C. Yilmaz

Demographic and clinical features of patients with subacute thyroiditis: Results of 169 patients from a single University Center in Turkey

Background: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. Methods: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. Results: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0±17.8 yr); 69% of the patients were between 30–50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42±39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. Conclusion: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Long-term treatment with acarbose for the treatment of reactive hypoglycemia

Objective: Acarbose, a potent alpha-glucosidase inhibitor, provides a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It reduces the postprandial blood glucose increment and insulin response. For this reason the drug has been successfully used not only in the treatment of type 1 and type 2 diabetes, but also in the management of reactive hypoglycemia and dumping syndrome. The primary aim of the present study is to evaluate the long-term effect of acarbose in reducing hypoglycemic symptoms and influencing laboratory measurements in patients with the diagnosis of reactive hypoglycemia. Design and Methods: 21 non-obese (BMI <27 kg/m2) patients (6 males, 15 females) complaining of postprandial symptoms suggesting hypoglycemia and who showed blood glucose values of <54 mg/dI on one or more occasions during a 5 h oral glucose tolerance test (OGTT) were selected. Results: Before treatment, ingestion of glucose decreased plasma glucose levels at the 3rd and 4th hours, the lowest levels being 39 mg/dl and 45 mg/dl respectively. Eighteen patients had hypoglycemic symptoms during OGTT. Following 3 months of acarbose treatment, the lowest plasma glucose levels at the 3rd and 4th hours increased to 67 mg/dI and 75 mg/dI respectively. Plasma insulin and c-peptide levels were reduced between the 1st and 5th hours, but only the 1st and 2nd hour decrements were statistically significant. The area under the curve (AUC) between 0–300 minutes for insulin was not significant. Plasma glucose levels were significantly increased during the last 3 hours The AUC for glucose was not significantly changed. Frequency of hypoglycemic attacks was reduced from 4 times a week to 1. C-peptide levels in 24-hour urine collection did not change significantly: 45 μg/I and 56 μg/I respectively before and after treatment. Conclusions: These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion, and in the treatment of reactive hypoglycemia.

The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients

Introduction: Interleukins and cytokines play an important role in the pathogenesis of many cancers. We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. Material and methods: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at −80 C in tubes containing Na-EDTA. Results: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05). We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). Discussion: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

The relation of adiponectin and tumor necrosis factor α levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor β, and tumor necrosis factor α gene polymorphism in adrenal incidentalomas

Objective: The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. Research design and methods: Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-α, transforming growth factor (TGF)-β genes polymorphisms, TNF-α, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). Results: There was statistically significant difference between TNF-α levels of patient and controls (p=0.048). We have not detected the connection between TGF-β, TNF-α, ACE, eNOS gene polymorphism with serum TNF-α and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. Conclusions: According to different cases of eNOS, TGF-β, ACE, and TNF-α gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells

PurposeGossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (−)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing’s disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells.MethodsCytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit.ResultsAT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly.ConclusionAT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.

Thermogenic response and leptin levels rise after recovery of the euthyroid state

Objective: The aims of the study were to compare: a) the thermogenic responses in subclinical hypothyroidism (SH) and euthyroid state; b) the relationship between thermogenic response and leptin level. Methods: Thirty women diagnosed with SH (mean age 39.9±4.1 yr; body mass index 23.2±2.5 kg/m2) were enrolled in the study. Thyroid function tests, leptin, and lipid profiles were measured during SH and after stable euthyroidism was recovered. Thermogenic response was measured by Water Immersion Calorimetry during SH and after the euthyroid state was attained. Results: The mean level of thermogenic response was found to be 1.45±0.43 kcal/kg.h in women with SH. It changed to 1.54±0.77 kcal/kg.h (p=0.01) in the euthyroid state; the change was statistically significant. Mean level of leptin was found to be 7.22±2.6 ng/ml in SH; and 15.8±8.0 ng/ml in the euthyroid state. There was a positive correlation between leptin and free T3 (r=0.460, p=0.009) levels in SH. There were positive correlations between leptin level and fat mass in SH (r=0.820, p=0.01) and in the euthyroid state (r=0.700, p=0.03). Conclusions: No correlations were found between thermogenic response and leptin levels in SH and in the euthyroid state. Thermogenic response and leptin levels rose after the euthyroid state was recovered.