Short-term bone marrow suppression in differentiated thyroid cancer patients after radioactive iodine treatment.

After thyroidectomy in differentiated thyroid cancer (DTC), radioactive iodine (RAI) treatment is often used for remnant ablation. However, RAI treatment has been associated with bone marrow suppression, and leukopenia, anemia, and thrombocytopenia may occur after a single RAI administration. In this study, we examined the change in complete blood counts at 1 week after RAI administration; this is less well studied. A group of 189 DTC patients who received RAI treatment and underwent blood tests before and after treatment, were included. Peripheral blood counts at baseline were compared to those obtained at 1 week, 1-6 months, and 6-12 months after RAI treatment in order to test for bone marrow suppression. At 1 week after RAI treatment, there was a significant decrease in the white blood cell count (WBC, 5.8 ± 1.6 × 109/L vs. 5.4 ± 1.5 × 109/L, p < 0.001) and hemoglobin level (Hb, 13.5 ± 1.7 g/dL vs. 13.3 ± 1.4 g/dL, p = 0.001). The WBC decrease was mostly due to lymphocyte counts (2.2 ± 0.6 × 109/L vs. 1.6 ± 0.5 × 109/L, p < 0.001), with no decrease in the neutrophil count. Although not significantly changed at 1 week, platelets counts were altered within 6 months (265 ± 69 × 109/L vs. 239 ± 53 × 109/L, p < 0.001). The decline in the WBC count recovered within 6 months; lymphocyte and platelet counts recovered within 12 months. In conclusion, RAI treatment after a thyroidectomy was associated with a statistically significant but temporary decline in WBC counts and Hb levels at 1 week. Physicians treating DTC patients should not decrease usage of moderate dose RAI treatments.

Concordance in postsurgical radioactive iodine therapy recommendations between Watson for Oncology and clinical practice in patients with differentiated thyroid carcinoma.

BACKGROUND: To the authors' knowledge, the indications for radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC) are unclear; treatment decisions are based on physician judgment. The objective of the current study was to identify the degree of concordance between postsurgical RAI therapy recommended by Watson for Oncology (WFO), a clinical decision support system for oncological therapy, and that recommended by physicians for patients with DTC. METHODS: The current retrospective cohort study included 207 patients with DTC who underwent thyroidectomy between 2017 and 2018. Treatment recommendations were considered concordant if WFO rendered recommendations consistent with those of the physicians. RESULTS: Treatment recommendations were concordant for 160 patients (77%). The concordance rate significantly differed according to the American Thyroid Association (ATA) risk category (P < .001) and American Joint Committee on Cancer TNM stage (seventh edition; P = .004). Logistic regression analysis demonstrated that treatment recommendations were significantly less likely to be concordant in patients with ATA intermediate-risk and stage III disease compared with those with ATA low-risk and stage I disease (odds ratio, 0.16 [P < .001] and OR, 0.35 [P = .004], respectively). CONCLUSIONS: The authors believe the concordance rate between postsurgical RAI therapy recommendations rendered by WFO and those rendered by physicians was too low to justify adopting WFO for the comprehensive screening of patients with DTC. This is particularly true among patients with ATA intermediate-risk and stage III disease, reflecting differences in practice patterns between the United States (where WFO was calibrated) and Korea. Hence, WFO is not a substitute for physicians, and also may require regional customization to improve its assistive capability.

Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) turner syndrome: a case report and literature review.

BACKGROUND: Cardiovascular disease (CVD) presents the most serious health problems and contributes to the increased mortality in young women with Turner syndrome. Arterial hypertension in Turner syndrome patients is significantly more prevalent than that in a general age-matched control group. The aetiology of hypertension in Turner syndrome varies, even in the absence of cardiac anomalies and obvious structural renal abnormalities. Pheochromocytoma is an extremely rare cause among various etiologies for hypertension in patients with Turner syndrome. Here, we reported a pheochromocytoma as a rare cause of hypertension in Turner syndrome patient. CASE PRESENTATION: A 21-year-old woman who has diagnosed with Turner syndrome with a karyotype of 46,X,i(X)(q10) visited for hypertension and mild headache. Transthoracic echography (TTE) showed no definite persistent ductus arteriosus shunt flow and cardiac valve abnormalities. Considering other important secondary causes like pheochromocytoma, hormonal studies were performed and the results showed increased serum norepinephrine, serum normetanephrine, and 24 h urine norepinephrine. We performed an abdominal computed tomography (CT) to confirm the location of pheochromocytoma. Abdominal CT showed a 1.9 cm right adrenal mass. I-131 meta-iodobenzylguanidine (MIBG) scintigraphy showed a right adrenal uptake. Laparoscopic adrenalectomy was performed and confirmed a pheochromocytoma. After surgery, blood pressure was within normal ranges and postoperative course was uneventful, and no recurrence developed via biochemical tests and abdominal CT until 24 months. CONCLUSION: Our case and previous literatures suggest that hypertension caused by pheochromocytoma which is a rare but important and potentially lethal cause of hypertension in Turner syndrome. This case underlines the importance of early detection of pheochromocytoma in Turner syndrome. Clinicians should keep in mind that pheochromocytoma can be a cause of hypertension in patients with Turner syndrome.

