Review and expert opinion on MAFLD, oxidative stress and multifunctional management.

Metabolic-associated fatty-liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most widespread and emerging chronic liver disease worldwide, with increasing prevalence rates also in the Asia-Pacific region. The disease has a high socio-economic burden as it negatively impacts the finances and quality of life of individuals affected and has a major burden on healthcare systems. The most important pathological event in MAFLD aetiopathogenesis is oxidative stress, which leads to functional and structural abnormalities in the liver as well as being involved in the development of other concomitant cardiometabolic diseases. MAFLD is a rather complex multisystemic clinical condition involving liver damage and a wide spectrum of extrahepatic manifestations such as obesity, type 2 diabetes, metabolic syndrome and cardiovascular diseases. This complexity requires the cooperation of multiple experts to identify MAFLD at an early stage, treat associated comorbidities, and promptly refer the patient to the hepatologist when needed. This review summarizes the current knowledge about MAFLD and reports the opinion of a group of experts on the increasing prevalence and burden of the disease in the southeast Asia region, the current journey of patients with MAFLD in developing countries, the role of oxidative stress and antioxidant treatment, and the importance of a multidisciplinary approach for early diagnosis and disease management. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Gaps in the Care of Subjects with Familial Hypercholesterolemia: Insights from the Thai Familial Hypercholesterolemia Registry.

AIMS: Familial hypercholesterolemia (FH) is currently underdiagnosed and undertreated. The establishment of a FH registry could facilitate a deeper understanding of this disease. We described the clinical characteristics of subjects with FH from the Thai FH Registry, compared our data with the regional and global data, and identified gaps in the care of these subjects. METHODS: A multicenter, nationwide prospective FH registry was established in Thailand. Our data were compared with those of the European Atherosclerosis Society-FH Studies Collaboration. Multiple logistic regression analyses were performed for variables associated with lipid-lowering medication (LLM) use and the attainment of low-density lipoprotein-cholesterol (LDL-C) goal. RESULTS: The study includes 472 subjects with FH (mean age at FH diagnosis: 46±12 years, 61.4% women). A history of premature coronary artery disease was found in 12%. The percentage of LLM use in subjects with a Dutch Lipid Clinic Network score of ≥ 6 (probable or definite FH) in our registry (64%) was slightly lower than the regional data but higher than the global data. Among those who received statins, 25.2% and 6.4% achieved LDL-C levels of ＜100 mg/dL and ＜70 mg/dL, respectively. Women with FH were less likely to achieve LDL-C ＜70 mg/dL (adjusted odds ratio: 0.22, 95% confidence interval: 0.06-0.71, p=0.012). CONCLUSIONS: FH in Thailand was diagnosed late, and treatment was inadequate for the majority of subjects. Women with FH were less likely to achieve LDL-C goals. Our insights could potentially help raise awareness and narrow the gap in patient care.

Injection of an improperly stored proprotein convertase subtilisin/kexin type 9 monoclonal antibody in a patient with secondary dyslipidemia from nephrotic syndrome: a case report.

BACKGROUND: Elevated plasma cholesterol and/or plasma triglyceride levels in nephrotic syndrome patients are the result of impaired lipoprotein clearance and a compensatory increase in hepatic lipoprotein synthesis. Plasma proprotein convertase subtilisin/kexin type 9 levels directly correlate to the amount of proteinuria in nephrotic syndrome patients. Proprotein convertase subtilisin/kexin type 9 monoclonal antibody has been used to treat dyslipidemia in some refractory nephrotic syndrome cases. As a therapeutic protein, proprotein convertase subtilisin/kexin type 9 monoclonal antibody simply deteriorates if stored in inappropriate temperatures or conditions. CASE PRESENTATION: In this article, we present the case of a 16-year-old Thai female with severe combined dyslipidemia secondary to refractory nephrotic syndrome. She received proprotein convertase subtilisin/kexin type 9 monoclonal antibody (alirocumab) treatment. However, the drugs were mistakenly frozen in a freezer for up to 17 hours before being stored at 4 °C. After using two frozen devices, serum total cholesterol, free proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) significantly decreased. Nonetheless, the patient developed a skin rash 2 weeks after the second injection and the lesion spontaneously resolved without any treatment approximately 1 month later. CONCLUSIONS: The effectiveness of proprotein convertase subtilisin/kexin type 9 monoclonal antibody seems to be stable after being stored under freeze-thaw conditions. However, improperly stored drugs should be discarded to avoid any potential undesirable side effects.

