Dyslipidemia Is a Risk Factor for Hypothyroidism in Women: A Longitudinal Cohort Study from South Korea.

Background: Hypothyroidism is a risk factor for dyslipidemia. We explored whether dyslipidemia is a risk factor for hypothyroidism. Methods: We performed a retrospective analysis of data from a longitudinal cohort study of South Korean adults who underwent medical examination and ≥4 biochemical assessments of thyroid function. The primary outcome was hypothyroidism (thyrotropin [TSH] >4.2 mU/L), and the secondary outcome was severe subclinical hypothyroidism (SCH; TSH ≥10.0 mU/L and normal free thyroxine [fT4] level) or overt hypothyroidism (OH; total triiodothyronine <80 ng/dL and/or fT4 < 0.93 ng/dL and high TSH values). The association of baseline dyslipidemia status with subsequent hypothyroidism was evaluated using Kaplan-Meier curves with the log-rank test and Cox proportional hazards regression models (for the entire population and respective genders). Subgroup analyses according to age (<40 and ≥40 years) and body-mass index (BMI; <23, 23-25, and ≥25 kg/m2) were performed according to gender. Results: We included 1665 participants. During a median follow-up period of 61.0 months, 24.3% (404/1665) individuals developed hypothyroidism. Among these, 36 participants (2.1%) had severe SCH or OH. Excluding patients with a first abnormal TSH level at last follow-up, 44.5% (126/283) of the patients with hypothyroidism had spontaneous TSH normalization. In respective multivariate analyses, dyslipidemia at baseline was independently associated with development of hypothyroidism in women (adjusted hazard ratio [HR] = 2.05 [1.31-3.19], p = 0.002), but not in men (adjusted HR = 1.00 [0.77-1.30], p = 0.991). In women, the presence of dyslipidemia at baseline was associated with development of severe SCH or OH (adjusted HR = 5.33 [1.41-20.12], p = 0.014). In women, respective associations according to age and BMI were as follows: age <40 years, adjusted HR = 2.90 (1.34-6.26, p = 0.007); age ≥40 years, adjusted HR = 1.85 (1.08-3.14, p = 0.023); BMI <23 kg/m2, adjusted HR = 1.68 (0.82-3.43, p = 0.151); BMI = 23-25 kg/m2, adjusted HR = 2.17 (0.93-5.07, p = 0.071); and BMI ≥25 kg/m2, adjusted HR = 2.82 (1.16-6.86, p = 0.022). Conclusions: In Korean adults, dyslipidemia was associated with development of hypothyroidism in women. Our findings require confirmation.

The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-world Data Study.

We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=-0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, -0.1% vs. -1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.

Personality traits and emotional status affecting academic achievements of medical students: testifying mediating effect of learning strategies.

PURPOSE: The purpose of this study is to identify possible causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students and to testify mediating effect of learning strategies in these relationships. METHODS: The study subjects are 424 medical students in the academic year of 2020 at the Gyeongsang National University, Jinju, Korea. Using the Multi-dimensional Learning Strategy Test-II, we assessed the students' academic achievements with personality traits, emotional status, and learning strategies. This study employed Structural Equation Modelling to explore the causal relationships among the latent variables. RESULTS: In the path model, personality traits directly affected academic achievements (ß=0.285, p<0.05) and indirectly affected academic achievements via emotional status (ß=0.063, p<0.01) and via learning strategies (ß=0.244, p<0.05), respectively. Further, personality traits indirectly affected academic achievements via emotional status first and learning strategies next (ß=0.019, p<0.05). Personality traits indirectly affected academic achievements through three multiple paths in the model (ß=0.326, p<0.05). Learning strategies partially mediated the relationship between personality traits and academic achievements as well as the relationship between emotional status and academic achievements of medical students. CONCLUSION: Study findings proved constructing the causal relationships among personality traits, emotional status, learning strategies, and academic achievements of medical students, thus supporting our hypotheses. Early habits of self-regulated learning are essential for the successful academic achievements of medical students. Therefore, medical students should know how to regulate personality traits and control emotional status, significantly affecting learning strategies.

Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson's Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways.