Prevalence of BRAFV600E Mutation in Follicular Variant of Papillary Thyroid Carcinoma and Non-Invasive Follicular Tumor with Papillary-Like Nuclear Features (NIFTP) in a BRAFV600E Prevalent Area.

BACKGROUND: BRAFV600E mutation status and prevalence of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been reported in Korea. The aim of this study was to investigate the significance of the BRAFV600E mutation in the follicular variant of papillary thyroid carcinoma (FVPTC) and to determine the prevalence of NIFTP in BRAFV600E mutation-prevalent Korean patients. METHODS: This study retrospectively analyzed 1,417 consecutive patients who underwent total thyroidectomy with routine prophylactic central lymph node dissection for papillary thyroid carcinoma (PTC). BRAFV600E mutation analysis was performed routinely using multiplex polymerase chain reaction by applying dual priming oligonucleotide. Clinicopathological characteristics and ultrasonographic findings were compared between BRAFV600E mutation-positive and -negative groups for FVPTC. Pathologists reviewed the pathology slides according to consensus diagnostic criteria for the encapsulated FVPTC and NIFTP. RESULTS: The prevalence of the BRAFV600E mutation in all subtypes of PTC was 61.0% (861/1,411). FVPTC presented a BRAFV600E mutation rate of 27.3%. The FVPTC patients with BRAFV600E mutation were older than those with no BRAFV600E mutation (P = 0.021). The prevalence of NIFTP was 0.18% among all PTC patients (2/1,411) and the proportion of NIFTP among FVPTC was 9.1% (2/22). CONCLUSION: The BRAFV600E mutation is prevalent in Korean patients with FVPTC in a region with high frequency of the BRAFV600E mutation and very low prevalence of NIFTP compared with that reported in western studies.

Changes in Urinary Angiotensinogen Associated with Deterioration of Kidney Function in Patients with Type 2 Diabetes Mellitus.

Urinary angiotensinogen (AGT) is potentially a specific biomarker for the status of the intrarenal renin-angiotensin system (RAS) in patients with diabetes mellitus. We explored whether changes in urinary AGT excretion levels were associated with the deterioration of kidney function in type 2 diabetes patients with preserved kidney function. Urinary baseline AGT levels were measured in 118 type 2 diabetic patients who were not taking RAS blockers and who had estimated glomerular filtration rates (eGFRs) ≥ 60 mL/min/1.73 m². A total of 91 patients were followed-up for 52 months. Changes in urinary levels of AGT (ΔAGT) were calculated by subtracting urinary AGT/creatinine (Cr) at baseline from urinary AGT/Cr after 1 year. ΔAGT was significantly inversely correlated with annual eGFR change (ß = -0.29, P = 0.006; ß = -0.37, P = 0.001 after adjusting for clinical factors). RAS blockers were prescribed in 36.3% of patients (n = 33) during follow-up. The ΔAGT values were lower in the RAS blockers users than in the non-RAS blockers users, but the differences were not statistically significant (7.37 ± 75.88 vs. 22.55 ± 57.45 µg/g Cr, P = 0.081). The ΔAGT values remained significantly correlated with the annual rate of eGFR change (ß = -0.41, P = 0.001) in the patients who did not use RAS blockers, but no such correlation was evident in the patients who did. ΔAGT is inversely correlated with annual changes in eGFR in type 2 diabetes patients with preserved kidney function, particularly in RAS blocker-naïve patients.

Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine Alone: A Propensity Score-Matched Analysis.

Background: Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM). Methods: We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder. Results: We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002-2.764, p = 0.049) and stroke (IRR = 1.757, CI 1.073-2.877, p = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy. Conclusions: The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations.

