Alper Gürlek

Complications of endoscopic surgery of the pituitary adenomas: analysis of 570 patients and review of the literature

Endoscopic transsphenoidal surgery is emerging as a minimally invasive and maximally effective procedure for pituitary adenomas. In this report we analyzed the complications in 624 procedures of endonasal transsphenoidal endoscopic surgery in the treatment of 570 patients with pituitary adenomas. The leading author (MB) operated pituitary adenomas via pure endoscopic endonasal transsphenoidal surgery between January 2006 and August 2011 at the Hacettepe University, Department of Neurosurgery in Ankara. Complications were assessed in 624 surgical procedures under five groups; rhinological, CSF leaks, infection, vascular and endocrinologic complications. We observed a total of 76 complications (12.1%). Rhinological complications occurred in 8 patients (1.3%): 4 epistaxis (0.6%) and 4 hyposmia (0.6%). Postoperative CSF leaks occurred in 8 patients (1.3%), and infectious complications occurred in 8 patients: 3 cases of sphenoidal sinusitis (0.4%), 5 cases of meningitis (0.8%). Only 1 case of internal carotid aneurysm rupture during the opening of sellar floor (0.16%) was observed. Endocrinologic complications occurred in 51 (8.1%) patients: Anterior pituitary deficiency in 12 (1.9%), transient diabetes insipidus (DI) in 29 (4.6%), permanent DI in 3 (0.4%) and inappropriate antidiuretic hormone secretion syndrome occurred in 7 (1.1%). There was no mortality directly related to the surgical procedure. The complication rates observed in our study suggests that the endoscopic pituitary surgery is at least as safe as microscopic transphenoidal surgery. These rates were obtained with due experience and well-coordinated teamwork. To further improve these rates, new technological developments will be helpful.

SERUM VASPIN LEVELS IN TYPE 2 DIABETIC WOMEN IN RELATION TO MICROVASCULAR COMPLICATIONS

OBJECTIVE Vaspin is a novel adipokine that has insulin sensitizing effects. The association between serum vaspin levels and diabetic complications is unknown. In this study, we aimed to evaluate serum vaspin levels as related to glycemic status and the presence of complications in a group of type 2 diabetic women. MATERIALS AND METHODS We evaluated 37 type 2 diabetic female patients and 37 control female subjects who were matched for age and body-mass index. Anthropometric measurements, insulin, hemoglobin A1c (HbA1c), C-reactive protein, and serum vaspin levels were measured in each participant. Furthermore, the patients were evaluated for diabetic neuropathy, nephropathy, and retinopathy. RESULTS In diabetic patients, serum vaspin levels correlated positively with HbA1c and correlated negatively with insulin levels and homeostasis model assessment. The patients with HbA1c levels <or=7% had lower levels of serum vaspin than patients with HbA1c levels >7% (0.11+/-0.06 ng/ml versus 0.20+/-0.09 ng/ml, P<0.05). In patients with neuropathy, retinopathy, and nephropathy, serum vaspin levels were lower than in patients without neuropathy (0.10+/-0.07 ng/ml versus 0.17+/-0.09 ng/ml, P=0.041), retinopathy (0.11+/-0.06 ng/ml versus 0.18+/-0.09 ng/ml, P=0.019), and nephropathy, (0.11+/-0.05 ng/ml versus 0.18+/-0.09 ng/ml, P=0.02). Diabetic patients receiving metformin therapy had lower vaspin levels than patients not receiving metformin. CONCLUSION Diabetic women with good glycemic control have lower levels of vaspin than those with poor glycemic control. However, presence of microvascular complications is also associated with low vaspin levels. In order to use serum vaspin levels as a marker, evaluating patients for complications and medications interfering with serum vaspin levels seems appropriate.

