Alterations of NIS expression in functioning thyroid nodules.

OBJECTIVES: This study aimed to analyze both the level and the cell site of the sodium-iodide symporter (NIS) protein expression in autonomously functioning thyroid nodules (AFTNs) and extranodular thyroid tissues. In addition, this study sought to compare the clinical results of patients with the levels of human NIS (hNIS) protein expression. PATIENTS AND METHODS: The histological slides consisted of 36 AFTNs and 31 extranodular thyroid tissues from 28 patients (5 males, 23 females; mean age 54.5±11.0 years; range 37 to 72 years) who underwent surgery for toxic multinodular goitre. The expression of NIS protein was investigated by immunohistochemistry in paraffin-embedded tissue sections using anti-hNIS monoclonal antibody by the labeled streptavidin-biotin method. RESULTS: The percentage of hNIS positive follicular cells was significantly higher in the AFTNs (13.33±12.09) than in the extranodular thyroid tissues (1.35±3.03). Staining for hNIS was mostly confined to the cell membrane in the AFTNs (88.9%) and in the extranodular thyroid tissues (54.5%). The clinical parameters and nodule volume did not establish any correlation with hNIS immunoreactivity. CONCLUSION: Our data indicate that functioning nodules express higher amounts of NIS protein than the extranodular thyroid tissue, but the level of hNIS immunoreactivity was lower than had been reported in the previous literature. This result may be due to interindividual variability between different populations, and iodine status. Furthermore, the localization of the NIS protein might not give an indication of its functional status.

Myasthenia gravis and autoimmune Addison disease in a patient with thymoma.

The association of thymoma with myasthenia gravis has been well documented. However, the relationship between these two syndromes and Addison disease are very rarely encountered in clinical practice. We report on a 32-year-old man who underwent a resection for thymoma 48 months ago. The diagnosis of Addison disease was made followed by a diagnosis of myasthenia gravis on the basis of a high titer of acetylcholine receptor levels. The treatment of oral prednisolone 7.5 mg/day and oral prostigmine 180 mg/day was initiated. His symptoms and physical signs were improved after this treatment. To our knowledge, this is the fourth reported case of thymoma synchronously associated with myasthenia gravis and Addison disease.

A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.

Similar prevalence of somatic TSH receptor and Gsalpha mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey.

OBJECTIVE: Differences in iodine intake could account for the variable prevalences reported for somatic TSH receptor (TSHR) mutations in toxic thyroid nodules (TTNs). However, this question has not been settled, since no study has yet determined the TSHR mutation prevalence in regions with different iodine supplies in the same population using the same methodology. Therefore, we studied the prevalence of somatic TSHR mutations in TTNs from patients living in iodine-deficient or -sufficient regions in Turkey. DESIGN AND METHODS: We screened 74 TTNs for somatic TSHR mutations. Exons 9 and 10 of the TSHR and 7 and 8 of the Gsalpha were screened by denaturing gradient gel electrophoresis. Determination of X-chromosome inactivation was used for clonality analysis. RESULTS: TSHR mutations were identified in 52 (70.2%) of 74 TTNs. A Gsalpha mutation was identified in one TTN. Three new TSHR mutations were detected (A627V, I640K, I486N). No significant difference between frequencies of TSHR mutations in iodine deficient/sufficient regions was found. The frequency of non-random X-chromosome inactivation was similar in iodine-sufficient or -deficient regions and in TSHR mutation positive or negative hot nodules. CONCLUSIONS: These findings suggest that TTNs in iodine deficient/sufficient areas predominantly arise from aberrant growth of a single cell. Our results suggest that neither the prevalence of TSHR mutations nor that of monoclonal TTNs is related to iodine supply.

A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue.

The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.

Is adiponectin level a predictor of nonalcoholic fatty liver disease in nondiabetic male patients?

AIM: Adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumor necrosis factor. We studied its levels in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD) and compared with control group. METHODS: Thirty-five patients who had elevated serum aminotransferase levels with bright liver and 34 healthy volunteers without liver disease were evaluated. Age, gender and body mass index (BMI) were recorded. Fasting plasma glucose, insulin, adiponectin, proinsulin and lipid profile were measured. A standard oral glucose tolerance test (OGTT) with insulin response was performed and the index of insulin resistance was calculated according to the homeostasis model assessment (HOMA) method. RESULTS: According to the OGTT results, none of the participants had diabetes. Serum adiponectin levels were statistically significantly lower in patients with NAFLD than in control group (8.14+/-3.4 microg/mL vs 12.4+/-9.4 microg/mL, respectively, P<0.01). A statistically significant correlation was found between adiponectin and BMI (r : -0.33, P<0.01), HOMA (r : -0.26, P<0.05), proinsulin (r : -0.32, P<0.01), AST (r : -0.25, P<0.05), ALT (r : -0.26, P<0.05) or GGT (r : -0.22, P<0.05). In multiple regression analysis models, adiponectin levels were the only predictor of NAFLD in males, whereas in female group it was the BMI. CONCLUSION: Low adiponectin level might be a predictor of NAFLD especially in male nondiabetics.

Prevalence of peripheral neuropathy in type 2 diabetic patients attending a diabetes center in Turkey.

The aim of this study was to determine the prevalence and risk factors for neuropathy in type 2 diabetic patients attending a major Turkish diabetes center. Eight hundred and sixty-six consecutive type 2 diabetic patients were included in the study. A single observer performed biothesiometry studies on these patients. The presence of diabetic neuropathy was investigated using neurological symptom scale (NSS) and neurological disability score (NDS) performed. Neuropathy was determined with standardized neurological examinations and defined as the presence of abnormal NSS and NDS together with abnormal sensory or motor signs and symptoms as well as decreased great toe vibration perception. Overall, 60% (n = 520) of the patients were diagnosed as having neuropathy. The prevalence of neuropathy increased with age (p < 0.001) and duration of diabetes (p < 0.001). Multiple logistic regression analysis revealed the duration of diabetes (p < 0.001) and HbA1c levels (p < 0.001) as the risk factors for neuropathy. The overall prevalence of neuropathy in Turkish type 2 diabetic population was 60%. Age, duration of diabetes, and poor glycemic control were considered to be the risk factors for neuropathy.