Association between visceral adipose tissue volume, measured using computed tomography, and cardio-metabolic risk factors.

We evaluated the associations between metabolic parameters with visceral adipose tissue (VAT) volume in women with prediabetes or type 2 diabetes (T2DM), and we compared the VAT volume with the VAT area. We enrolled women aged > 20 years with prediabetes or T2DM, who underwent oral glucose tolerance test and whose VAT was evaluated using computed tomography (CT) at our institution between 2017 and 2019. All participants underwent unenhanced spiral CT with a 3-mm slice thickness from the level of the diaphragm to the level of the mid-thigh. The two VAT areas were defined as the free drawn area on the levels of the umbilicus and L2 vertebra. The VAT areas were also manually drawn from the level of the diaphragm to the level of the pelvic floor and were used to calculate the VAT volumes by summing all areas with a slice thickness of 3 mm after setting the attenuation values from -45 to -195 Hounsfield Unit. All metabolic characteristics, except blood pressure, were significantly correlated with the VAT volume. The VAT areas measured at the level of the L2 vertebra and umbilicus were correlated with serum triglyceride, high-density lipoprotein cholesterol, and Framingham steatosis index alone. Multivariable regression analyses revealed that the VAT volume was significantly associated with several metabolic parameters. In conclusion, in women with prediabetes and T2DM, the VAT volume acquired from CT-based calculation has more significant correlations with metabolic risk factors compared with the VAT area.

Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society.

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Effect of tamoxifen with or without gonadotropin-releasing hormone analog on DXA values in women with breast cancer.

The purpose of this study was to compare the changes in DXA values including trabecular bone score (TBS) and bone mineral density (BMD) of lumbar spine (LS) and femur according to the hormone therapies including tamoxifen (TMXF) treatment with or without gonadotropin releasing hormone analog (GnRH analog) in women with breast cancer. We enrolled 119 women with breast cancer who had undergone breast-conserving surgery or mastectomy followed by TMXF treatment for postmenopausal women (TMXF group, n = 63, 52.9%) or by combination therapy of TMXF combined with GnRH analog for premenopausal women (TMXF + GnRH group, n = 56, 47.1%) from December 2013 to December 2017. The median follow-up period was 13 months (interquartile range [IQR], 12.0-14.75) for TMXF group and 13.5 months (IQR, 12.00-16.00) for TMXF + GnRH group, respectively. Patients did not receive bone-modifying therapy. The baseline dual-energy X-ray absorptiometry (DXA) scan before breast cancer surgery and follow-up DXA during hormone therapy. Comparing the first and follow-up DXA results, BMD in LS were significantly decreased in both TMXF (P < 0.001, mean difference: - 0.06) and TMXF + GnRH (P < 0.001, mean difference: - 0.09) groups. BMD values of femoral neck (P = 0.0011, mean difference: - 0.01) and total femur (P < 0.001, mean difference: - 0.03) was significantly changed between the baseline and follow-up DXA in TMXF + RnRH group. In the TMX group, a significant changed occurred in the BMD in total femur (P < 0.001, mean difference: - 0.030) but not the BMD of femoral neck (P = 0.095, mean difference: - 0.007). Regarding TBS, no significant change was found in the TMXF (P = 0.574, mean difference: - 0.004) group, whereas there was a significant decrease in TBS in the TMXF + GnRH (P < 0.001, mean difference: - 0.02) group during follow-up. TBS is more sensitive in reflecting the bone microarchitecture changes by TMXF or GnRH agonist in breast cancer patients than BMD. This finding demonstrates that TBS can be a useful parameter to detect bone microarchitectural changes in clinical applications.

Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis.

BACKGROUND: Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC. METHODS: Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues. RESULTS: The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher's exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs. CONCLUSION: This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

Preparation of Decellularized Kidney Scaffolds in Rats.

