THE OCCURRENCE OF SUBACUTE THYROIDITIS AFTER THE AMELIORATION OF HYPERCORTISOLISM FOLLOWING TRANSSPHENOIDAL SURGERY IN CUSHING'S DISEASE.

Only a few subacute thyroiditis (SAT) cases secondary to hypocortisolemia developed after successfully treating Cushing's disease (CD) have been reported. In this report, we present an SAT case, which developed immediately after discontinuation of steroid treatment for hypocortisolemia after the successful treatment of CD. A 54-year-old female patient who had recently been diagnosed with type 2 diabetes mellitus was admitted to our center with complaints of proximal myopathy and obesity. Serum cortisol did not suppress adequately after the 1 mg dexamethasone suppression test. Pituitary MRI of the patient with increased basal plasma ACTH level revealed a 6 x 5 mm right-sided adenoma. After successful surgical treatment, the patient was given ten months of steroid therapy due to a suppressed corticotroph axis. Shortly after the steroid treatment was discontinued, the patient was admitted with neck pain, fever, and thyrotoxicosis. The patient was diagnosed with SAT, and methylprednisolone treatment was started again. The underlying pathophysiological mechanisms in SAT cases that develop after the treatment of CD can only be speculated. One possible mechanism could be that the glucocorticoid deficiency develops after effective treatment of hypercortisolism alters the immunological responses or generates self-reactive cells and prepares an appropriate environment for the thyrolytic process.

A Rare Clinical Manifestation of Graves' Disease: Evans Syndrome and a Review of the Literature.

Evans syndrome is a rare combination of autoimmune hemolytic anemia and immune thrombocytopenia. Evans syndrome in cases of Graves' disease is extremely rare. The coexistence of these autoimmune diseases suggests that they may share a common pathogenic pathway. The case here presented is of a 36-year old female patient who was admitted for anemia and thrombocytopenia and was diagnosed with Evans syndrome associated with Graves' disease, and was then treated with methimazole and methylprednisolone (MPSL). During follow-up, MPSL was discontinued gradually over the course of two months. Interestingly, while Evans syndrome is characterized by frequent relapses, this patient has been in remission of Evans syndrome for approximately 1 year without MPSL therapy. The remission of Evans syndrome associated with Graves' disease in the absence of immunosuppressive therapy suggests that these 2 diseases have a common pathogenetic mechanism.

Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up.

OBJECTIVE: Caloric restriction (CR) is proven to be effective in increasing life span and it is well known that, nutritional habits, sleeping pattern and meal frequency have profound effects on human health. In Ramadan some Muslims fast during the day-light hours for a month, providing us a unique model of intermittent fasting (IF) in humans. In the present study, we have investigated the effects of IF versus CR on the same non-diabetic obese subjects who were followed for two years according to the growth hormone (GH)/Insulin like growth factor (IGF)-1 axis and insulin resistance. DESIGN: Single-arm Interventional Human Study. PARTICIPANTS: 23 female subjects (Body Mass Index (BMI) 29-39, aged between 28-42years). SETTING: Follow-up is designed as 12 months of CR, after which there was a month of IF and 11 months of CR again, to be totally 24 months. Subjects' daily diets were aligned as low calorie diet during CR and during the IF period, the same subjects fasted for 15 hours in a day for a month and there was no daily calorie restriction. Nutritional pattern was changed as 1 meal in the evening and a late supper before sleeping and no eating and drinking during the day light hours in the IF model. Subjects made brisk walking twice a day during the whole follow-up including both CR and IF periods. BMI, Blood glucose, insulin, TSH, GH, HbA1c, IGF-1, Homa-IR and urinary acetoacetate levels were monitored once in three months and twice in the fasting month. MEASUREMENTS AND RESULTS: While subjects lost 1250 ± 372g monthly during the CR, in the IF period, weight loss was decreased to 473 ± 146 g. BMI of all subjects decreased gradually and as the BMI decreased, glucose, HbA1c, insulin, Homa-IR and TSH levels were decreased. GH levels were at baseline at the beginning, increased in the first six months and stayed steady during the CR and IF period than began decreasing after the IF period, while IGF-I increased gradually during the CR period and beginning with the 7th day of IF period, it decreased and kept on decreasing till the end of the follow-up. Urinary acetoacetate levels were higher during the IF period suggesting a constant lipid catabolism. CONCLUSION: Our results suggest that, CR affects metabolic parameters positively which will help especially pre-diabetic and insulin resistant patients without any pharmacological approach. In addition IF without calorie restriction can enhance health and cellular resistance to disease without losing weight and those effects may be attributed to different signalling pathways and circulating ketones during IF. Changes observed during IF are probably due to the changes in eating and sleeping pattern and thus changes in metabolic rhythm.

