Improved Erythrocyte Deformability Induced by Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic Patients.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. RESULTS: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001). CONCLUSION: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system.

Association of Triglyceride-Glucose Index with Bone Mineral Density in Non-diabetic Koreans: KNHANES 2008-2011.

The association of insulin resistance (IR), as indicated by the homeostasis model assessment of insulin resistance, with bone metabolism is yet to be clarified. We aimed to investigate the relationship of IR with bone mass by using the triglyceride-glucose (TyG) index as an alternative marker of IR. Data of 4810 non-diabetes individuals (2552 men aged ≥ 50 years and 2258 postmenopausal women) from the Korean National Health and Nutritional Examination Survey IV and V were analyzed. Bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and whole body were measured using dual-energy X-ray absorptiometry. After adjusting for confounding factors, there were inverse relationships of TyG index with femoral neck, total hip, and whole body BMD in men (ß = - 0.085, P < 0.001 at femoral neck; ß = - 0.046, P = 0.037 at total hip; ß = - 0.098, P < 0.001 at whole body). However, in women, femoral neck and whole body BMD were negatively associated with the TyG index (ß = - 0.071, P = 0.008 at femoral neck and ß = - 0.065, P = 0.005 at whole body). The highest TyG index tertile exhibited reduced femoral neck BMD in both sexes (P = 0.003 in men and P = 0.013 in women) and reduced whole body BMD in men (P < 0.001) after adjusting for confounders. When the study subjects were divided into BMI (body mass index) < 23 kg/m2 and ≥ 23 kg/m2 groups, the TyG index was significantly associated with femoral neck BMD only in the women with BMI < 23 kg/m2 (P = 0.009). We observed a significant association between the highest TyG index tertile and low bone mass at the femoral neck in women with BMI < 23 kg/m2 (P = 0.003) that was not observed in women with BMI ≥ 23 kg/m2 and men. In conclusion, IR evaluated using the TyG index was inversely associated with femoral neck BMD in non-diabetic men aged ≥ 50 years and postmenopausal women. The negative influence of IR on femoral neck BMD was robust in the women with BMI < 23 kg/m2. This indicates a differential effect of IR on BMD according to skeletal site, sex, and BMI.

A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.

BACKGROUND: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION: A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION: We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Surgery is a safe, effective first-line treatment modality for noninvasive prolactinomas.

PURPOSE: Dopamine agonists (DAs) have long been the recommended first-line treatment for prolactinoma. Given the remarkable developments in surgical techniques, however, surgery is on the rise. We compared the treatment outcomes of patients with noninvasive prolactinomas receiving two different initial treatments (DAs and transsphenoidal surgery). METHODS: We reviewed 745 patients with hyperprolactinemia or pituitary tumors treated from 2004 to 2020 at Chonnam National University Hwasun Hospital and identified 310 with prolactinomas. After selecting patients who had pituitary tumors with Knosp grade 0 to 1 with follow-up period over 1 year, 70 patients (29 who underwent surgery and 41 who received DAs as the initial treatment) were finally included for a comparative study. RESULTS: The surgery group exhibited better outcomes in terms of DA-free remission and the structural response, although the tumor size was significantly larger than in the DA group. The groups exhibited comparable results in terms of symptom control and the biochemical response. Univariate and multivariate analyses indicated that surgery as the initial treatment modality provided significantly better clinical outcomes in terms of DA-free remission. In the surgery group, a postoperative prolactin level < 10 ng/mL was the only significant predictor of DA-free remission. CONCLUSIONS: Transsphenoidal surgery showed comparable clinical outcomes in patients with prolactinomas, and low complication rates. The decision regarding the first-line treatment modality for non-invasive prolactinomas should be made on an individual basis.

A case of masked toxic adenoma in a patient with non-thyroidal illness.

