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.

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.

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.

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.

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.

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 .

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.

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.

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.

Cardiovascular Outcomes in Thyroid Cancer Patients Treated With Thyroidectomy: A Meta-analysis.

CONTEXT: Thyroid dysfunction is associated with an increased risk of cardiovascular disease (CVD) in the general population; however, it remains controversial whether differentiated thyroid cancer (DTC) treatment, including thyroidectomy and thyroid-stimulating hormone suppression, further increases the risk of CVD. OBJECTIVE: This study aimed to evaluate the risk of CVD in patients with DTC. METHODS: We performed a review of observational studies on associations between DTC and cardiovascular outcomes, indexed in MEDLINE, Embase, and Web of Science. We excluded studies that evaluated CVD as comorbidity before DTC diagnosis and those that used active surveillance without thyroidectomy as an intervention. Risk estimates were pooled using random- and fixed-effects models when 3 or more studies reported on the outcome of interest. Echocardiographic and hemodynamic parameters were examined. RESULTS: Eighteen studies were included in the quantitative analysis (193 320 cases with DTC and 225 575 healthy controls). DTC was associated with an increased risk of atrial fibrillation (pooled risk ratio [RR] = 1.55 [95% CI: 1.30-1.84]), coronary artery disease (RR = 1.10 [1.00-1.21]), cerebrovascular accidents (RR = 1.15 [1.09-1.20]), and all-cause mortality (RR = 1.95 [1.03-3.69]). DTC was associated with higher diastolic blood pressure (standardized mean difference [SMD], 0.22 [0.01-0.42]), heart rate (0.37 [0.17-0.57]), left ventricular mass index (0.66 [0.45-0.88]), and interventricular septal thickness (0.91 [0.33-1.49]) and lower early to late ventricular filling velocities (-0.42 [-0.79 to -0.05]), but not with ejection fraction. CONCLUSION: Patients with DTC are at an increased risk of atrial fibrillation, CVD, increased heart rate, and left ventricular mass development.

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Because subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of TSH suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE: We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS: We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies' characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women's and men's lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean differences with 95% CIs are expressed for the differences in outcome measurements between groups. RESULTS: Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared with the controls. CONCLUSION: Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

Measurements of Bone Health after Thyroid-Stimulating Suppression Therapy in Postmenopausal Women with Differentiated Thyroid Carcinoma: Bone Mineral Density versus the Trabecular Bone Score.

BACKGROUND: Thyroid-stimulating hormone (TSH) suppression therapy is an important treatment modality for differentiated thyroid carcinoma (DTC), but it increases fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and trabecular bone score (TBS) in postmenopausal DTC patients receiving TSH suppression therapy. METHODS: A total of 410 postmenopausal DTC patients who underwent thyroidectomy and had at least two dual-energy X-ray absorptiometry measurements, including a preoperative measurement, were included. Patients who had osteoporosis medication for more than 1 year were classified as 'patients with osteoporosis'. RESULTS: In patients without osteoporosis, the change in %BMD was similar between TSH suppression (-) and (+) groups, while the decrease in %TBS was significantly greater in the TSH suppression (+) group than that of the TSH suppression (-) group. The relative risk of vertebral fracture was decreased by TBS changes but not by BMD changes. In patients with osteoporosis, both BMD and TBS showed significant increases in the TSH suppression (-) group but not in TSH suppression (+) group. At year 4, TBS was significantly lower in the TSH suppression (+) group than that in the TSH suppression (-) group, while BMD showed no difference between groups. CONCLUSIONS: TBS may better reflect bone health than BMD in postmenopausal DTC patients with TSH suppression therapy.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study.

BACKGROUND: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. METHODS: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. RESULTS: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. CONCLUSION: In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

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.

Association of Bone Mineral Density to Cerebral Small Vessel Disease Burden.

OBJECTIVE: To test the hypothesis that bone mineral loss is mechanistically related to cerebral small vessel disease (SVD), we investigated the relationship between bone mineral density and the prevalence and intensity of SVD among patients with stroke. METHODS: We analyzed data of 1,190 consecutive patients with stroke who were >50 years of age and underwent both brain MRI and dual-energy x-ray absorptiometry from the stroke registry of Chung-Ang University Hospital in Seoul, Korea. The patients were categorized into 3 groups according to their bone mineral density (normal, osteopenia, and osteoporosis). White matter hyperintensities, silent lacunes, cerebral microbleeds, and extensive perivascular space were assessed from brain MRI. Multinomial logistic regression model was used to examine the association between osteoporosis and total SVD score. We also recruited 70 patients with stroke to study serum bone turnover markers and microRNAs related to both cerebral atherosclerosis and bone metabolism to understand bone and brain interaction. RESULTS: Osteoporosis was determined among 284 patients (23.9%), and 450 patients (37.8%) had osteopenia. As bone mineral density decreased, total SVD score and the incidence of every SVD phenotype increased except strictly lobar cerebral microbleeds. Multinomial logistic regression analysis showed that osteoporosis was independently associated with severe SVD burden. The levels of microRNA-378f were significantly increased among the patients with osteoporosis and maximal total SVD score and positively correlated with parathyroid hormone and osteocalcin. CONCLUSIONS: These findings suggest a pathophysiologic link between bone mineral loss and hypertensive cerebral arteriolar degeneration, possibly mediated by circulating microRNA.

Trends in the Diagnosis and Treatment of Patients with Medullary Thyroid Carcinoma in Korea.

BACKGROUND: Thyroid cancer is becoming increasingly common worldwide, but little is known about the epidemiology of medullary thyroid carcinoma (MTC). This study investigated the current status of the incidence and treatment of MTC using Korean National Health Insurance Service (NHIS) data for the entire Korean population from 2004 to 2016. METHODS: This study included 1,790 MTC patients identified from the NHIS database. RESULTS: The age-standardized incidence rate showed a slightly decreasing or stationary trend during the period, from 0.25 per 100,000 persons in 2004 to 0.19 in 2016. The average proportion of MTC among all thyroid cancers was 0.5%. For initial surgical treatment, 65.4% of patients underwent total thyroidectomy. After surgery, external-beam radiation therapy (EBRT) was performed in 10% of patients, a proportion that increased from 6.7% in 2004 to 11.0% in 2016. Reoperations were performed in 2.7% of patients (n=49) at a median of 1.9 years of follow-up (interquartile range, 1.2 to 3.4). Since November 2015, 25 (1.4%) patients with MTC were prescribed vandetanib by December 2016. CONCLUSION: The incidence of MTC decreased slightly with time, and the proportion of patients who underwent total thyroidectomy was about 65%. EBRT, reoperation, and tyrosine kinase inhibitor therapy are additional treatments after initial surgery for advanced MTC in Korea.

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.

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.