Resolution of Metabolic Disorders and Overweight in a Patient with ACTH-independent Cushing's Syndrome after Unilateral Adrenalectomy.

Excessive production of cortisol by abnormal adrenocortical tissue causes clinical manifestations of Cushing's syndrome and is associated with metabolic abnormalities including abdominal obesity, hyperglycemia, dyslipidemia, and hypertension, which increase the risk for type 2 diabetes mellitus as well as vascular morbidity and mortality. Removing the cause of hypercortisolism is initially required to resolve metabolic disorders in patients with adrenal Cushing's syndrome. A 38-year-old woman with diabetes mellitus and hypertension, which were not well controlled by medications, complained of abdominal obesity, rounded face, thin limbs, and bruising. Based on clinical manifestations and laboratory findings, she was diagnosed with Cushing's syndrome due to unilateral cortisol-producing adrenal adenoma. After left adrenalectomy, the patient's blood glucose improved to a satisfactory level, and she rapidly discontinued insulin and oral glucose-lowering agent therapy. Her body mass index decreased to the normal range, and her other metabolic symptoms, dyslipidemia and hypertension, also improved significantly. She has maintained resolution of metabolic disorders and overweight for eight years since surgery without recurrence of Cushing's syndrome.

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Placental expression of D6 decoy receptor in preeclampsia.

OBJECTIVE: The purpose of this study was to investigate the expression of the D6 decoy receptor that can bind chemokines and target them for degradation, resulting in inhibition of inflammation in placentas from preeclamptic and normal pregnancies. METHODS: The current study was carried out in 35 pregnant women (23 patients with preeclampsia and 12 healthy, normotensive pregnant women) during the third trimester of pregnancy. The expressions of D6 decoy receptor in the placenta were determined with real time reverse transcriptase polymerase chain reaction and western blotting. RESULTS: The mRNA and protein of D6 decoy receptor were detected in all of placentas from preeclamptic and normal pregnancies. Placental D6 decoy receptor mRNA expression was significantly lower in patients with preeclampsia than in patients with normal pregnancies. Western blot analyses revealed decreased protein expression in cases of preeclampsia. CONCLUSION: The expression of the D6 decoy receptor in preeclamptic placentas was significantly lower than in normal placentas. Further studies are needed to clarify the underlying mechanisms that link decreased expression of placental D6 decoy receptor and preeclampsia.

Genetic Analysis of Multiple Endocrine Neoplasia Type 1 (MEN1) Leads to Misdiagnosis of an Extremely Rare Presentation of Intrasellar Cavernous Hemangioma as MEN1.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited disorder characterized by the simultaneous occurrence of endocrine tumors in target tissues (mainly the pituitary, endocrine pancreas, and parathyroid glands). MEN1 is caused by mutations in the MEN1 gene, which functions as a tumor suppressor and consists of one untranslated exon and nine exons encoding the menin protein. This condition is usually suspected when we encounter patients diagnosed with tumors in multiple endocrine organs, as mentioned above. METHODS: A 65-year-old woman who underwent surgery for a pancreatic tumor (serous cystadenoma) 5 years previously was referred to our hospital due to neurologic symptoms of diplopia and left ptosis. Brain magnetic resonance imaging revealed a 3.4-cm lesion originating from the cavernous sinus wall and extending into the sellar region. It was thought to be a nonfunctioning tumor from the results of the combined pituitary function test. Incidentally, we found that she also had a pancreatic tumor, indicating the necessity of genetic analysis for MEN1. RESULTS: Genomic analysis using peripheral leukocytes revealed a heterozygous c.1621G>A mutation in the MEN1 gene that was previously reported to be either a pathogenic mutation or a simple polymorphism. We pursued a stereotactic approach to the pituitary lesion, and microscopic findings of the tumor revealed it to be an intrasellar cavernous hemangioma, a rare finding in the sellar region and even rarer in relation to oculomotor palsy. The patient recovered well from surgery, but refused further evaluation for the pancreatic lesion. CONCLUSION: There is great emphasis placed on genetic testing in the diagnosis of MEN1, but herein we report a case where it did not assist in diagnosis, hence, further discussion on the role of genetic testing in this disease is needed. Also, in cases of pituitary tumor with cranial nerve palsy, despite its low prevalence, intrasellar cavernous hemangioma could be suspected.

Primary malignant melanoma of uterine cervix: a suggestion of new scheme of treatment combination.

Historically, the lack of melanocytes in the vaginal and cervical mucus membranes has deterred the findings of primary melanomas. Mainly due to its rarity, difficulty to diagnose, and poor prognosis, there has been no absolute agreement on comprehensive treatment so far. In this case report, we present a case of a 46-year-old woman with primary malignant melanoma of uterine cervix. She underwent neo-adjuvant chemotherapy initially followed by a radical hysterectomy. After adjuvant concurrent chemo-radiation, the patient has been followed up for 24 months. So far, she has not shown any symptoms or signs of recurrence. Further studies with more cases based on variable combinations of treatment regimen have been on the way.

