THE USE OF LOW DOSE PREDNISOLONE IN PATIENTS WITH SUBACUTE THYROIDITIS AND ITS EFFECT ON IMPAIRED LIFE AND SLEEP QUALITY.

Context: Subacute thyroiditis is an inflammatory thyroid disease, which is treated by nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. Objective: Defining characteristics of patients with subacute thyroiditis at diagnosis and during follow-up. Investigating the efficacies of NSAID and different doses of steroids and their effects on rates of relapse, recurrence, development of hypothyroidism and on quality of life and sleep parameters. Design: A 3-year observational study in a tertiary referral center. Subjects and Methods: A total of 63 patients with subacute thyroiditis were included. Clinical outcomes of patients treated with NSAIDs and NSAID unresponsive patients treated with prednisolone with initial doses of 0.5 mg/kg/day and 15 mg/day were evaluated. Results: White blood cell count at diagnosis was an independent predictor of NSAID unresponsiveness. No relapse or recurrence was observed in patients receiving low dose of steroids. Long symptom duration until diagnosis and treatment with NSAIDs were associated with development of hypothyroidism. Subacute thyroiditis caused significant deterioration in quality of life and sleep of patients and low dose of steroid was as effective as higher doses in improving these parameters. Conclusions: For patients with no response to NSAID therapy, an initial low dose of prednisolone (15 mg/day) is determined as a safe treatment method when dose reduction is performed with appropriate timing.

ASSOCIATION BETWEEN HASHIMOTO'S THYROIDITIS AND PAPILLARY THYROID CANCER: A SINGLE CENTER EXPERIENCE.

Purpose: To investigate the association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT). Design: This study is a retrospective study that conducted during 7 consecutive years with a median 119.5 months follow-up. Subjects and Method: Patients who underwent thyroidectomy in Dokuz Eylül University Hospital during 7 consecutive years were included. Patients' demographics, biochemical, radiological, and pathological results were retrospectively assessed. Results: Four hundred sixty nine patients were evaluated. Among 469 patients who underwent thyroidectomy, 132 (28.1%) were malignant, while 182 patients were diagnosed with HT (38.8%). PTC was ranked first at 92.4% (n: 122). The prevalence of HT was 54.9% in patients with PTC and 33.1% in patients without PTC diagnosis (p<0.001). Younger age and the presence of HT were independently associated with PTC. The presence of HT was associated with increased risk of development of PTC (OR: 2.2, %95 CI: 1.4-3.5, p<0.001) but not with TNM stage or recurrence. Lymph node metastasis at presentation was the strongest predictor of recurrence (OR: 13.9, CI: 3.5-54.6, p<0.001). Conclusions: HT was an independent risk factor for development of PTC. According to our findings, HT patients (particularly with nodular HT) should be observed carefully and thyroid fine needle aspiration biopsy (TFNAB) should be encouraged if necessary.

NIVOLUMAB ASSOCIATED ENDOCRINE ABNORMALITIES: CHALLENGING CASES FROM A REFERENCE CLINIC.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results: We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion: Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Is there an association between non-functioning adrenal adenoma and endothelial dysfunction?

