Higher Non-High-Density Lipoprotein Cholesterol Was Higher Associated With Cardiovascular Disease Comparing Higher LDL-C in Nine Years Follow Up: Cohort Study

Objective@#Non-high-density lipoprotein cholesterol (non-HDL-C) may be equivalent to or superior to low-density lipoprotein cholesterol (LDL-C) for the prediction of cardiovascular disease (CVD). However, studies comparing the predictive values of LDL-C and non-HDL-C levels for CVD have yielded conflicting results. In this study, we evaluated the relationship between non-HDL-C, LDL-C, and CVD using a large-scale population dataset from the National Health Information Database (NHID). @*Methods@#We performed a retrospective observational cohort study of 3,866,366 individuals ≥ 20 years, from 2009 to 2018, using the NHID. The participants were divided into LDL-C and non-HDL-C quartiles. The outcome variables included stroke, myocardial infarction (MI), and both. All outcomes were analyzed using Cox proportional hazards regression analysis while controlling for baseline covariates (age, sex, smoking, drinking, regular exercise, body mass index, diabetes, hypertension, and statin use). @*Results@#During 9.1 years of mean follow-up, stroke was diagnosed in 60,081 (1.55%), MI in 31,234 (0.81%), and both stroke and MI in 88,513 (2.29%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest non-HDL-C quartile demonstrated that these patients had a higher risk of stroke (HR, 1.254; 95% confidence interval [CI], 1.224–1.285), MI (HR, 1.918; 95% CI, 1.853–1.986), and both (HR, 1.456; 95% CI, 1.427–1.486) compared with participants in the lowest quartile. These were higher than the HRs for patients in the highest LDL-C quartile for stroke (HR, 1.134; 95% CI, 1.108–1.160), MI (HR, 1.601; 95% CI, 1.551–1.653), and both (HR, 1.281; 95% CI, 1.257–1.306). @*Conclusion@#In our large population study, higher non-HDL-C levels were associated with CVD than LDL-C levels.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever

Background@#Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. @*Methods@#All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. @*Results@#Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. @*Conclusion@#The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

Clinical Characteristics of Patients with Adrenal Insufficiency and Fever

Background@#Because persistent fever often occurs in adrenal insufficiency, it might be confused with infectious diseases. This study aimed to identify clinical characteristics and risk factors of patients with adrenal insufficiency and fever. @*Methods@#All adult patients (n = 150) admitted to a tertiary care hospital in South Korea and diagnosed with adrenal insufficiency between 1 March 2018, and 30 June 2019, were recruited. Patients were excluded if they had: 1) proven structural problems in the adrenal or pituitary gland; 2) a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency; and 3) other medical conditions that may cause fever. @*Results@#Among the included patients, 45 (30.0%) had fever at the time of the diagnosis of adrenal insufficiency. The mean C-reactive protein level was higher (11.25 ± 8.54 vs. 4.36 ± 7.13 mg/dL) in patients with fever than in those without fever. A higher proportion of patients with fever changed antibiotics (33.3% vs. 1.0%). On multivariate logistic regression analysis, female sex (odds ratio [OR], 0.32) lowered the risk of adrenal insufficiency with fever, while a history of surgery within 6 months (OR, 4.35), general weakness (OR, 7.21), and cough (OR, 17.29) were significantly associated with that. @*Conclusion@#The possibility of adrenal insufficiency should be considered in patients with fever of unknown origin, especially those with risk factors.

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.

The Association between Z-Score of Log-Transformed A Body Shape Index and Cardiovascular Disease in Korea

BACKGROUND: In order to overcome the limitations of body mass index (BMI) and waist circumference (WC), the z-score of the log-transformed A Body Shape Index (LBSIZ) has recently been introduced. In this study, we analyzed the relationship between the LBSIZ and cardiovascular disease (CVD) in a Korean representative sample. METHODS: Data were collected from the Korea National Health and Nutrition Examination VI to V. The association between CVD and obesity indices was analyzed using a receiver operating characteristic curve. The cut-off value for the LBSIZ was estimated using the Youden index, and the odds ratio (OR) for CVD was determined via multivariate logistic regression analysis. ORs according to the LBSIZ value were analyzed using restricted cubic spline regression plots. RESULTS: A total of 31,227 Korean healthy adults were analyzed. Area under the curve (AUC) of LBSIZ against CVD was 0.686 (95% confidence interval [CI], 0.671 to 0.702), which was significantly higher than the AUC of BMI (0.583; 95% CI, 0.567 to 0.599) or WC (0.646; 95% CI, 0.631 to 0.661) (P<0.001). Similar results were observed for stroke and coronary artery diseases. The cut-off value for the LBSIZ was 0.35 (sensitivity, 64.5%; specificity, 64%; OR, 1.29, 95% CI, 1.12 to 1.49). Under restricted cubic spline regression, LBSIZ demonstrated that OR started to increase past the median value. CONCLUSION: The findings of this study suggest that the LBSIZ might be more strongly associated with CVD risks compared to BMI or WC. These outcomes would be helpful for CVD risk assessment in clinical settings, especially the cut-off value of the LBSIZ suggested in this study.