Cluster analysis of Thai patients with newly diagnosed type 2 diabetes mellitus to predict disease progression and treatment outcomes : A prospective cohort study.

INTRODUCTION: Type 2 diabetes mellitus (T2D) is highly heterogeneous in disease progression and risk of complications. This study aimed to categorize Thai T2D into subgroups using variables that are commonly available based on routine clinical parameters to predict disease progression and treatment outcomes. RESEARCH DESIGN AND METHODS: This was a cohort study. Data-driven cluster analysis was performed using a Python program in patients with newly diagnosed T2D (n=721) of the Siriraj Diabetes Registry using five variables (age, body mass index (BMI), glycated hemoglobin (HbA1c), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C)). Disease progression and risk of diabetic complications among clusters were compared using the Χ2 and Kruskal-Wallis test. Cox regression and the Kaplan-Meier curve were used to compare the time to diabetic complications and the time to insulin initiation. RESULTS: The mean age was 53.4±11.3 years, 58.9% were women. The median follow-up time was 21.1 months (9.2-35.2). Four clusters were identified: cluster 1 (18.6%): high HbA1c, low BMI (insulin-deficiency diabetes); cluster 2 (11.8%): high TG, low HDL-C, average age and BMI (metabolic syndrome group); cluster 3 (23.3%): high BMI, low HbA1c, young age (obesity-related diabetes); cluster 4 (46.3%): older age and low HbA1c at diagnosis (age-related diabetes). Patients in cluster 1 had the highest prevalence of insulin treatment. Patients in cluster 2 had the highest risk of diabetic kidney disease and diabetic retinopathy. Patients in cluster 4 had the lowest prevalence of diabetic retinopathy, nephropathy, and insulin use. CONCLUSIONS: We were able to categorize Thai patients with newly diagnosed T2D into four clusters using five routine clinical parameters. This clustering method can help predict disease progression and risk of diabetic complications similar to previous studies using parameters including insulin resistance and insulin sensitivity markers.

Dyslipidemia management for primary prevention of cardiovascular events: Best in-clinic practices.

Dyslipidemia is a fundamental risk factor for cardiovascular diseases (CVDs) and can worsen the prognosis, if unaddressed. Lipid guidelines are still evolving as dyslipidemia is affecting newer patient subsets. However, these guidelines are governed by regional demographics and ethnic data. Primary care practitioners (PCPs) are the first to offer treatment, and hence placed early in the healthcare continuum. PCPs shoulder a huge responsibility in early detection of dyslipidemia for primary prevention of future cardiovascular (CV) events. Therefore, as members of Cardiovascular RISk Prevention (CRISP) in Asia network, the authors intend to align and shape-up the daily clinical practice workflow for PCPs and have a goal-directed strategy for managing dyslipidemia. This paper reviews the major international lipid guidelines, namely the American and European guidelines, and the regional guidelines from Indonesia, Malaysia, Philippines, Thailand, and Vietnam to identify their commonalities and heterogeneities. The authors, with a mutual consensus, have put forth, best in-clinic practices for screening, risk assessment, diagnosis, treatment, and management of dyslipidemia, particularly to reduce the overall risk of CV events, especially in the Asian context. The authors feel that PCPs should be encouraged to work in congruence with patients to decide on best possible therapy, which would be a holistic approach, rather than pursuing a "one-size-fits-all" approach. Since dyslipidemia is a dynamic field, accumulation of high-quality evidence and cross-validation studies in the future are warranted to develop best in-clinic practices at a global level.

