Evaluation of medical school faculty members' educational performance in Korea in 2022 through analysis of the promotion regulations: a mixed methods study.

PURPOSE: To ensure faculty members' active participation in education in response to growing demand, medical schools should clearly describe educational activities in their promotion regulations. This study analyzed the status of how medical education activities are evaluated in promotion regulations in 2022, in Korea. METHODS: Data were collected from promotion regulations retrieved by searching the websites of 22 medical schools/universities in August 2022. To categorize educational activities and evaluation methods, the Association of American Medical Colleges framework for educational activities was utilized. Correlations between medical schools' characteristics and the evaluation of medical educational activities were analyzed. RESULTS: We defined 6 categories, including teaching, development of education products, education administration and service, scholarship in education, student affairs, and others, and 20 activities with 57 sub-activities. The average number of included activities was highest in the development of education products category and lowest in the scholarship in education category. The weight adjustment factors of medical educational activities were the characteristics of the target subjects and faculty members, the number of involved faculty members, and the difficulty of activities. Private medical schools tended to have more educational activities in the regulations than public medical schools. The greater the number of faculty members, the greater the number of educational activities in the education administration and service categories. CONCLUSION: Medical schools included various medical education activities and their evaluation methods in promotion regulations in Korea. This study provides basic data for improving the rewarding system for efforts of medical faculty members in education.

Frequency of TERT Promoter Mutations in Real-World Analysis of 2,092 Thyroid Carcinoma Patients.

BACKGRUOUND: Telomerase reverse transcriptase (TERT) promoter mutations are associated with increased recurrence and mortality in patients with thyroid carcinoma. Previous studies on TERT promoter mutations were retrospectively conducted on a limited number of patients. METHODS: We prospectively collected data on all consecutive patients who underwent thyroid carcinoma surgery between January 2019 and December 2020 at the Samsung Medical Center, Seoul, Korea. We included 2,092 patients with thyroid carcinoma. RESULTS: Of 2,092 patients, 72 patients (3.4%) had TERT promoter mutations. However, the frequency of TERT promoter mutations was 0.5% in papillary thyroid microcarcinoma (PTMC) ≤1 cm and it was 5.8% in papillary thyroid carcinoma (PTC) >1 cm. The frequency of TERT promoter mutations was significantly associated with older age at diagnosis (odds ratio [OR], 1.12; P<0.001), larger primary tumor size (OR, 2.02; P<0.001), and aggressive histological type (OR, 7.78 in follicular thyroid carcinoma; OR, 10.33 in poorly differentiated thyroid carcinoma; OR, 45.92 in anaplastic thyroid carcinoma; P<0.001). Advanced T stage, advanced N stage, and distant metastasis at diagnosis were highly prevalent in mutated thyroid cancers. However, initial distant metastasis was not present in patients with TERT promoter mutations in PTMC. Although the C228T mutation was more highly detected than the C250T mutation (64 cases vs. 7 cases), there were no significant clinicopathological differences. CONCLUSION: This study is the first attempt to investigate the frequency of TERT promoter mutations in a real-world setting. The frequency of TERT promoter mutations in PTC was lower than expected, and in PTMC, young patients, and female patients, the frequency was very low.

Bone Mineral Density Screening Interval and Transition to Osteoporosis in Asian Women.

BACKGRUOUND: Bone mineral density (BMD) testing is indicated for women aged 65 years, but screening strategies for osteoporosis are controversial. Currently, there is no study focusing on the BMD testing interval in Asian populations. The current study aimed to evaluate the estimated time interval for screening osteoporosis. METHODS: We conducted a study of 6,385 subjects aged 50 years and older who underwent dual-energy X-ray absorptiometry screening more than twice at Samsung Medical Center as participants in a routine health checkup. Subjects were divided based on baseline T-score into mild osteopenia (T-score, <-1.0 to >-1.5), moderate osteopenia (T-score, ≤-1.5 to >-2.0), and severe osteopenia (T-score, ≤-2.0 to >-2.5). Information about personal medical and social history was collected by a structured questionnaire. RESULTS: The adjusted estimated BMD testing interval for 10% of the subjects to develop osteoporosis was 13.2 years in mild osteopenia, 5.0 years in moderate osteopenia, and 1.5 years in severe osteopenia. CONCLUSION: Our study provides extended information about BMD screening intervals in Asian female population. Baseline T-score was important for predicting BMD screening interval, and repeat BMD testing within 5 years might not be necessary in mild osteopenia subjects.

