Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency

Background@#Salivary cortisol is routinely used as a diagnostic test for Cushing syndrome. The diagnostic use of salivary cortisol for adrenal insufficiency (AI), however, is less established. We aimed to investigate the utility of morning basal and adrenocorticotropic hormone-stimulated salivary cortisol in diagnosing AI in Korean adults. @*Methods@#We prospectively included 120 subjects (female, n=70) from Seoul National University Hospital. AI was defined as a stimulated serum cortisol level of <496.8 nmol/L during the short Synacthen test (SST). Serum and saliva samples were drawn between 8:00 AM and 10:00 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit. @*Results@#Thirty-four patients were diagnosed with AI according to the SST results. Age, sex, body mass index, serum albumin levels, and serum creatinine levels did not significantly differ between the normal and AI groups. Basal and stimulated salivary cortisol levels were positively correlated with basal (r=0.538) and stimulated serum cortisol levels (r=0.750), respectively (all P<0.001). Receiver operating characteristic curve analysis yielded a cutoff level of morning basal salivary cortisol of 3.2 nmol/L (sensitivity, 84.9%; specificity, 73.5%; area under the curve [AUC]=0.822). The optimal cutoff value of stimulated salivary cortisol was 13.2 nmol/L (sensitivity, 90.7%; specificity, 94.1%; AUC=0.959). Subjects with a stimulated salivary cortisol level above 13.2 nmol/L but a stimulated serum cortisol level below 496.8 nmol/L (n=2) had lower serum albumin levels than those showing a concordant response. @*Conclusion@#The diagnostic performance of stimulated salivary cortisol measurements after the SST was comparable to serum cortisol measurements for diagnosing AI.

Diagnostic Role of Captopril Challenge Test in Korean Subjects with High Aldosterone-to-Renin Ratios

BACKGROUND: Diagnosis of primary aldosteronism (PA) begins with aldosterone-to-renin ratio (ARR) measurement followed by confirmative tests. However, the ARR has high false positive rates which led to unnecessary confirmatory tests. Captopril challenge test (CCT) has been used as one of confirmatory tests, but the accuracy of it in the diagnosis of PA is still controversial. We aimed to examine the clinical efficacy of CCT as a post-screening test in PA. METHODS: In a prospective study, we enrolled subjects with suspected PA who had hypertension and ARR >20 (ng/dL)/(ng/mL/hr). Sixty-four patients who underwent both the saline infusion test and the CCT were included. RESULTS: The diagnostic performance of plasma aldosterone concentration (PAC) post-CCT was greater than that of ARR post-CCT and ARR pre-CCT in PA (area under the curve=0.956, 0.797, and 0.748, respectively; P=0.001). A cut-off value of 13 ng/dL showed the highest diagnostic odds ratio considering PAC post-CCT at 60 and 90 minutes. A PAC post-CCT of 19 ng/dL had a specificity of 100%, which can be used as a cut-off value for the confirmative test. Determining the diagnostic performance of PAC post-CCT at 90 minutes was sufficient for PA diagnosis. Subjects with PAC post-CCT at 90 minutes <13 ng/dL are less likely to have PA, and those with PAC post-CCT at 90 minutes ≥13 but <19 ng/dL should undergo secondary confirmatory tests. CONCLUSION: The CCT test may be a reliable post-screening test to avoid the hospitalization in the setting of falsely elevated ARR screening tests.

Characterization of Patients with Type 2 Diabetes according to Body Mass Index: Korea National Health and Nutrition Examination Survey from 2007 to 2011

BACKGROUND: The present study aimed to investigate the clinical characteristics of type 2 diabetes mellitus (T2DM) in Korean adults according to body mass index (BMI) and to analyze the association with cardiovascular disease (CVD). METHODS: We conducted a cross-sectional study of data from the Korea National Health and Nutrition Examination Survey from 2007 to 2011. A total of 3,370 patients with T2DM were divided into categories according to BMI. We conducted a comparison of the T2DM patient population composition by BMI category between different countries. We investigated the prevalence of awareness, treatment, and target control of T2DM according to BMI. RESULTS: Patients with T2DM had a higher BMI, and were more likely to have a history of CVD than healthy controls. For Korean adults with T2DM, 8% had BMI > or =30 kg/m2. By contrast, the population of patients with T2DM and BMI > or =30 kg/m2 was 72% in patients in the USA and 56% in the UK. The rate of recognition, treatment, and control has worsened in parallel with increasing BMI. Even in patients with BMI 25 to 29.9 kg/m2, the prevalence of CVD or high risk factors for CVD was significantly higher than in patients with BMI 18.5 to 22.9 kg/m2 (odds ratio, 2.07). CONCLUSION: Korean patients with T2DM had lower BMI than those in Western countries. Higher BMI was associated with lower awareness, treatment, and control of diabetes, and a positive association was observed between CVD or high risk factors for CVD and BMI, even for patients who were overweight but not obese.

Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients. METHODS: We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with > or =25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks. RESULTS: At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level < or =7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of beta-cells. CONCLUSION: An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease

BACKGROUND: Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing' disease (CD) and compare it with that of the HDST results and serum DHEA-S level. METHODS: We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. RESULTS: Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. CONCLUSION: Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Pneumopericardium Caused by Gastropericardial Fistula after Use of NSAIDs in a Patient with Acute Pericarditis and Gastric Cancer / 대한내과학회지

Here, we report a case of gastropericardial fistula associated with the treatment of acute pericarditis using non-steroidal anti-inflammatory drugs (NSAIDs) in the presence of gastric cancer. The patient presented with acute pericarditis with pericardial effusion that had progressed into definite gastropericardial fistula with pneumopericardium after the administration of NSAIDs. The patient improved after conservative management. Based on the current case, we advise caution when using NSAIDs to treat acute pericarditis in the presence of gastric cancer or possible gastropericardial fistula.