Nicotinamide (NAM) is the amide form of niacin and an important precursor of nicotinamide adenine dinucleotide (NAD), which is needed for energy metabolism and cellular functions. Additionally, it has shown neuroprotective properties in several neurodegenerative diseases. Herein, we sought to investigate the potential protective mechanisms of NAM in an intraperitoneal (i.p) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25-30 g). The study had four groups (n = 10 per group): control, MPTP (30 mg/kg i.p. for 5 days), MPTP treated with NAM (500 mg/kg, i.p for 10 days) and control treated with NAM. Our study showed that MPTP increased the expression of α-synuclein 2.5-fold, decreased tyrosine hydroxylase (TH) 0.5-fold and dopamine transporters (DAT) levels up to 0.5-fold in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, NAM treatment significantly reversed these PD-like pathologies. Furthermore, NAM treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) between 0.5- and 1.0-fold. Lastly, NAM treatment regulated neuroinflammation by reducing Toll-like receptor 4 (TLR-4), phosphorylated nuclear factor-κB, tumor (p-NFκB), and cyclooxygenase-2 (COX-2) levels by 0.5- to 2-fold in the PD mouse brain. Overall, these findings suggest that NAM exhibits neuroprotective properties and may be an effective therapeutic agent for PD.

Oyster broth concentrate and its major component taurine alleviate acute alcohol-induced liver damage.

Our previous study showed that oyster hydrolysate (OH) protected against the liver damage caused by a single instance of ethanol (EtOH) binge drinking. Oyster broth concentrate (OBC) was discovered in the process of searching for a different substance derived from oysters (Crassostrea gigas) with economic value. OBC is a by-product of boiling oysters at 95°C for 3 min. In this study, we investigated the effects of OBC and its major component taurine on blood and liver tissues obtained from a single-EtOH-binge-drinking mouse model. The preadministration of OBC enhanced EtOH metabolism by increasing the activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and catalase. In addition, the preadministration of OBC reduced cytochrome P450 2E1 (CYP2E1) activity, reactive oxygen species (ROS) generation, Ca2+ concentrations, apoptotic signals, and inflammatory mediators in liver tissues. The reduction of apoptotic and inflammatory signals by OBC resulted from the downregulation of endoplasmic reticulum (ER) stress molecules and NF-κB activity. Taurine administration showed similar effects to OBC. These results show that OBC protected against acute EtOH-induced liver damage through the action of taurine. Our findings suggest that OBC could be an economically valuable substance and a functional food with hepatoprotective effects.

The impact of the COVID-19 pandemic on outpatients of internal medicine and pediatrics: A descriptive study.

ABSTRACT: This study analyzed the changes in the number of outpatients and disease presentation during the entirety of 2020, the period of COVID-19 pandemic.The average annual number of outpatient visits between 2017 and 2019 (before COVID-19) and the total number of outpatient visits in 2020 (COVID-19 period) were compared. Diagnostic codes were identified during 2 periods to analyze changes in the number of outpatient visits according to disease and month.The average annual number of outpatient visits was 47,105 before, and 40,786 during the COVID-19 pandemic, with a decrease of 13.4%. The number of outpatient visits in internal medicine decreased by 10.2% during the COVID-19 pandemic and tended to rebound during the second half of the year. However, the number of outpatient visits in the pediatric department decreased by 37.5% overall throughout the COVID-19 period and continued to decline in the second half of the year. The number of outpatients with infectious diseases decreased significantly (35.9%) compared to noninfectious diseases (cancer, 5.0%; circulatory disease, 4.1%). In addition, the number of outpatient visits due to viral diseases continued to decline, while the incidence of bacterial diseases increased rapidly in the second half of the year.This study confirmed that the number of outpatient visits due to bacterial or viral infections decreased throughout the COVID-19 crisis. Therefore, expanding public health and telemedicine services is necessary to prevent secondary health problems caused by essential medical use restrictions.

Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report.