Metastatic Lymph Node Ratio for Predicting Recurrence in Medullary Thyroid Cancer.

The lymph node ratio (LNR) has been investigated as a prognostic factor in many different types of cancers, including differentiated thyroid cancer; however, reports regarding medullary thyroid cancer (MTC) are limited. Therefore, this study aims to evaluate LNR as a risk factor for structural recurrence in patients with MTC. Medical records of patients treated for MTC in a single tertiary center between 1995 and 2017 were retrospectively reviewed. LNR is defined as the number of metastatic lymph nodes or lymph node metastases (LNM) divided by the number of retrieved lymph nodes or lymph node yield (LNY). In the survival analysis, recurrence-free survival was defined as the time from the date of total thyroidectomy to recurrence or last follow-up. To identify risk factors influencing structural recurrence, univariable and multivariable Cox proportional hazard models were used. A total of 132 patients were enrolled. The mean age of study participants was 49.7 years, and 86 patients (65%) were women. Structural recurrence was identified in 39 patients at the end of the study period, and the median follow-up period was 8.7 years. In univariable analyses, gross extra thyroidal extension, N stage, postoperative serum calcitonin and carcinoembryonic antigen (CEA) levels, and LNR were significant (p < 0.05) predictors of structural recurrence. In multivariable analysis, postoperative serum calcitonin, postoperative serum CEA, and LNR were identified as a predictor of disease-free survival (p < 0.05). LNR can potentially predict structural recurrence as a quantitative evaluation tool for lymph node metastasis in patients with MTC.

Beneficial effects of posttransplant dipeptidyl peptidase-4 inhibitor administration after pancreas transplantation to improve ß cell function.

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels and enhance the function of pancreatic ß cells. Yet, it is unknown whether posttransplant administration of DPP4 inhibitors is beneficial for pancreas transplant recipients. METHODS: We thus retrospectively analyzed the records of 312 patients who underwent pancreas transplantation between 2000 and 2018 at Asan Medical Center (Seoul, Korea) and compared the metabolic and survival outcomes according to DPP-4 inhibitor treatment. RESULTS: The patients were divided into the no DPP-4 inhibitor group (n = 165; no treatment with DPP-4 inhibitors or treated for <1 month) and the DPP-4 inhibitor group (n = 147; treated with DPP-4 inhibitors for ≥1 month). There were no significant differences in levels of glucose, hemoglobin A1c, and insulin between the 2 groups during 36 months of follow-up. However, the level of C-peptide was significantly higher in the DPP-4 inhibitor group at 1, 6, and 24 months posttransplant (all P < 0.05). Moreover, the DPP-4 inhibitor group had significantly higher rates of overall (log-rank test, P = 0.009) and death-censored (log-rank test, P = 0.036) graft survival during a 15-year follow-up. CONCLUSION: Posttransplant DPP-4 inhibitor administration may help improve the clinical outcomes including ß cell function after pancreas transplantation.

Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors.

Background: Although the incidence of thyroid cancer had been increasing until a few years ago, a decrease has been observed in the last years, probably due to the reduction of the screening tests in Korea. Childhood thyroid cancer has been increasing in the past with the same trend as in adults, but there have been few reports on recent trends. We analyzed the trends of thyroid cancer in Korean children and related factors. Methods: From national statistics and cancer register database, the data of age-specific incidence rate in Korean childhood thyroid cancer from 1999 to 2017 was obtained, and levels of seaweed intake, the number of computed tomography (CT) and neck ultrasonography (US), obesity prevalence rate, and smoking and alcohol consumption rates in children were analyzed. Results: The age-specific incidence of thyroid cancer in Korean children has increased in both genders between 1999 and 2017 (2.0 in 1999 vs. 7.2 in 2017, per population of 100,000), especially in the age group of 14-18 years (1.5 in 1999 vs. 5.5 in 2017, per population of 100,000). During the same period, levels of seaweed intake, number of CT scans and neck US, and prevalence of obesity in children increased significantly, while childhood smoking and alcohol consumption rates decreased. Conclusion: Unlike the adult thyroid cancer in Korea, childhood thyroid cancer continues to increase, and the cause might be accompanied by actual increases due to the environmental factors such as excessive iodine intake, exposure to medical radiation, and increased obesity prevalence as well as the screening effect.