BACKGROUND: Non-thyroidal illness (NTI) refers to changes in thyroid hormone levels in critically ill patients in the absence of primary hypothalamic-pituitary-thyroid dysfunction, and these abnormalities usually resolve after clinical recovery. However, NTI can be accompanied by primary thyroid dysfunction. We report herein a case of a woman with NTI accompanied by primary hyperthyroidism. CASE PRESENTATION: A 52-year-old female was admitted to the intensive care unit with heart failure and atrial fibrillation. She had a longstanding thyroid nodule, and a thyroid function test revealed low levels of triiodothyronine and free thyroxine as well as undetectable thyroid stimulating hormone (TSH). She was diagnosed with NTI, and her TSH level began to recover but not completely at discharge. The thyroid function test was repeated after 42 months to reveal primary hyperthyroidism, and a thyroid scan confirmed a toxic nodule. CONCLUSION: This case suggests that although NTI was diagnosed, primary hyperthyroidism should be considered as another possible diagnosis if TSH is undetectable. Thyroid function tests should be repeated after clinical recovery from acute illness.

Diffuse metastasis to the thyroid: unique ultrasonographic finding and clinical correlation.

Cases of metastases to the thyroid gland seem to be increasing in recent years. The clinical and ultrasonographic findings of diffuse metastases have been sparsely reported. Thirteen cases of diffuse metastases to the thyroid gland were documented by thyroid ultrasonography-guided fine needle aspiration cytology between 2004 and 2013. We retrospectively reviewed the patients with diffuse thyroid metastases. The most common primary site was the lung (n=9), followed by unknown origin cancers (n=2), cholangiocarcinoma (n=1), and penile cancer (n=1). Eleven patients were incidentally found to have thyroid metastases via surveillance or staging FDG-PET. Other 2 patients were diagnosed during work-up for hypothyroidism and palpable cervical lymph nodes. On ultrasonography, the echogenicity of the enlarged thyroid gland was heterogeneously hypoechoic or isoechoic, and reticular pattern internal hypoechoic lines were observed without increased vascularity found by power Doppler ultrasonography (3 right lobe, 2 left lobe, and 8 both lobes). In the 8 patients who had involvement of both lobes, 3 had hypothyroidism. In conclusion, ultrasonographic finding of diffuse metastasis is a diffusely enlarged heterogeneous thyroid with reticular pattern internal hypoechoic lines. Thyroid function testing should be performed in all patients with diffuse thyroid metastases, especially those with bilateral lobe involvement.

Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review.

BACKGRUOUND: Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). METHODS: Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. RESULTS: In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. CONCLUSION: AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Polyporus ulleungus mycelia cultured in MEB medium produce metabolites with anticancer property.

Cancer cells are characterized by apoptosis evasion and uncontrolled cell cycle progression. To combat these characteristics, efforts have been made to find novel natural-source anticancer compounds. The aim of this work is to find new anticancer compounds in Polyporus ulleungus (P. ulleungus) mycelial culture extracts. P. ulleungus mycelium was cultured on four individual media (DYB, MEB, MYB, and PDB) and four extracts were generated from the mycelium culture media. Extracts of P. ulleungus mycelium cultured in MEB medium (pu-MEB) significantly reduced cancer cell growth by triggering apoptosis and S phase arrest. Furthermore, the anticancer effects of pu-MEB were not confined to one type of cancer. Taken together, our results confirmed that P. ulleungus mycelia cultured in MEB medium produce metabolites that exhibit anticancer properties. Development of an optimal medium for P. ulleungus mycelium through optimization of medium components will enable P. ulleungus mycelium to produce metabolites with more anticancer efficacy.

Higher TSH level is a risk factor for differentiated thyroid cancer.

OBJECTIVES: Higher thyroid-stimulating hormone (TSH) levels are associated with differentiated thyroid cancers (DTC). To validate this association, we compared TSH levels obtained from euthyroid patients with DTC with TSH levels from controls in the general population. DESIGN AND PATIENTS: The case group included 1759 patients with DTC, who underwent thyroid surgery at Chonnam National University Hwasun Hospital. The control group (n = 1548), who had participated in the Thyroid Disease Prevalence Study were used as a healthy control group. The subjects were divided into four groups of similar size according to their TSH levels, with the first quartile used as a reference group. RESULTS: The mean TSH level of the case group was significantly higher than the mean TSH level of the control group (1.95 ± 0.9 mIU/l vs 1.62 ± 0.8 mIU/l, P < 0.001), and was associated with DTC risk. Multiple logistic regression, after controlling for age, gender and the presence of a family history of thyroid cancer, showed that the odds ratios and 95% confidence intervals for the second, third and fourth quartiles of TSH levels were 1.27 (1.03-1.57), 1.55 (1.25-1.92) and 2.21 (1.78-2.74) respectively. No significant differences were observed in mean TSH levels in patients with different tumour stages and tumour sizes. CONCLUSION: Having a high TSH level within the normal range is an independent risk factor for DTC, and may contribute to the initiation of thyroid carcinogenesis. TSH levels in patients with thyroid nodules may be used as diagnostic adjuncts for the identification of high-risk patients, who require further investigation and/or surgical intervention.

