Tuning the Threshold Voltage of an Oxide Thin-Film Transistor by Electron Injection Control Using a p-n Semiconductor Heterojunction Structure.

Herein, a heterojunction structure integrating p-type tellurium (Te) and n-type aluminum-doped indium-zinc-tin oxide (Al:IZTO) is shown to precisely modulate the threshold voltage (VT) of the oxide thin-film transistor (TFT). The proposed architecture integrates Te as an electron-blocking layer and Al:IZTO as a charge-carrier transporting layer, thereby enabling controlled electron injection. The effects of incorporating the Te layer onto Al:IZTO are investigated, with a focus on X-ray photoelectron spectroscopy (XPS) analysis, in order to explain the behavior of oxygen vacancies and to depict the energy band structure configurations. By modulating the thickness and employing both single and double deposition methods for the heterojunction Te layer, a remarkable VT shift of up to +20 V is achieved. Furthermore, this study also shows excellent stability to a positive bias stress of +2 MV/cm for 10,000 s without additional passivation layers, demonstrating the robustness of the designed TFT. By a thorough optimization of the Al:IZTO/Te interface, the results demonstrate not only the substantial impact of the introduced heterojunction structure on VT control but also the endurance, durability, and stability of the optimized TFTs under prolonged long-term operating stress, thus offering promising prospects for tailored semiconductor device applications.

Prognostic Roles of Inflammatory Biomarkers in Radioiodine-Refractory Thyroid Cancer Treated with Lenvatinib.

BACKGRUOUND: Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. METHODS: This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. RESULTS: No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). CONCLUSION: Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

Inflammatory biomarkers predict outcomes of patients with radioactive iodine refractory thyroid cancer treated with sorafenib.

BACKGROUND: The objective of this multicenter, retrospective cohort study was to evaluate the ability of inflammatory biomarkers representing the host immune system to predict outcomes in 70 patients with progressive radioactive iodine (RAI)-refractory thyroid cancer who were treated with sorafenib. METHOD: Patients were divided into low and high inflammatory biomarker groups based on median values. Progression-free survival (PFS) and overall survival (OS) were assessed based on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). RESULTS: The median LMR, NLR, and PLR values were 3.4, 2.2, and 140.1, respectively. No significant differences were observed in baseline characteristics of high and low LMR, NLR and PLR groups. Median PFS values were 6.6 and 19.5 months in the low and high LMR groups, respectively (P < 0.001). Compared with the high NLR and PLR groups, PFS was significantly prolonged in the low NLR and PLR groups (P = 0.003 and P = 0.041 respectively). In the multivariate analysis, low LMR and high NLR were associated with poor PFS after adjusting for multiple confounding factors including age, sex, pathology, disease-related symptoms, serum thyroglobulin level, lung-only metastasis, cumulative RAI dose, time from diagnosis, and longer diameter of the target lesion (hazard ratio, HR = 2.42; 95% confidence interval, CI 1.25-4.71; P = 0.009, and HR = 2.09; CI, 1.06-4.14; P = 0.033, respectively). High LMR, low NLR, and low PLR were significantly associated with prolonged OS (P = 0.011, P = 0.023, and P = 0.007, respectively). Patients with at least one risk factors for inflammatory biomarkers presented a significantly lower PFS (HR 2.29; CI, 1.36-3.84; P = 0.003) and OS (HR 2.95; CI, 1.49-5.81; P = 0.006) than patients without any risk factor. CONCLUSION: Baseline inflammatory biomarkers successfully predicted PFS and OS in patients with progressive RAI-refractory thyroid cancer treated with sorafenib. These prognostic biomarkers might help arrive at appropriate clinical decisions regarding the use of sorafenib.

Lenvatinib Compared with Sorafenib as a First-Line Treatment for Radioactive Iodine-Refractory, Progressive, Differentiated Thyroid Carcinoma: Real-World Outcomes in a Multicenter Retrospective Cohort Study.

