The prevalence of RET/PTC mutations in papillary thyroid cancers in Turkish population and its relation between tumor histopathology and prognostic factors.

OBJECTIVE: In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients. METHODS: The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fisher's Exact Test. RESULTS: RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers. CONCLUSION: While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.

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.

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.

Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry.

Glucose utilization studies show that sibutramine-induced thermogenesis is mediated via selective sympathetic activation of brown adipose tissue. The goal of the present study was to use a new calorimetry method in which resting metabolic rate is enhanced to evaluate the effects of sibutramine treatment on thermogenesis. Sixty obese women were included in the study. Subjects were divided into 2 equal groups-the placebo and sibutramine treatment groups. The sibutramine group was given sibutramine 10 mg daily for 12 wk. At baseline and at the end of the 12-wk treatment period, thermogenic measurements were taken with the use of water immersion calorimetry. Subjects were examined at weeks 4, 8, and 12 of treatment to identify adverse effects. Body mass index, measured at 31.5+/-2.05 kg/m2 in the placebo group, decreased to 30.4+/-2.94 kg/m(2) after 12 wk (P=.07). In the sibutramine group, it decreased from 33.5+/-4.1 kg/m(2) to 30.9+/-4.8 kg/m(2) (P<.05). In the sibutramine group, mean thermogenic response changed from a baseline value of 1.27+/-0.29 kcal/kg/h to 1.44+/-0.13 kcal/kg/h after 12 wk of treatment. In the placebo group, the baseline value was 1.56+/-0.27 kcal/kg/h; it changed to 1.33+/-0.36 kcal/kg/h at the end of 12 wk. The findings of this study suggest that sibutramine treatment promotes thermogenesis, thus facilitating weight loss. Calorimetry enhances resting metabolism through more efficient heat transfer from the body.

Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter.

The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC.

Triiodothyronine antibodies in patients with goiter.

OBJECTIVE: To investigate the prevalence of triiodothyronine (T(3)) antibodies in patients with goiter, the influence of these antibodies on the results of thyroid hormone measurements, and the potential relationship between T(3) antibodies and thyroid autoantibodies. METHODS: We undertook a study of 100 healthy control subjects (80 female and 20 male subjects) who had no clinical or biochemical evidence of thyroid disease and 100 patients (81 female and 19 male patients) with goiter. Serum concentrations of total T(3), total thyroxine, free T(3), and free thyroxine were measured by radioimmunoassay kits with a coated tube method. An immunoprecipitation method was used to detect anti-triiodothyronine auto-antibodies. RESULTS: Patients with a T(3) antibody binding ratio +3 standard deviations (SD) above the mean for the normal control group were considered to have T(3) antibodies. Normal control group binding was 2.4 +/- 1.3%. On the basis of +3 SD, seven patients had T(3) antibodies. The mean serum total T(3) level was 1.61 +/- 0.1 nmol/L in patients with binding ratios above +3 SD, whereas the mean serum total T(3) level was 2.23 +/- 0.3 nmol/L in patients without T(3) antibodies. Thus, patients with a binding ratio above +3 SD had a significant decrement in total T(3) levels. No correlation was found between the presence of T(3) antibody and antimicrosomal and antithyroglobulin antibodies. CONCLUSION: When serum thyroid hormone concentrations are measured with a coated tube-radioimmunoassay method, antibodies can result in low T(3) concentrations. T(3) antibodies should be suspected whenever a discordance is noted between the measured thyroid hormone concentrations and the clinical status.

Hypothalamus-hypophysis-thyroid axis, triiodothyronine and antithyroid antibodies in patients with primary and secondary Sjögren's syndrome.

