SURVIVIN POSITIVITY AND PROGNOSTIC FACTORS IN PAPILLARY THYROID CARCINOMAS.

Context: Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective: In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design: In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods: In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results: When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion: Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Case Report.

Background: Thyroid hormone resistance (RTH) is defined as a decrease in response to thyroid hormones in the target tissue. Most patients present with nonspecific findings. In this article, we aimed to represent a 22-year-old female patient who presented with palpitation, fatigue, and heat intolerance. She was thought to have thyroid hormone resistance and her genetic examination revealed NM_001128177.1 (THRß): c.1034G > A (p.Gly345Asp) pathogenic variation in the THRß gene. Case report: A 22-year-old female patient presented with complaints of fatigue, heat intolerance and palpitations. She was taking Propranolol twice daily at admission. Her family history revealed hypothyroidism in her grandmother. Her physical examination results were as follows: height 160 cm, weight 65 kg, body mass index 25.4kg/m2, body temperature 36.5°C, respiratory rate 18/min, heart rate 86 beats/min, blood pressure 120/80 mmHg. Her palms were sweaty. The heart sounds were normal, and no heart murmur was auscultated. The laboratory results were TSH: 5.31uU/mL, fT3: 6.83 pg/mL, and fT4: 2.43 ng/dL. THRß gene mutation analysis was requested for our patient whose clinical history and laboratory results were compatible with thyroid hormone resistance. The pathogenic variation NM_001128177.1(THRß):c.1034G>A (p.Gly345Asp) was detected after analysis. Conclusion: A diagnosis of RTH requires high clinical suspicion and a genetic mutation analysis should be requested in the case of clinical suspicion. In this way, unnecessary anti-thyroid treatment can be prevented.

Evaluation of SCUBE-1 and sCD40L biomarkers in patients with hypothyroidism due to Hashimoto's thyroiditis: a single-blind, controlled clinical study.

OBJECTIVE: This study was performed to investigate the levels of platelet activation marker SCUBE-1 and sCD40L which plays some role in the progression of atherosclerosis, in patients with hypothyroidism due to Hashimoto's thyroiditis. PATIENTS AND METHODS: The cohort of this study includes 90 patients and 35 healthy volunteers, who admitted to the internal medicine out-patient. Simultaneously in the same samples; SCUBE-1 and sCD40L measurements were accomplished by enzyme-linked immunosorbent assay (ELISA). The data obtained were analyzed statistically. RESULTS: Hypothyroidism due to Hashimoto's thyroiditis in comparison to the control group that includes healthy volunteers; SCUBE-1 and sCD40L, were increased. And these results were statistically significant (p < 0.05). CONCLUSIONS: SCUBE-1 and sCD40L levels were increased in Hashimoto's hypothyroidism patients. This may indicate an increased endothelial dysfunction, platelet activation and cardiovascular risk in hypothyroidism. SCUBE-1 and sCD40L may be helpful in cardiovascular risk assessment of hypothyroid patients.

A RARE CLINICAL PRESENTATION: A PATIENT WITH CHRONIC RENAL FAILURE, SECONDARY HYPERPARATHYROIDISM AND CALCIPHYLAXIS.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is usually observed in women and it is a serious complication of hyperparathyroidism secondary to chronic renal failure. CUA is characterized by ischemic tissue loss secondary to progressive vascular degeneration. Although it is rare, it may end up with sepsis and organ failure and can be fatal. Its pathogenesis is not fully understood, but it is thought that it occurs secondary to increased calcification activators such as oxidized LDL, TNF- α, calcitriol, fibronectin, collagen-I, and TGF-1α. The most effective treatment is managing underlying pathology and decreasing serum calcium and phosphorus levels. In this report, we aimed to present an end stage renal failure case with coexisting hyperparathyroidism, hyperthyroidism and calciphylaxis in whom cutaneous manifestations were healed 6 months after parathyroidectomy.

IODINE DEFICIENCY IN PREGNANT WOMEN LIVING IN WESTERN TURKEY (EDIRNE).

OBJECTIVE: Data about iodine status in pregnant women in Turkey is not sufficient. We aimed to determine the iodine status, goiter prevalence, iodized salt consumption among first trimester pregnant women living in Edirne. DESIGN AND SETTING: Cross-sectional study was performed on pregnant women living in Edirne. SUBJECTS AND METHODS: A total of 275 pregnant women in their first trimester were examined regarding iodized salt use, median urinary iodine concentration (UIC), presence or absence of goitre and thyroid function. Goitre status was determined by palpation. Participants filled out a questionnaire, which included questions regarding sociodemographic features, iodized salt consumption, knowledge, and behavior regarding iodine deficiency. UIC was measured using colorimetric method based on Sandell-Kolthoff reaction. Thyroid hormones and TSH were measured by chemiluminescence immunoassays. RESULTS: While the proportion of iodized salt use was 96.6%, UIC was below 150 µg/L in 88.4 % of the women. The median UIC was 77 µg/L, indicating insufficient iodine intake. Total goitre rate was 19.3%. CONCLUSIONS: Our study shows that iodine deficiency is a serious problem among pregnant women in Edirne. We suggest that pregnant women living in Edirne should be supplemented by iodine-containing preparations in addition to iodized salt.