Background: Sorafenib and lenvatinib have been widely adopted to treat radioactive iodine (RAI)-refractory differentiated thyroid carcinoma (DTC). However, limited data exist regarding a direct comparison of these tyrosine kinase inhibitors (TKIs). We aimed to evaluate the clinical efficacy and safety of two TKIs as first-line therapy in patients with distant metastatic or locally advanced, progressive, RAI-refractory DTC in real-world practice. Methods: In this multicenter, retrospective cohort study, we evaluated 136 patients with progressive distant metastatic or locally advanced, progressive, RAI-refractory DTC or poorly differentiated thyroid carcinoma (PDTC) who received first-line sorafenib or lenvatinib treatment. The primary outcome was progression-free survival (PFS). We also evaluated the objective response rate, disease-control rate, clinical benefit rate, and safety. Results: The median age of the patients was 68 years, and 35% (47/136) were male. Eighty and fifty-six patients were included in the sorafenib and lenvatinib groups, respectively. The median PFS was 13.3 months [95% confidence interval, CI, 9.9-18.1 months] in the sorafenib group and 35.3 months [CI, 18.2 months to upper limit not reported as the median was not reached] in the lenvatinib group (p = 0.001). A significantly prolonged PFS was observed in the lenvatinib group (compared with the sorafenib group) after adjusting for age, sex, pathology, disease-related symptom, lung-only metastasis, cumulative RAI dose, time from diagnosis, treatment duration, and longest diameter of the target lesion (hazard ratio = 0.34, CI, 0.19-0.60, p < 0.001). The partial response rate was 24% and 59% in the sorafenib and lenvatinib groups, respectively (p < 0.001). More common grade 3-4 adverse events were hypertension (16%, 9/56 vs. 1%, 1/80, p = 0.002) and proteinuria (32%, 18/56 vs. 0%, p < 0.001) in the lenvatinib group, and hand-foot skin reaction (24%, 19/80 vs. 4%, 2/56, p = 0.001) in the sorafenib group. Conclusion: In our study of Asian patients, first-line lenvatinib treatment of metastatic or locally advanced, progressive, RAI-refractory DTC or PDTC was associated with a longer PFS compared with sorafenib. However, severe hypertension and proteinuria were observed more frequently after lenvatinib treatment than after sorafenib treatment.

Serum Selenium Levels in Patients with Graves Disease: Associations with Clinical Activity and Severity in a Retrospective Case-control Study.

PURPOSE: To compare serum selenium levels in Graves patients and non-Graves control participants and to evaluate associations between serum selenium levels and clinical features of Graves orbitopathy (GO). METHODS: We conducted a single-center, retrospective case-control study among 33 patients with Graves disease without GO (GD), 31 patients with diagnosed GO, and 27 unaffected healthy participants enrolled between 2013 and 2020 at Severance Hospital. We compared serum selenium concentrations between the GD, GO, and healthy control groups, and analyzed associations between serum selenium and GO patients' clinical activity scores, severity (assessed through modified NOSPECS scores), and other clinical features using multivariate linear regression analysis. RESULTS: Mean serum selenium levels were 109.30 ± 16.39, 111.39 ± 14.04, and 126.09 ± 21.09 ng/mL in GO patients, GD patients, and healthy control participants, respectively. Mean serum selenium levels in Graves patients with and without orbitopathy were significantly lower than those in the healthy control group (p < 0.05), and mean selenium levels were slightly lower in GO than those in GD patients (p = 0.594). Serum selenium levels were significantly lower in GO patients with eyelid retraction than in patients without retraction (p = 0.038). However, serum selenium levels were not associated with clinical activity scores and modified NOSPECS scores (p = 0.241 and 0.801, respectively). CONCLUSIONS: Serum selenium levels were significantly lower in Graves patients with or without GO, compared to non-Graves control participants. Selenium levels were not associated with clinical activity scores or NOSPECS scores, though we observed an association with eyelid retraction.

The Use of a Light-Emitting Diode Device for Neck Rejuvenation and Its Safety on Thyroid Glands.

Home-use light-emitting diodes (LEDs) are attracting growing attention regarding their anti-aging effects. Although most previous studies on the use of LED devices as a form of low-level laser therapy reported no significant adverse events, questions regarding the safety of using a light source on secretory tissues have been raised. This study aimed to assess the safety and efficacy of a home-use LED device for neck skin rejuvenation, particularly regarding its effect on thyroid gland morphology and function. Thyroid function tests and ultrasonographic analyses showed no significant changes after 16 weeks of LED use. Evaluation using the Lemperle wrinkle scale and global improvement scales by both investigators and subjects showed significant improvement after 16 weeks of daily application, as well as 8 weeks after discontinuation. Biophysical parameters, such as hydration, elasticity, and density, also showed significant improvements. Hence, the long-term use of the LED device was safe and effective for neck rejuvenation, and showed no significant side effects on the adjacent thyroid and parathyroid glands.

Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights.

REGISTERED CLINICAL TRIAL: [NCT03677921]; www.clinicaltrials.gov [KCT0002726]; https://cris.nih.go.kr.

Unusual metastases from differentiated thyroid cancers: A multicenter study in Korea.

BACKGROUND: Although infrequent, distant metastasis from differentiated thyroid cancer is the main cause of mortality in patients and mostly involves the lung, bone, and brain. Distant metastases to other sites in differentiated thyroid cancer patients are rare, thus, the clinical course of unusual metastases has not been adequately researched. In the present study, the clinico-pathological findings and treatment outcomes of unusual metastases in differentiated thyroid cancer patients in Korea were evaluated. PATIENTS AND METHODS: We retrospectively reviewed the medical records of differentiated thyroid cancer patients with unusual metastases in four Korean tertiary hospitals (Chonnam National University Hwasun Hospital, Asan Medical Center, Busan National University Hospital, Severance Hospital). Unusual metastases were diagnosed using (1) cytology or histology and/or (2) imaging studies including fluorodeoxyglucose F 18 positron emission tomography/computed tomography and/or iodine 131 whole body scans with simultaneously elevated serum levels of thyroglobulin. The pathological findings of primary thyroid cancer, diagnostic method for unusual metastases, and treatment responses of unusual metastases were examined. RESULTS: In all, 25 unusual metastatic foci of 19 patients were analyzed; 13 patients (68.4%) had papillary thyroid carcinoma including 4 follicular variant papillary thyroid carcinomas. The median time interval between the first diagnosis of primary thyroid cancer and unusual metastases diagnosis was 110 months (11.0-138.0 months). Only 4 patients (21.1%) had synchronous unusual metastases and 6 patients (31.6%) were symptomatic. Unusual metastases included 19 metastases to solid organs (6 to kidney, 5 to liver, 4 to pancreas, 3 to adrenal gland, and 1 to ovary) and 6 to the skin and muscles. Unusual metastases were pathologically proven in 10 patients (52.6%) and 11 of 16 patients (68.8%) who received iodine 131 whole body scans had radioiodine-refractory differentiated thyroid cancer. Among 5 patients treated with tyrosine kinase inhibitors, 4 treated with lenvatinib showed stable disease or a partial response at the first treatment response. Six patients (31.6%) died due to disease progression during the median 20.0-month follow-up period (11.0-55.0 months). CONCLUSION: Unusual metastases from differentiated thyroid cancer are thought to be underestimated due to disease rarity and their metachronous nature with other distant metastases. The most of unusual metastases in differentiated thyroid cancer patients are existed with usual distant metastasis and clinical outcomes of those could not be significantly different from the prognosis of usual distant metastasis.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Lenvatinib for Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma and Candidate Biomarkers Associated with Survival: A Multicenter Study in Korea.