It has been well established that, anti-thyroglobulin antibodies (ATG) and anti-microsomal antibodies (AMC) may be present in various thyroid disorders and other systemic autoimmune diseases, including Sjögren's syndrome (SS). However, presence of circulating autoantibodies to thyroid hormones, i.e. both to triiodothyronine (T3) and tetraiodothyronine (T4), has not been studied extensively in SS. Autoantibodies to T3 and T4 are very important, because serum T3 and T4 levels may be detected spuriously higher or lower, due to the presence of these autoantibodies. Their presence should be suspected when measured serum thyroid hormone levels are not consistent with clinical status of the patient. SS is a slowly progressive, inflammatory autoimmune disease, affecting primarily the exocrine glands. Thyroid gland, being a target in some autoimmune diseases, is well known to be affected in SS as well. Keeping this possibility in mind, we investigated T3 autoantibody levels and thyroid gland involvement in patients with SS. Twenty-six SS patients (F/M:22/4) with a mean age of 46.6 years, were recruited in this study. Twelve of them were accepted as primary SS (pSS), while others had secondary SS (sSS) (7 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 3 with progressive systemic sclerosis (PSS) and 1 with sarcoidosis). Thyroid function tests, including T3, T4, fT3, fT4, TSH, ATG, AMC, T3 antibody measurements, thyroid scintigraphy, thyroid ultrasonography and TRH stimulation tests were performed in all patients. We compared our results with those of the twenty healthy normal controls. Serum ATG and/or AMC were detected in three patients with pSS (25%) and no patients with sSS. No significant difference could be shown in the other parameters, including T3 autoantibodies and thyroid function tests. TRH stimulation test was also normal, showing that the hypothalamus-hypophysis-thyroid axis was not affected in patients both with pSS and sSS. In conclusion, we found that T3 autoantibody levels in pSS, were not significantly higher than sSS and normal controls.

Human multidrug resistance-1 gene expression levels in graves-basedow disease.

OBJECT: Multidrug resistance 1 gene is responsible for the resistance of a large variety of drugs in human cells. We tried to evaluate this in the present study in thyroid stimulant hormone receptor antibody positive subjects. METHOD: In study enrolled 23 female and 10 male subjects. Hyperthyroid subjects were treated with PTU and remission was assured between 6-12 months. Blood samples were collected before the start of this treatment. Permission for this study was taken from the patients and the local ethical committee. RESULTS: Serum F-T3, F-T4 levels in Graves subjects were markedly high, whereas TSH levels were markedly low than normal range. We also found that with increased age of the Graves' subjects, MDR-1 gene expression decreased. There was also a direct correlation between blood MDR-1 gene expression and TSH-R Ab levels in patients with Graves's disease. We observed that the duration of being euthyroid was lengthened with the elevation of MDR-1 gene expression. There was a direct correlation between blood MDR-1 gene expression levels and ultrasonografic size of thyroid gland. CONCLUSION: As a result, raised blood MDR-1 gene expression levels in patients with Graves-Basedow disease may be associated with the activity of the disease and the resistance to its treatment. The more blood MDR-1 expression increases the more the duration of being euthyroid increases.

Dehydroepiandrosterone and human adipose tissue.

OBJECTIVE: The aim of this study was to investigate whether DHEA alters the proliferation and differentiation of human sc and visceral adipose cells in primary cultures. METHOD: Sc and omental adipose tissue was obtained from 10 female donors aged 36+/-3.6 yr with a body mass index (BMI) of 33+/-3.21 kg/m2. Stromal vascular cells were isolated and cultured using modified procedures described by Entenmann and Hauner. For the proliferation assay, stromal-vascular cells from sc and visceral adipose tissue cultures were fed with proliferation media containing 0, 25 or 100 microM DHEA for 3 days. At the end of this treatment period, two type cultures were prepared for determining their metabolic activity using the sulforhodamine B staining procedure. RESULTS: The metabolic activity of proliferating human visceral adipose tissue was higher than sc adipose tissue. The activity of proliferating human visceral tissue cultures decreased more than the sc tissue as the level of DHEA in the cultures was increased. CONCLUSIONS: These data suggest that DHEA predominantly influences the proliferation and differentiation of human omental adipose tissue.

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.

Occurrence of Riedel's thyroiditis in the course of sub-acute thyroiditis.