Hypokalemic periodic paralysis (HPP) is a neuromuscular disorder associated with muscular dysfunction caused by hypokalemia. There are various causes of HPPs and rarely, HPP appears to be relevant to tenofovir or glucocorticoid treatment. There have been several case reports of tenofovir-related nephrotoxicity or tenofovir-induced HPP. However, a case report of glucocorticoid-induced HPP in a patient using tenofovir temporarily has not been reported. Herein, we report a case of glucocorticoid-induced HPP with short-term use of tenofovir. A 28-year-old man visited the emergency room with decreased muscle power in all extremities (2/5 grade). In their past medical history, the patient was treated with tenofovir for two months for a hepatitis B virus infection. At the time of the visit, the drug had been discontinued for four months. The day before visiting the emergency room, betamethasone was administered at a local clinic for herpes on the lips. Laboratory tests showed hypokalemia, hypophosphatemia, and mild metabolic acidosis. However, urinalysis revealed no abnormal findings. Consequently, it can be postulated that this patient developed HPP by glucocorticoids after taking tenofovir temporarily. This is the first case report of glucocorticoid-induced HPP in a patient using tenofovir. Clinicians who prescribe tenofovir should be aware of HPP occurring when glucocorticoids are used.

Quinovic Acid Impedes Cholesterol Dyshomeostasis, Oxidative Stress, and Neurodegeneration in an Amyloid-ß-Induced Mouse Model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder typified by several neuropathological features including amyloid-beta (Aß) plaque and neurofibrillary tangles (NFTs). Cholesterol retention and oxidative stress (OS) are the major contributors of elevated ß- and γ-secretase activities, leading to excessive Aß deposition, signifying the importance of altered cholesterol homeostasis and OS in the progression of Aß-mediated neurodegeneration and cognitive deficit. However, the effect of Aß on cholesterol metabolism is lesser-known. In this study, we evaluated the effect of quinovic acid (QA; 50 mg/kg body weight, i.p.) against the intracerebroventricular (i.c.v.) injection of Aß (1-42)-induced cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in the cortex and hippocampal brain regions of wild-type male C57BL/6J mice. Our results indicated that Aß (1-42)-treated mice have increased Aß oligomer formation along with increased ß-secretase expression. The enhanced amyloidogenic pathway in Aß (1-42)-treated mice intensified brain cholesterol accumulation due to increased expressions of p53 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme. Importantly, we further confirmed the p53-mediated HMGCR axis activation by using pifithrin-α (PFT) in SH-SY5Y cells. Furthermore, the augmented brain cholesterol levels were also associated with increased OS. However, the QA administration to Aß (1-42)-injected mice significantly ameliorated the Aß burden, p53 expression, and cholesterol accumulation by deterring the oxidative stress through upregulating the Nrf2/HO-1 pathway. Moreover, the QA downregulated gliosis, neuroinflammatory mediators (p-NF-κB and IL-1ß), and the expression of mitochondrial apoptotic markers (Bax, cleaved caspase-3, and cytochrome c). QA treatment also reversed the deregulated synaptic markers (PSD-95 and synaptophysin) and improved spatial learning and memory behaviors in the Aß-treated mouse brains. These results suggest that Aß (1-42) induces its acute detrimental effects on cognitive functions probably by increasing brain cholesterol levels through a possible activation of the p53/HMGCR axis. However, QA treatment reduces the cholesterol-induced oxidative stress, neuroinflammation, and neurodegeneration, leading to the restoration of cognitive deficit after Aß (1-42) i.c.v. injection in mice.

Dipeptide YA is Responsible for the Positive Effect of Oyster Hydrolysates on Alcohol Metabolism in Single Ethanol Binge Rodent Models.

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

Hypoglycemic efficacy and safety of Momordica charantia (bitter melon) in patients with type 2 diabetes mellitus.

INTRODUCTION: Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes. METHODS: We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon. RESULTS: There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period. CONCLUSIONS: Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes.

Antioxidant and Anti-Inflammatory Effects of Citrus Flavonoid Hesperetin: Special Focus on Neurological Disorders.

Neurodegenerative disorders have emerged as a serious health issue in the current era. The most common neurodegenerative disorders are Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). These diseases involve progressive impairment of neurodegeneration and memory impairment. A wide range of compounds have been identified as potential neuroprotective agents against different models of neurodegeneration both in vivo and in vitro. Hesperetin, a flavanone class of citrus flavonoid, is a derivative of hesperidin found in citrus fruits such as oranges, grapes, and lemons. It has been extensively reported that hesperetin exerts neuroprotective effects in experimental models of neurodegenerative diseases. In this systematic review, we have compiled all the studies conducted on hesperetin in both in vivo and in vitro models of neurodegeneration. Here, we have used an approach to lessen the bias in each study, providing a least biased, broad understanding of findings and impartial conclusions of the strength of evidence and the reliability of findings. In this review, we collected different papers from a wide range of journals describing the beneficial effects of hesperetin on animal models of neurodegeneration. Our results demonstrated consistent neuroprotective effects of hesperetin against different models of neurodegeneration. In addition, we have summarized its underlying mechanisms. This study provides the foundations for future studies and recommendations of further mechanistic approaches to conduct preclinical studies on hesperetin in different models.