Background: Lenvatinib, an oral multikinase inhibitor, is the latest addition to the treatment options for radioactive iodine (RAI)-refractory progressive differentiated thyroid carcinoma (DTC). This study investigated the efficacy of lenvatinib in real-world practice and prognostic biomarkers of survival. Methods: This multicenter study included 43 patients receiving lenvatinib as first-line or second-line treatment after sorafenib for RAI-refractory DTC. Progression-free survival (PFS) was evaluated according to various clinical factors including thyroglobulin doubling time (TgDT), tumor volume DT (TVDT), and tumor growth slope (TGS; slope of tumor change rate). Results: Patients were treated with lenvatinib for a median of 14 months; 32 were previously treated with sorafenib. The median follow-up from lenvatinib initiation to the last censoring or death was 16 months. The median starting dose of 20 mg was reduced to a median sustainable dose of 10 mg in accordance with patient adverse events (AEs). The median PFS was 21.8 months; the median overall survival was not reached. The disease control rate was 97.7%, with the first objective response at 3.8 months. PFS was not significantly associated with previous sorafenib treatment, metastatic sites, or sustainable dose. TGS measured before (TGSpre, p = 0.003) and after (TGSpost, p = 0.036) the initiation of lenvatinib was associated with PFS. The sum of the largest diameters of target lesions (p = 0.043) and TgDT (p = 0.024) were associated with PFS, but TVDT calculated before (TVDTpre, p = 0.923) or after (TVDTpost, p = 0.966) lenvatinib treatment did not impact PFS. Lenvatinib was withdrawn in 24 patients (55.8%): in 6 patients because of treatment-induced AEs and in 18 patients because of disease progression or poor performance status. AEs of any grade were reported in all patients, and grade 3-4 AEs in 23.2% of the patients. The most frequent AE was fatigue or asthenia. Conclusions: Our results indicate that reduced doses of lenvatinib triggered by emergent AEs did not abrogate its apparent efficacy in patients with RAI-refractory DTCs. Rather, the sustained use of reduced doses of lenvatinib with a low rate of severe AEs may have contributed to the favorable outcomes. TgDT and TGS can assist in predicting the outcomes in these patients.

Effect of Steamed Onion (ONIRO) Consumption on Body Fat and Metabolic Profiles in Overweight Subjects: A 12-Week Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: The aim of the study is to investigate the effect of Jeju steamed onion (ONIRO) on body fat and metabolic profiles in overweight subjects.Methods: This randomized, double-blind, placebo-controlled clinical intervention was conducted and completed at one clinical research site. The subjects (n = 70) were randomly divided into placebo or test group and were instructed to take before each meal either the placebo or ONIRO capsule for 12 weeks. Anthropometric as well as serum and metabolic parameters, including triglycerides, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, leptin, adiponectin, C-peptide, and aspartate aminotransferase (AST) were measured at baseline and after 12 weeks. Body composition was also measured by dual-energy x-ray absorptiometry (DEXA) and computed tomography (CT). This trial is registered under the trial registration code clinicaltrials.gov: NCT03645382 (https://register.clinicaltrials.gov).Results: Compared to the placebo, ONIRO supplementation for significantly reduced the percentage of body fat and fat mass as measured by DEXA (p = 0.028 and 0.022, respectively) with no significant effects on lean body mass. CT analyses at the L1 level showed a significant decrease in the areas of whole fat, visceral fat, and subcutaneous fat (p = 0.009, p = 0.039, p = 0.020, respectively), while CT scan of L4 resulted in a significant reduction of whole fat area and subcutaneous area (p = 0.006 and p = 0.012, respectively). The levels of triglycerides (TG) and C-peptide were significantly lower after 12 weeks of ONIRO treatment.Conclusions: These findings suggest that ONIRO supplementation reduces total body fat, notably abdominal visceral fat, with positive changes of the clinically relevant metabolic parameters serum TG and C-peptide.

Actual causes of death in thyroid cancer patients in Korea: A Nationwide Case Control Cohort Study.

OBJECTIVE: Thyroid cancer (TC) incidence has increased robustly in Korea. However, the actual cause of death, overall mortality risk, and cause-specific mortality risk in TC patients have not been clearly elucidated. DESIGN: Retrospective cohort study. METHODS: We analyzed 4082 TC patients from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS, 2002-2013) with a median of 48-month follow-up. We compared these patients with 12 246 controls matched for age, sex, and histories of major cardiovascular disease (CVD) to investigate the cause of death and risks of overall and cause-specific mortality. RESULTS: Overall, 61 deaths (1.5%) occurred in the TC group. The most common cause of death was TC-specific mortality (32.8%), followed by other malignancy-related mortality (31.1%) and CVD mortality (13.1%). The overall mortality risk was comparable between the TC and control groups (unadjusted hazard ratio (HR): 1.17; 95% confidence interval (CI): 0.87-1.58); the adjusted HR remained at 1.25 (95% CI: 0.90-1.74) after multivariate adjustment for body mass index (BMI), socioeconomic status (SES), smoking, alcohol consumption, and histories of hypertension, diabetes mellitus, and dyslipidemia. In addition, there was not enough evidence against the surmise that the CVD mortality risk was similar between the TC and control groups, with an HR of 0.50 (95% CI: 0.22-1.16) after adjustment for CVD risk factors. CONCLUSIONS: Excellent overall survival was observed in TC patients. The most common cause of death was TC-specific mortality, suggesting the importance of thyroid cancer treatment. The overall and cause-specific mortality risks, particularly CVD mortality risk, did not differ between TC patients and the general population.

