Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition

Background@#Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. @*Methods@#Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. @*Results@#Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. @*Conclusion@#This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Questionnaire-based Survey of Demographic and Clinical Characteristics, Health Behaviors, and Mental Health of Young Korean Adults with Early-onset Diabetes

Background@#The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. @*Methods@#This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. @*Results@#Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. @*Conclusion@#Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Questionnaire-based Survey of Demographic and Clinical Characteristics, Health Behaviors, and Mental Health of Young Korean Adults with Early-onset Diabetes

Background@#The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. @*Methods@#This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. @*Results@#Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. @*Conclusion@#Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Background@#Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. @*Results@#In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. @*Conclusion@#This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Combined Effects of Baicalein and Docetaxel on Apoptosis in 8505c Anaplastic Thyroid Cancer Cells via Downregulation of the ERK and Akt/mTOR Pathways

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.

A Case of Severe Recurrent Painless Thyroiditis Requiring Thyroidectomy / 대한갑상선학회지

The course of painless thyroiditis is usually transient with a thyrotoxicosis phase that lasts for 2 months before recovery. Therefore, no treatment is required. This case is unusual because of the recurrence and severity of thyrotoxicosis, which required surgery of the thyroid gland to prevent a thyrotoxic crisis. A 43-year-old female who presented with severe thyrotoxicosis was found to have low radioactive iodine uptake, negative test results for TSH receptor antibodies, normal erythrocyte sedimentation rate and diffuse goiter without pain or tenderness; these findings suggested a diagnosis of painless thyroiditis. She was treated for relapsed painless thyroiditis for 10 years. However, in May 2014, she developed recurrent painless thyroiditis with severe thyrotoxicosis; free T4 41.5 ng/dL, TSH <0.005 mlU/mL. Owing to the severity and recurrence of thyrotoxicosis, total thyroidectomy was performed to prevent a thyrotoxic storm.

A Case of Cavernous Sinus Thrombophlebitis and Meningitis as a Complication in Osteopetrosis

Osteopetrosis is a rare genetic bone disease characterized by increased bone density but prone to breakage due to defective osteoclastic function. Among two primary types of autosomal dominant osteopetrosis (ADO), osteopetrosis type II is characterized by sclerosis of bones, predominantly involving the spine, the pelvis, and the skull base. Fragility of bones and dental abscess are leading complications. This report presents a case of osteopetrosis in a 52-years-old female, which was complicated by the development of cavernous sinus thrombophlebitis and meningitis. She was suffered from multiple fractures since one year ago. Laboratory data revealed elevated serum levels of tartrate resistant acid phosphatase (TRAP) without carbonic anhydrase II DNA mutation. A thoracolumbar spine X-ray showed, typical findings of ADO type II (ADO II; Albers-Schonberg disease), prominent vertebral endplates so called the 'rugger jersey spine'. Her older sister also showed same typical spine appearance. We report a case of ADO II with cavernous sinus thrombophlebitis and meningitis that was successfully treated with long-term antibiotics with right sphenoidotomy.

Curcumin Enhances Docetaxel-Induced Apoptosis of 8505C Anaplastic Thyroid Carcinoma Cells

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor kappaB (NF-kappaB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. METHODS: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-kappaB levels were assayed by Western blotting. RESULTS: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. CONCLUSION: We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-kappaB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment.

Safety and Efficacy of Modern Insulin Analogues

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Effects of Rosiglitazone on Inflammation in Otsuka Long-Evans Tokushima Fatty Rats / 당뇨병

BACKGROUND: Inflammation plays a role in the response to metabolic stress in type 2 diabetes. However, the effects of rosiglitazone on inflammation of skeletal muscle have not been fully examined in type 2 diabetes. METHODS: We investigated the effects of the insulin-sensitizing anti-diabetic agent, rosiglitazone, on the progression of skeletal muscle inflammation in Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetic rats. We examined the expression of serologic markers (serum glucose, insulin and free fatty acid) and inflammatory cytokines (tumor-necrosis factor-alpha, interleukin [IL]-1beta and IL-6) in OLETF rats from early to advanced diabetic stage (from 28 to 40 weeks of age). RESULTS: Serum glucose and insulin concentrations were significantly decreased in rosiglitazone-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone treatment significantly decreased the concentrations of serum inflammatory cytokines from 28 to 40 weeks of age. The mRNA expression of various cytokines in skeletal muscle was reduced in rosiglitazone-treated OLETF rats compared with untreated OLETF rats. Furthermore, rosiglitazone treatment resulted in the downregulation of ERK1/2 phosphorylation and NF-kappaB expression in the skeletal muscle of OLETF rats. CONCLUSION: These results suggest that rosiglitazone may improve insulin sensitivity with its anti-inflammatory effects on skeletal muscle.