Psychological Development during Medical School Clerkship: Relationship to Resilience.

OBJECTIVE: The authors investigated changes in medical students' defenses during clerkship and examined the effects of these changes on students' resilience. METHODS: Between 2012 and 2014, all year-2 preclinical students (N = 249) at Gyeongsang National University Medical School were asked to participate. Those who agreed to participate (N = 237) completed the Korean version of the Defense Style Questionnaire (K-DSQ) and the Connor-Davidson resilience scale-10 (CD-RISC-10). After clerkship, students who proceeded to year 4 in 2 years (n = 187 (93 females), aged 24-38 years (mean, 28.9 ± 2.8 years)) completed the K-DSQ, CD-RISC-10, and the Korean version of the Hospital Anxiety and Depression Scale (K-HADS) in September 2014, 2015, and 2016. RESULTS: The use of adaptive (W = 11,603.5, p < 0.001, r = 0.39) and self-inhibiting (W = 10,901.5, p < 0.001, r = 0.32) styles increased significantly after clerkship. A multiple linear regression analysis showed that changes in adaptive defense styles (B = 1.336, SE = 0.386, ß = 0.218, p = 0.001) during clerkship were significantly related to resilience after adjusting for age, sex, depression, and anxiety. CONCLUSIONS: Both positive personality development and maladaptive changes in defenses were evident. An increase in the adaptive defense style score was related to resilience.

Metabolic Stress Alters Antioxidant Systems, Suppresses the Adiponectin Receptor 1 and Induces Alzheimer's Like Pathology in Mice Brain.

Oxidative stress and insulin resistance play major roles in numerous neurodegenerative diseases, including Alzheimer's disease (AD). A high-fat diet induces obesity-associated oxidative stress, neuronal insulin resistance, microglial activation, and neuroinflammation, which are considered important risk factors for neurodegeneration. Obesity-related metabolic dysfunction is a risk factor for cognitive decline. The present study aimed to elucidate whether chronic consumption of a high-fat diet (HFD; 24 weeks) can induce insulin resistance, neuroinflammation, and amyloid beta (Aß) deposition in mouse brains. Male C57BL/6N mice were used for a high-fat diet (HFD)-induced pre-clinical model of obesity. The protein expression levels were examined via Western blot, immunofluorescence, and the behavior analysis was performed using the Morris water maze test. To obtain metabolic parameters, insulin sensitivity and glucose tolerance tests were performed. We found that metabolic perturbations from the chronic consumption of HFD elevated neuronal oxidative stress and insulin resistance through adiponectin receptor (AdipoR1) suppression in HFD-fed mice. Similarly, our in vitro results also indicated that knockdown of AdipoR1 in the embryonic mouse hippocampal cell line mHippoE-14 leads to increased oxidative stress in neurons. In addition, HFD markedly increased neuroinflammatory markers' glial activation in the cortex and hippocampus regions of HFD mouse brains. More importantly, we observed that AdipoR1 suppression increased the amyloidogenic pathway both in vivo and in vitro. Furthermore, deregulated synaptic proteins and behavioral deficits were observed in the HFD mouse brains. Taken together, our findings suggest that excessive consumption of an HFD has a profound impact on brain function, which involves the acceleration of cognitive impairment due to increased obesity-associated oxidative stress, insulin resistance, and neuroinflammation, which ultimately may cause early onset of Alzheimer's pathology via the suppression of AdipoR1 signaling in the brain.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity.

BACKGROUND: To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity. METHODS: In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index. RESULTS: During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable. CONCLUSION: Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Caffeine May Abrogate LPS-Induced Oxidative Stress and Neuroinflammation by Regulating Nrf2/TLR4 in Adult Mouse Brains.

