Hye-Seon Oh

Active Surveillance for Patients With Papillary Thyroid Microcarcinoma: A Single Center’s Experience in Korea

Context Papillary thyroid microcarcinoma (PTMC) usually has an excellent prognosis. Objective To evaluate the three-dimensional structures of PTMCs, using serial neck ultrasonography (US) in patients under active surveillance. Design and Setting A retrospective cohort study. Participants In total, 192 patients diagnosed with PTMC under active surveillance for >1 year were included in a median 30-month follow-up. Changes in tumor size were evaluated not only using the maximal tumor diameter but also the tumor volume. Results The median age of patients was 51.3 years and 145 patients (76%) were female. The median initial maximal tumor diameter and tumor volume were 5.5 mm and 48.8 mm3, respectively. The tumor size increased in 27 patients (14%); 23 patients showed a tumor volume increase >50% without a maximal diameter increase of ≥3 mm. The other four patients had both an increasing tumor volume and increasing maximal tumor diameter ≥3 mm. One patient (0.5%) had newly appeared cervical lymph node (LN) metastasis at 3 years after the initial diagnosis. There were no significant risk factors associated with increased tumor size, such as age, sex, or Hashimoto thyroiditis. Twenty-four patients (13%) underwent delayed thyroid surgery at a median of 31.2 months and seven (29%) had cervical LN metastasis on pathologic examination. Conclusion Some PTMCs could grow significantly after a relatively short period of active surveillance. We also found that the change in tumor volume was more sensitive to detect tumor progression than the change in the maximal tumor diameter.

Excessive Iodine Intake and Thyrotropin Reference Interval: Data from the Korean National Health and Nutrition Examination Survey

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.

Clinical outcomes after delayed thyroid surgery in patients with papillary thyroid microcarcinoma

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.

Association between urinary sodium levels and iodine status in Korea

Background/Aims To evaluate the association between the urinary sodium concentration and iodine status in different age groups in Korea. Methods This nationwide, population-based, cross-sectional study used data from the Korean National Health and Nutrition Examination Survey (VI 2-3, 2014 to 2015). We included 3,645 subjects aged 10 to 75 years with normal kidney function and without a history of thyroid disease. Adequate iodine intake was defined as a urinary iodine/creatinine (I/Cr) ratio of 85 to 220 µg/g. The urinary sodium/ creatinine (Na/Cr) ratios were classified as low (< 47 mmol/g), intermediate (47 to 114 mmol/g), or high (> 114 mmol/g). Results The median urinary iodine concentration (UIC) was 292 µg/L (interquartile range [IQR], 157 to 672), and the median urinary I/Cr ratio was 195 µg/g (IQR, 104 to 478). Iodine deficiency (< 100 µg/L) and iodine excess (> 300 µg/L) were observed in 11.3% and 49.0% of subjects, respectively. The UIC was significantly associated with the urinary sodium concentration, and the urinary I/Cr ratio was significantly correlated with the urinary Na/Cr ratio (both p < 0.001). The distributions of UIC, urinary I/Cr ratio, and Na/Cr ratio varied among age groups. Low urinary I/Cr and Na/Cr ratios were most common in young adults (age, 19 to 29 years), while high urinary I/Cr and Na/Cr ratios were most common in elderly people (age, 60 to 75 years). Conclusions Iodine intake was significantly associated with sodium intake in the Korean population. Our study suggested that an adequately low salt intake might be helpful for preventing iodine excess in Korea.

Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of the BRAFV600E Mutation in Thyroid Neoplasm

Background The BRAFV600E mutation is the most common genetic alteration identified in papillary thyroid carcinoma (PTC). Because of its costs effectiveness and sensitivity, direct Sanger sequencing has several limitations. The aim of this study was to evaluate the efficiency of immunohistochemistry (IHC) as an alternative method to detect the BRAFV600E mutation in preoperative and postoperative tissue samples. Methods We evaluated 71 patients who underwent thyroid surgery with the result of direct sequencing of the BRAFV600E mutation. IHC staining of the BRAFV600E mutation was performed in 49 preoperative and 23 postoperative thyroid specimens. Results Sixty-two patients (87.3%) had PTC, and of these, BRAFV600E was confirmed by direct sequencing in 57 patients (91.9%). In 23 postoperative tissue samples, the BRAFV600E mutation was detected in 16 samples (70%) by direct sequencing and 18 samples (78%) by IHC. In 24 fine needle aspiration (FNA) samples, BRAFV600E was detected in 18 samples (75%) by direct sequencing and 16 samples (67%) by IHC. In 25 core needle biopsy (CNB) samples, the BRAFV600E mutation was detected in 15 samples (60%) by direct sequencing and 16 samples (64%) by IHC. The sensitivity and specificity of IHC for detecting the BRAFV600E mutation were 77.8% and 66.7% in FNA samples and 99.3% and 80.0% in CNB samples. Conclusion IHC could be an alternative method to direct Sanger sequencing for BRAFV600E mutation detection both in postoperative and preoperative samples. However, application of IHC to detect the BRAFV600E mutation in FNA samples is of limited value compared with direct sequencing.

The value of preoperative anti-thyroidperoxidase antibody as a novel predictor of recurrence in papillary thyroid carcinoma: Anti-TPO antibody and clinical outcomes of PTC

The link between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC) is widely recognized. Considering the strong association between raised antithyroidperoxidase antibody (TPOAb) and CLT, we postulated that the preoperative TPOAb can predict the prognosis of PTC, particularly for recurrence. A total of 2,070 patients who underwent total thyroidectomy for classical type PTC with tumor size ≥1 cm and with available data on preoperative TPOAb and TgAb were enrolled to compare disease‐free survival (DFS) according to the presence of preoperative TPOAb, TgAb, and coexistent CLT. Patients with positive preoperative TPOAb had a significantly better DFS compared to patients without positive preoperative TPOAb (hazard ratio (HR) 0.53; 95% confidence interval (CI) 0.30–0.94, p = 0.028) while no difference in DFS was found according to preoperative TgAb status. Positive preoperative TPOAb was an independent prognostic factor for structural persistent/recurrent disease after adjustment for major preoperative risk factors such as age, sex, and tumor size (HR 0.52, 95% CI 0.28–0.99, p = 0.048). Although the coexistence of CLT lowered the risk for structural persistence/recurrence in univariate analysis (HR 0.52, 95% CI 0.31–0.86, p = 0.012), it was not an independent favorable prognostic factor by multivariate analysis (HR 0.65, 95% CI 0.38–1.10, p = 0.106). However, when coexistent CLT was combined with positive preoperative TPOAb, it indicated an independent protective role in structural persistent/recurrent disease (HR 0.39, 95% CI 0.16–0.98, p = 0.045). Our study clearly showed that presence of preoperative TPOAb can be a novel prognostic factor in predicting structural persistence/recurrence of PTC.

Do aggressive variants of papillary thyroid carcinoma have worse clinical outcome than classic papillary thyroid carcinoma

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.

Serum thyroid-stimulating hormone levels and smoking status: Data from the Korean National Health and Nutrition Examination Survey VI

We aimed to evaluate differences in serum thyroid‐stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI).

Influence of coexistent Hashimoto's thyroiditis on the extent of cervical lymph node dissection and prognosis in papillary thyroid carcinoma

Previous studies did not focus on the differences in the extent of cervical lymph node (LN) dissection according to coexistent Hashimotos thyroiditis (HT) in patients with papillary thyroid carcinoma (PTC) and its clinical impact. We aimed to determine whether extensive cervical LN dissection is responsible for favourable clinical outcomes in PTC patients with HT and whether the coexistence of HT itself has an independent protective effect regardless of LN status.

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy

Context Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. Objective We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). Methods This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Results Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Conclusions Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery.