A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin.

AIM: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. RESULTS: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. CONCLUSIONS: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: Results of a 12-week, multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIMS: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with glycated haemoglobin (HbA1c) of 7.0-10.0%, entered a 2-week placebo run-in period, and were randomized to receive once-daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. RESULTS: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (-0.79%, -0.89%, -0.92% and -0.08%, respectively; p < .001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were -30.5, -31.1, -35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. CONCLUSIONS: Once-daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well-tolerated treatment for Korean patients with type 2 diabetes mellitus.

Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: A 24-week, multicentre, randomized, double-blind, placebo-controlled, phase III trial.

AIMS: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%-10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study. RESULTS: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.99% (95% confidence interval -1.24%, -0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p < .0001). Placebo-adjusted mean changes in fasting plasma glucose (-40.1 mg/dl) and body weight (-2.5 kg) at week 24 were statistically significant (p < .0001). In addition, a significant decrease in blood pressure, low-density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high-density lipoprotein cholesterol. No significant increase in treatment-related adverse events was observed for enavogliflozin. CONCLUSIONS: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile.

Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.

OBJECTIVE: To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion. METHODS: C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH. RESULTS: GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro. CONCLUSION: Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Analysis of diabetes quality assessment findings and future directions for the appropriate management of diabetes in Korea.

BACKGROUND/AIMS: Due to recent increases in the disease burden of diabetes mellitus, the Health Insurance Review and Assessment Service (HIRA) of Korea implemented a quality assessment of the treatment of diabetes to improve patient care. The present study was conducted to identify any changes after the implementation of the diabetes quality assessment (DQA). METHODS: The present study evaluated eight quality assessment indicators that were proposed by the HIRA in all patients with diabetes who visited a university hospital in Korea between 2009 and 2014. The indicators were statistically compared according to the characteristics of the subjects. RESULTS: There were several significant differences in the indicators among the subjects according to their demographic characteristics. Female patients had a higher continuity of treatment (COT) than that of male patients, and the insulin-treated group had a higher COT than that of the non-treated group, as well as a higher rate of undergoing the diabetes complication tests (DCTs). Patients between 40 and 80 years of age had the highest COT, while patients under 40 years of age had the lowest COT but the highest rate of taking the DCTs. Patients receiving treatment from an endocrinologist exhibited higher numbers of DCTs performed but displayed lower proportions for the prescription indicators. CONCLUSION: The present analysis of the DQA findings revealed that endocrinologists combine prevention and management of diabetes complications with measures for glycemic control. Thus, the effective management of diabetes likely entails systematic joint treatment regimens that involve an endocrinologist.

Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus.

BACKGROUND: Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD). METHODS: This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed. RESULTS: Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score (<8, ≥8 and <9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P<0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007). CONCLUSION: In Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.

Perfluorooctanoic acid induces oxidative damage and mitochondrial dysfunction in pancreatic ß-cells.

Several environmental contaminants have been linked to the development of diabetes and increased diabetes­associated mortality. Perfluorooctanoic acid (PFOA) is a widely used perfluoroalkane found in surfactants and lubricants, and in processing aids used in the production of polymers. Furthermore, PFOA has been detected in humans, wildlife and the environment. The present study investigated the toxic effects of PFOA on rat pancreatic ß­cell­derived RIN­m5F cells. Cell viability, apoptosis, reactive oxygen and nitrogen species, cytokine release and mitochondrial parameters, including membrane potential collapse, reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release were assessed. PFOA significantly decreased RIN­m5F cell viability and increased apoptosis. Exposure to PFOA increased the formation of reactive oxygen species, mitochondrial superoxide, nitric oxide and proinflammatory cytokines. Furthermore, PFOA induced mitochondrial membrane potential collapse and reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release. These results indicate that PFOA is associated with the induction of apoptosis in RIN-m5F cells, and induces cytotoxicity via increased oxidative stress and mitochondrial dysfunction.

Tetrabromobisphenol A induces cellular damages in pancreatic ß-cells in vitro.