Herein, we assayed the antioxidant and anti-inflammatory potential of caffeine in a lipopolysaccharide (LPS)-injected mouse model of neurodegeneration and synaptic impairment. For this purpose, LPS was injected for two weeks on an alternate-day basis (250 µg/kg/i.p. for a total of seven doses), while caffeine was injected daily for four weeks (30 mg/kg/i.p/four weeks). According to our findings, there was a significant increase in the level of reactive oxygen species (ROS), as evaluated from the levels of lipid peroxidation (LPO) and ROS assays. Also, we evaluated the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and the enzyme hemeoxygenase 1 (HO-1) in the mouse groups and found reduced expression of Nrf2 and HO-1 in the LPS-treated mice brains, but they were markedly upregulated in the LPS + caffeine co-treated group. We also noted enhanced expression of toll-Like Receptor 4 (TLR4), phospho-nuclear factor kappa B (p-NF-kB), and phospho-c-Jun n-terminal kinase (p-JNK) in the LPS-treated mice brains, which was significantly reduced in the LPS + caffeine co-treated group. Moreover, we found enhanced expression of Bcl2-associated X, apoptosis regulator (Bax), and cleaved caspase-3, and reduced expression of B-cell lymphoma 2 (Bcl-2) in the LPS-treated group, which were markedly reversed in the LPS + caffeine co-treated group. Furthermore, we analyzed the expression of synaptic proteins in the treated groups and found a marked reduction in the expression of synaptic markers in the LPS-treated group; these were significantly upregulated in the LPS + caffeine co-treated group. In summary, we conclude that caffeine may inhibit LPS-induced oxidative stress, neuroinflammation, and synaptic dysfunction.

Long-term outcomes of renal function after radioactive iodine therapy for thyroid cancer according to preparation method: thyroid hormone withdrawal vs. recombinant human thyrotropin.

PURPOSE: Long-term effects of iatrogenic hypothyroidism on renal function from thyroid hormone withdrawal during radioactive iodine therapy (RAIT) have not been studied, especially in subjects with mildly impaired renal function. We compared renal function in thyroid cancer subjects according to preparation method of either thyroid hormone withdrawal (THW) or injection of recombinant human thyrotropin (rhTSH). METHODS: This retrospective study enrolled 241 thyroidectomized patients (rhTSH group, n = 87 and THW group, n = 154). Changes in glomerular filtration rate (GFR) were measured prior to surgery, at the time of RAIT, and during a regular follow-up at least one year after RAIT. RESULTS: Baseline renal function was comparable between the rhTSH group and the THW group (91.4 mL/min/1.73 m2 vs. 92.4 mL/min/1.73 m2). At the time of RAIT, GFR was significantly decreased in the THW group (70.6 mL/min/1.73 m2, -23.6%), whereas renal function was preserved in the rhTSH group (85.4 mL/min/1.73 m2, -6.6%). In the THW group, renal function was fully recovered within 6 months after RAIT and was maintained up to 24 months, even in subjects with baseline GFR less than 90 mL/min/1.73 m2. CONCLUSIONS: THW for RAIT preparation induced considerable reduction in renal function, but this change was transient. In contrast, injection of rhTSH did not decrease renal function, making it a good option for RAIT preparation for subjects with renal dysfunction.

Changes in Serum Electrolytes, ECG, and Baroreflex Sensitivity during Combined Pituitary Stimulation Test.

The mechanisms by which hypoglycemia increases cardiovascular mortality remain unclear. The aim of the study is to investigate changes in serum electrolytes, norepinephrine concentrations, electrocardiography, and baroreflex sensitivity (BRS) and associations between corrected QT (QTc) intervals and the changes in serum electrolytes during combined pituitary stimulation test (CPST). We recruited the subjects who were admitted to the Gyeongsang National University Hospital to undergo CPST between September 2013 and December 2014. Participants were 12 patients suspected of having hypopituitarism. Among 12 patients, cardiac arrhythmia in two patients occurred during hypoglycemia. There were significant differences in serum levels of potassium (P < 0.001), sodium (P = 0.003), chloride (P = 0.002), and calcium (P = 0.017) at baseline, hypoglycemia, and 30 and 120 minutes after hypoglycemia. Also, there was a significant increase in heart rate (P = 0.004), corrected QT (QTc) interval (P = 0.008), QRS duration (P = 0.021), and BRS (P = 0.005) at hypoglycemia, compared to other time points during CPST. There was a positive association between QTc intervals and serum sodium levels (P < 0.001) in 10 patients who did not develop arrhythmia during CPST. This study showed that there were significant changes in serum levels of potassium, sodium, chloride, and calcium, as well as heart rate, QTc interval, QRSd, and BRS during CPST. It was revealed that QTc intervals had a significant association with concentrations of sodium.