Tissue engineering is a cutting-edge discipline in biomedicine. Cell culture techniques can be applied for regeneration of functional tissues and organs to replace diseased or damaged organs. Scaffolds are needed to facilitate the generation of three-dimensional organs or tissues using differentiated stem cells in vivo. In this report, we describe a novel method for developing vascularized scaffolds using decellularized rat kidneys. Eight-week-old Sprague-Dawley rats were used in this study, and heparin was injected into the heart to facilitate flow into the renal vessels, allowing heparin to perfuse into the renal vessels. The abdominal cavity was opened, and the left kidney was collected. The collected kidneys were perfused for 9 h using detergents, such as Triton X-100 and sodium dodecyl sulfate, to decellularize the tissue. Decellularized kidney scaffolds were then gently washed with 1% penicillin/streptomycin and heparin to remove cellular debris and chemical residues. Transplantation of stem cells with the decellularized vascular scaffolds is expected to facilitate the generation of new organs. Thus, the vascularized scaffolds may provide a foundation for tissue engineering of organ grafts in the future.

Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study.

OBJECTIVE: Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. DESIGN: A nationwide cohort study. METHODS: Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). RESULTS: During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. CONCLUSIONS: Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

COVID-19 Vaccination for Endocrine Patients: A Position Statement from the Korean Endocrine Society.

Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients' health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.

A prospective cohort study on effects of gemigliptin on cardiovascular outcomes in patients with type 2 diabetes (OPTIMUS study).

This study was performed to evaluate the long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). After screening, eligible patients with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years. The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (3-point major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events. A total of 5179 patients were included in the study and 5113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients within 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% CI 0.29-0.69%) and in 54 patients within 54 months (estimated incidence from Cox proportional hazard model 1.35%, 95% CI 0.92-1.77%). During the study period, the incidence rates of each component of the primary composite outcome were 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years) and the incidences of other cardiovascular events were all less than 0.3%. In conclusion, T2DM patients who received gemigliptin exhibited a low incidence of the primary composite MACE and all-cause mortality. Therefore, the use of gemigliptin is expected to be safe without an increase in cardiovascular risk.Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02290301).

Association between Serum Free Thyroxine and Anemia in Euthyroid Adults: A Nationwide Study.

BACKGROUND: Studies on the relationship between thyroid function and anemia in the euthyroid range are scarce. We aimed to evaluate the association between anemia and serum free thyroxine (fT4) and thyrotropin (TSH) in euthyroid adults. METHODS: Data on 5,352 participants aged ≥19 years were obtained from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Anemia was defined as hemoglobin (Hb) <13 and <12 g/dL for men and women, respectively. RESULTS: Overall, 6.1% of participants had anemia, and more women (9.9%) had anemia than men (2.8%, P<0.001). In multivariate analysis, serum fT4 levels, but not TSH, were positively associated with serum Hb levels in both sexes (P<0.001, each). Serum Hb levels linearly reduced across decreasing serum fT4 quartile groups in both sexes (P<0.001, each). After adjusting for potential confounding factors, participants with low-normal fT4 had 4.4 (P=0.003) and 2.8 times (P<0.001) higher risk for anemia than those with high-normal fT4 among men and women, respectively. When participants were divided into two groups at 50 years of age, in younger participants, men and women with the first quartile were at higher risk of anemia than men with the second quartile (odds ratio [OR], 3.3; P=0.029) and women with the forth quartile (OR, 3.2; P<0.001), respectively. This association was not observed in older participants. CONCLUSION: These results suggest that a low-normal level of serum fT4 was associated with a lower serum Hb level and a higher risk of anemia in euthyroid adults, especially in younger participants.

Cerebral glucose metabolism differs according to future weight change.

The brain is known to play a central role in controlling the desire to eat. We aimed to evaluate the brain regions that might have a long-term effect on eating behavior and weight changes. We utilized the data of cognitively normal subjects who are examined by several neurologic tests, and followed-up for 36 months from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and investigated to search the brain regions that are associated with future weight change. The weight of each subject was measured on each visit at baseline (W0), 36 (W36) months after brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). Percentage (%) change of weight was calculated as follows: [(W36-W0)/W0]*100. We classified each subject's change into one of three categories: weight loss, stable, and weight gain. Dynamic 3-dimensional scans of six 5-min frames were acquired 30 mins after injection of 185 MBq of FDG. Image analysis was done using Statistical Parametric Mapping 12. Ninety-six subjects were included in this study (male 54, female 42). Subjects with future weight gain showed hypometabolism in left cerebellum compared with those with future weight loss & stable. Percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. In conclusion, subjects with future weight gain showed hypometabolism in left cerebellum, and percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. This study raises the possibility that the brain glucose metabolism precedes the future weight change.

High neutrophil-to-lymphocyte ratio is associated with relapse in Graves' disease after antithyroid drug therapy.

