THE ROLE OF THYROID FINE-NEEDLE ASPIRATION CYTOLOGY IN THE TREATMENT AND FOLLOW-UP OF THYROID NODULES IN THE PEDIATRIC POPULATION.

OBJECTIVE: Thyroid fine-needle aspiration (FNA) and cytology is a reliable diagnostic method used in the assessment of malignancy when evaluating thyroid nodules, in conjunction with clinical and ultrasonographic findings. The aim of this study is to compare clinical, ultrasonographic, cytological and histopathological findings in children who underwent thyroid FNA. METHODS: Subjects comprised 80 patients (52 female) aged 13.7±2.8 years at the time of FNA who where evaluated for thyroid nodules. Clinical, ultrasonographic and cytological findings of patients were evaluated retrospectively. RESULTS: Autoimmune thyroiditis was present in 30% and history of radiotherapy to the head or neck in 10%. The cytological diagnosis of patients included: inadequate or hemorrhagic sample in 10%; benign in 42.5%; atypia or follicular lesion of undetermined significance (AUS/FLUS) in 15%; suspicion of follicular neoplasia (SFN) in 7.5%; suspicion of malignancy (SM) in 8.8%; and malignant in 16.3%. Thirty-seven patients underwent thyroidectomy. Malignancy rates for histopathologic follow-up were 75%, 85.7% and 100% for SFN, SM and malignant categories, respectively. Only one benign and two AUS/FLUS FNAs were found to be malignant on histopathological examination. Among patients who had received radioiodinetherapy, 87.5% had malignancy. In this study, the sensitivity of FNA was 96%, specificity 50%, positive predictive value 90.9%, negative predictive value 75%, and diagnostic value of FNA was 89.2%. CONCLUSION: Thyroid FNA results were highly compatible with histopathological examination. Sensitivity, positive predictive value and diagnostic value of FNA were high.

Treatment failure may lead to accelerated fibrosis progression in patients with chronic hepatitis C.

Chronic hepatitis C (CHC) patients with treatment failure (TF) remain at risk of continuing fibrosis progression. However, it has not been investigated whether there is an increased risk of accelerated fibrosis progression after failed interferon-based therapy. We aimed to investigate long-term influence of TF on fibrosis progression compared with untreated patients with CHC. We studied 125 patients with CHC who underwent paired liver biopsies from 1994 to 2012. Patients with advanced fibrosis were excluded from the analysis. Sixty-three patients had TF, and 62 patients were treatment-naïve (TN). Annual fibrosis progression rate (FPR) was calculated, and significant fibrosis progression (SFP) was defined as ≥ 2 stage increase in fibrosis during follow-up. Multiple regression analyses were performed to find out independent predictors of FPR and SFP. Demographic characteristics and duration between paired liver biopsies were similar in TF and TN groups. Baseline alanine aminotransferase and gamma-glutamyl transferase (GGT) levels (71 ± 31 vs 47 ± 22, P < 0.001 and 49 ± 39 vs 36 ± 28, P = 0.027, respectively), baseline mean fibrosis stage (2.2 ± 0.7 vs 1.9 ± 0.7, P = 0.018) and histologic activity index (6.3 ± 1.9 vs 4.3 ± 1.6, P < 0.001) were higher in the TF group compared with the TN group. In regression analyses, the strongest independent predictor of fibrosis progression was the GGT level (OR: 1.03, 95%CI 1.01-1.5, P < 0.001). Treatment experience (OR: 5.97, 95%CI 1.81-19.7, P = 0.003) also appeared as an independent predictor of both FPR and SFP. Failed interferon-based CHC treatment may lead to accelerated FPR in the long-term compared with the natural course.

Increased risk of unfavorable metabolic outcome during short-term follow-up in subjects with nonfunctioning adrenal adenomas.

OBJECTIVE: To demonstrate long-term changes in the prevalence of several types of metabolic derangements in subjects with nonfunctioning adrenal adenomas. SUBJECTS AND METHODS: 273 subjects with adrenal adenomas, including 231 with nonfunctioning adenoma and 42 with subclinical Cushing's syndrome (sCS), were evaluated with respect to anthropometric and laboratory characteristics and prevalence of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, metabolic syndrome (MS), prediabetes and cardiovascular disease (CVD). Median duration was 24 months. Follow-up data of 114 participants with nonfunctioning adrenal adenomas are also presented while those of 117 were missing. Follow-up data regarding changes in anthropometric and laboratory parameters and prevalence rates of metabolic disturbances were obtained from the medical records. RESULTS: The prevalence rates for both patients with nonfunctioning adenoma and sCS were: dyslipidemia: 161 (59%), hypertension: 147 (54%), MS: 128 (47%), prediabetes: 62 (23%), T2DM: 49 (18%), and CVD: 21 (8%). Hypertension and CVD were prevalent in subjects with sCS compared to participants with nonfunctioning adenoma. In follow-up, body mass index (p = 0.005), systolic blood pressure (p < 0.001), waist circumference (p = 0.005), homeostasis model assessment (p = 0.046), high-sensitivity C-reactive protein (p = 0.023), total cholesterol (p < 0.001) and low-density lipoprotein cholesterol (p < 0.001) and prevalence of hypertension (p < 0.001), dyslipidemia (p < 0.001), prediabetes (p < 0.001) and MS (p < 0.01) significantly increased in subjects with nonfunctioning adenoma. CONCLUSION: The data showed that nonfunctioning adrenal adenomas were associated with the development or deterioration of atherosclerotic risk factors. Therefore, follow-up and management strategies should be developed to decrease atherosclerotic morbidity in those individuals.