Changes in Thyrotropin Receptor Antibody Levels Following Total Thyroidectomy or Radioiodine Therapy in Patients with Refractory Graves' Disease.

Background: The actions of thyrotropin-binding inhibitory immunoglobulins (TBIIs) against thyrotropin receptors in thyroid follicular cells have been studied as important etiological factors in Graves' disease (GD). The purpose of this study was to investigate changes in the TBII levels of patients undergoing total thyroidectomy (TTx) or radioactive iodine (RAI) therapy for GD refractory to antithyroid drugs (ATDs). Methods: We enrolled patients who underwent TTx or RAI for GD with previous ATD use between January 2011 and December 2017 at the Samsung Medical Center in Seoul, Korea. Thorough retrospective reviews of medical records were performed in 130 patients. Results: Patients with goiter, ophthalmopathy, high levels of TBIIs, and high doses of ATDs received TTx. Elderly patients with arrhythmia received RAI. We observed that TBII levels continued to decrease after TTx. On the contrary, TBIIs initially increased for 138 days (estimated median time) and then decreased slowly after RAI. A faster decline in TBII levels was observed in the TTx group than in the RAI group (p < 0.001). The estimated median time for TBIIs to decrease below 4.5 IU (3 × upper normal limit, which is known to be a risk factor for fetal hyperthyroidism) was 318 days in the TTx group and 659 days in the RAI group, respectively. In the RAI group, high levels of TBII (>4.5 IU/L) were present in 70 (82%) at 6 months, 57 (67%) at 1 year, and 3 (3%) at 2 years. In the TTx group, rapid decreases in TBII levels were observed in younger patients and those with lower baseline TBII levels. In the RAI group, smaller thyroid volume was correlated with more rapid decrease in TBII levels. Conclusions: The changes in TBII levels following TTx or RAI were different in patients with refractory GD. When deciding on TTx or RAI, this difference should be considered with patient age, severity of hyperthyroidism, goiter, ophthalmopathy, and future pregnancy plans (for young female patients).

Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research.

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1-10%), salicylic acid (0.2-2%), and lactobionic acid (1.2-12%) were used as representative substances for α-hydroxyacid (AHA), ß-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50-80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

Acute T cell-mediated rejection after administration of the BNT162b2 mRNA COVID-19 vaccine in a kidney transplant recipient: a case report.

The impact of the coronavirus disease 2019 (COVID-19) vaccination on humoral and cellular immunity in transplant recipients remains unknown. We report the case of a 78-year-old kidney transplant recipient who experienced acute T cell-mediated rejection after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech). She had no history of acute rejection throughout the 13 years after deceased donor kidney transplantation. Fifteen days after receiving the second dose of the BNT162b2 vaccine, the recipient visited our center with a mild headache and fever. Her serum creatinine level had increased from 0.61 to 4.95 mg/dL. Kidney allograft biopsy indicated acute T cell-mediated rejection (grade IB) with no pathologic evidence of antibody-mediated rejection. Anti-severe acute respiratory syndrome coronavirus 2 spike-immunoglobulin G and -immunoglobulin M measurements were weak positive and negative, respectively. Careful monitoring of kidney allograft function is vital for transplant recipients undergoing COVID-19 vaccination.

Changes in plasma volume before and after major abdominal surgery following stroke volume variation-guided fluid therapy: a randomized controlled trial.

BACKGROUND: The aim of intraoperative fluid therapy is to avoid both hypovolemia and hypervolemia; however, the patient's exact volume status is difficult to determine during surgery. Fluid optimization guided by stroke volume variation (SVV) has been widely used in patients undergoing major open abdominal surgery. The aim of this study was to evaluate the changes in plasma volume before and after surgery following SVV-guided fluid therapy. METHODS: Patients were randomly allocated into one of two groups according to the SVV criteria for fluid administration during surgery. In the fixed SVV fluid strategy group, fluid was administered to maintain the SVV below 13%. In the individual SVV group, individual SVV values of each patient were maintained until the end of surgery. Plasma volume, body weight, and extracellular water (ECW) were measured before and after surgery. Plasma volume was estimated using the indocyanine green dilution technique. RESULTS: A total of 118 patients were included. Median (25-75%) plasma volumes in the preoperative and postoperative period were 2.46 (2.20-2.88) L and 2.69 (2.33-3.12) L for the fixed SVV group (N.=57, P=0.133), respectively, and 2.56 (2.23-2.90) L and 2.89 (2.48-3.19) L for the individual SVV group (N.=61, P<0.001), respectively. CONCLUSIONS: Fluid administration during surgery to maintain SVV below 13% was effective for maintaining the preoperative plasma volume until the end of surgery in patients undergoing major open stomach or colorectal surgery. This result supports the validity of SVV-guided fluid therapy, which maintains the SVV value below 13%, in terms of maintaining patient volume status.