BACKGROUND AND AIM: Subtle changes in hypothalamic- pituitary-adrenal (HPA) axis of subjects with nonfunctioning adrenal adenoma may be associated with endothelial alterations. We sought to investigate endothelial function, visceral adiposity and osteoprotegerin (OPG) and interleukin- 18 (IL-18) levels in subjects with non-functioning adrenal adenomas. SUBJECTS AND METHODS: The adenoma group included 40 subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders. Twenty-two body mass index-matched controls were also enroled. The patients and control subjects underwent hormonal evaluation and assessment of anthropometric and metabolic parameters. Endothelial function was assessed with flowmediated dilatation (FMD) of the brachial artery and intima media thickness (IMT) of common carotid arteries. Visceral adipose tissue area was measured by computed tomography. Plasma OPG and serum IL-18 levels were also measured. RESULTS: When compared with healthy controls, the adenoma group had elevated systolic blood pressure, post-dexamethasone suppression test cortisol and reduced DHEAS. Visceral adipose tissue area and IMT of common carotid arteries were comparable. In the adenoma group, FMD of the brachial artery was significantly impaired and IL-18 level was significantly elevated. Visceral adipose tissue area was independently related with FMD. Homeostasis model assessment (HOMA) was the independent factor associated with visceral adipose tissue area. Cortisol, DHEAS and visceral adipose tissue area were independently associated with HOMA. CONCLUSIONS: We achieved evidence that could be attributable to endothelial alterations in subjects with non-functioning adrenal adenomas. Impaired FMD appeared to be a consequence of subtle changes in HPA axis in terms of elevated cortisol and reduced DHEAS as these conditions were known to disturb endothelial-dependent vasodilatation.

Prospective evaluation of tumor size and hormonal status in adrenal incidentalomas.

BACKGROUND: Because of the increased use of imaging interventions, more subjects have been diagnosed with adrenal incidentaloma in recent years. AIM: To evaluate the risk of mass enlargement, hormone hypersecretion and development of adrenal carcinomas during short-term followup. SUBJECTS AND METHODS: There were 317 subjects with incidentally discovered adrenal tumors in the registry. Forty subjects were excluded because of clinically overt hormone secretion at diagnosis and subjects with complete data were included in radiological (no.=150) and hormonal (no.=150) follow- up. Radiological evaluation was performed with computed tomography (CT) and/or magnetic resonance imaging (MRI). There were 143 subjects with adrenal adenomas and 7 subjects with other tumor types (cyst or myelolipoma). Median follow-up duration was 24 months. RESULTS: Increase in tumor size was detected in 25 subjects (17.4%) with adenomas and 1 subject with adrenal myelolipoma (14.3%). Decrease in tumor size was found in 7 subjects (4.8%) with adrenal adenomas. One patient was diagnosed with adrenocortical carcinoma during follow-up. In subjects with non-functioning adrenal adenoma (NFA, no.=120) or subclinical Cushing syndrome (sCS) (no.=30), no subject developed clinically overt hormone hypersecretion, while 8 (6%) subjects in the NFA group developed sCS. Tumor diameter and follow-up duration were significantly higher in subjects who developed sCS. CONCLUSION: In conclusion, we demonstrated that, despite being infrequent, adrenal tumors may increase in size, develop overt or subclinical hormone secretion or feature malignant transformation. Therefore, radiological and hormonal follow-up should be recommended to the patients. More investigations are needed for the establishment of long-term follow-up protocols.

Primary thyroid lymphoma: case series with literature review.

Non Hodgkin's lymphomas (NHL) of the thyroid are rare thyroid neoplasms. The majority of histopathologic types are extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and, diffuse large B-cell lymphoma (DLBCL). Most of them arise in a background of Hashimoto's thyroiditis and patients mostly present with a rapidly enlarging thyroid mass and with pressure symptoms. Treatment depends on the histological subtype and stage of the disease and includes radiotherapy and chemotherapy. The prognosis usually is favorable with proper treatment. Herein, we discuss the clinical diagnosis and treatment of thyroid lymphoma.

Non-functioning adrenal incidentalomas are associated with elevated D-dimer levels.