The impact of diabetes duration on left ventricular diastolic function and cardiovascular disease.

OBJECTIVES: The question of whether diabetes mellitus (DM) duration correlates with the severity of dysfunction has not been well studied. We hypothesised that the longer the duration of DM the worse the severity of left ventricular (LV) diastolic dysfunction and increased risk of cardiovascular disease (CVD). METHODS: We reviewed 547 diabetic patients between January 2005 and April 2010. Finally, 92 consecutive patients who presented with type 2 DM and who underwent echocardiographic assessment were enrolled according to the selection criteria. In all patients, ischaemic heart disease and heart failure were excluded. RESULTS: Diastolic parameters were significantly worsened with increasing duration of DM (p<0.05). In the ≥7 years DM duration group (n=50), the E/Ea ratio increased significantly and the Ea/Aa ratio decreased significantly, compared with those in the <7 years DM duration group (n=42). CVD developed in 28 patients (30.4%) during the follow-up period. However, the duration of DM showed less statistical correlation with the incidence of CVD (p=0.188) and other LV diastolic function indices did not differ significantly between groups with or without CVD. CONCLUSIONS: Alteration of diastolic function induced by DM worsens with increasing duration of DM. DM duration on echocardiographic evaluation time did not differ significantly between the CVD incident and the non-CVD incident groups. The rate of CVD development was not significantly different if the duration of DM was more than 7 years. Therefore, active medical care including echocardiography should be undertaken to prevent CVD from the point of diagnosis of type 2 DM.

Evaluation of stress in korean patients with diabetes mellitus using the problem areas in diabetes-Korea questionnaire.

BACKGROUND: It is known that diabetes and stress are directly or indirectly related, and that it is important to evaluate stress in patients with diabetes. The relationship between Korean diabetics and diabetes-related stress has never been reported. The objective of this study was to develop a stress questionnaire suitable for use with Korean diabetics and to evaluate its utility. METHODS: This study subjects were 307 Korean diabetics, aged 40 to 74 years old, who visited the Department of Endocrinology and Metabolism at Gachon University Gil Hospital, Yeungnam University Medical Center, and Inha University Hospital in Korea between March 2006 and February 2008. We developed a Korean version of Polonsky's Problem Areas in Diabetes (PAID) stress questionnaire (PAID-K) and used it to assess degrees of stress in our sample of Korean patients. We evaluated the utility of the questionnaire and analyzed the relationships between clinical characteristics of the study subjects and degrees of stress. RESULTS: Cronbach's alpha for PAID-K was 0.95, and PAID-K scores were significantly correlated with Hypoglycemia Fear Survey scores (r=0.44, P<0.05) and State Trait Anxiety Inventory-6 scores (r=0.21, P<0.05). PAID-K scores were significantly higher in patients with longer durations of diabetes, patients using insulin, and female patients (P=0.02, P=0.038, and P=0.001, respectively). The score also tended to increase as HbA1c levels increased, except for very high HbA1c levels (above 11%) (P for trend<0.05). CONCLUSION: We developed the PAID-K questionnaire and demonstrated its utility to evaluate levels of stress in diabetic patients in Korea.

Rarity of TLR4 Asp299Gly and Thr399Ile polymorphisms in the Korean population.

PURPOSE: Activation of the innate immune system and chronic low-grade inflammation are thought to be involved in the pathogenesis of atherosclerosis and also thought to be associated with type 2 diabetes and its complications. As a receptor for bacterial lipopolysaccharide and heat-shock proteins, Toll-like receptor 4 (TLR4) is one of the central regulators of the immune response. Recent studies have reported an association between TLR4 polymorphisms and diabetes and its complications in Caucasian populations. MATERIALS AND METHODS: In this study, we analyzed the association between TLR4 gene polymorphisms in patients with features of type 2 diabetes and healthy controls in Korea. Two polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) were examined in 225 diabetic patients and 153 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and single-strand conformation polymorphism (SSCP). RESULTS: No Asp299Gly or Thr399Ile mutations were detected in any of the 378 subjects. Seven subjects from each group who had slightly different SSCP patterns were selected for sequencing, but we found no TLR4 polymorphisms on Exon3. The Asp299Gly and Thr399Ile TLR4 gene polymorphisms were absent in both groups, which was similar to the results for Japanese and Chinese Han subjects. CONCLUSION: Our data and other Asian data suggest that a racial difference can be found in the frequency of the TLR4 polymorphism.