Cumulative incidence of and risk factors for herpes zoster among patients with diabetes mellitus: Results from a 10-year nested case-control study.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for herpes zoster (HZ). Data specific to the incidence of and risk factors for HZ among Thai DM patients are scarce. METHODS: This nested case-control study evaluated a 10-year cohort of DM patients (N = 1428) treated at Siriraj Hospital (Bangkok, Thailand). We included 40 cases with ≥1 episode of HZ, and we randomly sampled 175 non-HZ controls. Data were obtained from chart review and the ICD-10 diagnosis code, pharmacy database, and laboratory database. RESULTS: During 2005-2014, the cumulative incidence and incidence rate of HZ among all study patients was 2.80% [95%CI: 2.00-3.79%] and 3.96 [95%CI: 2.90-5.28] per 1000 person-years, respectively. The most common site was trunk (27.5%) followed by zoster ophthalmic (22.5%). Only 1 case required hospitalization. Independent risk factors for HZ included underlying hypertension [aOR: 3.48, 95%CI: 1.28-9.43; p = 0.01], number of hypoglycemic drugs used [aOR: 1.46, 95%CI: 1.03-2.08; p = 0.04], and previous herbal remedy use [aOR: 3.83, 95%CI: 1.06-13.84; p = 0.04]. Higher body mass index was a protective factor against HZ [aOR: 0.89, 95%CI: 0.81-0.98; p = 0.02]. CONCLUSION: The incidence of HZ among DM patients at our center is comparable to other Asian countries. The identified independent risk factors can be used to discern patients who would benefit most from preventive interventions.

Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity within the Asia-Pacific region, with the prevalence of CVD risk factors such as plasma lipid disorders increasing in many Asian countries. As members of the Cardiovascular RISk Prevention (CRISP) in Asia network, the authors have focused on plasma lipid disorders in the six countries within which they have clinical experience: Indonesia, Malaysia, Philippines, Thailand, Vietnam, and Australia. Based on country-specific national surveys, the prevalence of abnormal levels of total cholesterol, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and triglycerides (TG) are reported. An important caveat is that countries have used different thresholds to define plasma lipid disorders, making direct comparisons difficult. The prevalence of abnormal lipid levels was as follows: high total cholesterol (30.2-47.7%, thresholds: 190-213 mg/dL); high LDL-C (33.2-47.5%; thresholds: 130-135 mg/dL); low/abnormal HDL-C (22.9-72.0%; thresholds: 39-50 mg/dL); and high/abnormal TG (13.9-38.7%; thresholds: 150-177 mg/dL). Similarities and differences between country-specific guidelines for the management of plasma lipid disorders are highlighted. Based on the authors' clinical experience, some of the possible reasons for suboptimal management of plasma lipid disorders in each country are described. Issues common to several countries include physician reluctance to prescribe high-dose and/or high-intensity statins and poor understanding of disease, treatments, and side effects among patients. Treatment costs and geographical constraints have also hampered disease management in Indonesia and the Philippines. Understanding the factors governing the prevalence of plasma lipid disorders helps enhance strategies to reduce the burden of CVD in the Asia-Pacific region.

An Implementation Framework for Telemedicine to Address Noncommunicable Diseases in Thailand.

To maintain the continuity of noncommunicable disease (NCD) services and ascertain the health outcomes of patients with NCDs during the COVID-19 (coronavirus disease 2019) outbreak in Thailand, various telemedicine services have been developed. To achieve this determination, the implementation framework has been constructed based on recommendations from multidisciplinary experts (Thai NCD Collaboration Group). Within the framework, all key elements are illustrated with their priority and expected collaborations. Ultimately, active collaborations from multi-stakeholders are vitally important to ensure that telemedicine services for NCDs will finally become practical, successful, and sustainable.

