Epidemiologic studies after the disaster in Czernobyl in the population of children in the Krakow region]

In 1989-1990 the epidemiologic studies about the impact of of Czarnobyl events on the health of children in Kraków and Nowy Sacz region were performed. The morphologic and functional changes of thyroid gland in children were estimated. Almost 90% of children in both districts received the iodine preparations for prophylactic reason. The mean time of intake was between 5-10 days following the Czarnobyl explosion. There were no relationship between the dose of iodine absorbed during prophylactic action and incidence of goiter. The prevalence of goiter amounted to 34.8-47.6% in boys and girls consecutively in Kraków district and 53.8-70.5% in Nowy Sacz. No hormonal changes in T3, T4 and TSH serum concentration were found in children with goiter and those without goiter. The complications after iodine intake were transient and seen only in a small number of children.     

Congenital iodide organification defect accompanied by a large nodular goiter: a case report

A girl who had a nontoxic diffuse goiter with a congenital organification defect of iodide was first seen at the age of 8 years, and since then she has been followed up for a long period. The nodularity of the thyroid gland had gradually progressed, because of intermittent failure of ingestion of thyroid hormone preparation which was followed by excess TSH secretion. 18 years later, a nodular goiter developed and the patient underwent subtotal thyroidectomy. In order to prevent the development of nodular change in the thyroid gland in this disorder, supplemental thyroid hormone medication should be started as soon as the diagnosis is confirmed, and the therapy should be carried out regularly.     

Physiological and Morphological Specific Features of the Formation of the Thyroid Status in the Aboriginal and Migrant Populations of Magadan Oblast

Ultrasonographic determinations of the thyroid gland volumes and measurement of the blood plasma content of thyroxin and triiodothyronine were carried out in 1176 apparently healthy residents of the Magadan oblast, all those examined being divided by sex, age, and the adaptation time in the North. Special attention was given to the thyroid system parameters of the aborigines 17 to 40 years old living in the urban area and not involved in the traditional life style. The indigenous population of the Extreme North and migrants were shown to have marked functional adaptive hyperplasia of the thyroid gland and diffuse goiter in 15% of cases. The size of the thyroid gland and the level of the thyroid hormones in the aboriginal population are within the average European range. Diffuse goiter manifestations in males virtually do not occur; in women, the incidence does not exceed 5%. The assumption is advanced as to the formation in aborigines of the northern hypothyroid phenotype providing for the sustained optimal level of the thyroid system functioning without an increase in the thyroid volume.     

Thyroid: an Unusual Hideout for Sarcoidosis

ObjectiveTo present a case of dysphagia secondary to a progressively increasing nontoxic multinodular goiter caused by sarcoidosis.MethodsWe summarize the clinical presentation and pertinent pathology in a patient with sarcoidosis involving the thyroid gland. A review of literature regarding this topic is also presented.ResultsA 54-year-old man was noted to have asymptomatic nontoxic thyromegaly. Biopsy of right thyroid nodule was benign while the biopsy from the isthmus nodule was nondiagnostic. He presented with acute onset of dysphagia two months later and the work-up for gastrointestinal causes was negative. Chest imaging showed left-sided lymphadenopathy, and biopsy of a lymph node showed sarcoidosis. Two years after the initial presentation a repeat biopsy of the isthmus nodule was again reported as nondiagnostic. Because he had persistent dysphagia, he underwent total thyroidectomy with resolution of dysphagia. Histopathological examination of the thyroid revealed non necrotizing granulomas consistent with sarcoidosis.ConclusionThis case brings to light this uncommon etiology of a nontoxic multinodular goiter. Involvement of the thyroid gland by sarcoidosis is very rare. It has been reported in 4.2 to 4.6% of patients with sarcoidosis. In patients with pulmonary or extrapulmonary sarcoidosis and associated thyromegaly, possible involvement of the thyroid by this process should be considered. (Endocr Pract. 2013;19:e40-e43)     

Content of thyroglobulin polyribosomes in normal and pathological thyroid cells]

The content of individual thyreoglobulin (TG) polyribosomes in human thyroid gland was studied in healthy persons and in patients with thyroid pathology. The content of TG polyribosomes makes up to 16.2% in normal thyroid tissue and is found to decrease down to 7.8% and 7% under nodal euthyroid goiter and toxic adenoma, respectively. This content is decreased to 12.5% under diffuse toxic goiter and is intermediate between nodal and diffuse toxic goiter under mixed goiter (9.4%).     

