Intravenous Glucocorticoid Treatment for Korean Graves' Ophthalmopathy Patients.

BACKGROUND: High-dose intravenous steroids are the first-line treatment for patients with moderate-to-severe and active Graves' ophthalmopathy (GO). We aimed to investigate the response rate of methylprednisolone (MPD) treatment among Korean patients with active moderate-to-severe GO and to identify predictive factors of treatment response. METHODS: This is a retrospective observational study. We included 54 active moderate-to-severe GO patients treated with 4.5 g intravenous MPD over 12 weeks between November 2011 and November 2018. Response was defined as an improvement in at least two of five indicators (clinical activity score [CAS], soft-tissue involvement, exophthalmos, diplopia, and visual acuity) at immediate and 3 months after treatment completion. We examined predictive factors for response using logistic regression analysis. RESULTS: Twenty-four (44.4%) and 22 (40.7%) patients showed response at immediate and 3 months after intravenous (IV) steroid treatment. Of the five ophthalmic parameters, all patients in the responsive group (100.0%) showed a decrease in CAS and 90.9% showed less soft tissue involvement after IV steroid treatment. Among variables, the sum of extraocular muscle width was positively (odds ratio [OR], 1.163; 95% confidence interval [CI], 0.973-1.389; P = 0.096) associated with treatment response. While, the OR of age was 0.918 (95% CI, 0.856-0.985; P = 0.017) and thyrotropin binding inhibitory immunoglobulin (TBII) was 0.921 (95% CI, 0.864-0.982; P = 0.012). CONCLUSION: In Korean active moderate-to-severe GO patients, intravenous steroid treatment is not as effective as previously reported. Parameters associated with CAS and soft-tissue involvement were found to be influenced by IV MPD treatment. Extraocular muscle enlargement, younger age and lower TBII are predictive factors for a good steroid treatment response.

The risk of second primary malignancy is increased in differentiated thyroid cancer patients with a cumulative (131)I dose over 37 GBq.

BACKGROUND: The aim of this study was to investigate the risk factors for second primary malignancy (SPM) diagnosed after differentiated thyroid cancer (DTC). METHODS: A total of 2468 DTC patients who underwent thyroidectomy were reviewed. SPM was defined as a non-thyroidal malignancy, diagnosed at least 1 year after the diagnosis of thyroid cancer. Patients were divided into five groups according to cumulative (131)I dose: very high-activity (≥ 37.0 GBq), high-activity (22.3-36.9 GBq), intermediate-activity (5.56-22.2 GBq), low-activity (1.1-5.55 GBq) and no RAI. RESULTS: Among the 2468 patients, 61 (2.5%) had SPMs during 7.0 (1.0-33.0) years of median follow-up. Age above 40 years, male sex and very high-activity RAI were independent risk factors for the development of SPM. SPM-related mortality was highest in the very high-activity group, while DTC-related mortality was highest in the high-activity group. The overall mortality both from SPM and DTC was highest in the high-activity group. CONCLUSION: A cumulative (131)I dose <37.0 GBq did not increase the risk of SPM. A cumulative (131) I dose ≥ 37.0 GBq increased the risk of SPM and SPM-related mortality and decreased the DTC-specific mortality, resulting in a similar all-cause mortality compared with the low-activity RAI group. Using repeated high-dose RAI for treating RAI-responsive but persistent DTC patients needs careful consideration of the individual benefits from RAI vs the risk of developing SPM.

Loss of ERß expression in papillary thyroid carcinoma is associated with recurrence in young female.

OBJECTIVES: We investigated the expression of oestrogen receptors (ERs) in papillary thyroid cancers (PTCs) and evaluated their prognostic role. METHODS: We enrolled 81 female patients who underwent thyroid surgery and had a confirmed diagnosis of PTC between 01 January 1995 and 31 December 1996. Data on clinicopathologic parameters were obtained from patients' medical records. Tissue paraffin blocks of these 81 patients were collected for immunohistochemistry for ERα and ERß. RESULTS: ERα expression was observed in only eight patients (9·9%). In contrast, ERß expression was positive in 36 (44·4%) patients. Total thyroidectomy (84·4% vs 61·1%, P = 0·017) and cervical lymph node metastasis (62·2% vs 22·2%, P = 0·000) were more frequent in the ERß-negative group than in the ERß-positive group. Among younger female patients (<45 years), the ERß-negative group showed a tendency towards more frequent recurrent or persistent disease than the ERß-positive group (42·3% vs 13·6%, P = 0·029). In contrast, the ERα-positive group showed more recurrent or persistent disease than the ERα-negative group in older female patients (100% vs 24·1%, P = 0·024). In multivariate analysis, ERß negativity, extrathyroidal invasion and radioactive iodine treatment were risk factors for recurrence in young female patients. CONCLUSION: Loss of ERß expression was associated with recurrence in young female PTC patients. This finding suggests that oestrogen might play a protective role in the progression of PTC via ERß, especially in young female patients.