Tetrabromobisphenol A (TBBPA) is a well-known organobrominated flame retardant. TBBPA has been detected in the environment. The roles played by environmental pollutants in increasing the prevalence of metabolic syndrome are attracting increasing concern. In the present work, we investigated the effects of TBBPA on rat pancreatic ß-cells (the RIN-m5F cell line). RIN-m5F cells were incubated with different concentrations of TBBPA for 48 h, and cell viability and the extent of apoptosis were determined. We also measured the levels of inflammatory cytokines, reactive oxygen species (ROS), mitochondrial adenosine triphosphate (ATP), and cardiolipin, as well as the extent of cytochrome c release from mitochondria. TBBPA reduced the ATP level, induced cardiolipin peroxidation and cytochrome c release, and triggered apoptotic cell death. Moreover, TBBPA increased the levels of inflammatory cytokines (TNF-α and IL-1ß), nitric oxide, intracellular ROS, and mitochondrial superoxide. Together, our results indicate that TBBPA damages pancreatic ß-cells by triggering mitochondrial dysfunction and inducing apoptosis.

Exposure to tetrabromobisphenol A induces cellular dysfunction in osteoblastic MC3T3-E1 cells.

This study was undertaken to investigate the possible involvement of oxidative stress in tetrabromobisphenol A (TBBPA)-induced toxicity in osteoblastic MC3T3-E1 cells. To examine the potential effect of TBBPA on cultured osteoblastic cells, we measured cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, cardiolipin content, cytochrome c release, cyclophilin levels, and differentiation markers in osteoblastic MC3T3-E1 cells. TBBPA exposure for 48 h caused the apoptosis and cytotoxicity of MC3T3-E1 cells. TBBPA also induced ROS and mitochondrial superoxide production in a concentration-dependent manner. These results suggest that TBBPA induces osteoblast apoptosis and ROS production, resulting in bone diseases. Moreover, TBBPA induced cardiolipin peroxidation, cytochrome c release, and decreased ATP levels which induced apoptosis or necrosis. TBBPA decreased the differentiation markers, collagen synthesis, alkaline phosphatase activity, and calcium deposition in cells. Additionally, TBBPA decreased cyclophilin A and B releases. Taken together, these data support the notion that TBBPA inhibits osteoblast function and has detrimental effects on osteoblasts through a mechanism involving oxidative stress and mitochondrial dysfunction.

Perfluorooctanoic acid induces mitochondrial dysfunction in MC3T3-E1 osteoblast cells.

Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.

Effects of Rebamipide on Gastrointestinal Symptoms in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with type 2 diabetes mellitus (T2DM). Rebamipide is an effective gastric cytoprotective agent, but there are few data on its usefulness in T2DM. The aim of this study is to evaluate the improvement of GI symptoms after rebamipide treatment in patients with T2DM. METHODS: Patients with T2DM and atypical GI symptoms were enrolled. They took rebamipide (100 mg thrice daily) for 12 weeks and filled out the diabetes bowel symptom questionnaire (DBSQ) before and after rebamipide treatment. The DBSQ consisted of 10 questions assessing the severity of GI symptoms by a 1 to 6 scoring system. Changes in the DBSQ scores before and after rebamipide treatment were analyzed to evaluate any improvements of GI symptoms. RESULTS: A total of 107 patients were enrolled, and 84 patients completed the study. The mean age was 65.0±7.8, 26 patients were male (24.8%), the mean duration of T2DM was 14.71±9.12 years, and the mean glycosylated hemoglobin level was 6.97%±0.82%. The total DBSQ score was reduced significantly from 24.9±8.0 to 20.4±7.3 before and after rebamipide treatment (P<0.001). The DBSQ scores associated with reflux symptoms, indigestion, nausea or vomiting, abdominal bloating or distension, peptic ulcer, abdominal pain, and constipation were improved after rebamipide treatment (P<0.05). However, there were no significant changes in symptoms associated with irritable bowel syndrome, diarrhea, and anal incontinence. No severe adverse events were reported throughout the study. CONCLUSION: Rebamipide treatment for 12 weeks improved atypical GI symptoms in patients with T2DM.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

A Smartphone Application Significantly Improved Diabetes Self-Care Activities with High User Satisfaction.

