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis (TNM) staging system (TNM-8) compared to the seventh edition (TNM-7) in patients with differentiated thyroid carcinoma (DTC)., Methods: The seventh and eighth editions of the TNM staging system were applied to 1613 DTC patients who underwent thyroid surgery between 1996 and 2003. The proportion of variation explained and Harrell's c-index were evaluated to compare the predictive capability of DSS., Results: The mean age of the patients was 44.7 years, and the median follow-up period was 11.2 years. When TNM-8 was applied, 63% of T3 and 3% of N1b DTCs were downgraded to T1/T2 and N1a, respectively. About 38% of patients were downstaged according to TNM-8. The 10-year DSS rates in TNM-7 stages I, II, III, and IV were 99.7%, 98.2%, 98.8%, and 83.2%, respectively. Those in TNM-8 stages I, II, III, and IV were 99.6%, 95.4%, 72.3%, and 48.6%, respectively. The proportion of variation explained values of TNM-7 and TNM-8 were 6.0% and 7.0%, respectively. The Harrell's c-index of TNM-7 was 0.86 and that of TNM-8 was 0.88., Conclusions: A significant number of patients were reclassified to lower stages with the application of TNM-8 compared to TNM-7. Applying TNM-8 could improve the accuracy of the staging system for predicting DSS in patients with DTC.

Background: Iodine intake is associated with various thyroid diseases and serum thyrotropin (TSH) levels. The aim of this study was to investigate iodine intake and its impact on the distribution of serum TSH levels using nationwide data from Korea, a country known to be iodine replete., Methods: The sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean general population. Participants were selected using two-stage stratified cluster sampling of the population and housing census data. A total of 6564 participants aged ≥10 years who underwent thyroid function tests and urinary iodine level measurements during the survey were included in this study., Results: The median urinary iodine concentration (UIC) was 299.3 μg/L (interquartile range 158.8-699.8), suggesting more than adequate iodine intake in Korea. With high-iodine intake in all age groups and in both females and males, the TSH reference interval in the Korean reference population was right-shifted at 0.62-6.84 mIU/L. The prevalence of overt and subclinical hypothyroidism in Korea according to this reference interval was 0.73% and 3.12%, respectively, and was significantly associated with nutritional iodine status (p = 0.011 and p < 0.001, respectively)., Conclusions: This first nationwide survey demonstrates more than adequate iodine intake and a right-shifted distribution of serum TSH levels in the Korean general population. Nutritional iodine status is important for determining serum TSH levels and is associated with a high prevalence of hypothyroidism. Nutritional iodine status might need to be considered when establishing TSH reference intervals of populations in iodine-replete areas.

Background: Papillary thyroid cancer (PTC) is a common malignancy diagnosed during pregnancy. However, there is little information on the behavior of PTC during pregnancy. The aim of this study was to evaluate the natural course of PTC in pregnant women., Methods: The study included 19 patients with PTC who delayed thyroid surgery because they were diagnosed with PTC just before or during the early stages of pregnancy. Serial neck ultrasonography (US) was used to evaluate PTCs before surgical treatment and the clinical outcomes after surgery., Results: The median maximal PTC size at initial diagnosis on US was 0.91 cm (interquartile range [IQR] 0.61-1.11), and 13/19 (68.4%) patients had micro-PTCs (≤1 cm). The median maximal PTC size after a median 9.5 months of follow-up was 0.98 cm (IQR 0.72-1.12). There were three (16%) patients who showed a size increase, and five (26%) patients showed a volume increase during the follow-up periods. There was no clinically relevant change in the maximal tumor size during the follow-up period (p = 0.16). Serial US measurements of PTC size in seven available patients in each trimester showed no significant differences between the different trimesters (first vs. second trimester p = 0.81; second vs. third trimester p = 0.99). No newly developed lesions in the thyroid or cervical lymph nodes were detected by neck US during the follow-up period. Among 19 patients, 16 underwent thyroid surgery after delivery, and the median duration from diagnosis to surgery was 11.9 months., Conclusions: No clinically relevant changes associated with a progression of PTC were observed during pregnancy. Delayed thyroid surgery with active surveillance can be an appropriate approach for pregnant patients with PTC.

Background: Increased incidence of small differentiated thyroid cancer (DTC) has emphasized the need for risk stratification and individualized disease management for these low risk DTCs. The aim of this study was to validate a new dynamic risk stratification (DRS) system for the prediction of structural recurrent/persistent disease in patients with DTC treated without radioactive iodine (RAI) remnant ablation therapy., Methods: This historical cohort study included 357 patients with DTC treated with lobectomy or total thyroidectomy without RAI therapy. We stratified patient response to initial treatment as excellent, indeterminate, biochemical incomplete, and structural incomplete according to the DRS system., Results: During a median follow-up of 8.6 years, 3.6% patients had structural recurrent DTC. The response was excellent in 71.7% patients, indeterminate in 18.5%, biochemical incomplete in 8.4%, and structural incomplete in 1.4%. There were significant differences in DFS among the DRS groups (p < 0.001). The hazard ratio (HR) of recurrent/persistent disease was significantly higher in the biochemical incomplete group (HR = 20.8, p < 0.001) and structural incomplete group (HR = 243.3, p < 0.001) compared with the excellent group. However, the Tumor Node Metastasis staging system and the American Thyroid Association initial risk classification did not effectively predict recurrence of DTC., Conclusions: The new DRS system was effective for predicting risk of recurrent/persistent disease in patients with DTC who underwent lobectomy or total thyroidectomy without RAI remnant ablation.