PURPOSE: Antithyroid drugs (ATDs) are effective in controlling hyperthyroidism due to Graves' disease (GD); however, long-term remission rates are low. The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic marker in many inflammatory diseases. We aimed to evaluate whether NLR can be used as a prognostic marker for relapse in patients with GD after ATD therapy. METHODS: This retrospective cohort study included 108 patients with newly diagnosed GD who achieved remission after ATD therapy and were followed-up for >12 months after ATD discontinuation. The primary outcome was relapse-free survival (RFS). RESULTS: Patients were classified into two groups according to baseline NLR: low NLR group with NLR < 1.14 (n = 59; 55%) and high NLR group with NLR ≥ 1.14 (n = 49; 45%). During the median follow-up of 6.5 years, disease relapse after a year of ATD withdrawal occurred in 23 (21%) patients. The patients with high NLR had poorer RFS than those with low NLR, and RFS curves were significantly different between the two groups (p = 0.002). In multivariate analysis, a high NLR (OR = 4.22, p = 0.016) was an independent prognostic factor for relapse in patients with GD after adjusting for age, sex, goiter, orbitopathy, thyroid hormone levels, thyrotropin binding inhibiting immunoglobulin titer, and the duration of ATD therapy. CONCLUSIONS: This study showed that NLR can be an early and cost-effective prognostic biomarker for relapse in patients with GD after ATD therapy. Further studies are needed to validate the prognostic role of NLR in GD.

The Relationship between Thyroid Function and Different Obesity Phenotypes in Korean Euthyroid Adults.

BACKGROUND: Thyroid disease and metabolic syndrome are both associated with cardiovascular disease. The aim of this study was to investigate the correlation between thyroid hormones and obesity sub-phenotypes using nationwide data from Korea, a country known to be iodine replete. METHODS: This study was based on data obtained from the sixth Korea National Health and Nutrition Examination Survey, administered from 2013 to 2015. A total of 13,873 participants aged ≥19 years were included, and classified into four groups: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) by body fat on the basis of body mass index and metabolic health. RESULTS: At baseline, serum free thyroxine (fT4) values were significantly higher in the MHNO phenotype (MHNO, 1.27±0.01 ng/dL; MHO, 1.25±0.01 ng/dL; MUNO, 1.24±0.01 ng/dL; MUO, 1.24±0.01 ng/dL, P<0.001) in total study population. However, this significant association no longer remained after adjustment for age, urine iodine concentration, and smoking (P=0.085). After adjustment for confounders, statistically significant association was observed between lower thyroid stimulating hormone (TSH) and MHNO phenotype (P=0.044). In men participants (not women), higher fT4 values were significantly associated with MHNO phenotype (P<0.001). However, no significant association was observed between thyroid function (TSH or fT4) and obesity phenotypes in groups classified by age (cutoff age of 55 years). CONCLUSION: Although there was a difference by age and sex, we found that the decrease of TSH and the increase of fT4 values were associated with MHNO.

Effects of Thyrotropin Suppression on Bone Health in Menopausal Women with Total Thyroidectomy.

BACKGROUND: This study examined the change in the trabecular bone score (TBS), areal bone mineral density (aBMD), and osteoporosis in postmenopausal women who underwent thyrotropin (TSH)-suppressive therapy for treating papillary thyroid cancer after a total thyroidectomy procedure. METHODS: We evaluated 36 postmenopausal women who received a total thyroidectomy for papillary thyroid cancer and were undergoing TSH suppressive therapy with levothyroxine. Postmenopausal women (n=94) matched for age and body mass index were recruited as healthy controls. The aBMD and TBS of the lumbar spine were compared between dual energy X-ray absorptiometry (DXA) at baseline and at follow-up after an average of 4.92 years. RESULTS: There was no significant difference in the rate of diagnoses of osteoporosis, osteopenia, or normal bone status between the 2 groups during the baseline DXA evaluation. However, the TBS was significantly lower whereas aBMD did not show significant difference at the time of baseline DXA measurement (1st DXA, 1.343±0.098 vs. 1.372±0.06317, P<0.001; 2nd DXA, 1.342±0.095 vs. 1.370±0.062, P<0.001). The TBS and aBMD did not differ significantly between the initial and follow-up DXA images in both groups of TSH suppressive patients and controls. CONCLUSIONS: The average value of TBS and aBMD did not significantly change during the follow-up period. The TSH suppressive therapy was revealed as not a significant factor for the progressive deterioration of bone status during long term follow-up.