Comparison of the Efficacy and Safety of Insulin Detemir Administered Once Daily According to Two Titration Algorithms (3-0-3 and 2-4-6-8) in Patients with Type 2 Diabetes Mellitus

BACKGROUND: This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin.METHODS: This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3, n=23) or 2-4-6-8 (G2, n=23) algorithm. The primary endpoint was change of haemoglobin A1c (HbA1c), and the secondary safety endpoint included hypoglycaemic events.RESULTS: After 20 weeks, HbA1c decreased similarly in the G3 and G2 groups, with a mean change of −0.9% from baseline. The mean change in fasting plasma glucose was numerically similar in both groups. The hypoglycaemia event rate per 100-patient-years of exposure (r) in the G2 group (r=1,427) was higher than that in the G3 group (r=807).CONCLUSION: Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

Adefovir-induced Fanconi syndrome associated with osteomalacia

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Thyroid Associated Ophthalomopathy in a Patient with Hashimoto's Thyroiditis

A 53-year-old man consulted an ophthalmologist with a chief complaint of diplopia and bilateral eyelid swelling. He was diagnosed with hypothyroidism 2 years prior at a local clinic and had been taking levothyroxine 150 mcg daily. CT scan of the orbits showed enlargement of bilateral extraocular muscles. Laboratory findings revealed hyperthyroidism due to high dose levothyroxine. Active ophthalmopathy with Hashimoto's hypothyroidism was diagnosed and the patient was treated with steroid pulse therapy. We reported a rare case of severe ophthalmopathy with Hashimoto's thyroiditis that needed steroid pulse therapy.

Thyroid Associated Ophthalomopathy in a Patient with Hashimoto's Thyroiditis

A 53-year-old man consulted an ophthalmologist with a chief complaint of diplopia and bilateral eyelid swelling. He was diagnosed with hypothyroidism 2 years prior at a local clinic and had been taking levothyroxine 150 mcg daily. CT scan of the orbits showed enlargement of bilateral extraocular muscles. Laboratory findings revealed hyperthyroidism due to high dose levothyroxine. Active ophthalmopathy with Hashimoto's hypothyroidism was diagnosed and the patient was treated with steroid pulse therapy. We reported a rare case of severe ophthalmopathy with Hashimoto's thyroiditis that needed steroid pulse therapy.

Survey of Depression in the Elderly Patients with Diabetes Mellitus / 신경정신의학

OBJECTIVES: Depression is commonly comorbid in elderly patients with physical illness. This study examined the prevalence of depression in the elderly with Diabetes Mellitus (DM). METHODS: Eighty-nine patients, over 60 years old, with DM were enrolled. The medical and psychiatric history, Hamilton Rating Scale for Depression (HDRS), Patient Health Questionnaire-9 (PHQ-9), Geriatric Depression Scale-Short form Korean (GDS-SF-K), and Mini-Mental Status Examination Korean version were examined. RESULTS: The prevalence of depression was estimated as 21.3% (male 4.5% ; female 16.9%) in HDRS, 32.6% (male 9.0% ; female 23.6%) in PHQ-9, and 24.7% (male 5.6% ; female 19.1%) in GDS-SF-K. CONCLUSION: The self-reporting scale, such as GDS-SF-K, PHQ-9 is an effective screening test for depression. The prevalence of elderly depression with DM ranged from 20% to 30%, the prevalence of depression is almost three times more common in women.

The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study / 임상당뇨병

BACKGROUND: The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy. METHODS: In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment. RESULTS: After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin addon treatment compared to placebo (-0.54 +/- 0.52%, P = 0.001 and -14.80 +/- 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed. CONCLUSION: Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.