Association between Serum Selenium Level and the Presence of Diabetes Mellitus: A Meta-Analysis of Observational Studies

BACKGROUND: Epidemiological studies have suggested an association between selenium (Se) and diabetes mellitus (DM). However, different studies have reported conflicting results. Therefore, we performed a comprehensive meta-analysis to clarify the impact of Se on DM. METHODS: We searched the PubMed database for studies on the association between Se and DM from inception to June 2018. RESULTS: Twenty articles evaluating 47,930 participants were included in the analysis. The meta-analysis found that high levels of Se were significantly associated with the presence of DM (pooled odds ratios [ORs], 1.88; 95% confidence interval [CI], 1.44 to 2.45). However, significant heterogeneity was found (I2 =82%). Subgroup analyses were performed based on the Se measurement methods used in each study. A significant association was found between high Se levels and the presence of DM in the studies that used blood (OR, 2.17; 95% CI, 1.60 to 2.93; I2 =77%), diet (OR, 1.61; 95% CI, 1.10 to 2.36; I2 =0%), and urine (OR, 1.49; 95% CI, 1.02 to 2.17; I2 =0%) as samples to estimate Se levels, but not in studies on nails (OR, 1.24; 95% CI, 0.52 to 2.98; I2 =91%). Because of significant heterogeneity in the studies with blood, we conducted a sensitivity analysis and tested the publication bias. The results were consistent after adjustment based on the sensitivity analysis as well as the trim and fill analysis for publication bias. CONCLUSION: This meta-analysis demonstrates that high levels of Se are associated with the presence of DM. Further prospective and randomized controlled trials are warranted to elucidate the link better.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement / 대한내과학회지

Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement / 대한내과학회지

Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.

Epigenetic inactivation of RUNX3 in colorectal cancer

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

The Necessity of the Simple Tests for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus Patients without Neuropathic Symptoms in Clinical Practice

Early recognition and appropriate management of diabetic peripheral polyneuropathy (DPNP) is important. We evaluated the necessity of simple, non-invasive tests for DPNP detection in clinical practice. We enrolled 136 randomly-chosen patients with type 2 diabetes mellitus and examined them with the 10-g Semmes-Weinstein monofilament examination, the 128-Hz tuning-fork, ankle-reflex, and pinprick tests; the Total Symptom Score and the 15-item self-administered questionnaire of the Michigan Neuropathy Screening Instrument. Among 136 patients, 48 had subjective neuropathic symptoms and 88 did not. The abnormal-response rates varied depending on the methods used according to the presence of subjective neuropathic symptoms (18.8% vs. 5.7%, P < 0.05; 58.3% vs. 28.4%, P < 0.005; 81.3% vs. 54.5%, P < 0.005; 12.5% vs. 5.7%, P=0.195; 41.7% vs. 2.3%, P < 0.001; and 77.1% vs. 9.1%, P < 0.001; respectively). The largest abnormal response was derived by combining all methods. Moreover, these tests should be implemented more extensively in diabetic patients without neuropathic symptoms to detect DPNP early.

