Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

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Few studies have focused on the quantification of glycemic lability and hypoglycemic events in Asian patients with type 1 diabetes; therefore, we conducted a study to assess glycemic lability and the severity of hypoglycemia in type 1 diabetic patients in Korea. A total of 124 type 1 diabetic patients were enrolled. Several glycemic lability indexes and hypoglycemic indexes were calculated using four-week self-monitoring of blood glucose (SMBG) data. Due to the dependence of the lability index (LI) on the frequency of glucose measurements, we generated a modified LI by dividing by the number of SMBG measurements per day for a given patient. The numbers of patients in our study with a composite hypoglycemic score ≥ 1,047 or LI ≥ 433 mmol/L²/h•week^-1, which was found in a previous study to indicate high risk of severe hypoglycemia or lability, were 0 (0%) and 44 (35%), respectively. Compared to previously reported hypoglycemia indexes, the low blood glucose index was lower in our study. However, the glycemic lability indexes were similar to those in previous studies, with the exception of the LI. The modified LI and the average daily risk range (ADRR) showed higher concordance with other glycemic lability indexes than did the LI or mean amplitude of glycemic excursions (MAGE). The results showed that the hypoglycemic indexes in this study population were lower than the results from Ryan et al. Furthermore, the ADRR or modified LI were better measures for high risk of severe lability than were the LI and MAGE.

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The aim of this study is to develop strategies to screen diabetic subjects with isolated postload hyperglycemia (IPH) in Chinese population. We included 1175 adult subjects who did not report diabetes were included. Diabetes was diagnosed by oral glucose tolerance tests. IPH was defined as fasting plasma glucose (FPG)<7 mmol/l and 2-hour post-load plasma glucose (2hPG) greater than 11.1 mmol/l. Using FPG criteria, only 59.8% of diabetic subjects were not identified, showing a poor agreement between FPG and 2hPG criteria (kappa 0.294). Age, FPG, total cholesterol, triglycerides, blood pressure, body mass index, HbA1c and medication for hypertension were associated factors for IPH. Four scores were constructed using all these factors, age and blood test results, age and HbA1c, and data from non-invasive examinations, respectively. The area under the ROC curve were 0.9296(95%CI 0.8948-0.9643), 0.9111(95%CI 0.8713-0.9508), 0.8902(95%CI 0.8341-0.9646), 0.8924(95%CI 0.7835-0.8753), and 0.8654(95%CI 0.7963-0.9345) for score 1, 2, 3, 4, and HbA1c, respectively. The sensitivity of all four risk scores to detect IPH was better than that of impaired fasting glucose (IFG). The sensitivity and specificity of HbA1c at cutoff 6.2% for detecting IPH was also better than that of IFG. In conclusion, the risk scores and HbA1c are useful to identify subjects with undiagnosed IPH, with better performance than IFG.

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Hypercholesterolemia is one of the most representative disorders of the common diseases. To evaluate the prevalence of hypothyroidism in the population of adult hypercholesterolemia, we prospectively examined the thyroid function in patients with untreated or treated hypercholesterolemia as a multi-center survey. Subjects were the patients who were treated with some antilipemic agents or the untreated patients whose total cholesterol (TC) was over 220 mg/dL and/or LDL-cholesterol (LDL-C) over 140 mg/dL. Among 737 cases recruited, 725 cases (300 males and 425 females) participated in the survey including the thyroid function test. The patient's backgrounds include hypertension (51%), diabetes mellitus (49%), fatty liver (17%), smoking (15%), and habitual drinking (10%). The 72% of the patients were treated with some antilipemic agents and the mean values of TC, LDL-C, triglyceride (TG), HDL-cholesterol (HDL-C), and LDL-C/HDL-C ratio (L/H) were 204.5 mg/dL, 119.6 mg/dL, 144.4 mg/dL, 60.7 mg/dL and 2.25, respectively. The primary hypothyroidism was seen in 27 cases (3.7%) (11 males, 16 females) with subclinical hypothyroidism in 17 cases (2.4%) and overt hypothyroidism in 10 cases (1.4%). The central hypothyroidism was seen in 4 cases (0.6%). The prevalence of hypothyroidism was 4.3% in patients with hypercholesterolemia. Taking account of the large number of patients with dyslipidemia and importance of avoiding unnecessary administration and associated adverse effects, evaluation of the thyroid function could be warranted in patients with dyslipidemia although cost-benefit issues waits further investigation.