AIM: Although the majority of adrenal incidentalomas (AI) are non-functioning, studies evaluating metabolic disturbances in this particular group are limited. The objective of this study is to investigate metabolic syndrome components and levels of plasma von Willebrand factor (VWF), fibrinogen, and D-dimer in subjects with non-functioning AI. SUBJECTS AND METHODS: Forty-five subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders and 37 healthy controls were enrolled. The patients and controls underwent hormonal evaluation including morning cortisol, ACTH, post-dexamethasone suppression test (DST), morning cortisol, DHEAS, and urinary free cortisol. Anthropometric and metabolic parameters and body composition were assessed and fibrinogen, D-dimer, and VWF were measured. RESULTS: When compared with healthy controls, subjects with AI had significant elevations in several metabolic and anthropometric parameters, uric acid, post-DST cortisol, and D-dimer. When compared with body mass index-matched controls, blood pressure (p=0.004), uric acid (p=0.009), post-DST cortisol (p=0.014), and D-dimer (p=0.045) remained significantly elevated. We demonstrated weak correlations between D-dimer and other metabolic and anthropometric variables. Morning cortisol was demonstrated as an independent variable associated with homeostasis model assessment levels in subjects with AI (beta=410, p=0.004). CONCLUSION: Individuals with clinically and hormonally inactive adrenal adenomas feature insulin resistance and a variety of metabolic disturbances. The subtle cortisol autonomy seems to be associated with insulin-resistant state. D-dimer elevation in AI group was a consequence of insulin-resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol secretion.

Reduction of major amputations after starting a multidisciplinary diabetic foot care team: single centre experience from Turkey.

INTRODUCTION: It is widely recognized that a multidisciplinary team is effective in the management of diabetic foot ulcers. Contrary to developed countries, multidisciplinary diabetic foot care teams and/or clinics have not been constructed in most centres in developing countries. The aim of this study was to present our data regarding amputation rates and profiles before and after starting the Dokuz Eylul University multidisciplinary diabetic foot care team. METHODS: This study includes data from diabetic foot ulcer episodes which were managed in Dokuz Eylul University Hospital between January 1999 and January 2008. The data was collected prospectively during a minimum follow-up of 6 months in all ulcers. After January 2002, management of ulcers was coordinated by the diabetic foot care team (n=437). Amputation rates were compared to those who were admitted before January 2002 (n=137). RESULTS: Overall amputation and minor amputation rates were similar for both periods. However, major amputations were observed to be decreased after starting the Dokuz Eylul University multidisciplinary diabetic foot care team (20.4% vs. 12.6%, p=0.026). CONCLUSIONS: Our results demonstrated that major amputation rates can be reduced by team work. Formation of multidisciplinary diabetic foot care teams and clinics should be encouraged in Turkey.

Hypercalcemia of primary hyperparathyroidism was treated by cinacalcet in a patient with liver cirrhosis.

Cinacalcet is a type II calcimimetic agent which is an allosteric modulator of the calcium-sensing receptor (CaR) located on the surface of the parathyroid cells. Cinacalcet increases the sensitivity of CaR via binding to the transmembrane region of CaR. Increasing sensitivity of CaR causes reduced secretion of parathyroid hormone (PTH) and suppression of serum calcium levels. Cinacalcet has recently been approved by Federal Drug Administration (FDA) for the treatment of patients with secondary hyperparathyroidism on maintenance dialysis and hypercalcemia in patients with parathyroid cancer. It is used also in Europe for both indications. Several controlled studies have shown that cinacalcet is effective in normalizing serum calcium levels also in primary hyperparathyroidism. Cinacalcet is metabolized primarily in the liver by N-dealkylation leading to carboxylic acid and oxidation of naphthalene ring to form dihydrodiols. The safety and optimal dosage of the drug in hypercalcemic patients with liver impairment remains unclear. We present a patient with Child-Pugh B class primary biliary cirrhosis who presented with moderate hypercalcemia and was diagnosed as primary hyperparathyroidism. As she refused having parathyroid surgery for her parathyroid adenoma at first, her hypercalcemia was treated successfully with 30 mg/day cinacalcet for 6 months. Cinacalcet was discontinued after 6 months. Her calcium level increased gradually. As she accepted surgery this time, her parathyroid adenoma was removed by minimally invasive parathyroidectomy. Parathyroid adenoma was confirmed pathologically. Her calcium levels maintained within the normal ranges after surgery.

Low transforming growth factor-beta1 serum levels in idiopathic male osteoporosis.