Usefulness of the neutrophil-to-lymphocyte ratio to prediction of type 2 diabetes mellitus in morbid obesity.

BACKGROUND: There is growing consensus in the literature that inflammation plays a central role in the pathophysiology of obesity and type 2 diabetes mellitus (T2DM) and cardiovascular complications. Neutrophil-to-lymphocyte ratio (NLR) provides a simple method for assessment of inflammatory status and it is a new, inexpensive marker. The aim of the present study was to investigate the predictive value of preprocedural (before the OGTT) NLR on development of type 2 diabetes (T2DM) in morbid obesity patients (MOP). METHODS: 306 MOP (body mass index ≥ 40 kg/m(2)) and 95 normal weight patients with normal OGTT [fasting plasma glucose (FPG)<100mg/dL. Two-hour glucose during OGTT<140 mg/dL] were evaluated in this study. RESULTS: The mean ± SD NLR of MOP was significantly higher than that of patients with normal weight healthy patients (3.67 ± 0.95 vs. 1.82 ± 1.02, P<0.001, respectively). In receiver operating characteristics curve analysis, NLR>3.12 had 79.2% sensitivity and 64.9% specificity in predicting T2DM. Logistic regression analysis showed that elevated NLR (OR: 2.577, 95% CI: 1.363-4.872, P=0.004) was an independent variable for predicting T2DM in MOP. CONCLUSIONS: MOP have higher NLR than healthy controls. High NLR is a powerful and independent predictor of T2DM in MOP. Elevated NLR levels are usually considered as an inflammatory marker. The results of this study suggested that inflammation plays a role in the pathogenesis of T2DM with MOP.

Serum nesfatin-1 levels in overt and subclinical hyperthyroidism.

AIM: Nesfatin-1 was recently discovered anorexigenic peptide in the brain which is derived from nucleobindin-2. Central and peripheral administration of nesfatin-1, inhibits food intake, dose-dependently. Hyperthyroid patients have increased appetite and food intake with a craving for carbohydrate-rich food, at the beginning of disease, but the physiological mechanisms underlying this behavior is not known exactly. In this study, we investigated whether nesfatin-1 is involved in the regulation of appetite and body weight in hyperthyroidism, or not. METHODS: A total of 70 patients with subclinical (35) and overt hyperthyroidism (35) compared with 35 control patients. Serum nesfatin-1 level was measured from all samples by commercial ELISA kit. RESULTS: Serum nesfatin-1 levels were similar between three groups (P=0.293). After adjusting for age and body mass index, nesfatin-1 levels in control group was not different from subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.519). CONCLUSION: These data showed that serum nesfatin-1 levels do not significant change in overt and subclinical hyperthyroidism.

Cardiovascular risk factors, carotid artery intima media thickness, and HSCRP levels in patients with impaired glucose metabolism.

AIM: The aim of this paper was to compare serum high sensitivity C-reactive protein (HsCRP) levels and carotid artery intima-media thickness (CIMT) of patients with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) with that in control subjects. METHODS: Ninety-six subjects with prediabetes, 48 with IFG, of mean age 50.7±11.3 years, and 48 with IGT, of mean age 50.9±12.3 years, were enrolled, along with 44 age-, sex-, and body mass index-matched controls with normal glucose tolerance. Serum HsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) was evaluated. High-resolution B-mode ultrasonography was performed. RESULTS: Serum HsCRP levels were significantly elevated in pre-diabetic patients when compared with that of control subjects. Median HsCRP values were 3.1 mg/L in IFG group, 3.47 mg/L in IGT group, and 1.5 mg/L in the controls (P<0.001). CIMT was significantly higher in pre-diabetic groups than that in the control group (IFG: 0.612±0.09; IGT: 0.625±0.1; control: 0.517±0.09, P<0.001). CIMT and HsCRP levels were similar in pre-diabetic groups. CIMT values were positively correlated with HsCRP (r=0.793, P=0.000), age (r=0.435, P=0.000), waist-hip ratio (r=0.170, P=0.044), fasting plasma glucose (r=0.302, P=0.000), HOMA-IR (r=0.173, P=0.041), and low-density lipoprotein cholesterol (r=0.168, P=0.047) levels. CONCLUSION: Both IFG and IGT were associated with increased cardiovascular risk as assessed by serum hsCRP levels and CIMT. In contrast to previous studies, risk appears to be the same in the two categories of prediabetes.