Liver tests in hyperthyroidism : Effect of antithyroid therapy

Changes in liver biochemical test results have been described in hyperthyroid patients before and after antithyroid therapy. In the present study, we analyzed liver tests at diagnosis and after 6 weeks of treatment with propylthiouracil (PTU) in 43 patients with hyperthyroidism. At diagnosis, 60.5% of the patients had at least one liver abnormality. Elevations of alkaline phosphatase, alanine and aspartate aminotransferase, and gamma-glutamyl transpeptidase levels were observed in 19 (44.2%), 10 (23.3%), six (14%), and six (14%) of the patients, respectively. At the end of the 6-week treatment with PTU, elevations in liver test values, possibly induced by PTU, were found in seven (16.3%) patients. Age, sex, type of goiter (either diffuse or multinodular), and presence or absence of abnormal liver biochemical tests at diagnosis were not significant in determining the possibility of PTU-induced elevations in liver tests. These data suggest that liver test abnormalities are frequently found at the time of diagnosis of hyperthyroidism. However, the presence or absence of these abnormalities does not predict elevations in liver test results, which are possibly induced by PTU during therapy.

Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria

OBJECT Acromegaly is a disease that has significant morbidity and mortality related to high levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I), and is usually caused by pituitary adenomas. The goal in this study was to investigate the role of endoscopic transsphenoidal surgery and surgical experience in the treatment of GH adenoma cases in relation to surgical results and hormonal cure rates, and to perform a review of the literature. METHODS The authors present a retrospective analysis of 214 GH adenoma cases. Restoration of IGF-I levels to normal for age and sex, suppression of GH levels below 0.4 μg/L on the oral glucose tolerance test, and demonstration of the total removal of the tumor on MRI studies obtained after administration of contrast material at the 3-month postoperative follow-up visit were the criteria for cure. RESULTS In total 214 patients with a mean age of 41.9 ± 12 years (range 17-75 years) and a male/female ratio of 106/108 were enrolled in the study. Cure was achieved in 134 (62.6%) of 214 patients. One hundred sixty-nine patients were primary cases, and of these 109 (64.5%) were cured, whereas 61 patients were previously operated cases and of these 25 (41%) were cured. With a 51.1% decrease in the 1st month postoperatively, IGF-I levels were found to be predictive of cure (74.4% sensitivity and 73.7% specificity). Cut-off values for GH levels in predicting cure for the 1st day, 1st week, and 1st month postoperatively were 2.33, 2.05, and 2.25 μg/L, respectively. The cut-off value for surgical experience was 57 for primary surgeries (58.5% cure rate before this cut-off value compared with 72.6% after it; p = 0.025) and 108 for all operations (45.8% vs. 79.4%, p = 0.037). Although 28 patients were found to be in remission according to the criteria in 2000, they were not in remission according to the new consensus criteria. Nine of these cases (32.1%) had random GH levels < 1 μg/L at the 1-year follow-up. The 1-year IGF-I and GH levels in these 28 patients showed no significant difference when compared with the cases defined as cured according to the current criteria. CONCLUSIONS In acromegaly treatment, transsphenoidal endoscopic surgery performed by an expert senior surgeon and increased surgical experience are important for higher cure rates. Random GH levels < 2.33 μg/L after the 1st day postoperatively and a > 50% decrease in IGF-I levels after the 1st month postoperatively are predictive of cure. Moreover, there is no urgency for additional therapy in patients with GH levels of 0.4-1 μg/L and MRI sequences showing no tumor at the 3-month follow-up, because for these cases remission can be achieved at the 1-year follow-up.