The Role of Hypothalamic FoxO1 on Hyperphagia in Streptozotocin-Induced Diabetic Mice / 당뇨병

BACKGROUND: Streptozotocin-induced diabetic animals are characterized by hyperphagia due to deficiencies of insulin and leptin. Forkhead box-containing protein of the O subfamily-1 (FoxO1) regulates energy homeostasis by regulating energy expenditure and food intake as well as mediating insulin and leptin signals in the hypothalamus. To identify the mediator of diabetic hyperphagia, we examined the effects of insulin or leptin on hypothalamic FoxO1 expression in a diabetic animal model. METHODS: Diabetes was induced in mice (C57BL/6) by intraperitoneal administration of streptozotocin (200 mg/kg). Stainless steel cannula was implanted into the lateral ventricle of the brain in each mouse. After three weeks, the mice were administered saline, insulin or leptin via intracerebroventricular (ICV) route. The medial hypothalamus was isolated to evaluate the mRNA expressions of FoxO1 and neuropeptides. RESULTS: Streptozotocin-induced diabetic mice exhibited significant elevations of blood glucose and food intake and significantly low levels of serum insulin and leptin. The levels of hypothalamic FoxO1 mRNA were significantly increased in diabetic mice. The hypothalamic expression of neuropeptide Y (NPY) mRNA was increased, but the expression of preproopiomelanocortin (POMC) mRNA was decreased in diabetic mice. ICV administration of insulin or leptin attenuated the upregulation of hypothalamic FoxO1 mRNA, and resulted in downregulation of NPY mRNA and upregulation of POMC mRNA in diabetic mice. CONCLUSION: We observed that the expression of hypothalamic FoxO1 mRNA was increased in streptozotocin-induced diabetic mice, and that it was significantly attenuated by central administration of insulin or leptin. These results suggest that hypothalamic FoxO1 is the direct mediator of diabetic hyperphagia.

A case of insulin autoimmune syndrome / 대한내과학회지

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.

Diabetic Ketoacidosis in a Patient with Acromegaly / 대한내분비학회지

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). Impaired glucose tolerance is present in about 20-40% of acromegaly, with diabetes mellitus developing in about 10~15% of patients, but diabetic ketoacidosis is a rare association. Herein is reported a case of diabetic ketoacidosis in a 33 year-old female, with a 4 year history of typical acromegaly features. She presented with severe hyperglycemia and ketoacidosis, but with no other cause for this metabolic derangement. She had elevated plasma GH (50 ng/mL) and IGF-1 (1533 ng/mL) levels, and a pituitary macroadenoma. About 200 units of insulin per day were required for her glycemic control. However, the serum IGF-1 level and daily insulin requirement were significantly tapered after a transsphenoidal adenomectomy and long acting somatostatin analogue treatment. There was a good correlation with the daily insulin requirement and plasma IGF-1 level. This case demonstrates that severe GH excess can cause diabetic ketoacidosis, and that its successful treatment improves glucose metabolism.

Diabetic Ketoacidosis in a Patient with Acromegaly / 대한내분비학회지

Acromegaly is a chronic, debilitating condition caused by excessive secretion of growth hormone (GH). Impaired glucose tolerance is present in about 20-40% of acromegaly, with diabetes mellitus developing in about 10~15% of patients, but diabetic ketoacidosis is a rare association. Herein is reported a case of diabetic ketoacidosis in a 33 year-old female, with a 4 year history of typical acromegaly features. She presented with severe hyperglycemia and ketoacidosis, but with no other cause for this metabolic derangement. She had elevated plasma GH (50 ng/mL) and IGF-1 (1533 ng/mL) levels, and a pituitary macroadenoma. About 200 units of insulin per day were required for her glycemic control. However, the serum IGF-1 level and daily insulin requirement were significantly tapered after a transsphenoidal adenomectomy and long acting somatostatin analogue treatment. There was a good correlation with the daily insulin requirement and plasma IGF-1 level. This case demonstrates that severe GH excess can cause diabetic ketoacidosis, and that its successful treatment improves glucose metabolism.

Regulation of Prolactin Gene Expression by Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Female Rat Pituitary Gland / 대한내분비학회지

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) plays the role of a hypophysiotropic factor, which regulates the synthesis and secretion of pituitary hormones through the hypothalamo-hypophysial portal system. No clear evidence has yet been reported regarding the regulation of prolactin (PRL) by PACAP. In the present study, we tested a hypothesis that PACAP regulates the synthetic machinery of PRL during the estrus cycle and pubertal process using intracerebroventricular (i.c.v.) injection of an antisense oligodeoxynucleotide (ODN) against type I PACAP receptor (PAC1). METHODS: An RNase protection assay (RPA) was used to determine the pattern of hypothalamic PACAP and PAC1 mRNA expressions during the estrus cycle. Antisense PAC1 ODN was administered via i.c.v. injection to the female rats in normal estrus cycle of pubertal process. Northern blot analysis was used to determine the mRNA ievel of PRL in the pituitary gland. RESULTS: 1) PACAP mRNA in the medial basal hypothalamus was significantly increased at the diestrus I, while PAC1 mRNA showed no significant change. 2) PRL mRNA level of pituitary was increased by an injection of antisense PAC1 ODN at the proestrus and estrus stages. 3) PRL mRNA level of pituitary was significantly decreased by antisense PAC1 ODN injection at stage of prepuberty and initiate puberty, while its level was increased at stage of puberty. CONCLUSION: These data suggest that PACAP suppresses PRL mRNA synthesis through the PAC1 signaling pathway in the certain estrus cycle environments. It may be also involved in the regulation of pituitary PRL gene expression during the pubertal process

