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.

Subjective Assessment of Diabetes Self-Care Correlates with Perceived Glycemic Control but not with Actual Glycemic Control

BACKGROUND: We investigated whether patients' perceived glycemic control and self-reported diabetes self-care correlated with their actual glycemic control. METHODS: A survey was administered among patients with diabetes mellitus at an outpatient clinic with structured self-report questionnaires regarding perceived glycemic control and diabetes self-management. Actual glycemic control was defined as a change in glycated hemoglobin (A1C) or fasting plasma glucose (FPG) since the last clinic visit. RESULTS: Patients who perceived their glycemic control as "improved" actually showed a mild but significant decrease in the mean A1C (-0.1%, P=0.02), and those who perceived glycemic control as "aggravated" had a significant increase in the mean FPG (10.5 mg/dL or 0.59 mmol/L, P=0.04) compared to the "stationary" group. However, one-half of patients falsely predicted their actual glycemic control status. Subjective assessment of diabetes self-care efforts, such as adherence to a diet regimen or physical activity, correlated positively with perceived glycemic control but showed no association with actual glycemic control. CONCLUSION: Patients should be encouraged to assess and monitor diabetes self-care more objectively to motivate behavioral modifications and improve their actual glycemic control.

Is the Indicator Magnifying Window for Insulin Pens Helpful for Elderly Diabetic Patients?

Patients with type 2 diabetes who require insulin therapy are commonly elderly and have poor visual acuity. In this study, we examined the clinical usefulness of the indicator magnifying window (IMW) for elderly patients with type 2 diabetes. We recruited 50 patients with type 2 diabetes over the age of 60 who had used insulin pens for glucose control. They were asked to set the insulin pen at randomly selected doses with or without an IMW. We assessed dosing accuracy, convenience, self-confidence, need for eyeglasses, preference, and willingness to recommend the IMW to other patients. Although the IMW did not improve the dosing accuracy or convenience, it significantly decreased the need for eyeglasses. Overall, the clinical usefulness of the IMW is quite limited in elderly patients with type 2 diabetes.

A case of mediastinal ectopic thyroid presenting with a paratracheal mass

Mediastinal ectopic thyroid is a very rare condition, with few reported cases in the literature and no reported cases in Korea. This report describes an asymptomatic 65-year-old man with a right paratracheal mass compressing the superior vena. Additionally, the epidemiology, clinical manifestation, diagnosis, and management of mediastinal ectopic thyroids are discussed. A mediastinal ectopic thyroid should be considered in the differential diagnosis of all mediastinal masses. Surgical excision is recommended for both the diagnosis and treatment of this condition, because of its potential for malignancy and compression of mediastinal structures. This case demonstrates the clinical importance of mediastinal etopic thyroid.

Primary Hyperaparathyroidism due to Cystic Parathyroid Adenoma not Detected on 99mTc-Sestamibi Scan

Parathyroid cysts, which can be divided into functional and non-functional cysts, are rare causes of primary hyperparathyroidism. A technetium-99m-methoxyisobutylisonitrile (99mTc-sestamibi) parathyroid scan is a sensitive diagnostic tool for the localization, although it sometimes shows a false-negative result. Here we report a case of presumed cystic parathyroid adenoma based on clinical findings and analysis of cystic fluid with negative findings in a parathyroid scan. A 44-year-old male patient visited the hospital due to leg pain and compressive symptoms (dysphagia, hoarseness) that had started 4-5 months before. His serum calcium level was 14.4 mg/dL and his intact parathyroid hormone (iPTH) had increased to 478.1 pg/mL. On neck computed tomography, a cystic nodule measuring 6.2 cm was detected in the inferior part of the right thyroid gland. Sestamibi uptake for this nodule was not detected on 2-h delayed imaging, and fluorodeoxyglucose positron emission tomography showed only subtle uptake. Fine-needle aspiration was performed and intracystic iPTH had increased to 61,600 pg/mL. Focused parathyroidectomy guided by intraoperative iPTH monitoring led to successful enucleation of the right inferior parathyroid gland. A parathyroid adenoma was confirmed, and his laboratory results had normalized. This study shows that cystic parathyroid adenoma can sometimes be difficult to detect on a 99mTc-sestamibi parathyroid scan.

Malignancy Rate in Sonographically Suspicious Thyroid Nodules of Less than a Centimeter in Size Does Not Decrease with Decreasing Size

We evaluated the malignancy and nondiagnostic rates using fine needle aspiration cytology (FNAC) results in thyroid nodules smaller than 1 cm according to the subdivided size. We retrospectively reviewed the medical records of all subjects underwent FNAC from 2003 to 2009 in our hospital, and 2,756 patients of subcentimeter thyroid nodules with one or more suspicious sonographic features and 7,105 with nodule sized 1 cm or more were included. The malignancy rate was higher in those subcentimeter nodules with suspicious sonographic findings than the nodule sized 1cm or more (19.7% vs 7.8%, P < 0.001). We grouped the nodules based on size with mm interval and observed that the malignancy rate did not decrease but the nondiagnostic results increased its size decrement. When we divided the subjects arbitrarily into a 5 mm or smaller and a 6-9 mm sized group, nondiagnostic cytology findings were reported more frequently in the smaller group (24.3% vs 18.1%, P = 0.001), while the rate of "malignant" was similar (18.3% vs 15.5%, P = 0.123) and the rate of "suspicious for malignancy" was higher (6.8% vs 2.9%, P < 0.001). Therefore when we decide to perform FNAC or not in subcentimeter-sized nodules, we should consider sonographic findings and other clinical risk factors but not the nodular size itself.