Isolated interrupted inferior vena cava with azygos continuation mimicking paraesophageal lymph node enlargement.

We report a case of interrupted inferior vena cava with azygos continuation diagnosed as a isolated finding in a patient with lung carcinoma. Findings of the unopacified CT scan initially simulated a paraesophageal lymphadenopathy. The contrast-enhanced spiral CT scan showed a dilated azygos vein in the absence of definable inferior vena cava.

Predicting chronic leukaemias from assessment of complete peripheral blood counts.

The chronic leukaemias include two distinct chronic neoplastic disease states, namely chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL). The aim of this study was to assess the utility of leucocyte count, neutrophil percentage and absolute lymphocyte count from differential complete blood count analyses as indicators of the possible presence of CML and CLL. Blood counts from 102 patients with histopathologically confirmed CML and CLL were compared with counts for 858 cancer-free control subjects. Optimal cut-off values were identified by selecting values with the highest sensitivity-specificity combination for each blood count parameter for the two diseases. The results indicated that any individual with mature-appearing lymphocytes at a level > 6.65 x 10(9)/l in the peripheral blood should be examined further for CLL, and that any individual with a leucocyte count > 18.0 x 10(9)/l or a neutrophil proportion > 72.6% should be investigated for CML.

Basal cell adenoma of prostate.

A case of basal cell adenoma of the prostate accompanying benign prostatic hypertrophy is presented. This is an uncommon, benign lesion which is usually mistaken for a carcinoma. In order to emphasize the importance of differential diagnose and to better define this entity, we present a case report.

Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis.

BACKGROUND: Recent studies of the role of bacteria in chronic bronchitis have shown that bacterial colonisation is associated with enhanced inflammation and that purulent acute exacerbations of chronic bronchitis (AECB) are associated with bacteria and characterised by increased inflammation. Changes in bronchial inflammation in response to the success or failure of bacterial eradication following AECB were therefore studied. METHODS: Bacterial quantitative culture and sputum markers of inflammation (myeloperoxidase (MPO), neutrophil elastase, leukotriene B4 (LTB4), sol:serum albumin ratio, and secretory leukoprotease inhibitor) were measured in patients presenting with culture positive purulent AECB and repeated 10 days and 2 months later. 41 patients provided sputum sufficient for both bacteriology and assessment of inflammation at baseline and day 10, and 46 provided sufficient sample for bacteriology, 40 of which could also be analysed for inflammation at 2 months (when clinically stable). RESULTS: At day 10, 17 of the 41 patient samples had a positive bacterial culture. In the stable state, 18 of the 46 samples had a positive culture, but with a significantly lower bacterial load than at presentation. Although there was no difference between the groups at presentation, the concentration of MPO was lower (p<0.05) in those in whom bacteria were eradicated by day 10 than in those with persisting bacteria. The LTB4 concentration was similarly lower (p<0.001) in those in whom bacteria were eradicated than in those with persistent bacteria. In the stable clinical state the concentrations of both MPO and LTB4 were lower in those in whom bacteria were eradicated than in patients with persisting bacteria. CONCLUSION: Resolution of bronchial inflammation following AECB is related to bacterial eradication. Those in whom bacteria continue to be cultured in their sputum have partial resolution of inflammation which may reflect continued stimulation by the reduced bacterial load.

Detection of inflammatory lymph nodes in rabbits by 99mTc-HIG lymphoscintigraphy.