Thyroid function tests in patients at the emergency department compared to a prior healthy setting.

We examined the changes in thyroid hormone levels in patients with an acute clinical condition and compared these to levels in the healthy subjects. Serum total triiodothyronine (T3), thyroid stimulating hormone (TSH), and free thyroxine (fT4) measurements were recorded from 555 patients (mean age: 55.0 years, men: 65.9%) admitted to the emergency department (ED) 1-91 months (median: 34 months) after a regular health examination (HE). Serological data were analyzed; mean change in hormone levels was stratified by emergency classification system and quintiles of changes in inflammatory marker values, such as neutrophil lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (CRP). The mean decrease in T3 levels from HE and ED samples was 10.6 ng/dL (p< 0.001). Mean decrease in T3 levels was 21.6 ng/dL among patients classified as having an infection status and 11.0 ng/dL among patients classified as having an urgency status. A decrease 3.7 ng/dL among emergency patients was observed. TSH and fT4 levels did not change across all groups. When patients were stratified into quintiles according to changes in NLR values, mean decreases in T3 were 6.21, 8.14, 14.37, 12.76, and 21.98 ng/dL and showed significant linear reduction (p<0.001). For quintiles of changed CRP values, mean decreased T3 levels were 10.57, 3.05, 4.47, 7.68, and 28.07 ng/dL. TSH and fT4 were not associated with significant changes (p = 0.100, p = 0.561, respectively). In this study, thyroid function changes in individuals with an acute condition revealed that T3 significantly decreased, more markedly in infectious diseases compared to their healthy counterparts, and decline in T3 measurements correlated with inflammatory markers. TSH and fT4 levels remained stable. It is necessary to consider the severity of acute conditions when abnormal T3 levels are detected in subjects with emergent status.

Effects of lobeglitazone on insulin resistance and hepatic steatosis in high-fat diet-fed mice.

Lobeglitazone (Lobe) is a novel thiazolidinedione antidiabetic drug that reduces insulin resistance by activating peroxisome proliferator-activated receptor-gamma (PPARγ). However, the exact mechanisms of antidiabetic effects of Lobe have not been established in an animal model. The aim of this study was to evaluate the hypoglycemic effects of Lobe and investigate possible factors involved in Lobe-enhanced hepatic steatosis in high-fat diet (HFD)-fed mice. Mice were fed an HFD for 15 weeks. Lobe was administrated orally during the last 9 weeks. Lobe treatment significantly reduced insulin resistance and increased expression of hepatic glucose transporter 4 (GLUT4) and PPARs in HFD-fed mice. However, increased body weight and hepatic steatosis were not reduced by Lobe in these mice. Metabolomics fingerprinting showed that several lipogenesis-related hepatic and serum metabolites in HFD-fed mice had positive or negative correlations with Lobe administration. In particular, increased leptin levels during HFD were further increased by Lobe. HFD-induced signaling transducer and activator of transcription 3 (STAT3) phosphorylation in the hypothalamus was increased by Lobe. In addition, immunohistochemical analysis showed more proopiomelanocortin (POMC)-positive neurons in the hypothalamus of HFD-fed mice (with or without Lobe) compared with normal diet-fed mice. Despite improving leptin signaling in the hypothalamus and enhancing insulin sensitivity in HFD-fed mice, Lobe increased body weight and steatosis. Further research is necessary regarding other factors affecting Lobe-enhanced hepatic steatosis and hyperphagia.

Protective Effect of Metformin Against Thyroid Cancer Development: A Population-Based Study in Korea.

BACKGROUND: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. METHODS: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. RESULTS: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 105 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. CONCLUSIONS: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.