Lysates of a Probiotic, Lactobacillus rhamnosus, Can Improve Skin Barrier Function in a Reconstructed Human Epidermis Model.

The main function of the skin is to protect the body from the external environment. The barrier function of the skin is mainly provided by the stratum corneum, which consists of corneocytes bound with the corneodesmosomes and lamellar lipids. Skin barrier proteins like loricrin and filaggrin also contribute to the skin barrier function. In various skin diseases, skin barrier dysfunction is a common symptom, and skin irritants like detergents or surfactants could also perturb skin barrier function. Many efforts have been made to develop strategies to improve skin barrier function. Here, we investigated whether the microfluidized lysates of Lactobacillus rhamnosus (LR), one of the most widely used probiotic species for various health benefits, may improve the skin barrier function in a reconstructed human epidermis, Keraskin™. Application of LR lysate on Keraskin™ increased the expression of tight junction proteins; claudin 1 and occludin as determined by immunofluorescence analysis, and skin barrier proteins; loricrin and filaggrin as determined by immunohistochemistry and immunofluorescence analysis and qPCR. Also, the cytotoxicity of a skin irritant, sodium lauryl sulfate (SLS), was alleviated by the pretreatment of LR lysate. The skin barrier protective effects of LR lysate could be further demonstrated by the attenuation of SLS-enhanced dye-penetration. LR lysate also attenuated the destruction of desmosomes after SLS treatment. Collectively, we demonstrated that LR lysate has protective effects on the skin barrier, which could expand the utility of probiotics to skin-moisturization ingredients.

Impact of Polyimide Film Thickness for Improving the Mechanical Robustness of Stretchable InGaZnO Thin-Film Transistors Prepared on Wavy-Dimensional Elastomer Substrates.

We report on the In-Ga-Zn-O thin-film transistors (IGZO TFTs) with outstanding mechanical stretchability, which were fabricated on ultrathin polyimide (PI) film/prestrained elastomer with a wavy-dimensional structure. The device characteristics of the fabricated devices were evaluated under mechanically strained conditions with various strains. The operational reliabilities against the bias stress conditions and during the cyclic stretching tests were also carefully examined. The stretchable IGZO TFTs exhibited good device operations without any marked degradation under stretching/compressed conditions with a strain of 40%. Under positive bias stress with a prestrain of 50%, the turn-on voltage instabilities for the TFTs prepared on 0.9 and 2.0 µm-thick PI films were estimated to be 1.5 and 3.9 V, respectively. During the cyclic stretching tests with a strain of 50%, the device operations failed after 20,000 and 100,000 stretching cycles for the TFTs fabricated on 2.0 and 0.9 µm-thick PI films, respectively. As a result, the IGZO TFTs fabricated on a thinner PI film presented more reliable operations after the repeated stretching events. The robust mechanical stretchability dependent on the PI film thickness was suggested to be due to the difference in critical values of bending radii and the influence of the local strain induced by the spatial fluctuations of the wavy structures.

Urinary iodine concentration and thyroid hormones: Korea National Health and Nutrition Examination Survey 2013-2015.

PURPOSE: An epidemiologic study that evaluated population's iodine nutrition status and its relationship with thyroid hormones is lacking in iodine-sufficient area. This nationwide study aimed to evaluate the iodine nutrition status in Korea and relationship between urine iodine concentration (UIC) and thyroid hormones. METHODS: A total of 8318 subjects of the Korea National Health and Nutrition Examination Survey VI (2013-2015) with UIC and thyroid hormone evaluation were included. Median UIC level and estimated 24-h iodine intake were calculated. The prevalence of iodine deficiency or excess was obtained using estimated average requirement or above the tolerable upper intake level cut-point method by estimated iodine intake. We analyzed UIC with regard to age, sex, social economic status, and geographic characteristics. RESULTS: The median UIC in general population and estimated iodine intake in adult population were 293.9 µg/L (above requirement according to World Health Organization classification) and 249.3µg/day, respectively. The prevalence of iodine deficiency and excess was 14.0 and 13.4%. The median UIC was higher among SAC [511 (299.9-948.5)] and lower among seventies [251.2 (98.9-761.6)] compared to other age groups. The median UIC increased with household income level (p for trend < 0.001). The subjects living in rural and inland region had lowest UIC among the enrolled subjects. The subgroups with higher median UIC were associated with higher mean TSH levels. CONCLUSIONS: This first nationwide study in Korea demonstrated that the median of UIC and estimated iodine intake lie at nearly 300 µg/L and 250 µg/day, respectively, which shows an overall excellent iodine nutrition.