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.

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.

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.

Transforming growth factor-beta 1 levels in women with prior history of gestational diabetes mellitus.

It is known that women with prior history of gestational diabetes mellitus (pGDM) feature obesity, insulin resistance and endothelial dysfunction which cause premature atherosclerosis. Transforming growth factor-beta 1 (TGF-beta1) is a key cytokine in obesity and insulin resistance and also play important roles in the development of atherosclerosis. This study was conducted to demonstrate the serum TGF-beta1 levels of people with pGDM. Thirty women with pGDM, 20 women with type 2 diabetes mellitus (T2DM) and 20 healthy women were enrolled. Serum TGF-beta1 levels of people with pGDM were found to be significantly higher than healthy controls and significantly lower than women with T2DM. TGF-beta1 levels were found to be correlated with postprandial glucose and age and inversely correlated with body mass index (BMI) and waist circumference. On multiple regression analysis postprandial glucose level, age and BMI were determined as the most important factors affecting TGF-beta1 levels. This study demonstrates elevated TGF-beta1 levels in pGDM. The inflammatory response to hyperglycemia and insulin resistance could be the major factors for the increased expression of TGF-beta1.

Hydroxyurea associated leg ulcer succesfully treated with hyperbaric oxygen in a diabetic patient.

Oxygen tension in healing tissues is heterogeneous. Increased oxygen mostly stimulates repair mechanisms and enhances tissue healing. Hyperbaric oxygen therapy increases blood and tissue oxygen content and may help maintain cellular integrity and function. Hydroxyurea (HU) is a cytotoxic agent, which leads to inactivation of ribonucleotide reductase, inhibition of cellular DNA synthesis, and cell death in the S phase. HU induced leg ulcers occur after use of this agent for a long time and at higher cumulative doses. Here we describe a diabetic patient with foot ulcer associated with HU treatment for polycythemia vera, who was treated successfully with hyperbaric oxygen and general wound care after discontinuation of HU. Faster improvement of leg ulcer in our patient compared to literature regarding HU withdrawal as single therapy suggests that hyperbaric oxygen may be helpful in the management of HU associated leg ulcers, especially in diabetic subjects.

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.

Plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor levels in non-alcoholic steatohepatitis.

AIM: This study was conducted to demonstrate the plasminogen activator inhibitor- 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor antigen (TAFI-Ag) levels in non-alcoholic steatohepatitis (NASH). MATERIALS AND METHODS: Twenty-seven patients with biopsy-proven NASH and 18 healthy controls (HC) were recruited for the study. Anthropometric data, liver histology (no.=20) and laboratory parameters including PAI-1 and TAFI-Ag assessments were recorded. RESULTS: When compared with HC, patients with NASH had higher body weight, higher waist circumference, elevated blood pressure, higher fasting plasma glucose (FPG) levels and higher homeostasis model assessment (HOMA) scores. The mean plasma PAI-1 levels of patients was found to be higher than HC (87.60 ng/ml vs 30.84 ng/ml p=0.000) and mean plasma TAFI-Ag levels of patients was found to be significantly lower (8.69 microg/ml vs 12.19 microg/ml p=0.000). PAI-1 levels were correlated with systolic blood pressure, age, body weight, transaminases, waist circumference, FPG, body mass index, and HOMA score. TAFI-Ag levels were found to be negatively correlated with transaminases, waist circumference, and body weight. In multiple regression analysis, BMI was the independent variable effecting PAI-1 levels. We did not show any association between PAI-1, TAFI-Ag, disease activity score and fibrosis score. HOMA was the independent variable effecting liver fibrosis in our patients. CONCLUSION: In this study we demonstrated that patients with biopsy-proven NASH had higher PAI-1 and lower TAFI-Ag expression than HC. Elevated levels of PAI-1 in NASH is the consequence of insulin resistance state. Lower TAFI-Ag levels may be related to the overactivation of TAFI pathway resulting in TAFI-Ag depletion. Furthermore, liver function disturbances may impair TAFI production in NASH. We also showed that NASH patients even with slight elevations of transaminases feature marked insulin resistance and components of metabolic syndrome.

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.

MHC class I antigen expression in patients with IDDM and their siblings.

