Further indications for genetic heterogeneity of euthyroid familial goiter

Iodine deficiency is the most important etiological factor for euthyroid endemic goiter. However, family and twin pair studies also strongly indicate a genetic prediposition. In euthyroid goiters molecular defects in the thyroglobulin (TG), and Na⁺/I^– symporter (NIS) gene have been identified. Numerous mutations in the Pendrin (PDS) gene have been found in families with PDS characterized by deafness and euthyroid goiter. Moreover, family studies indicated two major candidate loci MNG-1 on chromosome 14q31 and Xp22. However, all previous linkage studies investigated only one family. To clarify the general relevance of these previously identified two major candidate loci for the etiology of euthyroid goiter we investigated four families with a total number of 74 family members by linkage analysis with microsatellite markers. Moreover, we analyzed the thyroid candidate genes TG, thyroperoxidase (TPO), NIS, TSH receptor, and PDS. In a further family with 12 members in whom we have previously demonstrated linkage to the MNG-1 locus we investigated the Xp22 locus and the PDS gene in addition to our initial study. Linkage analysis results of our study are not significant enough to definitely exclude or confirm linkage to the investigated candidate genes and loci. Nevertheless, we obtained very weak indications for possible linkage to Xp22 in one family by a maximal multipoint LOD score of 1.15, and cosegregation of haplotypes among affected family members. Moreover, in another family linkage to PDS was indicated by a maximal multipoint LOD score of 1.87 as well as cosegregation of haplotypes. However, sequencing of the PDS gene did not reveal germline mutations. A significant total NPL score of 6.5 for PDS over all families most likely indicated linkage to a genomic region close to PDS. Furthermore, the likelihood of linkage to MNG-1 and Xp22 is reduced, because multipoint LOD scores were below 1 or negative. In all families there was no significant evidence for linkage for the thyroid candidate genes TG, TPO, NIS, or the TSH receptor. In conclusion, a general role of MNG-1 and Xp22 for the etiology of euthyroid goiter is unlikely but cannot clearly excluded. The multipoint parametric and nonparametric LOD scores further suggest genetic heterogeneity in the etiology of familial euthyroid goiter. To identify other susceptibility loci it is necessary to perform genome-wide linkage analysis studies with more families.Abbreviations MNG Euthyroid multinodular goiter - NIS Sodium iodide symporter - NPL Nonparametric linkage - PDS Pendred syndrome - TG Thyroglobulin - TPO Thyroid peroxidase - TSH Thyroid-stimulating hormone - TSHR Thyroid-stimulating hormone receptor     

Thyroid volume of east Slovakian adolescents determined by ultrasound 40 years after the introduction of iodized salt

Summary Thyroid volume was examined by ultrasonography in 207 boys and 220 girls aged 15–16 years from East Slovakia and it was found that 49.3% of the boys and 52.3% of the girls had thyroids between 10 and 15 ml. These thyroid volumes resemble those found in school children from areas of mild iodine deficiency (e.g. FRG) and are twice as large as those reported from Sweden, where iodine intake is sufficient. The findings were compared to these reported by others in 1949–53 before the introduction of iodine prophylaxis. It may be concluded that 40 years of goiter prophylaxis with iodized salt, though resulting in urinary excretion of approximately 100 µg/24 hr (as found by others in 1984), abolished large and medium size goiters in adolescents and decreased a prevalence of goiter grade I to about 25 percent, but appeared still to be insufficient to prevent goiter grade I completely.Abbreviations FRG Federal Republic of Germany - WHO World Health Organization - SD standard deviation     

Amino Acid Composition of Proteins Extracted from Endemic Goiter Glands

Proteins were isolated and characterized in thyroid tissue of six patients from Brazil with endemic goiter. Biochemical studies of these thyroidal proteins included gel filtration, electrophoresis, and amino acid analysis. In addition to thyroglobulin, two of the most abundant proteins found in all goiters studied had molecular weights of 68 and 14 kDa. One protein was identified as albumin based on its immunoreactivity with antibodies to serum albumin. The other protein was identified as a hemoglobin subunit using reversephase high-performance liquid chromatography (HPLC). Identification was confirmed by partial N-terminal amino acid sequencing that showed several nonconservative differences in thyroid albumin when compared to human serum albumin (HSA). Biochemical findings were correlated with iodine and hormone contents in serum and thyroglobulin from these patients. Based on these findings, we suggest that hemoglobin and albumin are taken up from the blood by the hyperplastic thyroid tissue. Albumin would be processed by the thyroid follicular cell, becoming iodinated and released into the circulation.     

Adrenal Medullary Hyperplasia: Hyperplasia-pheochromocytoma Sequence

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with-clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.     

Breast filariasis diagnosed by needle aspiration cytology.

A case of nodular lesion of the breast in a 37 year old female caused by filariasis is described. The case is instructive since the diagnosis was made by fine-needle aspiration cytology.     

Pathology of the Liver in "Idiopathic Portal Hypertension" Associated with Autoimmune Disease

The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. Acta Pathol Jpn 39: 586-592, 1989.     

高蛋白质营养抗高碘致甲状腺肿作用的实验研究

目的 :复制小鼠高碘甲状腺肿模型 ,研究高蛋白质营养对高碘状腺肿的预防作用。方法 :将昆明雄性小鼠随机分成 4组 :H组饮高碘水 (碘浓度为 2 50 0 μg/L) ,食普通鼠饲料 ,不含酪蛋白 ;C1和C2 组饮高碘水 ,同时饲养高蛋白饲料 (C1组为鼠饲料混入 2 5%酪蛋白 ,C2 组混入 50 %酪蛋白 ) ;N组为对照组食普通鼠饲料 ,饮自来水 (碘浓度为 7.5μg/L)。实验时间 150d ,观察小鼠甲状腺重量、甲状腺碘含量 (Riesco碘测定方法 )、甲状腺组织学结构 (光镜和电镜 )、甲状腺和垂体功能及TPO活性 (愈创木酚分析法 )。结果 :H组甲状腺碘含量、血FT4 水平较对照组、C1和C2 组明显升高 (P <0 .0 0 1) ,TPO活性明显下降 (P <0 .0 0 1) ,甲状腺呈典型的胶质性甲状腺肿。结论 :高碘对甲状腺有损伤作用 ,高酪蛋白膳食能明显抑制高碘甲状腺肿的发生 ,机制可能是其阻止过量碘进入甲状腺内。