The High Proportion of Painless Thyroiditis as a Cause of Thyrotoxicosis in Korea / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: The most common cause of thyrotoxicosis is Graves' disease (GD), while painless thyroiditis (PT) comes in second. In Korea, the treatment of choice for GD is antithyroid drugs (ATDs). Since most cases of PT spontaneously improve, an accurate diagnosis is very important for the proper management of patients presenting with thyrotoxicosis. MATERIALS AND METHODS: Ninety-nine thyrotoxic patients were routinely checked with 99m Technetium (99mTc) thyroid scan except in pregnant or lactating women. We assessed the patients' clinical characteristics, serum levels of free T4 (FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), thyrotropin-binding inhibitory immunoglobulin (TBII), and findings of 99mTc thyroid scan. RESULTS: Among the 99 thyrotoxic patients, 69 were diagnosed with GD and 30 had PT. All of the patients with GD, diagnosed by scan, improved clinically and the thyroid hormone returned to normal with ATDs. All patients with PT improved spontaneously without ATDs. TPOAb and TGAb were positive in 13 (43.3%) and 20 (66.7%) patients with PT, respectively. TPOAb and TGAb were positive in 45 (65.2%) and 44 (63.8%) patients with GD, respectively. TBII was positive in only 73.5% of GD, and was entirely negative in the PT group. Mean FT4 level in GD was higher than in PT, but some patients with PT showed the highest level of FT4. CONCLUSION: PT accounted for a very high proportion of thyrotoxicosis in this study. All parameters investigated such as age, sex, goiter size or nature, level of FT4, TPOAb or TGAb, and TBII were unable to differentiate GD from PT. Considering the increased proportion of PT in the current study, we recommend routine thyroid scan in all thyrotoxic patients except in pregnant or lactating women.

The Usefulness of the Glycosylated Hemoglobin Level for the Diagnosis of Gestational Diabetes Mellitus in the Korean Population

BACKGROUND: An oral glucose tolerance test (OGTT) is the current method used for screening and diagnosis of gestational diabetes mellitus (GDM). OGTT is a relatively complicated procedure and is expensive. Thus, new strategies that do not require fasting or more than a single blood draw may improve the diagnosis of GDM and increase the rate of GDM testing. We investigated the utility of monitoring glycosylated hemoglobin (HbA1c) levels for the diagnosis of GDM. METHODS: The data from 992 pregnant women with estimated gestational ages ranging from 24 to 28 weeks were retrospectively reviewed. There were 367 women with plasma glucose levels > or =140 mg/dL 1 hour after a 50-g OGTT. GDM was diagnosed according to the Carpenter-Coustan criteria for a 3-hour 100 g OGTT. A HbA1c assessment was performed at the same time. RESULTS: We enrolled 343 women in this study, and there were 109 women with GDM. The area under the curve the receiver operating characteristic curve for HbA1c detection of GDM was 0.852 (95% confidence interval, 0.808 to 0.897). A HbA1c cutoff value > or =5.35% had maximal points on the Youden index (0.581). The sensitivity was 87.2% and the specificity was 70.9% for diagnosing GDM. A threshold value > or =5.35% indicated that 163 patients had GDM and that 68 (41.7%) were false positive. The positive predictive value was 58.3% at this threshold value. CONCLUSION: Despite substantial progress in methodology, HbA1c values cannot replace OGTT for the diagnosis of GDM.

Actinomyces-like organisms in cervical smears: the association with intrauterine device and pelvic inflammatory diseases

OBJECTIVE: To investigate the incidence of actinomyces-like organisms in routine cervical smears of Korean women and to evaluate its association with the development of pelvic inflammatory disease (PID) in these women. METHODS: The results of cervical smears between 2011 and 2012 at a single university hospital were searched. If positive for actinomyces-like organisms, the medical record of the patient was searched and development of PID was followed. If the data were not available in the medical record, the patient was contacted by telephone. RESULTS: The incidence of actinomyces-like organisms in cervical smears was 0.26% (52/20,390). Forty-two women (80.8%) were intrauterine device (IUD) users: the copper-IUD in 25 women and the levonorgestrel-releasing intrauterine system in 13 women (type unknown in 4 women). The majority (71.4%, 30/42) of the IUD users maintained the IUD. Prophylactic antibiotics were prescribed to 12 women. Two continuous IUD users were later diagnosed with PID, but these cases were not pelvic actinomycosis. CONCLUSION: It would be a reasonable option to choose the expectant management for asymptomatic women who incidentally showed actinomyces-like organisms in their cervical smear.

A General Hospital-Based Model for Early Detection of Depression in the Geriatric Patients with Chronic Medical Diseases

The geriatric patients with chronic physical diseases are frequently associated with the continuous clusters of depression including nonpathological sadness, subsyndromal depression, minor depressive disorder, and major depressive disorder. Because of the complex and reciprocal relationships among depression, elderly, and chronic physical diseases, screening approaches with specific nosological methods should be needed in the realm of early detection of depression. Cognitive decline is frequently manifested in geriatric depression with medical or neurological diseases. Also, somatic symptoms of depression or emotional symptoms of physical diseases can play a role as a hampering factor in the early detection of depression. Furthermore, after-care has been regarded as an essential factor of depression screening in the geriatric patients with chronic physical diseases. We reviewed the most popular examples of integrated medicine for depression in primary care. Thus, we propose a general hospital-based model for early detection of depression which includes favorable response loop between screening and therapeutic intervention. Our model can be a basis for evidence-based detection and after-care for depression in the geriatric patients with chronic medical diseases.