IGF-1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH-stimulated goiter.

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

Increased risk of diabetes mellitus and hyperlipidemia in patients with differentiated thyroid cancer.

OBJECTIVE: This study aimed to assess the risk of cardiometabolic disease (CMD) in patients with differentiated thyroid cancer (DTC) using a population-based nationwide cohort in Korea. DESIGN: This was a population-based cohort study. METHODS: We selected 2649 patients with DTC and 7947 matched controls. The primary outcome was the composite of CMD including diabetes mellitus (DM), hypertension, hyperlipidemia, cerebrovascular disease, and ischemic heart disease. The secondary outcomes were each individual type of CMD, all-cause mortality, and CMD-specific mortality. The cause-specific hazard ratios (HRs) for each outcome were estimated based on cause-specific Cox proportional hazard regression models. RESULTS: Patients with DTC had an 11% higher risk of the primary composite outcome than controls (HR, 1.11; 95% confidence interval [CI], 1.04-1.19). The risks of DM (HR, 1.22; 95% CI, 1.08-1.38) and hyperlipidemia (HR, 1.36; 95% CI, 1.24-1.48) were higher in patients with DTC. In contrast, the risk of CMD-specific mortality was lower in those with DTC (HR, 0.24; 95% CI, 0.09-0.68). A nonlinear, U-shaped relationship was observed between the daily dose of levothyroxine and the risk of DM (P = .021), but the risk of hyperlipidemia was low with high doses of levothyroxine in patients with DTC (P = .003). CONCLUSIONS: Patients with DTC had an increased risk of CMD, especially DM and hyperlipidemia, but a low risk of CMD mortality. Special attention to metabolic diseases is required in the long-term follow-up of patients with DTC.

Graves' orbitopathy development in thyroid cancer patients: a 16-year nationwide cohort study in South Korea.

BACKGROUND/OBJECTIVES: We aimed to investigate the prevalence, risk factors, and prognosis of Graves' orbitopathy (GO) in patients with thyroid cancer without a history of hyperthyroidism. SUBJECTS/METHODS: This retrospective cohort study analysed a sample from the Korean National Health Insurance Service database, which included 1,137,861 subjects from 2002 through 2019. Patients diagnosed with thyroid cancer, without a history of hyperthyroidism, were identified according to the Korean Standard Classification of Disease codes. The study compared the type of surgery, dose of radioactive iodine (RAI), and daily average thyroid hormone dose between patients who developed GO after being diagnosed with thyroid cancer and those who did not develop GO. We analysed the course of GO and the type of treatment. RESULTS: A total of 8499 cancer patients without a history of hyperthyroidism were identified, among whom 7836 underwent thyroidectomy. Of those who underwent thyroidectomy, 12 developed GO postoperatively. Among the 663 patients who did not undergo thyroidectomy, none developed GO. The prevalence of GO among thyroid cancer patients was 0.14%. The GO group received a significantly higher total RAI dose than the non-GO group (p = 0.036). There were no significant differences in sex, age, type of surgery, rate of RAI treatment, or average thyroid hormone dose between the two groups. One of the 12 patients who developed GO required intravenous steroids. CONCLUSIONS: Although GO rarely develops in thyroid cancer patients without coexisting hyperthyroidism, the total RAI dose may increase its risk. Further research would help clarify GO's association with thyroid cancer.

Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile.