MHC class I antigen expression was found to be low on the lymphocytes of patients with insulin dependent diabetes mellitus (IDDM). Thus, it has been proposed that the defective expression of MHC antigens could lead to faulty immunological responses with the eventual destruction of the pancreatic beta cells. The objective in this study was to compare MHC antigen expression in IDDM patients and their presently healthy siblings. Nineteen children (mean age 10.8 +/- 3.9 years) with diabetes and their 25 siblings (mean age 10.7 +/- 4.6 years) were enrolled in the study. Peripheral blood lymphocytes isolated from venous blood samples were incubated with FITC conjugated monoclonal antibody W6/32. The amount of antibody binding by cell surface MHC class I antigens was assessed by flow cytometry. MHC class I molecule expression did not differ significantly among IDDM patients and their siblings. It was concluded that MHC class I antigen expression did not appear to be indicative of a susceptibility to develop autoimmune diabetes.

ACE inhibitors and cough.

Probably the most common and irritating side effect of angiotensin-converting enzyme (ACE) inhibitors is cough. In this retrospective study the incidence of cough was investigated in 1113 patients with arterial hypertension who were receiving ACE inhibitors alone or in combination with other antihypertensive agents. Patients were treated with one of the following ACE inhibitors: enalapril 10-20 mg/day (n:668), captopril 25-75 mg/day (n:234), perindopril 2-8 mg/day (n:90), or lisinopril 5-20 mg/day (n:121). Mean follow-up periods were twenty-six months with enalapril, twenty-nine months with captopril, eleven months with perindopril, and thirteen months with lisinopril. Spontaneously declared cough incidence in enalapril, captopril, perindopril, and lisinopril groups were 7%, 5.1%, 2.2%, and 1.6%, respectively. Cough was not dose related. Treatment was stopped in all patients with cough. In 59% of patients the onset of cough occurred after the first month of treatment (thirty to one hundred eighty days). Cough decreased by 50% within three days of drug cessation and disappeared in ten days. Mean age of patients with cough was 58.7 years and 79% of them were women. In patients without cough, mean age was 57.8 years and 56% of them were women. There was no significant difference between the two groups regarding mean age, but the sex difference between groups was statistically significant (P < 0.05). In conclusion, although cough may occur with all four types of ACE inhibitors, the incidence of this side effect was higher during enalapril and captopril treatment than during lisinopril and perindopril treatment. The incidence was also greater in women than in men.

Effect of different analgesics on pain relief during extracorporeal shock wave lithotripsy.

BACKGROUND/AIM: The aim of this study was  to compare  three drugs for pain relief during shock wave lithotripsy (SWL). MATERIALS AND METHODS: Seventy six male patients that were treated for renal stones with SWL were included in this study. They were randomized into four groups. A different treatment protocol was used for each group.  Intramuscular (IM) diclofenac 75mg was given in group 1 (n=20), dexketoprofen, 50mg, IM in group 2 (n=20) and hyoscine 10 mg plus paracetamol 500mg, orally in group 3 (n=20). In group 4 (control, n=16) saline solution   was given 30 min before SWL. Pain during SWL was assessed using the 10-score linear visual analogue pain scale (VAS) and was compared among groups. Age, weight, height, body mass index (BMI), stone size, stone location, duration of SWL, total shock waves performed and mean energy level (kV) for each patient were recorded. A p value of <0.05 was considered statistically significant. RESULTS: The mean patients' age was 45.4 ± 12.9 years. The highest VAS value was observed in Group 4 (8.4 ± 1), and the lowest  in Group 1 (6.25 ± 2.2).  Statistically significant  difference was noted  only when Group 1 and Group 4 were compared. The remaining groups provided similar results and there were no significant statistical differences according to VAS values. Other parameters were similar  in all groups. CONCLUSION: In conclusion, this study shows that reducing the pain with a single dose injection of intramuscular diclofenac sodium before SWL is superior compared to others.

Effects of sildenafil treatment on patients with Peyronie's disease and erectile dysfunction.

INTRODUCTION: It has been shown on experimental rat models that type 5-phosphodiesterase isoenzyme (PDE5) inhibitors have anti-fibrotic effects for Peyronie's disease (PD); however, this issue has not been addressed clinically. The aim of this study was to document the effects of PDE5 inhibitors used for erectile dysfunction (ED) seen in PD patients on the main course of the PD clinically. METHODS: A total of 39 PD patients with ED were divided into two groups. Patients in Group 1 (n = 18) served as controls and received 400 IU vitamin E per day. Those in Group 2 (n = 21) received 50 mg sildenafil per day for 12 weeks. Penile plaque volume was assessed by palpation and by duplex ultrasound. Erectile capacity, penile deformity and plaque characteristics were assessed by the International Index of Erectile Function questionnaire form (IIEF-5) and penile duplex ultrasound. RESULTS: Statistically significant improvement in all parameters was observed within both groups except for IIEF score in Group 1 when compared with the initial values. Significant reduction in plaques and pain were observed in 7 (33.3 %) and 14 (66.6 %) patients in Group 2 and 6 (33.3 %) and 9 patients (42.8 %) in Group 1, respectively. At the end of the therapy, improvement in IIEF score and reduction in pain were statistically significant in Group 2 compared with Group 1 (p = 0.028 and p = 0.045, respectively). CONCLUSION: We conclude that continuous administration of oral PDE5 inhibitors may be a candidate for medical treatment of PD; however, more controlled studies are needed.