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Pulmonary function impairment has a connection with abdominal obesity, type 2 diabetes, and insulin resistance. Sex differences in lifestyle factors, and pulmonary structure and function may affect pulmonary function in different manners. This study focused on sex differences in the relationship of MetS and its component with pulmonary function. Among 2,614 Korean adults (1,059 men; 1,555 women), pulmonary function was measured by the percentage of predicted forced vital capacity (FVC (%)) and a ratio between forced expiratory volume in 1 second (FEV₁)/FVC. FVC (%) and FEV₁/FVC were compared according to the presence of MetS and its components. Multiple linear regression analysis was conducted to assess the association between FVC (%), FEV₁/FVC and clinical variables. We found sex differences in the relationship of MetS and its components with pulmonary function. FVC (%) was significantly lower in subjects with MetS than in those without MetS in both men and women, and FEV₁/FVC was lower in subjects with MetS only in women. Among components of MetS, waist circumference, blood pressure and fasting plasma glucose, and HDL-cholesterol were independently related to FVC (%) in men, whereas waist circumference was significantly associated with FVC (%) in women. Blood pressure was found to be an independent factor of FEV₁/FVC in men, whereas blood pressure, fasting plasma glucose and HDL-cholesterol independently determined FEV₁/FVC in women. These findings suggest that sex-specific association between MetS and lung function measures should be considered in clinical practice.

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Primary granulomatous hypophysitis (PGH) is a rarely occurred inflammatory disease of unknown etiology. We retrospective review a case of PGH treated by microsurgical transsphenoidal approach and review the appropriately documented cases of PGH collected from the literatures. The patient was a 56-year-old female who presented with 4 months history of headache and 2 months history of polyuria and polydipsia. Clinic examination did not find remarkable neurological signs, except endocrinological abnormalities of secondary hypothyroidism and hypocorticalism. MRI revealed a symmetric sellar mass, which was isointensity as gray matter on T1-weighted and T2-weighted images with heterogeneous enhancement. The mass was partially resected via transsphenoidal approach. Histological assessment revealed a non-necrotizing granulomatous lesion with chronic inflammation. Although the resection was limited, repeatedly MRI scanning in 3 months following surgery revealed almost normal pituitary soft tissue without evidence of the lesion. Searching in PubMed, we found 21 papers published from 1985 to 2009 and 37 patients with PGH were reported. In order to identify the clinical and radiological presentation, treatment strategy, and prognosis of PGH, we analyzed these 38 cases together. The results indicate that the clinical presentations and radiological signs are helpful for the diagnosis of PGH. The outcome of surgery for PGH is favorable for immediate mass reduction and histological diagnosis, but hormone replacement is required in most cases and long-term follow up is very important.

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The prevalence of and risk factors for lipodystrophy (LD) among patients receiving combined antiretroviral treatment (cART) in the Asia-Pacific region are largely unknown. LD diagnosis was based on the adverse event definition from the US NIH Division of AIDS (2004 version), and only cases with a severity grade of ≥ 3 were included. TAHOD patients who had recently commenced cART with ≥ 3 drugs after 1996 from sites which had ever reported LD were included in the analysis. Covariates for the forward multivariate logistic regression model included demographic variables, CDC disease classification, baseline CD4 and viral load, hepatitis B/C virus co-infection, and regimen and duration of cART. LD was diagnosed in 217 (10.5%) of 2072 patients. The median duration of cART was 3.8 (interquartile range, 2.2-5.3) years [stavudine, 2.0 (1.0-3.5) years; zidovudine, 1.8 (0.6-3.9) years; and protease inhibitors (PI), 2.6 (1.3-4.5) years]. In the multivariate model, factors independently associated with LD included use of stavudine (≤ 2 years vs. no experience: OR 25.46, p<0.001, > 2 years vs. no experience: OR 14.92, p<0.001), use of PI (> 2.6 years vs. no experience: OR 0.26, p<0.001), and total duration of cART (> vs. ≤ 3.8 years: OR 4.84, p<0.001). The use of stavudine was strongly associated with LD in our cohort. Stavudine-sparing cART strategies are warranted to prevent the occurrence of LD in the Asia-Pacific region.

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While TSH-producing adenoma (TSHoma) is rare, the diagnosis is often delayed because the clinical features are heterogeneous. The patient was a 69-year-old woman who had been referred to the Yachiyo Medical Center in August 2008, because of dyspnea, loss of appetite, weight loss of 10 kg, and diarrhea that lasted 4 years. We diagnosed this patient with pituitary TSH-producing macroadenoma. Thyroid hormone concentration was increasing although the serum TSH level was within a normal range after trans-sphenoidal surgery. We considered that because of enlargement of the thyroid gland due to long-term stimulation by TSH, a low concentration of TSH could stimulate the thyroid gland to produce excess T3 or T4. The somatostatin analogue, octreotide was used to control the TSHoma and serum TSH concentration but not thyroid hormone. The octreotide in combination with thiamazole treatment for 14 months controlled thyroid hormone concentration and decreased the thyroid mass, and ultimately, the thiamazole could be stopped. To date, the use of combination therapy of octreotide with thiamazole in patients with remaining TSH-producing adenoma without Basedow’s disease is rare, and we suggest that this treatment is one of the therapeutic means to treat recurrence of TSH-producing adenoma after surgery with progressive complications or large thyroid gland.