The Cutoff Pericardial Adipose Tissue Volume Associated with Metabolic Syndrome / 가정의학회지

BACKGROUND: Metabolic syndrome (MS) is a well-known risk factor of cardiovascular diseases that is focused on central obesity. Recent studies have reported the association between pericardial adipose tissue (PAT) volume and MS. However, no studies have demonstrated the cutoff PAT volume that represents the best association with MS. METHODS: The data of 374 subjects were analyzed cross-sectionally to compare PAT, measured on coronary multidetector computed tomography, and various metabolic parameters according to MS. After PAT volumes were divided into tertiles, various metabolic parameters were compared among tertiles; furthermore, the odds ratio for developing MS was calculated. Finally, we demonstrated the cutoff PAT volume that represented the best association with MS by using the receiver-operating characteristic curve. RESULTS: We found that 27.5% of the subjects had MS, and the mean PAT volume was 123.9 cm3. PAT showed a significant positive correlation with body mass index, waist circumference, and levels of glucose, triglyceride, high-sensitivity C-reactive protein, uric acid, and homocysteine, but a negative correlation with high-density lipoprotein cholesterol. Furthermore, after dividing into tertiles, PAT volume was also significantly associated with various metabolic parameters. The odds ratio for having MS was 4.19 (95% confidence interval, 2.27–7.74) in the top tertile of PAT volumes after adjusting for age, sex, and smoking. The cutoff PAT volume that represented the best association with MS was 142.2 cm3. CONCLUSION: PAT was significantly associated with MS and various metabolic parameters. The cutoff PAT volume of 142.2 cm3 showed the best association with MS.

Surrogate Measures of Insulin Resistance in an Apparently Healthy Population: a Simpler and Easier, yet Reliable Index

No abstract available.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer

Correction of funding statement in ACKNOWLEDGEMENTS section.

Associations between Hashimoto Thyroiditis and Clinical Outcomes of Papillary Thyroid Cancer: A Meta-Analysis of Observational Studies

BACKGROUND: Epidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC. METHODS: We searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins I 2 statistic was used to test for heterogeneity. RESULTS: The meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61). CONCLUSION: In this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

Response: The Necessity of the Simple Tests for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus Patients without Neuropathic Symptoms in Clinical Practice (Diabetes Metab J 2018;42:442–6)

No abstract available.

Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia

Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

Hyperinsulinemic Hypoglycemia Caused by Acute Reduction of Renal Function on an Eldery Patient Without Diabetes

In patient with renal failure, hypoglycemia may develop because of decreased caloric intake, diminished renal insulin degradation and clearance, reduced renal gluconeogenesis and hepatic glucose production, impaired release of counter-regulatory hormone such as glucagon and epinephrine. We report here on a 80-year-old female patient with hypoglycemia due to endogenous hyperinsulinemia with acute kidney injury. She had chronic kidney disease and had no history of diabetes mellitus or insulin use. She had experienced recurrent hypoglycemia despite of intravenous dextrose injection and eventually generalized tonic clonic seizure occurred as a result of hypoglycemia. As serum creatinine level decreases, serum insulin and C-peptide level decreased and hypoglycemia was not occurred. We present this case along with a review of the literature.

A Case of Calcium Pyrophosphate Dihydrate Deposition Disease Associated with Primary Hyperparathyroidism

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a heterogeneous group of diseases with CPPD crystal deposition. Aging is the most common risk factor for CPPD deposition, followed by osteoarthritis and previous injury. Occasionally, CPPD depositions are associated with familial predisposition and metabolic diseases, including hemochromatosis, primary hyperparathyroidism, hypophosphatasia, and hypomagnesemia. CPPD deposition diseases associated with primary hyperparathyroidism in Koreans have rarely been reported. Thus, we report a case of a relatively young female patient with CPPD deposition disease associated with primary hyperparathyroidism, which was diagnosed through a polarized microscopic examination of the synovial fluid and a subtotal parathyroidectomy.

A Case of Acute Suppurative Thyroiditis with Thyrotoxicosis in an Elderly Patient

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

A Case of Metformin-Induced Acute Kidney Injury without Lactic Acidosis: A Case Report / 대한구급학회지

Metformin is an oral antidiabetic drug in the biguanide class, which is used for type 2 diabetes. The side effects of metformin are mostly limited to digestive tract symptoms, such as diarrhea, flatulence and abdominal discomfort. The most serious potential adverse effect of metformin is lactic acidosis. A 51-year-old man was admitted due to hypoglycemia as a result of an overdose of antidiabetic drugs. He took massive dose of metformin. Conservative treatment failed for metabolic acidosis without lactic acidosis accompanied by acute kidney injury. Hemodialysis was executed to correct the high anion gap metabolic acidosis and acute kidney injury, and the patient recovered fully from metabolic acidosis. This case illustrates that the presence of clinical conditions, such as metformin-induced acute kidney injury and metabolic acidosis, can be developed without lactic acidosis. Prompt recognition of metabolic acidosis and early intervention with hemodialysis can result in a successful clinical outcome.