Tc-Human immunoglobulin G ( Tc-HIG) is a well-known radiopharmaceutical for the evaluation of inflammatory lesions. Recently, it has been demonstrated as a new agent for the visualization of the lymphatic system by our group. Our aim was to investigate the feasibility of detection of inflammatory lymph nodes by Tc-HIG lymphoscintigraphy. Ten adult New Zealand rabbits were used as group A. In a baseline study, 37 MBq Tc-HIG (0.1 ml) was injected into both hind legs of the rabbits, and sequential posterior gamma imaging with the rabbits lying prone was performed at 5, 15, 30, 60, 90 and 120 min using a single-headed gamma camera (Toshiba GCA G01 E). One week later, microorganisms ( ) were injected in a volume of 0.1 ml intradermally into the web space between the second and third toes in the bilateral hind legs of each rabbit in order to obtain inflammation in the popliteal lymph nodes. After 4 days, 37 MBq Tc-HIG (0.1 ml) was injected into the hind legs of the rabbits bilaterally, and sequential posterior gamma imaging was performed as described above (second study). Another group of 10 adult New Zealand rabbits (group B) was injected with the same microorganisms in the right hind legs only. After 4 days, scintigraphic imaging was carried out in the same way as described above (third study). Regions of interest were drawn over the injection sites and popliteal lymph nodes on each image for semiquantitative analysis. Count rates for each were calculated and a decay correction was applied. Time-activity curves were generated to show the percentage retention of radioactivity in each region. After the scintigraphic study, some of the group B rabbits were killed by intravenous injection of pentobarbitone (100-150 mg.kg, and both left and right lymph nodes were removed for microscopic examination. On the scintigrams, lymphatic channels and popliteal lymph nodes were visualized within 15 min. In the second study, bilateral popliteal lymph nodes were visualized more clearly than in the baseline study. The right popliteal lymph nodes of the rabbits were more clearly visualized in the third study. Semiquantitative analysis showed a higher percentage uptake of radioactivity in the right compared to the left popliteal lymph nodes in group B rabbits. Microscopic examination of the tissue sections demonstrated inflammation in the right lymph nodes of group B rabbits. In this preliminary study, it was found that Tc-HIG is a new promising agent for the demonstration and evaluation of inflammatory lymph nodes.

Elevated levels of nitrate in rheumatoid arthritis.

Nitric oxide (NO) is a free radical that plays important roles in many physiological and pathological processes. Evidence suggests that NO participates in the pathogenesis of inflammatory reactions in many autoimmune and inflammatory diseases such as rheumatoid arthritis (RA). The purpose of this study was to evaluate serum concentrations of NO in patients with RA and to determine whether they correlate with clinical and laboratory parameters of RA disease activity. Twenty-seven RA patients were recruited for the study and compared with 20 healthy subjects. Serum NO concentrations were measured indirectly in terms of nitrate using colorimetric assay. Disease activity was determined by laboratory and clinical findings. Mean serum concentrations of nitrate were significantly higher than those of healthy controls (P < 0.05). Among the disease activity parameters, C-reactive protein, number of swollen and tender joints, Ritchie articular index, and disease activity scores correlated significantly with serum NO levels. Our results suggest that these levels can serve as a reliable parameter of disease activity in patients with RA. Further knowledge about the precise role of NO may lead to better understanding of the pathogenesis of RA. Furthermore, modulation of NO synthesis may represent a new approach to the treatment of inflammatory and autoimmune conditions.

Systemic glucocorticoids in severe exacerbations of COPD.

OBJECTIVE: This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure. DESIGN: Prospective, randomized, single-blind study. SETTING: Tertiary-care center. PATIENTS AND METHODS: Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study. RESULTS: Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group. CONCLUSION: In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates.

Morbidity of flank incision in 100 renal donors.

OBJECTIVE: The purpose of this study is to determine the morbidity of lumbotomy incision used in the last 100 living related donor nephrectomies retrospectively. METHODS: Since March 1991, 100 donor nephrectomies were made to living donors with lumbar incision. Incisions made in lateral decubitus position, subcostally or by an 11th or 12th rib resection. Left nephrectomy to 83, and right nephrectomy to 17 donors was performed. In 2 patients, there had been a peritoneal defect which was closed with primary sutures. In 19 patients 3 cm or shorter and in 5 patients longer than 3 cm of pleural entry had occurred. In all of the patients laceration was repaired without placement of a chest tube, however a chest tube had to be placed in 2 donors after obtaining a control chest x-ray postoperatively. RESULTS: All the patients mobilized and began to take orally in the first post-operative day. Wound infection, pneumonia and deep vein thrombosis had detected in none of the patients. The patients were discharged on the 4th and 5th postoperative day. During their control after 1 month from the operation it was found that all of them had returned to their daily life. In the postoperative period incisional hernia occurred in 7 patients which didn't need surgical repair and none of them complained of cosmetic problem. There was no any other late term complication was seen due to flank incision. CONCLUSION: Lumbotomy incision in donor nephrectomy, either a rib resection or supracostal approach, is reliable, provides excellent exposure for surgeon and has minimal morbidity.