Ultrasonography-guided Fine Needle Aspirations of Thyroid Incidentaloma: Correlation with Pathologic Findings / 대한내분비외과학회지

PURPOSE: There are many reports that diagnostic accuracy of fine needle aspiration (FNA) of thyroid is improved with ultrasound guidance, especially for impalpable nodules. Despite its general acceptance, routine use of ultrasound guided fine needle aspiration (USGFNA) has been the source of much controversy due to the lack of large-scale studies and lack of data on the natural course of welldifferentiated thyroid cancer of small size. METHODS: The aim of our study was to define the rate of malignancy in relatively large numbers of patients with incidentally detected impalpable thyroid nodules and to assess the extent of disease in patients with suspicious or malignant cytology on USGFNA of thyroid nodules by surgery. We retrospectively reviewed the medical records of the 267 patients who underwent USGFNA of incidental thyroid nodules from January 2000 through December 2001. RESULTS: Three hundred and seventeen nodules from 267 patients were aspirated. The average size of nodules was 0.9±0.3 cm, a range of 0.2 cm to 1.5 cm. All 317 lesions were impalpable. Cytological diagnosis included 101 inadequate specimen (32%), 139 benign (44%), 29 indeterminate (9%), 4 suspicious of follicular or Hrthle cell neoplasm (1%), 42 papillary carcinoma (13%), and 2 others. The size of the nodule was not related to the probability of getting an adequate specimen for cytological diagnosis. Forty of 48 patients with suspicious or malignant cytology underwent surgery. All 35 patients with a cytological diagnosis of papillary carcinoma were confirmed to have papillary carcinoma on histological results. One of 3 patients with a cytological diagnosis of follicular neoplasm had a follicular carcinoma. In 36 patients with well-differentiated thyroid cancer, extrathyroidal extension was observed in 44% (16/36), regional lymph node metastasis was found in 50% (18/36), and multifocal tumors were found in 39% (14/36). CONCLUSION: The rate of malignancy in incidentally detected impalpable thyroid nodules was 12% in retrospective analysis of our patients. Among those, 69% (25/36) of patients had either extrathyroidal extension or regional node involvement and 39% had multifocal tumors at surgery. This suggests that the small size itself could not guarantee a good prognosis in incidentally found thyroid cancers. USGFNA is a useful diagnostic method in those patients.

Postoperative Findings and Risk for Malignancy in Thyroid Nodules with Cytological Diagnosis of the so-called "Follicular Neoplasm"

BACKGROUND: Malignant follicular lesion is not differentiated from benign lesions cytologically. The objective of this study was to assess the rate and the risk of malignancy in thyroid nodules which were cytologically diagnosed as follicular neoplasm by fine-needle aspiration (FNA) cytology. METHODS: All the patients who had undergone surgery with cytological diagnosis of follicular neoplasm from January 1996 through December 2001 in Asan Medical Center were studied retrospectively. Patients' and nodule characteristics were analyzed for factors associated with the presence of cancer. Two hundred and fifteen patients (196 females, 19 males) were included and their mean age was 39.4 years (range: 12~76). RESULTS: About half of the patients (102 out of 215, 47.4%) had malignancy with 29 papillary carcinomas, 57 follicular carcinomas, 15 H rthle cell carcinomas and 1 medullary carcinoma. Previously suggested factors associated with risk for malignancy, such as male gender, large tumor size (> 4 cm) or age of patients (> 45 years), were not associated with increased risk. Diagnosis of H rthle cell neoplasia on FNA was also not associated with increased risk. Only the extremes in age of the patients (below 20 or above 60 years) were associated with increased risk for malignancy. CONCLUSION: In our findings, prevalence of carcinoma in thyroid nodule patients with cytological diagnosis of follicular neoplasm was much higher than those reported. Clinical characteristics, such as male gender, age and nodule size, are not useful predictors for the presence of malignancy. Thyroid nodules with cytological diagnosis of follicular neoplasm warrant immediate surgery.

Biliary Stricture Associated with Common Bile Duct Stone Caused by Endoscopic Snare Papillectomy of Ampullary Adenoma / 대한소화기내시경학회지

Neoplasms of the major duodenal papilla or the ampulla of Vater are rare but are clinically important since they are premalignant. Recently endoscopic snare papillectomy for the ampullary adenoma is being increasingly performed. The procedure is now regarded as a clinically effective treatment, however, various complications such as bleeding, perforation, cholangitis, and pancreatitis have been reported. To our knowledge, biliary stricture of this case has not been reported as a complication of endoscopic snare papillectomy for ampullary adenoma. Also, secondary common bile duct stone was formed by biliary stasis associated with biliary stricture in our case. We performed the balloon dilation at the biliary stricture site and could remove the stone successfully by endoscopic method.