CLINICALLY UNDETECTABLE OCCULT THYROID PAPILLARY CARCINOMA PRESENTING WITH CERVICAL LYMPH NODE METASTASIS.

BACKGROUND: Occult papillary thyroid carcinoma presented as isolated cervical lymphadenopathy without clinical and radiologic findings has been rarely reported. CASE REPORT: A 47 years old female patient admitted to otorhinolaryngology clinic with 4X3 cm sized cervical mass. Physical examination of the patient was noted as a nontender, firm, mobile lymph node at right lateral cervical region. There was no inflammatory or infection disease in the history of patients anamnesis and no abnormal value on laboratory tests. Ultrasound screening of the neck detected a lymph node with suspicious features for malignancy. Head and neck examination was normal and there is no evidence of a tumoral mass or nodule in the thyroid gland. Whole body scan of MRI showed no pathologic sign both in the neck and body. Excisional biopsy was performed and revealed a carcinoma with papillary morphology. Immunohistochemical staining features of the tumor confirmed a papillary carcinoma derived from the thyroid gland. Second look USG of the neck and thyroid was performed but it revealed no tumoral mass. The patient underwent total thyroidectomy with right functional and central lymph node dissection. Histological examination of the thyroid gland showed multicentric 2 mm sized, three foci of papillary carcinoma located in bilateral thyroid lobes and metastatic lymph nodes in the right side of the neck. CONCLUSION: A metastatic cervical lymph node can be evidence of a clinically undetected occult papillary thyroid carcinoma. Specific immunohistochemistry staining of specimen may lead to appropriate surgery and progression of carcinoma may be hindered by application of additional RAI therapy.

Asymmetric dimethylarginine and nitric oxide levels in migraine during the interictal period.

Nitric oxide (NO), which modulates endothelial function, is thought to be pivotal in the pathophysiology of migraines. The connection between migraine and cardiovascular diseases has also drawn attention to the endothelial dysfunctions and NO pathway abnormalities seen in patients with migraine. Our goal was to assess the levels of NO and the endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), in people with migraine during the interictal period. A total of 49 patients with migraine and 22 control subjects were enrolled in the study. Their plasma NO metabolites (nitrite [NO2-] and nitrate [NO3-]) and ADMA levels were measured using the enzyme-linked immunosorbent assay method, and were then compared with their cardiovascular risk factors, anthropometric measurements, and headache frequency and severity. The plasma ADMA, NO2- and NO3- levels of the patients with migraine during the interictal period did not differ from the control group, and no relationship was found between cardiovascular risk factors and migraine attack severity and frequency. We conclude that, in patients with migraine, there is no dysfunction of baseline NO and ADMA metabolism during the interictal period.

Asymmetric dimethylarginine levels in thyroid diseases.

Thyroid diseases may lead to endothelial dysfunction; however, the mechanism underlying the endothelial dysfunction in thyroid disease is not clear yet. Asymmetric dimethylarginine (ADMA), a novel inhibitor of endothelial nitric oxide synthase (eNOS), blocks nitric oxide (NO) synthesis from L-arginine. Symmetric dimethylarginine (SDMA) is the structural isomer of the eNOS inhibitor ADMA. SDMA does not directly inhibit eNOS but is a competitive inhibitor of arginine transport. Increased plasma ADMA, SDMA concentrations, and low L-arginine/ADMA ratio were considered as possible contributing factors for endothelial dysfunction in hyperthyroid patients. On the other hand, plasma ADMA, SDMA levels and L-arginine/ADMA ratio in the hypothyroid group were unexpectedly found to be similar to those of the control subjects. The aim of this study is to evaluate and compare the plasma ADMA levels in hyperthyroid, hypothyroid and healthy subjects. Plasma ADMA, SDMA, and L-arginine levels were measured by high performance liquid chromatography. Plasma ADMA levels were significantly higher in both patients with hyperthyroidism and hypothyroidism than in the control group. SDMA concentrations were significantly increased in hypothyroid patients compared to control subjects. Patients with hyperthyroidism and hypothyroidism had significantly higher plasma L-arginine levels compared with healthy controls. L-arginine/ADMA ratio, which shows NO bioavailability, was significantly lower in hyperthyroid patients than in both hypothyroid and control subjects. In hyperthyroidism, plasma ADMA levels were related to age, L-arginine, and SDMA levels. SDMA was associated with age and L-arginine. L-arginine/ADMA ratio was negatively associated with freeT4 levels. There was a relationship between ADMA and L-arginine in hypothyroid patients. SDMA was significantly related to L-arginine, total cholesterol, and LDL. In conclusion, not only hyperthyroidism but also hypothyroidism was associated with alterations of ADMA and SDMA metabolism.