Extended Real-World Observation of Patients Treated with Sorafenib for Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma and Impact of Lenvatinib Salvage Treatment: A Korean Multicenter Study.

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.

Lesion-Based Evaluation Predicts Treatment Response to Lenvatinib for Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Korean Multicenter Retrospective Study.

Background: Lenvatinib, a tyrosine kinase inhibitor (TKI) recently approved for treating radioactive iodine-refractory differentiated thyroid cancer, has been shown to delay disease progression and provide meaningful benefit for overall survival (OS). However, there is no predictive marker for response to lenvatinib before initiating treatment. We comprehensively analyzed clinical and radiological parameters to predict response to lenvatinib using lesion-based assessments. Methods: Medical records were collected from 67 patients treated with lenvatinib in 11 referral hospitals across Korea from June 2015 to December 2017. Up to 96 measurable lesions, defined as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, were evaluated serially until progressive disease (PD) occurred, and tumor doubling time (TDT) was calculated based on changes between historical computed tomography (CT) scans and baseline CT scans performed at treatment initiation. Results: Excluding patients with anaplastic thyroid cancer, no thyroidectomy, nontarget lesions only, or treatment periods of <1 month, 57 patients were analyzed, of whom 7 (12.2%) were TKI-naive. The median progression-free survival was 5.1 months (95% confidence interval [CI], 4.4-9.5), the median OS was 19.3 months (95% CI 12.4-not reached), the mean duration of response was 6.0 ± 4.4 months, and the objective response rate was 38%. In lesion-based assessments, 31 lesions (32.2%) with significant tumor shrinkage (complete remission or partial response) were significantly associated with shorter TDT (<12 months; p = 0.02). Patients with rapidly PD with a shorter initial TDT (<6 months) were more likely to respond to lenvatinib (p = 0.03). Patients exposed to lenvatinib at an average of ≥16 mg per day, or who were TKI-naive before treatment with lenvatinib, had a lower risk of progression; however, the risk reduction did not reach statistical significance (daily dosage p = 0.07, TKI exposure p = 0.09). Conclusions: TDT calculations at the beginning of treatment and lesion-based tumor assessment may help identify potential responders to lenvatinib therapy and predict therapeutic responses.

The relationship of comorbidities to mortality and cause of death in patients with differentiated thyroid carcinoma.

Understanding how comorbidities contribute to death in cancer patients is becoming an important topic. The present study assessed the role of comorbidities in overall mortality and causes of death in patients with differentiated thyroid carcinoma (DTC). This retrospective cohort study included 2070 patients who underwent thyroidectomy for DTC at a single institution between 2002 and 2005. Probabilities of overall, DTC-specific and other-cause death were examined according to the number of comorbidities, with consideration for competing events. The estimated 15-year cumulative incidences of overall, DTC-specific, and other-cause death were 7.3%, 1.6%, and 5.7%, respectively. Taking the group without comorbidities as a reference, we found that the group with 1-2 comorbidities and the group with ≥3 comorbidities had higher probabilities of other-cause death (subhazard ratios = 2.48 and 9.41, respectively; p < 0.01) and consequently shorter overall survival (hazard ratio = 1.95 and 5.33, respectively; p < 0.01), with adjustment for age, sex, and tumor-node-metastasis classification. In contrast, the probability of DTC-specific death was reduced in patients with ≥3 comorbidities (subhazard ratio = 6.81e-10, p < 0.01). For overall death, the relative proportion of death from DTC reduced when the number of comorbidities increased, and DTC-specific death was not observed in patients with ≥3 comorbidities. Our results show that death from DTC itself accounted for only a fraction of the overall deaths among patients who underwent surgery for DTC. Comorbidities increased overall mortality by increasing the probability of other-cause death. Patients with multiple comorbidities had a low probability of dying from DTC because they died earlier from comorbidities.