The effect of temperature on the stability of PCSK-9 monoclonal antibody: an experimental study.

BACKGROUND: PCSK9 monoclonal antibody lowers plasma PCSK9 and LDL-cholesterol levels. The manufacturers recommend drug storage at 2-8 °C, and not above 25 °C. This study aimed to investigate drug stability at various temperatures that this drug could be exposed to during medication handling and transportation in tropical countries. METHODS: Alirocumab and evolocumab were tested in 3 study conditions: room temperature (RT), cooler device with cold pack, and freeze-thaw for 9 and 18 h. Heated drugs were used as negative control. Free plasma PCSK9 levels from 9 hyperlipidemia subjects were measured with ELISA. RESULTS: Average subject age was 49.2 ± 18.4 years. Percent PCSK9 inhibition significantly declined in heated drugs compared to baseline. Average RT during the study period was 30.4 ±2.6 °C. Change in percent PCSK9 inhibition of PCSK9 mAb at RT from baseline was - 5.8 ± 4.4% (P = 0.005) and - 11.0 ± 8.9% (P = 0.006) for alirocumab at 9 h and 18 h, and - 9.7 ± 11.8% (P = 0.04) and - 15.1 ± 14.3% (P = 0.01) for evolocumab at 9 and 18 h, respectively. In contrast, there were no significant changes in percent PCSK9 inhibition from baseline when PCSK9 mAb was stored in a cooler. In freeze-thaw condition, changes in percent PCSK9 inhibition from baseline to 9 and 18 h were - 5.2 ± 2.9% (P = 0.001) and - 2.6 ± 4.9% (P = 0.16) for alirocumab, and - 1.8 ± 4.2% (P = 0.24) and 0.4 ± 6.1% (P = 0.83) for evolocumab. CONCLUSION: Proper drug storage according to manufacturer's recommendation is essential. Drug storage at RT in tropical climate for longer than 9 h significantly decreased drug efficacy; however, storage in a cooler device with cold pack for up to 18 h is safe.

Effect of Switching from Low-Dose Simvastatin to High-Dose Atorvastatin on Glucose Homeostasis and Cognitive Function in Type 2 Diabetes.

BACKGROUND: High-intensity statin is recommended in high-risk type 2 diabetes (T2D); however, statin dose dependently increases the risk of developing new-onset diabetes, can potentially worsen glycemic control in T2D, and may cause cognitive impairment. This study aimed to investigate the effect of statin intensification on glucose homeostasis and cognitive function in T2D. MATERIALS AND METHODS: T2D patients who were taking simvastatin ≤20 mg/day were randomized to continue taking the same dosage of simvastatin (low-dose simvastatin group; LS, n=63) for 12 weeks, or to change to atorvastatin 40 mg/day for 6 weeks, and if tolerated, atorvastatin was increased to 80 mg/day for 6 weeks (high-dose atorvastatin group; HS, n=62). Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and of ß-cell function (HOMA-B), cognitive functions using Montreal Cognitive Assessment (MoCA), and Trail Making Test (TMT) were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Mean age of patients was 58.8±8.9 years, and 72% were female. Mean baseline FPG and HbA1c were 124.0±27.5 mg/dl and 6.9±0.8%, respectively. No differences in baseline characteristics between groups were observed. Change in HbA1c from baseline in the LS and HS groups was -0.1% and +0.1% (p=0.03) at 6 weeks, and -0.1% and +0.1% (p=0.07) at 12 weeks. There were no significant differences in FPG, fasting plasma insulin, HOMA-B, HOMA-IR, MoCA score, or TMT between groups at 6 or 12 weeks. CONCLUSION: Switching from low-dose simvastatin to high-dose atorvastatin in T2D resulted in a slight increase in HbA1c (0.1%) without causing cognitive decline.