INTRODUCTION: Although the etiology of osteoporosis is different between men and women, the underlying pathophysiological mechanism is similar, namely an absolute or relative increase in bone resorption, leading to progressive bone loss. Transforming growth factor (TGF)-beta1 is a growth factor in human bone, which is produced by osteoblasts, and which has various effects on osteoclasts and osteoblasts. The aim of our study was to determine serum TGF-beta1 levels in male patients with idiopathic osteoporosis. METHODS: Twenty five males with idiopathic osteoporosis and 25 age-matched controls were studied. Osteoporosis was defined by a T score of <-2.5 in the lumbar spine or at the femoral neck. We measured levels of TGF-beta1, estradiol, total and bioactive testosterone. Various markers of bone remodeling were also measured. RESULTS: TGF-beta1 was significantly lower in osteoporotic patients than in controls (3.706 ng/dl, 25-75 percentiles: 2.81-5.33 vs 8.659 ng/dl, 25-75 percentiles: 4.837-11.835; p=0.000). Moreover, TGF-beta1 levels were positively correlated with bone mineral density (BMD) at the femoral neck (r=0.439, p=0.028), and at the lumbar spine (r=0.41, p=0.042). No correlation was found between serum estradiol, testosterone and TGF-beta1 levels. DISCUSSION: Serum TGF-beta1 levels are depressed in osteoporotic men and are positively correlated with hip and spine BMD. The results of our study suggest that TGF-beta1 may play a role in the pathogenesis of idiopathic male osteoporosis.

The combined use of brachial artery flow-mediated dilatation and carotid artery intima-media thickness measurements may be a method to determine vasculogenic erectile dysfunction.

The aim of this study was to investigate the relationship between penile color Doppler sonography (CDS) findings and sonographic endothelial parameters in patients with erectile dysfunction (ED), including intima-media thickness (IMT) of common carotid arteries (CCA) and flow-mediated dilatation (FMD) of brachial artery. Fifty-six ED patients were included in the study. Penile CDS, IMT of CCA and FMD of brachial artery were performed in all patients. According to penile CDS findings, 27 (48%) patients had non-vasculogenic and 29 (52%) patients had vasculogenic ED. Among 29 patients, 17 (30%) patients had cavernous veno-occlusive disease (CVOD) and 12 (22%) patients had arterial/combined insufficiency (AI). Median (interquartile range) FMD values of non-vasculogenic ED, CVOD and AI were 12.50 (6.54)%, 12.82 (7.41)% and 6.25 (7.17)%, respectively. FMD was found to be impaired significantly in AI group when compared to the other groups. FMD values of CVOD group were lower when compared to non-vasculogenic group, but the difference was not statistically significant. IMT values of vasculogenic ED patients were higher than non-vasculogenic ED patients (P<0.05). Although IMT values were higher in AI group when compared to CVOD, the difference was not statistically significant. The combined use of IMT and FMD established the diagnosis of vasculogenic ED with 100% sensitivity and 59.2% specificity. The positive predictive value was 72%, negative predictive value 100% and accuracy 80%. The combined use of brachial artery FMD and carotid arteries IMT measurements may be suggested as an alternative method to evaluate vasculogenic ED.

Cushing's syndrome due to ectopic CRH secretion by adrenal pheochromocytoma accompanied by renal infarction.

Ectopic production of corticotropin-releasing hormone (CRH) by a pheochromocytoma is an infrequent cause of Cushing's syndrome. We report the case of a 43-year-old man with Cushing's syndrome due to a CRH-producing adrenal pheochromocytoma. The patient had clinical and biochemical evidence of hypercortisolism in conjunction with high ACTH levels and non-suppressible serum cortisol levels on low-dose and high-dose dexamethasone suppression testing. In addition to these clinical features of one month's duration, the patient developed symptoms of pheochromocytoma including headache, hypertension that was resistant to conventional therapy and excessive sweating. Biochemical testing confirmed elevated 24-hour urinary catecholamines and metabolites. Abdominal CT revealed a 4.5 x 4 x 3.5 cm mass in the left adrenal gland. He underwent elective left adrenalectomy. Light microscopic and immunochemical studies revealed a pheochromocytoma that contained immunoreactive CRH and was negative for ACTH. Plasma ACTH and dexamethasone supression tests normalized after surgery. This is an unusual case of a CRH-secreting pheochromocytoma. This was complicated by renal infarction, illustrating further the complexity of Cushing's syndrome in a patient with pheochromocytoma caused by CRH hypersecretion.