Prevalence of Thyroid Disease in Patients Surgically Treated for Pituitary Disease.

Thyroid disease mainly has a thyroid origin but can occasionally have a pituitary origin. Clinicians face several challenges when these conditions occur together. We aimed to determine the prevalence of thyroid disorders in patients undergoing trans-sphenoidal adenomectomy (TSA) for pituitary disease. We reviewed the medical records of patients undergoing TSA for pituitary disease between 2008 and 2017 at Severance Hospital. Thyroid disorders were categorized using blood test results and medical histories at the time of preoperative evaluation. Among 2202 patients, 44 (2%), 218 (9.9%), and 74 (3.4%) had hyperthyroidism, hypothyroidism, and post-thyroidectomy status before TSA, respectively. Among the 44 patients with hyperthyroidism, 30 (68.2%) had central hyperthyroidism. Among the 218 patients with hypothyroidism, 165 (75.7%) had central hypothyroidism. Central hypothyroidism was more common in patients with adrenocorticotropic hormone-secreting pituitary adenomas (aOR (adjusted odds ratio) 1.85), Rathke's cleft cysts (aOR 2.34), and craniopharyngiomas (aOR 2.58) (all p < 0.05) than in those with nonfunctioning pituitary adenomas. Contrastingly, thyroid cancer had an increased prevalence in patients with growth hormone- (aOR 3.17), prolactin- (aOR 3.66), and thyroid-stimulating hormone-secreting (aOR 6.28) pituitary adenomas (all p < 0.05). Pituitary disease sometimes accompanies thyroid disorders; their characteristics vary according to the type of pituitary disease.

Association between Thyroid-Stimulating Hormone Level after Total Thyroidectomy and Hypercholesterolemia in Female Patients with Differentiated Thyroid Cancer: A Retrospective Study.

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03-0.3, 0.3-2, and 2-5 mIU/L groups was -3.69 mg/dL (p = 0.006), +0.13 mg/dL (p = 0.926), +12.46 mg/dL (p < 0.001), and +16.46 mg/dL (p < 0.001), respectively. When compared with TSH levels of 0.03-0.3 mIU/L, those of 0.3-2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2-5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130-159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.

The Prognosis of Papillary Thyroid Cancer with Initial Distant Metastasis is Strongly Associated with Extensive Extrathyroidal Extension: A Retrospective Cohort Study.

BACKGROUND: Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis. METHODS: This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7 years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event. RESULTS: The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55 years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013). CONCLUSIONS: Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Changes in the Diagnostic Efficiency of Thyroid Fine-Needle Aspiration Biopsy during the Era of Increased Thyroid Cancer Screening in Korea.

PURPOSE: The volume of thyroid cancer screening and subsequent thyroid fine-needle aspiration (FNA) have rapidly increased in South Korea. We analyzed the thyroid cancer diagnoses/thyroid FNA ratio according to the annual number of FNA to evaluate changes in the diagnostic efficiency of FNA. MATERIALS AND METHODS: This was a nationwide population-based retrospective cohort study. The overall thyroid cancer diagnoses/thyroid FNA ratio and annual incremental thyroid cancer diagnoses/incremental thyroid FNA ratio were indirectly calculated using data obtained from the Korea Central Cancer Registry database and the Korean National Health Insurance Service claims database from 2004 to 2012. Pearson correlation analyses were performed to evaluate the strength of linear associations between variables. RESULTS: The number of thyroid FNA increased from 28,596 to 177,805 (6.2-fold increase) from 2004 to 2012. The overall thyroid cancer diagnoses/thyroid FNA ratio decreased from 36.5% in 2004 to 25.1% in 2012 and was negatively correlated to the number of FNA (R=‒0.977, p < 0.001). The annual incremental thyroid cancer diagnoses/incremental thyroid FNA ratios (range, 15.3% to 30.7%) were always lower than the overall thyroid cancer diagnoses/thyroid FNA ratio in each year and also worsened according to the increase in the number of FNA (R=‒0.853, p=0.007). CONCLUSION: The diagnostic performance of both overall and annual incremental thyroid FNA worsened, whereas the number of thyroid FNA procedures increased. More sophisticated indications for FNA are required to improve its diagnostic efficiency, considering the increased burden of screening-detected thyroid nodules.