Non-immune-related hypothyroidism and its relationship with excess iodine.

PURPOSE: In iodine-sufficient areas, autoimmune hypothyroidism has been regarded as the major subtype of hypothyroidism. Non-immune-related hypothyroidism has received little attention because it is considered to be rare. The aim of this study was to evaluate the prevalence of non-immune-related hypothyroidism in Korea and to identify its associating factors. METHODS: A total of 6434 participants in the Korea National Health and Nutrition Examination Survey VI (2013-2015) without known thyroid disease who were examined for thyroid stimulating hormone, free thyroxine, TPO Ab, and urine iodine concentration (UIC) were enrolled. The weighted proportions, demographic variables, and severity of immune-related and non-immune-related hypothyroidism were compared. To assess the effect of iodine on hypothyroidism in TPO Ab positive or negative populations, the weighted prevalence of hypothyroidism was assessed in each population according to UIC or estimated iodine intake subgroups. RESULTS: The prevalence of undetected hypothyroidism in Korea was 3.8% (n = 233). Of these 233 cases, 171 (71.8%) were non-immune-related. In the TPO Ab negative population, the prevalence of hypothyroidism was increased significantly in the subgroup with UIC between 250 and 749 µg/L (HR 2.12 [1.17, 3.83]) and ≥ 750 µg/L (HR 3.42 [1.93, 6.04]) or the subgroups with estimated iodine intake ≥ 750 µg/day (HR 2.81 [1.64, 4.80]). CONCLUSIONS: This nationwide study demonstrated that most cases of hypothyroidism in iodine-sufficient areas are non-immune-related and are associated with excess iodine above a certain level. More attention to this unrecognized but widespread potential health risk is needed.

In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the Lateral Ventricle and Cisterna Magna in Rat Model.

OBJECTIVE: The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. METHODS: We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. RESULTS: Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. CONCLUSION: These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.

Use of dynamic images in radiology education: Movies of CT and MRI in the anatomy classroom.

Radiology education is a key component in many preclinical anatomy courses. However, the reported effectiveness of radiology education within such anatomy classrooms has varied. This study was conducted to determine if a novel educational method using dynamic images of movies of computed tomography (CT) and magnetic resonance imaging (MRI) was effective in radiology education during a preclinical anatomy course, aided by clay modeling, specific hand gestures (digit anatomy), and reports from dissection findings uploaded to the anatomy course website (digital reports). Feedback surveys using a five-point Likert scale were administered to better clarify students' opinions regarding their understanding of CT and MRI of anatomical structures, as well as to determine if such preclinical radiology education was helpful in their clinical studies. After completion of the anatomy course taught with dynamic images of CT and MRI, most students demonstrated an adequate understanding of basic CT and MR images. Additionally, students in later clinical years generally believed that their study of radiologic images during the preclinical anatomy course was helpful for their clinical studies and clerkship rotations. Moreover, student scores on imaging anatomy examinations demonstrated meaningful improvements in performance after using dynamic images from movies of CT and MRI.

Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: Data from Korean National Health and Nutrition Examination Survey IV (2013-2015).