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In this study, we mainly focused on how aldosterone regulates Nox1, a catalytic subunit of NADPH oxidase (NOX) in vascular smooth muscle cells (VSMC). We found that aldosterone can induce the expression of Nox1, which is upregulated by the activation of the Src and activating transcription factor 1 (ATF1), but can not be suppressed by the inhibitors of the epidermal growth factor receptor (EGFR) or Matrix Metalloproteinase (MMP). Aldosterone triggers ATF1 phosphorylation in dose dependent fashion, but this effect is not blocked by actinomycin D, suggesting a non-genomic effect of aldosterone. On the other hand, aldosterone induced Nox1 expression can be suppressed by the gene silencing of the ATF1 using RNA interference. Furthermore, silencing ATF1 can also attenuate aldosterone-induced O₂^- production and protein synthesis, and inhibit hypertrophy in this vascular cell lineage. In short, our results primarily unveiled the relationship between aldosterone and Nox1 expression and the regulation mechanism of their signal pathways in the hypertrophy of vascular smooth muscle cell. Src, ATF1, Nox1 and MR are likely efficient targets in the treating of vascular diseases but need more study.

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Development of a testicular adrenal rest tumor (TART) is common in males with congenital adrenal hyperplasia, and it can be an important cause of infertility. In the present study, we observed the prevalence of TARTs, and analyzed its associated factors in patients with 21-hydroxylase deficiency. Testicular ultrasonography was performed in 48 postpubertal male patients aged 10.6 to 27.1 years. To determine whether patients were undertreated, we analyzed the serum 17-hydroxyprogesterone (17-OHP) levels to the time of ultrasonographic measurement and calculated the percentage of measurements when serum 17-OHP level was >10 ng/mL relative to the total number of measurements during the follow-up period. We divided the 6-year period before ultrasonographic measurement (time 0) into three 2-year intervals and calculated the average concentration of serum 17-OHP in each interval to give a -2^nd to 0 year-average concentration (-2-0YAC), -4-2YAC and -6-4YAC. A TART was detected by ultrasonography in 31 of 48 patients (64.6%) and the median maximal cross-sectional area of the TARTs was 0.71 (0.03, 4.95) cm². The corrected final adult height was lower, and -4-2YAC and body mass index were higher in patients with TART than in those without. After controlling for the type of 21-hydroxylase deficiency, hydrocortisone-equivalent dose, age, and -6-4YAC, the size of TART was associated with a high undertreatment percentage with a marginal statistical significance. These results suggest that strict disease control is mandatory and regular examination with testicular ultrasonography is recommended in male patients, regardless of the type of 21-hydroxylase deficiency.

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A promising new option as the treatment of choice for premenopausal patients with metastatic breast cancer (MBC) could be the combination of a luteinising hormone-releasing hormone analog and an aromatase inhibitor. Very little data about the use of goserelin with anastrozole in advanced breast cancer are available, and no cohort studies on the efficacy of goserelin with letrozole in advanced premenopausal breast cancer patients have been reported. We present the single-centre, retrospective, experience of goserelin plus letrozole in a total of 52 premenopausal women with MBC. All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks along with letrozole 2.5 mg daily as first-line (n=36) and second-line (n=16) hormonal treatment. The median duration of goserelin with letrozole treatment was 11 (range, 2-61) months, and the median duration of overall follow-up was 31 (range, 3-66) months. The objective response rate (ORR) was 21.1%, with two complete response (CR) (3.8%) and nine partial response (PR) (17.3%). Stable disease (SD) lasting more than 6 months was achieved by 26 patients (50.0%). Thus, goserelin with letrozole conferred clinical benefit (CB) in 37 women (71.1%). The progression-free survival (PFS) was 10 months. CR was exclusively observed in hormone receptor-double-positive patients. Drug therapy was well tolerated; no grade 3/4 toxicities were reported. Goserelin plus letrozole appears to be an efficacious and well-tolerated regimen in women with advanced breast cancer. Further prospectively randomized studies involving more patients and longer follow-up are indicated.

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