Survey of Depression in the Elderly Patients with Chronic Obstructive Pulmonary Disease / 신경정신의학

OBJECTIVES: Depression is commonly comorbid in the elderly patients with physical illness. This study examined the prevalence of depression in the elderly with chronic obstructive pulmonary disease (COPD). METHODS: The eighty-seven patients with COPD were enrolled. The subjects are over 60 years old. The medical and psychiatric history, Hamilton Rating Scale for Depression (HDRS), Patient Health Questionnaire-9 (PHQ-9), Patient Health Questionnaire-2 (PHQ-2), Geriatric Depression Scale-Short form Korean (GDS-SF-K), Mini-Mental Status Exam Korean version (MMSE-KC) were investigated. Global Initiative for Chronic Obstructive Lung Disease (GOLD), which predict the severity of COPD, also investigated. RESULTS: The prevalence of depression was estimated to be 24.7% (male 19.3% ; female 35.7%) in HDRS, 31.0% (male 24.6% ; female 43.3%) in PHQ-9, 8.0% (male 10.5% ; female 3.3%) in PHQ-2, 23.0% (male 17.5% ; female 33.3%) in GDS-SF-K. The severity of COPD (GOLD) was associated with the prevalence of depression (HDRS, p=0.027 ; PHQ-9, p=0.045 ; PHQ-2, p=0.112 ; GDS-SFK, p=0.089). CONCLUSION: The prevalence of elderly depression with COPD ranged from about 20% to 30%, the prevalence of depression is nearly two times more common in women. The severity of COPD (GOLD) was associated with the prevalence of depression. The self-reporting scale, such as GDS-SF-K, PHQ-9 and PHQ-2 is the effective screening test of depression.

Airway Compression Caused by Bilateral Thyroid Hematoma after Fine-Needle Aspiration

Fine-needle aspiration (FNA) is considered the most accurate, cost-effective and relatively safe method in the evaluation of thyroid nodules and fatal complications after thyroid FNA are uncommon. In particular, the large hematomas after FNA causing airway compromise are extremely rare complications and were reported in only a few literatures. We reported a 51-year-old woman who showed airway compromise caused by bilateral intrathyroidal and perithyroidal hematoma after FNA of thyroid. A large thyroid hematoma after FNA is a rare but possible complication and sometimes can be fatal for the patient. Proper preventive efforts should be considered while performing thyroid FNA and prompt intervention is mandatory for patients with acute hematoma after FNA.

Clinical Characteristics of Thyrotoxicosis Presented by Coronary Spasm / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Cardiovascular symptoms are integral and often the most predominant clinical presentation in patients with thyrotoxicosis. In patients with known or suspected coronary artery disease, myocardial ischemia and angina-like chest pain may be presented due to increase in cardiac output and cardiac contractility as a result of thyrotoxicosis. In addition, coronary spasm may result in angina-like chest pain in thyrotoxicosis patients without any fixed coronary artery stenosis. However, there are few reports about clinical characteristics of thyrotoxicosis associated with coronary artery spasm. MATERIALS AND METHODS: Coronary angiography, thyroid function test, and follow-up clinical data of patients were analyzed retrospectively. RESULTS: Twelve patients with coronary artery spasm were included over 4.5 years (male:female, 5:7). The mean age of patients was 53.3 years (range, 27 to 68), and female patients were younger than male patients (mean, 56.2 vs. 51.2 years). Only 4 patients (33%) presented typical thyrotoxic symptoms. The causes of thyrotoxicosis were Grave's disease (75%) and painless thyroiditis (25%). On coronary angiography, severe coronary spasm was observed by provocation in 6 patients, and total occlusion of right coronary artery and left circumflex artery with chest pain developed in 2 of 6 patients. After antithyroid treatment, all patients became free of chest pain. CONCLUSION: Severe coronary artery spasm can be associated with thyrotoxicosis. Thyroid function test might be a differential diagnostic test in patients with coronary artery spasm. It should be considered that thyrotoxicosis can be presented by coronary artery spasm without typical symptom of thyrotoxicosis.