BACKGROUND: We developed for the first time a smartphone application designed for diabetes self-management in Korea and registered a patent for the relevant algorithm. We also investigated the user satisfaction with the application and the change in diabetes related self-care activities after using the application. METHODS: We conducted a questionnaire survey on volunteers with diabetes who were using the application. Ninety subjects responded to the questionnaire between June 2012 and March 2013. A modified version of the Summary of Diabetes Self-Care Activities (SDSCA) was used in this study. RESULTS: The survey results exhibited a mean subject age of 44.0 years old, and males accounted for 78.9% of the subjects. Fifty percent of the subjects had diabetes for less than 3 years. The majority of respondents experienced positive changes in their clinical course after using the application (83.1%) and were satisfied with the structure and completeness of the application (86.7%). Additionally, the respondents' answers indicated that the application was easy to use (96.7%) and recommendable to others (97.7%) and that they would continue using the application to manage their diabetes (96.7%). After using the Diabetes Notepad application, diabetes related self-care activities assessed by SDSCA displayed statistically significant improvements (P<0.05), except for the number of days of drinking. CONCLUSION: This smartphone-based application can be a useful tool leading to positive changes in diabetes related self-care activities and increase user satisfaction.

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor.

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.

Celiac Disease in a Predisposed Subject (HLA-DQ2.5) with Coexisting Graves' Disease.

Celiac disease is an intestinal autoimmune disorder, triggered by ingestion of a gluten-containing diet in genetically susceptible individuals. The genetic predisposition is related to human leukocyte antigen (HLA) class II genes, especially HLA-DQ2-positive patients. The prevalence of celiac disease has been estimated to be ~1% in Europe and the USA, but it is rarer and/or underdiagnosed in Asia. We report a case of celiac disease in a predisposed patient, with a HLA-DQ2 heterodimer, and Graves' disease that was treated successfully with a gluten-free diet. A 47-year-old woman complained of persistent chronic diarrhea and weight loss over a 9 month period. Results of all serological tests and stool exams were negative. However, the patient was found to carry the HLA DQ2 heterodimer. Symptoms improved after a gluten-free diet was initiated. The patient has been followed and has suffered no recurrence of symptoms while on the gluten-free diet. An overall diagnosis of celiac disease was made in a genetically predisposed patient (HLA-DQ2 heterodimer) with Graves' disease.

Insufficient experience in thyroid fine-needle aspiration leads to misdiagnosis of thyroid cancer.

BACKGROUND: Fine-needle aspiration (FNA) of the thyroid is a widely accepted confirmatory test for thyroid cancer with high sensitivity and specificity. FNA is a simple procedure that is learned by many clinicians to enable accurate diagnosis of thyroid cancer. However, it is assumed that because the FNA test is a relatively simple procedure, its cytologic results are reliable regardless of the operator's experience. The aim of this study was to evaluate the differences in the diagnostic indices of FNA between operators with different levels of experience. METHODS: A total of 694 thyroid FNA specimens from 469 patients were reviewed, and were separated based on the experience of the clinicians who performed the procedure. One hundred and ninety were categorized in the experienced group, and 504 in the inexperienced group. All FNA results were then compared with histological data from surgically resected specimens, and the sample adequacy and diagnostic accuracy of the groups were compared. RESULTS: The age, gender, and nodule size and characteristics were similar in both groups. The sample adequacy rate was not significantly different between the experienced and nonexperienced groups (96.3% vs. 95.4%, P=0.682). However, the non-experienced group had a higher false-negative rate than the experienced group (6.4% vs. 17.2%, P=0.038), and the sensitivity of the FNA test also tended to be lower in the nonexperienced group (95.6% vs. 88.9%, P=0.065). CONCLUSION: These results suggest that FNA operators who have less experience may miss cases of thyroid cancer by performing the procedure incorrectly. As such, the experience of the FNA operator should be considered when diagnosing thyroid cancer. When clinicians are being trained in FNA, more effort should be made to increase the accuracy of the procedure; therefore, enhanced teaching programs and/or a more detailed feedback system are recommended.

Change in somatostatinergic tone of acromegalic patients according to the size of growth hormone-producing pituitary tumors.

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (ΔGHIO), and between the OGTT and the OST at the same time point (ΔGHOS) were compared according to the size of the tumor and the response pattern to the OST. ΔGHIO of macroadenomas (n=22) was non-significantly higher than those of microadenomas while ΔGHOS of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. ΔGHOS showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.