Dysphagia as a primary manifestation of hyperthyroidism: a case report.

Myopathy effecting mainly skeletal muscles of the limbs are frequently seen in hyperthyroidism. Rarely bulbar muscles may also be involved, causing dysphagia, nasal speech, and aspiration. We report a 70-year-old woman with severe dysphagia and aspiration pneumonia. Clinical examination and laboratory tests showed an underlying Graves' disease. Her dysphagia improved dramatically by antithyroid therapy. Considering its excellent response to medical therapy, hyperthyroidism--being a very rare factor - is well-worth to remember for the unexplained dysphagia cases.

Visceral fat thickness determined using ultrasonography is associated with anthropometric and clinical parameters of metabolic syndrome.

The aim of this study is to find out the relation between the ultrasonographic (USG) measurements of the abdominal fat thickness and cardiovascular risk factors in metabolic syndrome. The thickness of subcutaneous fat (SF), visceral fat (VF) and preperitoneal fat (PF) was measured using USG in 75 subjects (35 women and 40 men) with metabolic syndrome. The body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressures, fasting plasma glucose, fasting insulin and lipid parameters of all participants were recorded. Insulin resistance was estimated using HOMA-IR formula. BMI (p < 0.05), WC (p < 0.01), SBP (p < 0.001), DBP (p < 0.05), fasting insulin (p < 0.05), total cholesterol (p < 0.001) and triglyceride (p < 0.001) levels were found in correlation with VF thickness in the female group. There was a positive association between WC and SF thickness (p < 0.05) in the same group. In the male patients, BMI (p < 0.001), WC (p < 0.01), SBP (p < 0.05), DBP (p < 0.05) and triglyceride level (p = 0.01) were significantly correlated with VF thickness. SF thickness was associated with BMI (p < 0.001) and WC (p < 0.01) in this group. There was no relation between PF thickness and clinical variables in both groups (p > 0.05). It can be concluded that VF thickness may have a significant pathophysiological role in the development of the metabolic syndrome.

Autoimmune polyglandular syndrome type III in monozygotic twins: a case report.

Autoimmune polyglandular syndrome is characterized by the coexistence of several autoimmune diseases, affecting predominantly the endocrine glands. Autoimmune polyglandular syndrome type III, as a subdivision of autoimmune polyglandular syndrome type II, is the co-occurrence of autoimmune thyroid disease with other autoimmune disorders without Addison disease. We present a rare case of autoimmune polyglandular syndrome type III in monozygotic twins. One of the twins also had autoimmune leukopenia. To our knowledge, leukopenia is the first mentioned coexistence in the literature of autoimmune polyglandular syndrome.

Complete relief of pain in acute painful diabetic neuropathy of rapid glycaemic control (insulin neuritis) with venlafaxine HCL.

This article reports a case of a diabetic patient who suffered from acute painful diabetic neuropathy, following an intensive insulin treatment after a poor glycaemic control period of 8 yr. On the 15th day of the insulin treatment, which enabled rapid successful glycaemic control, the patient began complaining of pain and a burning sensation in the lower extremities, especially during the night. Venlafaxine HCL was initiated and the patient was completely free of pain on the third day of the treatment. As insulin neuritis is infrequent among diabetic patients we consider it is worth reporting the dramatic effect of the venlafaxine HCL treatment.

Exacerbations of Graves' disease after unilateral adrenalectomy for Cushing's syndrome.

Cushing's syndrome is characterized by endogenously increased production of glucocorticoids. The activity of immune system is regulated mainly by two systems in the body. Glucocorticoids and NF-kappaB counteract the effects of each other on the immune system. It has been reported that immune response is exaggerated after the amelioration of Cushing's syndrome. We report a rare case of exacerbation of Graves' disease after unilateral adrenalectomy for Cusing's syndrome. A 50-yr-obese woman with hypertension, dyslipidemia, impaired glucose tolerance and insulin resistance wasadmitted to outpatients clinic of endocrinology. The results of evaluation of glucocorticoids metabolism and adrenal magnetic resonance imaging revealed the Cusing's syndrome. We also assessed thyroid function tests because of the diagnosis of goiter and thyroid hormone replacement in her medical history, and the presence of exophthalmia and tachycardia in examination. Althoug TSH level was detected at the lower border of normal range, free T4 and free T3 were in normal range and autoantibody of thyroidal peroxidase and thyroglobulin was higer than normal reference range. An operation was performed and a mass was removed from her left adrenal gland. The pathologic examination confirmed adrenal adenoma. She was re-admitted to the outpatient clinic 9 months after with complaints of palpitation, malaise and weight loss. Tests carried out to determine the thyroid function revealed Graves' disease. We prescribed propylthiouracil and beta-blocker treatment.