A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review.

BACKGRUOUND: There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB. METHODS: Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers. RESULTS: Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate. CONCLUSION: FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients' medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study.

OBJECTIVES: To investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. METHODS: This nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. RESULTS: During follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03-1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33-2.28]) of baseline TG level versus the lowest quartile. CONCLUSIONS: In statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Early Thyroid Volume Reduction in Subacute Thyroiditis Can be a Potential Indicator for Hypothyroidism.

Background: Thyroid volume has been reported to decrease significantly after episodes of subacute thyroiditis (SAT); however, the relationship between thyroid volume and hypothyroidism remains unclear. This study assessed the association between thyroid volume changes and the hypothyroid phase in patients with SAT, a condition that can progress to persistent hypothyroidism. Methods: This retrospective study evaluated 37 patients diagnosed with SAT at the Department of Endocrinology and Metabolism of Chonnam National University Hwasun Hospital (CNUHH) between 2016 and 2021. Since we could not determine the clinical characteristics of patients with SAT before their episodes, 120 healthy individuals who underwent thyroid ultrasonography during regular check-ups from 2019 to 2021 at CNUHH were selected for comparison. Subgroup analyses were performed on patients with SAT with and without the hypothyroid phase during their clinical course. Results: Thyroid volume was significantly greater in SAT patients at the first visit than in controls (p<0.05), and it decreased constantly throughout the follow-up period. Subgroup analysis showed that the initial thyroid volumes were similar in patients with SAT with and without the hypothyroid phase. However, SAT patients with the hypothyroid phase had significantly smaller thyroid volumes at the 1 month (p=0.025) and 3 month (p=0.006) follow-up visits. The reduction rate of the thyroid volume was significantly different within the first month (p=0.009). Conclusion: A greater reduction in thyroid volume in SAT patients within 1 month of episode had a higher chance of developing a subsequent hypothyroid phase, which can lead to persistent hypothyroidism. Serial thyroid ultrasonography in patients with SAT, especially within the first month, may help in predicting the disease course of SAT.

Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors.

BACKGROUND: Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH). METHODS: We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center. RESULTS: A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy. CONCLUSION: PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

Association between triglyceride-glucose index and thyroid function in euthyroid adults: The Korea National Health and Nutritional Examination Survey 2015.

OBJECTIVES: Low-normal thyroid function is associated with numerous metabolic risk factors including insulin resistance (IR). Triglyceride-glucose (TyG) index is a new surrogate marker of IR calculated by fasting triglyceride and glucose levels. Here, we investigated the association between thyroid function and TyG index in non-diabetic euthyroid adults. METHODS: This cross-sectional study was based on data from the Korean National Health and Nutritional Examination Survey 2015 including 1482 individuals (741 men and 741 women). Serum thyrotropin (TSH) and free thyroxine (fT4) levels were measured. RESULTS: After adjusting for confounders, there was an inverse relationship of TyG index with fT4 in men (ß = -0.094, P = 0.009) and a positive relationship of TyG index with TSH in women (ß = 0.078, P = 0.018). The lowest fT4 tertile in men (P = 0.001) and the highest TSH tertile in women (P = 0.010) exhibited increased TyG index after adjusting for confounders. The lowest fT4 tertile also showed increased homeostatic model assessment for IR (HOMA-IR) only in men (P = 0.006). Odds ratios (ORs) for the high TyG index, which was defined as the highest TyG quartile decreased in the highest and second highest tertile of fT4 in men (OR = 0.41 and OR = 0.45, respectively; P < 0.001) and increased in highest tertile of TSH in women (OR = 1.81, P = 0.031) after adjusting for confounders. The OR for high HOMA-IR defined as the highest HOMA-IR quartile was also lower in the highest and second highest fT4 tertiles in men (both OR = 0.47; P = 0.003). CONCLUSIONS: This is the first study to suggest that TyG index is a good surrogate marker of IR in evaluating its relationship with thyroid function.