BACKGROUND: Establishment of the reference interval of thyroid-stimulating hormone (TSH) is critical in the diagnosis of thyroid dysfunction and is affected by age, gender, iodine nutrition, and ethnicity. The aim of this study was to determine the reference intervals of TSH and free thyroxin (FT4) from a large, nationwide data of Korea where iodine intake is more than adequate. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey VI that measured serum TSH, FT4, and thyroid peroxidase antibody from 7,061 individuals (urinary iodine measurement in 6,565). Age- and gender-specific reference intervals were established from 95% confidence limits from the 2.5 to 97.5 percentile of TSH (log-transformed) and FT4 in reference populations. RESULTS: The geometric mean of TSH was 2.16 ± 0.01 mIU/L, with the lowest value found in the middle aged group (2.04 ± 0.02 mIU/L) and higher values noted in age groups of 10-19 and over 70 years (2.38 ± 0.02 and 2.32 ± 0.07 mIU/L, respectively). The association of TSH and age was U-shaped. The overall reference interval of TSH was 0.59-7.03 mIU/L. Mean FT4 was 1.25 ± 0.003 ng/dL (16.09 ± 0.039 pmol/L), and it showed a small but continuous decrease after 20 years of age (P < 0.001). There was a significant positive correlation between TSH and urine iodine concentration (r = 0.154, P < 0.001). CONCLUSIONS: The reference interval of TSH in Korea, where iodine intake is above the requirement, was 0.59-7.03 mIU/L and showed U-shaped change with age, which was a similar pattern to iodine intake. The reference interval of FT4 was 0.92-1.60 ng/dL. The geometric mean and upper limit of TSH were higher than those of Western populations, reflecting the paramount importance of iodine intake on thyroid function.

Reference intervals of thyroid hormones during pregnancy in Korea, an iodine-replete area.

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.

High Serum TSH Level Is Associated With Progression of Papillary Thyroid Microcarcinoma During Active Surveillance.

Objective: Thyroid-stimulating hormone (TSH) is a growth factor affecting initiation or progression of papillary thyroid cancer (PTC), which supports TSH suppressive therapy in patients with PTC. In patients with papillary thyroid microcarcinoma (PTMC) during active surveillance, however, the association between serum TSH level and growth of PTMC has not been demonstrated. Patients: We analyzed 127 PTMCs in 126 patients under active surveillance with serial serum TSH measurement and ultrasonography. Design: The patients were categorized into groups with the highest, middle, and lowest time-weighted average of TSH (TW-TSH). PTMC progression was defined as a volume increase of ≥50% compared with baseline. Kaplan-Meier survival analysis according to TW-TSH groups and Cox proportional hazard modeling was performed. We identified the cutoff point for TSH level by using maximally selected log-rank statistics. Results: During a median follow-up of 26 months, PTMC progression was detected in 28 (19.8%) patients. Compared with the lowest TW-TSH group, the adjusted hazard ratio (HR) for PTMC progression in the highest TW-TSH group was significantly higher [HR 3.55; 95% confidence interval (CI), 1.22 to 10.28; P = 0.020], but that in the middle TW-TSH group was not (HR 1.52; 95% CI, 0.46 to 5.08; P = 0.489). The cutoff point for the serum TSH level for PTMC progression was 2.50 mU/L. Conclusions: Sustained elevation of serum TSH levels during active surveillance is associated with PTMC progression. Maintaining a low-normal TSH range with levothyroxine treatment during active surveillance of PTMC might be considered in future studies.

Restratification of survival prognosis of N1b papillary thyroid cancer by lateral lymph node ratio and largest lymph node size.

The current 7th TNM staging stratifies N1b papillary thyroid cancer (PTC) patients without distant metastasis into either stage I or stage IV merely by an age threshold (45 years). To date, no studies have adequately quantified the mortality risk of PTC patients with N1b disease. We hypothesized that incorporating lymph node (LN) factors into the staging system would better predict cancer-specific mortality (CSM). A total of 745 nonmetastatic PTC patients with N1b disease were enrolled. We identified factors related to LNs and cut-points using Cox regression and time-dependent ROC analysis. New prognostic groupings were derived based on minimal hazard differences for CSM among the groups stratified by LN risk and age, and prediction of CSM was assessed. Lateral lymph node ratio (LNR) and largest LN size were significant prognostic LN factors at cut-points of 0.3 and 3 cm. Without LN risk (lateral LNR >0.3 or largest LN size >3 cm), stage IV patients had prognosis [adjusted HR 1.10 (98% CI 0.19-6.20); P = 0.906] similar to stage I patients with LN risk. Patients were restratified into three prognostic groups: Group 1, <45 years without LN risk; Group 2, <45 years with LN risk or ≥45 years without LN risk; and Group 3, ≥45 with LN risk. This system had a lower log-rank P-value (<0.001 vs. 0.002) and higher C-statistics (0.80 vs. 0.71) than the 7th TNM. New prognostic grouping using lateral LNR and largest LN size predicts CSM accurately and distinguishes N1b patients with different prognosis.