Evaluation of 99mTc labelled poly lactic acid microspheres for diagnostic radioembolization.

Radioembolization is used in diagnostic imaging of the lungs and for radioembolization therapy of hepatic tumours. Presently, 99mTc labelled macroaggregates or microspheres of human serum albumin (HAM) are used for this purpose. Poly lactic acid (PLA) is biodegradable, like HAM, and, unlike HAM, is not a blood product. The aim of the present study was to evaluate the uptake and biodegradation of PLA microspheres in lungs. PLA (MW = 48720 Da) microspheres of 1.0-100 microm (mean = 39.5 microm) in diameter were prepared by solvent evaporation from methylene chloride. They were labelled with 99mTc by stannous chloride reduction at pH 3, with an efficiency of 98% and a stability of 96% at 24 h. For biodistribution studies, 15 mice were i.v. injected with 20 microCi 99mTc-PLA microspheres in 0.1 ml and sacrificed at 15 min, 1, 3, 6 and 24 h (three at each time point). All the organs were removed, weighed and counted against a standard prepared from 1/100 dilution of the injected radioactivity. Some mice were similarly injected and sacrificed at 30 min, 15 and 30 days. The lungs were removed and frozen, and 10 microm sections were obtained, stained with haemotoxylin and eosin and examined under a light microscope. Five rabbits were i.v. injected with 1 mCi of 99mTc-PLA microspheres. Scintigrams were obtained at various intervals up to 24 h. In mice, the lung uptake was significant at 30 min-1h post-injection. In rabbits, the lungs were the only organs visualized up to 24 h. Microscopic examination of tissue sections demonstrated slow biodegradation of PLA particles. In conclusion; (1) The high lung uptake obtained in mice and rabbits indicates the suitability of PLA microspheres for lung imaging, and (2) although the slow biodegradation rate might be a disadvantage in patients with lung disorders in diagnostic studies, it may be an advantage in therapeutic applications with radionuclides which have long physical half lives.

Mixed anxiety-depressive disorder and major depressive disorder: comparison of the severity of illness and biological variables.

Mixed anxiety-depressive disorder (MADD) is a new diagnostic category defining patients who suffer from both anxiety and depressive symptoms of limited and equal intensity accompanied by at least some autonomic features. Patients do not meet the criteria for specific anxiety or depressive disorders. The emergence of the symptoms is independent of stressful life events. There are many issues presently under investigation about the validity of this clinical entity. In this study, a group of 29 patients with MADD was compared with a group of 31 patients with major depressive disorder (MDD) to assess the differences and similarities between these two disease categories in terms of severity measures and biological variables. The dexamethasone suppression test (DST) was employed, and thyroid hormones and thyrotropin (TSH) levels were measured for the evaluation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes, respectively. The patients with MADD were found to be less depressive and more anxious compared to those with MDD. DST responses and thyroid functions were found to be similar in the two groups. When severity of depression was controlled, k(max) and 2300-h cortisol values were found to be significantly higher in the MADD group. Although the patients with MDD and MADD presented with relatively different clinical features, there is not enough biological evidence indicating that MADD represents a discrete diagnostic category. However, there may be relatively higher HPA activity in MADD patients.

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: importance of ACE polymorphism.

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

Relationship between endogenous sex hormone levels, lipoproteins and coronary atherosclerosis in men undergoing coronary angiography.

This study was carried out in order to investigate the relationship between endogenous sex steroid hormones and coronary artery disease (CAD). Three hundred and thirty-seven men undergoing coronary angiography were enrolled in the study. Total testosterone, estradiol, free testosterone levels in men with CAD (n = 213) were compared to those of men without CAD (n = 124). No significant differences were found in the serum concentrations of estradiol, total and free testosterone and serum lipid profile between the two groups. Total and free testosterone were negatively (p < 0.05 to p < 0.001) and estradiol was positively (p < 0.05) correlated with age in both groups. Total cholesterol and low-density-lipoprotein levels were positively correlated with the level of free testosterone (r = 0.221, p < 0.01; r = 0.173, p < 0.05, respectively), and high-density-lipoprotein levels were negatively correlated with total testosterone in patients with CAD (r = -0.166, p < 0.05). The results of this study do not support the role of sex steroid hormones in CAD. However, the relationship between sex steroids and serum lipids needs further clarification.