Real-World Efficacy and Safety of Dulaglutide in Korean Patients with Type 2 Diabetes Mellitus: A Retrospective Study in a Tertiary Referral Center.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by -1.13% in all patients (p<0.001), and by -1.36 and -0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of -2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

Real-world experience of lenvatinib in patients with advanced anaplastic thyroid cancer.

PURPOSE: We aimed to evaluate the clinical efficacy and safety of lenvatinib in patients with advanced anaplastic thyroid cancer (ATC) in real-world practice. METHODS: This multicenter, retrospective cohort study included 14 patients with advanced ATC who received lenvatinib. We evaluated the response rate according to RECIST. RESULTS: Ten patients had de novo ATC, and lenvatinib was used as a neoadjuvant treatment in eight patients. During a median follow-up of 6.7 months, patients received lenvatinib at a median dose of 13 mg daily. Overall, four patients (29%) showed partial response, nine (64%) had stable disease, and one (7%) had progressive disease. Tumor burden was reduced in 13 patients (93%), and the median best percent change from the baseline was -15.8%. The median progression-free survival and overall survival were 5.7 months (95% confidence interval [CI], 2.2-8.3) and 6.7 months (95% CI, 3.0-8.4), respectively. All patients experienced adverse events (AEs). Most AEs were manageable but two AEs-tracheal perforation, and pneumothorax and pneumomediastinum-were life-threatening. One patient underwent flap surgery for reconstruction of their tracheal perforation, and another died of pneumothorax and pneumomediastinum, which seemed to be related to lenvatinib. CONCLUSIONS: In this multicenter real-world study, lenvatinib demonstrated limited clinical activity in advanced ATC. It effectively reduced the tumor burden but showed doubtful survival benefit. Although most AEs were manageable, one fatal AE was related to rapid tumor shrinkage. Further studies are needed to clarify the efficacy and optimal dose of lenvatinib in patients with advanced ATC.

Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves' Disease and Hashimoto's Thyroiditis in Korean Patients.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). METHODS: A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. RESULTS: Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. CONCLUSION: The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 µg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98-0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48-4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41-4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves' Disease: A Retrospective Multicenter Study.

BACKGROUND: The association between Graves' disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography. METHODS: Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules). RESULTS: Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020). CONCLUSION: The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Is acute kidney injury after laparoscopic adrenalectomy related to the progression of chronic kidney disease in patients with primary aldosteronism?

PURPOSE: This study was conducted to investigate the predictors of kidney outcome after laparoscopic adrenalectomy in patients with primary aldosteronism (PA). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 74 patients who underwent unilateral adrenalectomy for the treatment of PA from January 2011 to December 2019. Patient characteristics and serial data on postoperative changes in kidney function were analyzed and compared between the two groups according to the presence of acute kidney injury (AKI). Postoperative AKI was defined as a decline in the estimated glomerular filtration rate (eGFR) of >50% or an increase in the serum creatinine level of ≥0.3 mg/dL at 1 week after surgery compared with perioperative levels. Chronic kidney disease (CKD) was defined as an eGFR < 60 mL/min/1.73 m² present for 3 months. RESULTS: Nineteen patients (25.7%) had postoperative AKI. Patients who experienced postoperative AKI had higher aldosterone-to-renin ratios, higher rates of dyslipidemia, and more left ventricular hypertrophy than did patients without postoperative AKI (p=0.015, 0.036, and 0.033, respectively). Twenty-eight patients (37.8%) had CKD at 6 months after surgery, including 15 patients who had newly progressed to CKD postoperatively. In the multivariate regression analysis of patients without preoperative CKD, the only independent predictor of the progression to CKD was preoperative albuminuria (p=0.007). CONCLUSIONS: In this study, one-quarter of the patients had postoperative AKI after unilateral adrenalectomy for the treatment of PA. However, postoperative AKI was not directly correlated with CKD progression. Preoperative albuminuria was an independent predictor of the progression of CKD.