Effect of Thunbergia laurifolia Herbal Tea on Glucose Homeostasis in Healthy Volunteers: A Single-Arm Phase I Study.

BACKGROUND: Thunbergia laurifolia (TL) is a commonly used herbal medicine in Thailand and in other Asian countries. TL has been approved as a Thai traditional medicine for detoxifying poisons, and the list of possible adverse effects includes hypoglycemia. TL showed hypoglycemic effect in animals possibly due to antioxidant effect and beta-cell preservation. However, the safety of TL herbal tea and its effects on glucose homeostasis have never been investigated in humans. METHODS: Twenty healthy volunteers (10 men and 10 women) drank TL herbal tea 3 times/day for 2 weeks. Ten subjects took TL herbal tea 9 grams daily. After the safety of TL herbal tea was established, 10 more subjects took TL 12 grams daily. Clinical and biochemical tests were assessed at baseline and at 2 weeks. RESULTS: Mean age was 34.9 ± 10.2 years, and mean body mass index was 27.5 ± 5.8 kg/m2. Baseline and posttreatment plasma concentrations were as follows: fasting plasma glucose (89 ± 6 vs. 89 ± 7 mg/dL), fructosamine (213 ± 32 vs. 212 ± 33 µmol/L), fasting insulin (8.8 [IQR: 5.9-18.4] vs. 10.4 [IQR: 7.4-15.2] µU/mL), HOMA-B (101.6 [IQR: 82.3-189.8] vs. 120.4 [IQR: 93.2-153.2]), and HOMA-IR (1.1 [IQR: 0.8-2.3] vs. 1.4 [IQR: 0.9-2.0]), all respectively. There were no significant changes in these parameters, including body weight, blood pressure, lipid profile, and C-reactive protein. No serious adverse events were observed during the study period. CONCLUSIONS: TL herbal tea at doses of 9 and 12 grams daily had good tolerability without any significant adverse effects on fasting plasma glucose level or other glucose homeostasis parameters measured.

Efficacy and Safety of Switching from Low-Dose Statin to High-Intensity Statin for Primary Prevention in Type 2 Diabetes: A Randomized Controlled Trial.

INTRODUCTION: Statin intensification is required in patients who have high-risk for cardiovascular events. However, it is unclear if this is needed in whom plasma LDL-C target was achieved with low-dose statin for primary prevention. We investigated the efficacy and safety of switching from low-dose statin to high-intensity statin among type 2 diabetes (T2D) who had achieved plasma LDL-C <100 mg/dl with low-dose statin treatment. METHODS: T2D patients with no atherosclerotic cardiovascular disease who had plasma LDL-C level <100 mg/dl while taking simvastatin ≤20 mg/day were randomized to continue using the same dosage of simvastatin (low-dose statin group; LS) for 12 weeks, or to switch to atorvastatin 40 mg/day for 6 weeks, and then, if tolerated, to atorvastatin 80 mg/day for 6 weeks (high-intensity statin group; HS). Biochemical test and adverse events were evaluated at baseline, 6 weeks, and 12 weeks. RESULTS: One hundred and fifty patients (76 LS, 74 HS, mean age 58.9±8.9 years, 72% female) were included. The mean baseline plasma LDL-C level on statin was slightly higher in the HS group (71.9±13.6 vs. 68.1±14.2 mg/dl, p=0.09). The HS group had a significantly lower plasma LDL-C level at both 6 and 12 weeks (both p<0.001). Plasma LDL-C <40 mg/dl was found more frequently in the HS group (23.0% vs. 3.9%, p<0.001). Discontinuation of statin due to adverse effects was more frequent in the HS group (5.4% vs. 1.3%, p=0.38 for atorvastatin 40 mg/day, 12.2% vs. 1.3%, p=0.03 for atorvastatin 80 mg/day). No serious adverse events were observed in either group. CONCLUSION: Switching from low-dose statins to high-intensity statins resulted in a significant reduction in plasma LDL-C levels, and was fairly well tolerated during a 12-week study period.