Riedel's Thyroiditis is an uncommon form of chronic thyroiditis characterized by an invasive fibrosclerosis of the gland, often involving surrounding tissue. The relationship of Riedel's Thyroiditis to other forms of thyroiditis is not clear. We presented a 47 year-old woman first diagnosed with sub-acute thyroiditis based on clinical findings and laboratory results. Eight months later, she had a thyroidectomy operation due to an enlargement of the thyroid gland and symptoms of compression. Histopathologic evaluation showed that she had Riedel's Thyroiditis, but there were some histopathologic findings of sub-acute thyroiditis as well. Until now, there has only been one case reported in which Riedel's Thyroiditis was diagnosed in a patient with a history of sub-acute thyroiditis in the literature. Although aetiology of Riedel's Thyroiditis is unknown, it may develop in the course of sub-acute thyroiditis.

Is the effect of fine-needle aspiration biopsy on the thyroid nodule volume important to evaluate the effectiveness of suppression therapy?

Fine-needle aspiration biopsy (FNAB) is recommended for the initial evaluation of thyroid nodule. If a benign cytology is obtained, suppression therapy with levothyroxine is the first choice in the management of nodular goiter with a follow-up of nodule size with ultrasonography, but the effects of FNAB have not been taken into consideration in this approach. We aimed at evaluating the effect of FNAB on thyroid volume and other ultrasonographic dimensions by measurement of these parameters before and immediately after the procedure, and in later periods, and to clarify the necessity of regarding the effects of FNAB on thyroid. Forty-six patients (34 females, 12 males; mean age: 36.3+/-10.7 yr) with solitary thyroid nodules were included in the study. The nodules were solid in ultrasonography, thyroid function tests were normal and results of FNAB were found as benign cytology. Thyroid hormone suppression therapy was not initiated. Ultrasonographic measurements were made before FNAB, repeated immediately after FNAB, and 1 month and 6 months later. There were no statistically significant changes in the mean thyroid nodule volume, nodule area and circumference of patients before, immediately after FNAB, 1 month and 6 months later. Size differences and individual variability at each time period were analyzed. These parameters changed by more than 10% in a great majority (69.5-78.2%) of patients, and more than 50% change was observed in 17.3-26.0% of patients. Changes in thyroid dimensions were bi-directional, both increment and decrement being noticed. It was thought that this is the reason why there was no significant change in mean nodule volume, area and circumference. Evaluating the difference in nodule volume according to ultrasonographic parameters obtained before FNAB may be misleading because of the individual change in these parameters with FNAB. It may be useful to evaluate the nodule size and volume closely after FNAB to make a true correspondence of these parameters in the long term.

Acarbose treatment in obesity: a controlled study.

UNLABELLED: Acarbose is an alpha-glucosidase inhibitor which reversibly inhibits oligosaccharidase and disaccharidase at the brush border of the small intestine. The aim of this study was to observe its effectiveness in the treatment of obesity. METHODS: Two groups of 25 obese women were put on a 15 kcal/kg/day low-calorie diet for 12 weeks. One group (the study group) received 150 mg/day acarbose for the first 2 weeks and 300 mg/day acarbose for the remaining 10 weeks. The second group (controls) received no additional treatment. Body weight, BMI, skinfold thickness, serum lipids, OGTT, and insulin and C-peptide responses to OGTT were assessed before and after the study. RESULTS: Body weight, BMI and skinfold thickness decreased significantly in both groups. Basal insulin and triglyceride levels in the study group, total and LDL cholesterol and triglyceride levels in the control group decreased significantly. No difference was found between the two groups when these decrements were compared, but the triglyceride level fell more in the control group. CONCLUSION: Additional acarbose therapy is not more beneficial than low-calorie diet therapy alone.

Salivary cortisol levels in children during dental treatment.

Cortisol which is also called as stress hormone, is used as an indicator in the stress evaluation studies. 60 children who never visited a dentist before, participated in the present study. Saliva samples were collected from 30 children without any dental treatment (control group). Experimental group comprised 30 children with caries. Saliva samples were obtained at various stages during dental treatment. Totally 180 samples were collected and the cortisol levels were measured. Paired-t test has shown that the salivary cortisol levels at various stages of dental treatment in the experiment group were significantly higher in comparison with the control group. It is concluded that dental treatment may cause extreme stress in children who never had dental treatment experience before.

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/dl 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 micrograms/I and 56 micrograms/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.