Thyroid hormone is a potent regulator of metabolic and energy homeostasis implicated in various metabolic diseases. Fibroblast growth factor 21(FGF21) is a systemic metabolic regulator known to modulate various biological functions similar to the actions of thyroid hormone. We investigated the differences in plasma FGF21 concentrations in patients with varying thyroid function. Ninety drug-naïve subjects who underwent thyroid evaluation at Seoul National University Bundang Hospital were enrolled and classified into euthyroid, subclinical hypothyroid, and overtly hypothyroid groups. Biochemical markers and plasma FGF21 levels were measured and analyzed. The mean age of the subjects was 42.6 ± 9.1 years. The mean body mass index (BMI), waist circumference, and fasting glucose concentrations were similar between groups. Overtly hypothyroid subjects exhibited significantly higher concentrations of total cholesterol, triglyceride, and LDL-cholesterol than the other groups (p<0.01). Mean plasma FGF21 concentrations in euthyroid, subclinical hypothyroid and overtly hypothyroid groups were 43.2 ± 39.2 pg/mL, 63.6 ± 73.6 pg/mL, and 101.5 ± 74.9 pg/mL, respectively (p<0.01 between groups). Plasma FGF21 concentrations remained significantly higher in overtly hypothyroid subjects after adjusting for serum triglyceride concentrations (p<0.005). Multivariate analysis revealed a significant positive linear relationship between serum TSH concentrations and plasma FGF21 concentrations (ß = 0.192, p = 0.002) and a significant negative linear relationship between free T4 and plasma FGF21 concentrations (ß = -0.382, p = 0.037) after adjusting for gender, BMI and serum concentrations of triglycerides and glucose. Plasma FGF21 levels were significantly increased in patients with hypothyroidism independently of BMI, or lipid or glucose metabolism.

Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum: 2023 Revised Korean Thyroid Association Guidelines.

Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.

Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review.

BACKGRUOUND: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. METHODS: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published. RESULTS: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone. CONCLUSION: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

Sex-specific risk factors associated with graves' orbitopathy in Korean patients with newly diagnosed graves' disease.

OBJECTIVE: To assess sex-specific risk factors for Graves' orbitopathy (GO) in newly diagnosed Graves' disease (GD) patients. METHODS: A retrospective cohort study was conducted using the National Health Insurance Service's sample database, which consisted of 1,137,861 subjects from 2002 to 2019. The international classification of disease-10 codes was used to identify those who developed GD (E05) and GO (H062). A multivariable Cox proportional hazards model was used to estimate the effect of risk factors on GO development. RESULTS: Among 2145 male and 5047 female GD patients, GO occurred in 134 men (6.2%) and 293 women (5.8%). A multivariable Cox regression model revealed that GO development was significantly associated with younger age (HR = 0.84, 95% CI = 0.73-0.98), low income (HR = 0.55, 95% CI = 0.35-0.86), and heavy drinking (HR = 1.79, 95% CI = 1.10-2.90) in men, and with younger age (HR = 0.89, 95% CI = 0.81-0.98), lower body mass index (HR = 0.55, 95% CI = 0.33-0.90), high total cholesterol (HR = 1.04, 95% CI = 1.01-1.06), hyperlipidaemia (HR = 1.37, 95% CI = 1.02-1.85), and lower statin dose (HR = 0.37, 95% CI = 0.22-0.62) in women. There was no association between smoking and GO development in both men and women. CONCLUSIONS: The risk factors for GO development were sex-dependent. These results show the need for more sophisticated attention and support considering sex characteristics in GO surveillance.

Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database.

The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study.

BACKGRUOUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. CONCLUSION: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Efficacy of selenium supplementation for mild-to-moderate Graves' ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial.

BACKGROUND: The therapeutic effect of selenium has been demonstrated in mild Graves' ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea. METHODS: The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6. DISCUSSION: The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO. TRIAL REGISTRATION: KCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160 .

The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis.

BACKGROUND: The effects of the BRAF(V600E) mutation on prognostic factors and poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully quantified. The authors performed comprehensive meta-analysis to assess the strength of associations between these conditions and the BRAF(V600E) mutation. METHODS: The authors identified the clinical studies that examined the association of the BRAF(V600E) mutation in surgical specimens with clinicopathologic outcomes between January 2003 and October 2010 using the Medline database. One hundred thirty-one relevant studies were hand-searched. The authors selected 27 studies that included 5655 PTC patients. They calculated the pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for each study using a random effect model. RESULTS: The average prevalence rate of the BRAF(V600E) mutation was 49.4%. In 26 studies, compared with the patients who had the wild-type BRAF genes, the PTC patients with the BRAF(V600E) mutation had increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14-fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The associations were generally consistent across the different study populations. CONCLUSIONS: This meta-analysis demonstrates that the BRAF(V600E) mutation is closely related to the high-risk clinicopathological factors and poorer outcome of PTC. The results obtained here suggest that the BRAF(V600E) mutation should be considered as a poor prognostic marker in PTC and may lead to better management for individual patients.

Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study.

OBJECTIVE: We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug-naïve type 2 diabetic patients. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0-10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and ß-cell function (HOMA-B), insulinogenic index (IGI, defined as 30-0 min insulin/30-0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test. RESULTS: After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P < 0·01). HOMA-B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and HOMA-IR. No severe adverse events were observed. CONCLUSION: These results suggest that drug-naïve type 2 diabetic patients with low ß-cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.

Serum thyroglobulin level measured after thyroxine withdrawal is useful to predict further recurrence in whole body scan-negative papillary thyroid cancer patients after reoperation.

The best treatment option for recurrent papillary thyroid carcinoma (PTC) is reoperation when the recurrent lesion is locoregional. The prognostic significance of serum thyroglobulin (Tg) levels before reoperation and the association between the outcome of reoperation and Tg level remain unclear. Our study aimed to determine the outcomes of patients who underwent reoperation and their association with serum Tg levels. We retrospectively studied 79 patients with PTC with locoregional recurrence whose whole-body scan results were negative for any recurrence but whose serum Tg levels were detectable after first-line treatment. All the patients underwent reoperation and follow-up examinations, which involved serial serum Tg measurements after thyroxine withdrawal (T4-off Tg), neck ultrasonography, chest computed tomography, and/or fluorodeoxyglucose-positron emission tomography, to detect further recurrence. During the median follow-up duration of 89 months (range, 38-332 months), 30 patients (38.0%) experienced a second recurrence even after the reoperation. Among all patients, only 12 whose Tg levels decreased postoperatively to undetectable levels showed no recurrence. Most recurrences were detected in the patients with high T4-off Tg levels after the reoperation (T4-off Tg level (ng/mL), number of patients with recurrence, %: <1, 0/12, 0%; 1-10, 9/31, 33.3%; >10, 16/22, 72.7%; P < 0.001). In conclusion, recurrence occurred in 38.0% of the patients even after the reoperation. The postoperative T4-off Tg level was a good indicator of recurrence after the reoperation. Therefore, patients who experience recurrence should undergo follow-up examinations that involve routine measurements of T4-off Tg levels, especially when postreoperative values exceed 10 ng/mL.

Predictive Model for Graves' Ophthalmopathy in Patients with New-Onset Graves' Disease.

Background: The most prevalent extrathyroidal manifestation of Graves' disease (GD) is Graves' ophthalmopathy (GO). However, only few methods allow for predictions of GO occurrence or progression in patients with GD. Methods: We retrospectively analyzed 1,074 patients with new-onset GD, and divided them into a derivation and a validation cohort based on the date of their GD diagnosis. We then separately analyzed clinical risk factors affecting the occurrence and progression of GO using multivariable regression analysis and created a predictive model based on the factors we identified as significant. Results: Of the 853 GD patients included in the derivation cohort, 101 (11.8%) developed GO. Those who developed GO were more likely to be smokers (25.7% vs. 8.5%, p < 0.001), were younger at the time of their GD diagnosis (35.0 years vs. 42.0 years, p < 0.001), more commonly had a family history of GD (27.7% vs. 17.2%, p = 0.015), and had higher thyrotropin-binding inhibitor immunoglobulin (TBII) levels at the time of their diagnosis (13.5 IU/L vs. 10.0 IU/L, p = 0.020) than those who did not develop GO. Of the 101 GO patients in the derivation cohort, after excluding 8 who initially had active and moderate-to-severe GO, 11 of the remaining 93 had progressed to more active or severe GO. GO patients with confirmed progression had a higher proportion of those older than 45 years (54.5% vs. 19.8%, p = 0.031), and they had a different initial clinical activity score distribution. The multivariable regression analysis identified age at GD diagnosis, sex, smoking history, family history of GD, total cholesterol level, and TBII level at the time of the diagnosis as significant risk factors of GO occurrence, and a predictive model including these risk factors was built to create a nomogram. Conclusions: The predictors of GO occurrence in patients with new-onset GD were female sex, positive smoking history, young age, family history of GD, high cholesterol level, and high TBII level. The predictive nomogram developed in this study may be useful in patient counseling and facilitating informed treatment decision-making.