Expert opinion on the applicability of dyslipidemia guidelines in Asia and the Middle East.

Cardiovascular disease (CVD) is a growing burden across the world. In Asia and the Middle East, in particular, CVD is among the most prevalent and debilitating diseases. Dyslipidemia is an important factor in the development of atherosclerosis and associated cardiovascular events, and so effective management strategies are critical to reducing overall cardiovascular risk. Multiple dyslipidemia guidelines have been developed by international bodies such as the European Society of Cardiology/European Atherosclerosis Society and the American College of Cardiology/American Heart Association, which all have similarities in practice recommendations for the optimal management of dyslipidemia. However, they differ in certain aspects including pharmacological treatment, lifestyle modification and the target levels used for low-density lipoprotein cholesterol. The evidence behind these guidelines is generally based on data from Western populations, and their applicability to people in Asia and the Middle East is largely untested. As a result, practitioners within Asia and the Middle East continue to rely on international evidence despite population differences in lipid phenotypes and CVD risk factors. An expert panel was convened to review the international guidelines commonly used in Asia and the Middle East and determine their applicability to clinical practice in the region, with specific recommendations, or considerations, provided where current guideline recommendations differ from local practice. Herein, we describe the heterogeneous approaches and application of current guidelines used to manage dyslipidemia in Asia and the Middle East. We provide consensus management recommendations to cover different patient scenarios, including primary prevention, elderly, chronic kidney disease, type 2 diabetes, documented CVD, acute coronary syndromes and family history of ischemic heart disease. Moreover, we advocate for countries within the Asian and Middle East regions to continue to develop guidelines that are appropriate for the local population.

Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin.

Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d = 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P < 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P < 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.

Efficacy of low- and moderate-intensity statins for achieving low- density lipoprotein cholesterol targets in Thai type 2 diabetic patients.

BACKGROUND: Low dose statins are commonly used among Asians, because plasma low-density lipoprotein cholesterol (LDL-C) reductions similar to those observed in Westerners are achieved at lower doses. We aimed to assess the efficacy of low- and moderate-intensity statins for achieving plasma lipid targets in Thai type2 diabetes (T2D) and to evaluate factors associated with greater LDL-C reduction by statins. METHODS: T2D patients who were treated with low- and moderate-intensity statins at the Siriraj Diabetes Clinic during the January 2013 to December 2014 study period were eligible for inclusion(n = 978), 400 patients were randomly recruited. Patients were classified into 1 of the following 2 groups according to their plasma LDL-C reductions by statins (N = 393); very favorable response (LDL-C reduction ≥50%) or less favorable response (LDL-C reduction <50%). RESULTS: Of the 400 patients, 41.3% were low-intensity statin users. Mean age was 64.4 ± 12.7 years, 64% were female. Median duration of diabetes was 13.3 years and mean HbA1C was 8.1 ± 1.9%. Plasma LDL-C goal of <100 mg/dl and <70 mg/dl was achieved in 84.3% and 38.0% respectively, with no significant difference between the low- and moderate-intensity statin users. LDL-C reductions ≥50% can be achieved in 38.4%. Factors associated with very favorable responses from statins were age, hypertension, patients with stable or reduced weight, and better glycemic control. CONCLUSION: Low- and moderate-intensity statins achieved plasma LDL-C goal of <100 mg/dl and <70 mg/dl in 84.3%, and 38.4% of the patients respectively. Due to the improved response to lower doses observed in Asians, a titration dosage strategy should be considered.

Coexistence of Graves' disease and unilateral functioning Struma ovarii: a case report.