Case of Synchronous Central Neck Node Metastases from Both Primary Thyroid Cancer and from Endometrial Cancer to the Thyroid / 대한내과학회지

A 54-year-old woman presenting with dizziness was diagnosed with a metastatic brain tumor. Imaging studies to identify the primary cancer revealed endometrial thickening with a left adnexal mass, enlarged bilateral external iliac lymph nodes, and multiple attenuated nodules in both lobes of the thyroid gland with enlarged central neck nodes. After curettage of the uterine endometrium and ultrasonography-guided gun biopsy of the thyroid gland to confirm uterine and thyroid cancers, respectively, total abdominal hysterectomy with bilateral salpingo-oophorectomy and total thyroidectomy with bilateral central neck dissection were performed. Histopathologic examination of the removed tissues demonstrated both endometrial carcinoma metastasis to the thyroid gland and primary thyroid cancer with synchronous central neck node metastasis originating in the endometrium and thyroid. Three of the four right central lymph nodes were positive for metastatic papillary carcinoma; on the other hand, the remaining right central lymph node and one of the two left central lymph nodes were confirmed to be positive for metastatic endometrial carcinoma.

A Case of Acute Appendicitis in a Patient with Methimazole-Induced Agranulocytosis / 대한내과학회지

Agranulocytosis is a rare, but life-threatening, adverse effect of methimazole, which usually manifests as an upper respiratory infection. Agranulocytosis together with acute appendicitis is especially rare in patients with Graves' disease taking methimazole. A 44-year-old woman presented to our hospital with abdominal pain and a fever. She had been taking methimazole and propranolol for Graves' disease for the previous 8 weeks. Her symptoms were compatible with acute appendicitis. Computed tomography of the abdomen revealed acute appendicitis with impending rupture. However, the circulating absolute neutrophil count was 10/mm3. We managed her with antibiotics and granulocyte colony stimulating factor rather than with emergency surgery. The thyrotoxicosis was treated with intravenous contrast medium while fasting, followed by Lugol's solution and lithium. After recovering from the neutropenia, she underwent a total thyroidectomy combined with an appendectomy. Here, we report a patient with Graves' disease who developed methimazole-induced agranulocytosis presenting as acute appendicitis.

A Case of Acute Appendicitis in a Patient with Methimazole-Induced Agranulocytosis / 대한내과학회지

Agranulocytosis is a rare, but life-threatening, adverse effect of methimazole, which usually manifests as an upper respiratory infection. Agranulocytosis together with acute appendicitis is especially rare in patients with Graves' disease taking methimazole. A 44-year-old woman presented to our hospital with abdominal pain and a fever. She had been taking methimazole and propranolol for Graves' disease for the previous 8 weeks. Her symptoms were compatible with acute appendicitis. Computed tomography of the abdomen revealed acute appendicitis with impending rupture. However, the circulating absolute neutrophil count was 10/mm3. We managed her with antibiotics and granulocyte colony stimulating factor rather than with emergency surgery. The thyrotoxicosis was treated with intravenous contrast medium while fasting, followed by Lugol's solution and lithium. After recovering from the neutropenia, she underwent a total thyroidectomy combined with an appendectomy. Here, we report a patient with Graves' disease who developed methimazole-induced agranulocytosis presenting as acute appendicitis.

Clinical Characteristics of the Responders to Dipeptidyl Peptidase-4 Inhibitors in Korean Subjects with Type 2 Diabetes

We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (DeltaHbA1c). The Student's t-test between good responders (GR: DeltaHbA1c > 1.0%) and poor responders (PR: DeltaHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with DeltaHbA1c. In the multivariate analysis, age (r2 = 0.006), duration of diabetes (r2 = 0.019), HbA1c (r2 = 0.296), and creatinine levels (r2 = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.

Particulate Matter 10 from Asian Dust Storms Induces the Expression of Reactive Oxygen Species, NF-kappaB, TGF-beta and Fibronectin in WI-26 VA4 Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Particulate matter may be toxic to human tissue. Ambient air particulate matter < or =10micrometer in aerodynamic size (PM10), which changes under different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also spread unique particulate matter in affected areas. We evaluated production of ROS, TGF-beta, fibronectin, and NF kappa B by exposing normal epithelial cells to Asian dust particulate matter. METHODS: Bronchial epithelial cells were exposed to 0, 50, 100microgramg/ml of a suspension of PM10 for 24 h. ROS were detected by measurement of DCF release from DCF-DA by FACScan. TGF-beta, fibronectin, and NF kappa B were detected by western blotting. RESULTS: PM10 exposure increased the expression of TGF-beta, fibronectin, and NF kappa B. ROS production and TGF-betalevels were significantly higher with 50 or 100microgram/ml PM10. Fibronectin and NF kappa B production were significantly higher after 100microgram/ml of PM10. CONCLUSION: PM10 from Asian dust particles might have fibrotic potential in bronchial epithelial cells via ROS induction after PM10 exposure.