Inappropriate Reference Range for Peak Bone Mineral Density in Dual-energy X-ray Absorptiometry: Implications for the Interpretation of T-scores

Abstract: An inappropriate reference range for peak bone mineral density (BMD) may result in identification of an incorrect proportion of subjects with osteopenia and osteoporosis at dual-energy X-ray absorptiometry (DXA). In this study, we assessed the prevalence of low BMD in Turkish young adults with respect to local population reference range T-scores and the US reference range T-scores. The BMD values of lumbar spine (L1–L4) and proximal femur (femoral neck, intertrochanter, trochanter, Ward”s triangle and total) were measured by DXA in 323 healthy young adults (171 women, 152 men) aged 19–25 years. The World Health Organization criteria for the diagnosis of osteopenia (−2.5 <T-score <−1) and osteoporosis (T-score ≤−2.5) were applied. In women, the means of the US reference range T-scores were significantly lower than zero at the spine and proximal femoral sites (p<0.0001). In men, the means of the US reference range T-scores were significantly lower than zero at the spine, femoral neck, intertrochanter, total femur (p<0.0001) and trochanter (p<0.05), but not at Ward”s triangle (p=0.92). When the diagnoses were based on local population reference range T-scores instead of the US reference range T-scores, the prevalence of low BMD (T-score <−1) in women fell from 50.3% to 14.0% at the lumbar spine and from 60.8% to 14.6% at the femoral neck, and in men from 42.8% to 15.8% at the lumbar spine and from 30.9% to 17.1% at the femoral neck. Our data suggest that individual populations should use their own reference range T-scores to avoid misdiagnoses of osteopenia and osteoporosis by DXA.

QT dispersion and autonomic nervous system function in patients with type 1 diabetes

Cardiac arrhythmias and markedly increased mortality rate have been demonstrated in patients with diabetic autonomic neuropathy. Abnormal prolonged QT dispersion interval (QTd) is associated with a higher risk of ventricular arrhythmias. The aim of this study was to evaluate the relationship between autonomic dysfunction, QT and JT interval dispersion parameters and ventricular arrhythmias. Twenty-six patients with type 1 diabetes mellitus and 20 healthy subjects as controls were enrolled in the study. Resting 12-lead electrocardiograms were recorded for measurement of QTd, corrected QTd (QTcd), JT dispersion (JTd) and corrected JT dispersion (JTcd). After taking ECG, all patients underwent autonomic function tests. Patients and control group were also evaluated by 24-h Holter monitoring. Fourteen patients were identified who had autonomic dysfunction. QTd, QTcd, JTd, and JTcd values were significantly higher in patients with autonomic dysfunction than both patients without autonomic dysfunction and the control group (QTd: 78+/-16 vs. 51+/-13 ms, P=0.002; 78+/-16 vs. 48+/-9 ms, P<0.001; QTcd: 91+/-14 vs. 66+/-12 ms, P=0.001; 91+/-14 vs. 61+/-11 ms, P<0.001; JTd: 81+/-12 vs. 58+/-13 ms, P=0.001; 81+/-12 vs. 49+/-7, P<0.001; JTcd: 96+/-15 vs. 73+/-11 ms, P<0.001; 96+/-15 vs. 67+/-8 ms, P=0.001). There was no significant difference between the dispersion parameters in diabetic patients without autonomic dysfunction and the control subjects (P>0.05). Also, patients with autonomic dysfunction had higher Lown classes of ventricular arrhythmias and patients with higher Lown classes of ventricular arrhythmias had more prolonged QTd and QTcd values. The data suggest that diabetic patients with autonomic dysfunction have increased dispersion of ventricular refractoriness, which may be one of the factors contributing to the increased incidence of arrhythmias and sudden death observed in these patients.

Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density

An association exists between adiposity, insulin resistance, and osteoporosis; however, the mechanism of this relationship remains enigmatic. We aimed to determine whether the insulin resistance index (HOMA-IR), serum adiponectin, or leptin levels are associated with bone mineral density (BMD). A cross-sectional, observational study was designed. Eighty-four postmenopausal ambulant women [52.5 (50.0–58.0) years; body mass index (BMI): 29.4 (25.9–33.8) kg/m2] referred for osteoporosis screening were enrolled. Anthropometric measures, fasting serum adiponectin and leptin levels, and the HOMA-IR were determined. The relationships between these variables and lumbar, hip, and forearm BMD measured by dual-energy X-ray absorptiometry (DXA) were analyzed. Considering all 84 participants, the HOMA-IR index was 1.82 (1.17–2.86), serum adiponectin was 13.25 (10.49–16.88) μg/ml, and serum leptin was 19.26 (14.94–24.90) ng/ml. BMI, waist circumference, and leptin positively correlated with hip and lumbar BMD, whereas adiponectin negatively correlated. Multivariate analysis confirmed an inverse relation between serum adiponectin level and femoral neck and lumbar BMD measurements. In total hip and forearm areas, there was no independent association of adipocytokines with BMD measurements. Instead, waist circumference was independently associated with BMD measurements. In conclusion, adiponectin may represent a biomarker in the relationship between visceral fat mass and BMD. However, this association is probably confounded by the specific body composition parameters (i.e., waist circumference, BMI) in postmenopausal women.

Role of adipocytokines in predicting the development of diabetes and its late complications

Diabetes is an important health problem since the incidence of diabetes is continuously increasing. Early diagnosis is important as type 2 diabetes begins long before we diagnose it, leading to a complicated course of the disease. In order to prevent delay in the diagnosis of type 2 diabetes, novel predictors and pathways for type 2 diabetes are mounting. Diabetic complications are common cause of morbidity and mortality among subjects with diabetes. In the pathogenesis of diabetic complications some factors other than chronic hyperglycemia may be involved. Adipocytokines play important roles in the pathogenesis of diabetes mellitus, insulin resistance, and associated metabolic conditions such as hypertension and dyslipidemia. The investigations on the role of adipocytokines in developing diabetes and its complications have been made. In this review, we discussed the implications of adipocytokines in predicting diabetes and diabetic complications, with particular attention on the roles of adiponectin, leptin, visfatin, and vaspin.

Simultaneous determination of rosiglitazone and metformin in plasma by gradient liquid chromatography with UV detection

A novel, fast and simple liquid chromatographic method was developed and validated for the simultaneous determination of rosiglitazone and metformin in human plasma. The analysis was performed on a phenyl column (250mmx4.6mm i.d., 5mum) using a gradient method starting with mobile phase composed of acetonitrile:5mM acetate buffer pH 5.5 (75:25, v/v). The flow rate was 1mLmin(-1). UV detection was performed at 245nm and verapamil was used as internal standard. The total run time was less than 10min. Sample preparation included a simple protein precipitation step with acetonitrile. Validation experiments were performed to demonstrate stability, specificity, sensitivity, linearity, accuracy, precision and robustness. The limit of quantification was 100ngmL(-1) for rosiglitazone and 250ngmL(-1) for metformin. The extraction recoveries were 100.02-105.0% for rosiglitazone and 105.64-103.88% for metformin. The method was applied with success to plasma samples obtained from diabetic patients undergoing treatment with rosiglitazone and metformin.

Change in amputation predictors in diabetic foot disease: effect of multidisciplinary approach

Diabetic foot disease causes important morbidity in diabetic population, and amputation due to diabetic foot disease occurs more often than in general population. We have been evaluating patients with diabetic foot disease in a multidisciplinary approach since year 2000. In the current study, we sought to investigate the change in amputation rate and its predictors in diabetic foot with a multidisciplinary team approach. Seventy-four patients (52 male, 22 female) hospitalised between January 2002 and December 2007 were retrospectively analysed. Sixteen out of 74 have undergone amputation. We found overall amputation rate as 21.6%, which is lower than previously reported from our institution (36.7 and 39.4%, respectively). Major amputations (syme, below-knee, above-knee) were applied to 11 patients (14.9%). A logistic regression model including osteomyelitis, peripheral neuropathy, peripheral vascular disease, hypertension, gangrene and age revealed that gangrene is now the only significant predictor for amputation. Our observations confirm that amputation rate has declined after implementation of a multidisciplinary team work, and risk factors apart from presence of gangrene are no longer amputation predictors in our centre.