Endoscopic comparison of alendronate alone and the enteric-coated alendronate with calcitriol combination in postmenopausal Korean females

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 microg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.

DNA Methylation of RUNX3 in Papillary Thyroid Cancer

BACKGROUND/AIMS: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. METHODS: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). RESULTS: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. CONCLUSIONS: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

Insulin Autoimmune Syndrome with Diabetic Ketoacidosis / 임상당뇨병

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, elevated insulin level and a high level of insulin autoantibodies without previous insulin exposure. Among the clinical manifestations of insulin autoimmune syndrome, diabetic ketoacidosis is extremely rare. A 72-year-old diabetic woman was hospitalized with diabetic ketoacidosis. She suffered repeated fasting hypoglycemia after treatment of the diabetic ketoacidosis. Here we describe this case of insulin autoimmune syndrome manifested as diabetic ketoacidosis followed by recurrent hypoglycemia with a review of the relevant literature.

A Case of Isolated Thyroid Stimilating Hormone Deficiency

Isolated thyroid stimulating hormone (TSH) deficiency is very rare. Only a few patients are reported in the world. A 50-year-old woman was admitted to Soonchunhyang University Cheonan Hospital because of a distal radius fracture. She was diagnosed with hypothyroidism incidentally. Serum free T4 and TSH were low. After administration of exogenous TSH releasing hormone, no TSH response was noted. The response of prolactin and other pituitary hormones were appropriate after stimulation. Pituitary magnetic resonance image did not reveal any abnormalities. The diagnosis of isolated TSH deficiency was established for this patient.

Successful Pregnancy and Childbirth in a Patient with Diabetic Kidney Disease Receiving Hemodialysis

Pregnancy outcomes for women uncontrolled diabetes mellitus are poor. Women with chronic kidney disease and end-stage renal disease, if pregnant, will develop pregnancy-related complications. In the case of severe renal failure and diabetes mellitus, the incidence of prematurity, low birth weight, and neonatal death increases. Despite these risks, there have been few reported cases of successful pregnancy outcomes for these women. Adherence to a schedule of strict glucose monitoring, blood pressure and volume control, correction of anemia, and intensive hemodialysis may play important roles in the management of these women. Successful pregnancy and childbirth in a patient with diabetic kidney disease receiving hemodialysis have not been previously reported in Korea, to our knowledge. Herein, we report a case of a successful pregnancy outcome in a patient with diabetic end-stage renal disease undergoing hemodialysis.

A Case of Idiopathic Granulomatous Hypophysitis

Granulomatous hypophysitis is a rare pituitary condition that commonly presents with enlargement of the pituitary gland. A 31-year-old woman was admitted to the hospital with a severe headache and bitemporal hemianopsia. Magnetic resonance imaging (MRI) showed an 18 x 10-mm sellar mass with suprasellar extension and compression of the optic chiasm. Interestingly, brain MRI had shown no abnormal finding 4 months previously. On hormonal examination, hypopituitarism with mild hyperprolactinemia was noted. The biopsy revealed granulomatous changes with multinucleated giant cells. We herein report this rare case and discuss the relevant literature.

Papillary Thyroid Carcinoma Manifesting as an Autonomously Functioning Thyroid Nodule

Hyperfunctioning thyroid carcinoma is very rare. Hence, radionuclide imaging of thyroid hot nodules usually suggests a benign tumor, and less than 4% of cases have been reported as malignant. We would like to present a case of a hyperfunctioning papillary thyroid carcinoma that was initially treated with radioactive iodine. A 58-year-old woman was referred to our hospital for palpable thyroid nodule and a 5-kg weight loss within 6 months. Thyroid function test revealed thyrotoxicosis, and thyroid autoantibodies were absent. 99mTc thyroid scintigraphy showed a 2 x 2 cm-sized hyperactive hot nodule at the left lobe. Despite radioactive iodine treatment with a dose of 10 mCi 131I, thyroid function did not improve. Fine needle aspiration revealed papillary thyroid cancer. The patient underwent total thyroidectomy. Although clinical features and thyroid scans suggest a benign nodule, the possibility of malignancy should not be ruled out. Malignant thyroid hot nodules are rare; however, its possibility should be taken into account. Therefore, we suggest that ruling out malignancy by existing diagnostic guidelines can misdiagnose even a typical case with benign features. As thyroid nodule detection is getting sensitive and accurate, we present this case to discuss whether additional diagnostic approaches would be necessary for thyroid nodules.