BACKGROUND: Coexisting of Graves' disease and functioning struma ovarii is a rare condition. Although the histology of struma ovarii predominantly composed of thyrocytes, the majority of the patients did not have thyrotoxicosis. The mechanism underlying the functioning status of the tumor is still unclear but the presence of thyroid stimulating hormone receptor (TSHR) is thought to play a role. Here we describe the patient presentation and report the TSHR expression of the tumor. CASE PRESENTATION: A 56-year old Asian woman presented with long standing thyrotoxicosis for 23 years. She was diagnosed with Graves' disease and thyroid nodules. She had bilateral exophthalmos and had high titer of plasma TSHR antibody. Total thyroidectomy was performed and the histologic findings confirmed the clinical diagnosis. The patient had persistent thyrotoxicosis postoperatively. Thyroid uptake demonstrated the adequacy of the thyroid surgery and the whole body scan confirmed the presence of functioning thyroid tissue at pelvic area. The surgery was scheduled and the patient had hypothyroidism after the surgery. The pathological diagnosis was struma ovarii at right ovary. We performed TSHR staining in both the patient's struma ovarii and in 3 cases of non-functioning struma ovarii. The staining results were all positive and the intensity of the TSHR staining of functioning struma ovarii was the same as that in other cases of non-functioning tumors, suggesting that the determinant of functioning struma ovarii might be the presence of TSHR stimuli rather than the intensity of the TSHR in the ovarian tissue. CONCLUSION: In patients with Graves' disease with persistent or recurrent thyrotoxicosis after adequate ablative treatment, the possibility of ectopic thyroid hormone production should be considered. TSHR expression is found in patients with functioning and non-functioning struma ovarii and cannot solely be used to determine the functioning status of the tumor.

Rosuvastatin Enhances the Catabolism of LDL apoB-100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner.

Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54% (both P < 0.0001), triacylglycerol by 14% (ns) and 35% (P < 0.01), apoB by 30 and 36% (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46% (both ns) and LDL apoB-100 by 63 and 102% (both P < 0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12%, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.

Withdrawal of sulfonylureas from patients with type 2 diabetes receiving long-term sulfonylurea and insulin combination therapy results in deterioration of glycemic control: a randomized controlled trial.

BACKGROUND: The benefit of sulfonylureas (SUs) to patients with type 2 diabetes mellitus receiving long-term insulin treatment is unclear. This study evaluated glycemic control and beta-cell function after SU withdrawal in these patients. METHODS: In this 8-week randomized controlled study, patients with type 2 diabetes who had been treated with insulin for at least 3 years plus moderate to high doses of SUs were randomly assigned to withdrawal (n=16) or continuation (n=16) of SUs. Clinical characteristics, glycemic control, hypoglycemic events, and insulin secretion, including homeostasis model assessment of beta-cell function (HOMA-B) score, C-peptide concentration, and Matsuda index, were evaluated at baseline and after 2 and 8 weeks. RESULTS: Thirty patients (16 in the SU withdrawal group and 14 in the SU continuation group) completed the study. Median duration of diabetes was 17 (range 5-40) years. Baseline clinical characteristics, glycemic control, and HOMA-B were similar in the two groups, but the mean fasting C-peptide concentration was higher in the SU withdrawal group. After 8 weeks, the SU withdrawal group showed a significant increase in mean glycosylated hemoglobin levels from 7.8%±0.5% (62±5 mmol/mol) to 8.6%±1.2% (71±13 mmol/mol; P=0.002), whereas the SU continuation group showed a slight but not significant increase from 7.7%±0.5% (61±5 mmol/mol) to 7.9%±1.2% (63±13 mmol/mol; P=0.37). Insulin secretion, as measured by C-peptide and HOMA-B, decreased by 18% and 36%, respectively, in the SU withdrawal group. Hypoglycemic events were significantly more frequent in the SU continuation group whereas body weight did not change significantly in either group. CONCLUSION: Withdrawal of SU from patients with type 2 diabetes receiving long-term combination treatment with SU and insulin resulted in deterioration of glycemic control and insulin secretion.