Incidence of Subacute Thyroiditis During the COVID-19 Pandemic in South Korea Using the National Health Insurance Service Database.

Background: Subacute thyroiditis (SAT) is a thyroid disease initiated by viral infection. Whether severe acute respiratory syndrome coronavirus 2 infection can cause SAT is unclear. This study investigated changes in the nationwide incidence of SAT during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This is a retrospective, cross-sectional population-based study. Data regarding SAT and related viral diseases, including COVID-19, from 2017 to 2020 were collected from the National Health Insurance Service and Korea Disease Control and Prevention Agency databases. Results: In a total of 15,447 patients, 2484 men and 12,963 women diagnosed with SAT from 2017 to 2020 were included in this study. The incidence of SAT was significantly higher in 2020 than in 2017-2019 (8.30 vs. 7.27 per 100,000 persons, p < 0.001), while the incidence of SAT-related respiratory viral diseases, except for COVID-19, markedly decreased in 2020. The peak age of SAT incidence in 2020 was 50-59 years, and the women-to-men ratio was 5.4 (similar to that in 2017-2019). Corticosteroids were prescribed more often (72% vs. 58%, p < 0.001), and the prescription rate exceeding 1 month was significantly higher (45% vs. 40%, p < 0.01) in 2020 than in 2017-2019. Conclusions: The incidence of SAT increased in 2020 in association with COVID-19. A diagnostic approach to COVID-19 needs to be considered in patients with SAT during the COVID-19 pandemic.

Malignancy rate in sonographically suspicious thyroid nodules of less than a centimeter in size does not decrease with decreasing size.

We evaluated the malignancy and nondiagnostic rates using fine needle aspiration cytology (FNAC) results in thyroid nodules smaller than 1 cm according to the subdivided size. We retrospectively reviewed the medical records of all subjects underwent FNAC from 2003 to 2009 in our hospital, and 2,756 patients of subcentimeter thyroid nodules with one or more suspicious sonographic features and 7,105 with nodule sized 1 cm or more were included. The malignancy rate was higher in those subcentimeter nodules with suspicious sonographic findings than the nodule sized 1cm or more (19.7% vs 7.8%, P < 0.001). We grouped the nodules based on size with mm interval and observed that the malignancy rate did not decrease but the nondiagnostic results increased its size decrement. When we divided the subjects arbitrarily into a 5 mm or smaller and a 6-9 mm sized group, nondiagnostic cytology findings were reported more frequently in the smaller group (24.3% vs 18.1%, P = 0.001), while the rate of "malignant" was similar (18.3% vs 15.5%, P = 0.123) and the rate of "suspicious for malignancy" was higher (6.8% vs 2.9%, P < 0.001). Therefore when we decide to perform FNAC or not in subcentimeter-sized nodules, we should consider sonographic findings and other clinical risk factors but not the nodular size itself.

Expression of Estrogen and Progesterone Receptors in Papillary Thyroid Carcinoma in Korea.

PURPOSE: The aim of this study was to examine the rate of expression of estrogen receptor α (ERα) and ß1 (ERß1), progesterone receptor (PR), and rate of overexpression of epidermal growth factor receptor (EGFR) in a relatively large cohort of patients with papillary thyroid carcinoma (PTC). We also aimed to examine whether each receptor influenced clinicopathological characteristics and prognosis of PTC. MATERIALS AND METHODS: We made a microarray of paraffin-embedded PTC surgical tissues from 436 patients. We compared the results of the immunohistochemical staining for each hormone receptor with clinicopathological characteristics. RESULTS: The positive expression rate of hormonal receptors was 40.4% for ERα, 83.7% for ERß1, and 71.3% for PR in patients with PTC. Overexpression of EGFR was shown in 19.3% of patients with PTC. The age was lower (44.6±12.1 years vs. 47.1±12.5 years, p=0.040) and tumor smaller (0.96±0.69 cm vs. 1.13±0.82 cm, p=0.020) in the ERα positive group, which also showed higher PR positivity (80.7% vs. 65.0%, p < 0.001) and overexpression of EGFR (27.3% vs. 13.8%, p < 0.001). However, neither the positivity of hormone receptors nor overexpression of EGFR affected the recurrence of PTC. CONCLUSION: In conclusion, most (94.6%) patients with PTC were found to exhibit positive expression for ERs or PR. We also found that neither the positive expression of hormone receptors nor overexpression of EGFR were associated with the recurrence of PTC.