Clinical Characteristics of Langerhans Cell Histiocytosis with Hypothalamo-Pituitary Involvement

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disease that involves a clonal proliferation of Langerhans cells. LCH has a predilection for hypothalamo-pituitary axis (HPA) dysfunction, and this leads to diabetes insipidus (DI) and/or anterior pituitary dysfunction. Here, we describe the endocrine dysfunction and clinical characteristics of adult patients with LCH and we analyzed the differences between an adult-onset type and a childhood-onset type. METHODS: The data was obtained from a retrospective chart review of the patients with LCH that involved the HPA and who attended Seoul National University Hospital. The patients were classified into the adult-onset type (age at the time of diagnosis > or = 16) and the childhood-onset type (age at the time of diagnosis < or = 15). RESULTS: Ten patients (9 males and 1 female) were diagnosed with LCH involving the HPA. Five patients were classified as an adultonset type and the other five patients were classified as a childhood-onset type. The median follow-up duration was 6 (3-12) years for the adult-onset type and 16 (15-22) years for the childhood-onset type. All the patients presented with DI as the initial manifestation of HPA involvement. Four adult-onset patients and three childhood-onset patients had a multi-system disease. Panhypopituitarism developed in three adult-onset patients and in one childhood-onset patient. The pituitary lesion of the three adult-onset patients had spread to the brain during the follow-up duration. In contrast, the pituitary lesion of the other two adult-onset patients without panhypopituitarism and all the childhood-onset patients had not changed. CONCLUSION: DI was the initial presentation symptom of HPA involvement. Anterior pituitary hormone deficiency followed in some patients. Compared with the childhood-onset patients, the adult-onset patients were more likely to have panhypopituitarism and a poor prognosis.

Association of the Parathyroid Adenoma Volume and the Biochemical Parameters in Primary Hyperparathyroidism

BACKGROUND: The objective of this study is to demonstrate the relationship between the volume of a parathyroid adenoma and the preoperative biochemical parameters in patients undergoing surgery for primary hyperparathyroidism. METHODS: The medical records of 68 patients who underwent a parathyroidectomy for a single parathyroid adenoma were retrospectively reviewed. The volume of the adenoma was estimated using its measured size and a mathematical formula. The correlation between the volume of the parathyroid adenoma and the preoperative laboratory data was assessed. RESULTS: There were no correlations between the estimated volume of the adenoma and the serum calcium, alkaline phosphatase and parathyroid hormone levels. However, the volume of the adenoma was associated with the preoperative level of serum phosphorus. After excluding 5 adenomas with cystic degeneration, a positive correlation was noted between the adenoma volume and the preoperative levels of alkaline phosphatase and parathyroid hormone. CONCLUSION: The preoperative serum levels of calcium, alkaline phosphatase and parathyroid hormone are of limited use to predict the volume of the parathyroid adenoma in patients with a single parathyroid adenoma. We suggest that the absence of a correlation between the volume of the adenoma and the biochemical parameters can be attributed to the cystic degeneration of the adenomas.

A Case of von Hippel-Lindau Disease Presenting with Pancreatic Neuroendocrine Tumor

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that results from a germline mutation of the VHL gene. The affected individuals might develop several benign or malignant tumors such as central nervous system or retinal haemangioblastomas, endolymphatic sac tumors, renal cell carcinomas, pheochromocytomas or pancreatic cysts and neuroendocrine tumors. We report here on a case of a 21 year old female with von Hippel-Lindau disease and she presented with only pancreatic neuroendocrine tumor and no evidence of haemangioblastomas or other visceral complications. Further, direct sequencing of the VHL gene reveals a novel germline frameshift mutation of codon 198 from the deletion of nucleotide 592 (cytosine), leading to truncation of the VHL protein.

Investigation of Sarcopenia and Its Association with Cardiometabolic Risk Factors in Elderly Subjects

BACKGROUND: The aim of this study was to investigate sarcopenia and its association with cardiometabolic risk factors in a community-based elderly cohort in Korea. METHODS: We recruited 287 men and 278 women aged 65 years or older and without physical disability. Appendicular skeletal muscle mass (ASM) was measured with dual energy X-ray absorptiometry. We used two definitions for sarcopenia-ASM divided by height2 (kg/m2) or by weight (%) <1 SD below the sex-specific mean for young adults. We compared RBP-4, adiponectin, hsCRP, lipid profiles, and insulin resistance between the sarcopenic and normal groups using ASM/Ht2 and ASM/Wt. RESULTS: The prevalence of sarcopenia was 35.3% in men and 13.4% in women with sarcopenia defined by ASM/Ht2. However, it was 38.3% in men and 62.6% in women by ASM/Wt. In correlation analysis, body mass index was positively correlated with ASM/Ht2 and negatively correlated with ASM/Wt. The sarcopenic group, when defined as ASM/Ht2, showed lower RBP4, fasting plasma glucose, and HOMA-IR and higher adiponectin than the normal group but not significantly different lipid profiles. The sarcopenic group defined by ASM/Wt had higher RBP4, fasting plasma glucose, and HOMA-IR, and lower adiponectin than the normal group in both sexes. Only in the males did the sarcopenic group defined by ASM/Wt reveal higher total cholesterol, triglycerides, and LDL cholesterol, and lower HDL cholesterol than the normal group. CONCLUSION: In conclusion, the sarcopenic group defined by ASM/Wt was more closely associated with cardiometabolic risk factors than the normal group in a community-based elderly cohort.