Comparison of leptin levels in serum and follicular fluid during the oestrous cycle in cows.

Leptin is mainly synthesised in white adipose tissue. Besides its effects on body weight and metabolic homeostasis, leptin also has effects on puberty, sexual maturation and reproduction. In this study the relationship between leptin, IGF-1, oestradiol (E2) and progesterone levels were investigated in serum and follicular fluid from cows. This study included 72 healthy, Brown Swiss cows aged 4-5 years. Samples from the jugular vein and follicular fluids were collected. Phases of the oestrus cycle of cows were classified according to their serum progesterone levels (< 3.18 nmol/l, follicular phase and the others as luteal phase). Follicles were grouped as large (> or = 8 mm) or small (< 8 mm). Leptin, IGF-1, oestradiol and progesterone levels were measured from serum and follicular fluid. Leptin concentrations were found to be significantly higher in luteal-phase follicular fluid of small follicles (P < 0.05). These were classified as atretic follicles. There was a positive correlation between serum and follicular fluid leptin levels in the luteal phase. Serum leptin was found to have a positive correlation with follicular fluid progesterone level (P = 0.01) in the preovulatory follicles. The present study shows that there is a relationship between the concentration of leptin in follicular fluid and atresia in small follicles.

Ret proto-oncogene mutations in apparently sporadic Turkish medullary thyroid carcinoma patients: Turkmen study.

OBJECTIVE: Medullary thyroid carcinoma (MTC) frequently occurs in a sporadic form, but a substantial number of cases are hereditary and appear as part of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Germline mutations in ret proto-oncogene have been shown to be the underlying cause of MEN2 syndromes. DESIGN: We carried out a multi-center study that aimed to perform mutational analysis of so called sporadic MTC patients. METHODS: Fifty-six MTC patients verified by histopathologic examination were subjected to genetic analysis. Exon 10, 11, 13, 14, 15 and 16 of the ret gene were analyzed by DNA sequencing and restriction enzyme digestion method. RESULTS: Among 56 apparently sporadic MTC patients, we identified 6 (10.7%) ret germline mutation carriers. Three individuals carried mutations at codon 634 in exon 11, one at codon 618 in exon 10, and two at codon 804 in exon 14. Identification of the predisposition gene mutation has allowed DNA-based strategy for direct mutation detection in patients with apparently sporadic MTCs. A substantial number of patients with apparently sporadic MTC carried germline mutations and 50% of their first degree relatives are expected to have or to develop MTC and/or other endocrine tumors. CONCLUSIONS: These results indicate the importance of careful genetic surveillance of any patient with apparently sporadic MTCs.

A case of recurrent pancreatitis due to hyperlipidemia misdiagnosed as familial Mediterranean fever.

Familial Mediterranean fever (FMF) is prevalent among Arabic, Turkish, Armenian, and Jewish people and it must always be considered in the differential diagnosis of patients from these ethnic groups presenting with recurrent abdominal pain with fever. In cases of fever and recurrent abdominal pain, acute pancreatitis is an important clinical condition, which should be considered in the differential diagnosis. Serum amylase concentration in acute pancreatitis is usually more than three times the upper limit of normal. However, in recurrent pancreatitis secondary to hypertriglyceridemia, serum amylase levels, for reasons that are not well understood, may be normal or mildly elevated. Recurrent pancreatitis secondary to hypertriglyceridemia may thus pose a problem in the differential diagnosis and may lead to an erroneous diagnosis of FMF. Measurement of serum triglyceride along with amylase levels should be required for a suspected diagnosis. Computerized examination of the abdomen may need to be undertaken to exclude acute pancreatitis in the presence of hypertriglyceridemia since serum amylase levels may be normal or slightly elevated.

Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis.

BACKGROUND: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. METHODS: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. RESULTS: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. CONCLUSIONS: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.

Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin.

Pleural effusion is a common diagnostic problem. The analysis of serum and body fluids for tumor markers has been intensively applied to clinical diagnosis. The aim of the present study was to determine the usefulness of simultaneous quantification of carbohydrate antigen 19.9, carbohydrate antigen 125, neuron specific enolase, mucinous-carcinoma-associated antigen, and ferritin in samples of pleural fluids in the malign pleural effusion and its differentiation from benign effusions. A total of 61 pleural effusions were collected from the patients, who were subjected either to simple needle aspiration or to tube drainage for the diagnosis of pleural effusion. Tumor markers were determined in benign patient groups with nonspecific pleurisy, tuberculous pleurisy, empyema, congestive heart failure and in malignancy groups consisting of adenocarcinoma, small cell lung carcinoma, mesothelioma, epidermoid lung cancer. The tumor markers CA-19.9, CA-125, NSE, and ferritin levels were quantified by the sandwich assay using the streptavidin technology of ELISA in an ES-300 Boehringer-Mannheim analyser. MCA was measured by employing a two-side solid phase EIA method. MCA measurements were done by the Cobas-Core. For all patients, the effusions correctly or incorrectly identified by the different procedures as being malignant or nonmalignant are defined as true positive, false positive, true negative, and false negative, the term 'positive' referring to histologically proven malignant pleural effusion while nonmalignant effusions are referred to as 'negative'. Therefore, sensitivity, specificity, positive predictive value, and negative predictive value were defined as diagnostic parameters. The cut-off values calculated were 352 U/ml for CA-125, 54 U/ml for CA-19.9, 555 for ferritin, 11.1 for MCA and 8.7 for NSE. In our study, the highest sensitivity is found to be MCA with 100%; specificity, CA-19.9 with 97%; PPV, CA-19.9 and MCA with 95% and NPV, MCA with 100%. Our data imply that the co-measurement of MCA+CA-19.9+CA-125 levels may further improve their diagnostic value in malignant pleural effusion compared with that of each tumour marker alone and may be useful in distinguishing malignant from benign pleural effusions.

Serum concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in patients with chronic hepatitis.

BACKGROUND: Insulin-like growth factor-I is a liver-derived humoral factor, which has important anabolic and metabolic actions and is predominantly bound by insulin-like growth factor binding protein-3. Low serum concentrations of both insulin-like growth factor-I and insulin-like growth factor binding protein-3 have been reported in patients with chronic liver disease, especially cirrhosis, but their conditions in chronic hepatitis are uncertain. The aim of this study was to evaluate the effect of chronic hepatitis on serum concentrations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 and their association with hepatic inflammation activity and fibrosis. METHODS: Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 were measured by RIA (ng/ml) in 17 patients with mild to severe chronic viral hepatitis (12 chronic hepatitis C, 5 chronic hepatitis B) and 16 healthy subjects. The hepatic inflammation activity and the severity of fibrosis were evaluated using Desmet classification. RESULTS: Both insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels did not correlate with inflammation activity, fibrosis or transaminase levels. In the chronic hepatitis group, insulin-like growth factor-I levels were significantly higher than the control group (mean, 263.8 +/- 27.33 versus 127.14 +/- 10.83 ng/ml, P < 0.001, respectively), whereas insulin-like growth factor binding protein-3 levels were significantly lower when compared with the controls (1643.47 +/- 60.68 versus 2728.87 +/- 284.61 ng/ml, P < 0.05, respectively). CONCLUSIONS: These results suggest that the concomitant states of serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in patients with chronic hepatitis may be different from cirrhotic patients and high serum IGF-I levels may be a specific finding of the stage of chronic hepatitis before developing cirrhosis.