H-RAS gene expression in human multinodular goiter

The RAS protooncogene has an important, although not yet established role in thyroid neoplasia. In this study, we evaluated the H-RAS mRNA and protein levels in human samples of nontoxic and toxic multinodular goiter samples, according to serum TSH levels. The mean of H-RAS mRNA levels in nodules of nontoxic nodular goiter were significantly increased compared to nonnodular tissue (1.49+/-1.21 vs. 0.94+/-0.81 AU, P=0.016). Nine of the 18 specimens (50%) of nontoxic multinodular goiter exhibited increased levels of H-RAS mRNA. The increased H-RAS mRNA levels were paralleled by inRAcreased H-Ras protein levels in about 90% of the cases. Interestingly, no differences were observed in H-RAS expression between nodules and adjacent nonnodular tissue in toxic nodular goiters (0.58+/-0.27 vs. 0.58+/-0.20 AU, P=0.88). None of the 10 samples from toxic multinodular goiters exhibited overexpression of H-RAS. The H-RAS expression was positively correlated with thyroglobulin expression (r2=0.51; P=0.04). In conclusion, we demonstrated increased levels of H-RAS mRNA and protein in samples of nontoxic multinodular goiter, indicating that it might be involved in goiter pathogenesis. In contrast, H-RAS overexpression was not detected in any of the samples of toxic multinodular goiter, suggesting different mechanisms for cell proliferation in nodular goiter according to thyroid status.     

Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats

Cruciferous plants viz. cabbage, cauliflower, turnip, radish, mustard etc. that contain goitrogenic/antithyroid substances, constitute a portion of regular human diet. The effect of chronic feeding of fresh and cooked radish, R. sativus under varying state of iodine intake on morphological and functional status of thyroid in albino rats was evaluated by thyroid gland morphology and histology, thyroid peroxidase activity, serum triiodothyronine, thyroxine and thyrotropin levels. The consumption pattern of iodine and goitrogens of cyanogenic origin was evaluated by measuring urinary iodine and thiocyanate levels respectively. After chronic radish feeding, increased weight of thyroid gland, decreased thyroid peroxidase activity, reduced thyroid hormone profiles and elevated level of thyrotropin were observed resembling a relative state of hypoactive thyroid gland in comparison to control even after supplementation of adequate iodine.     

Cytologic appearance of toxic nodular goiter after thyrostatic treatment. A karyometric study

OBJECTIVE: To assess whether the cytologic appearance of aspirates from toxic nodular goiter is substantially modified during the course of therapy with thyrostatic drugs. STUDY DESIGN: Morphometric features of thyrocyte nuclei in aspirates obtained from nontoxic nodular goiter (NTNG), toxic nodular goiter before treatment (TNG-untreated) and toxic nodular goiter during thyrostatic administration (TNG-treated) were examined. The relationship between the degree of morphologic changes and the duration of therapy was evaluated. An analysis of the composition of aspirates was also performed. RESULTS: The sizes of thyrocyte nuclei in the TNG-untreated group were larger than in the NTNG and TNG-treated groups, and treatment with thyrostatics was accompanied by a gradual decrease in the sizes of thyrocyte nuclei. However, karyometric features showed a tendency to increase again in patients treated for longer than 1 year, with the variability of nuclear size in a smear (anisokaryosis) increasing more markedly than the mean size of nuclei. Moreover, in those patients, nuclei with visible nucleoli were found. CONCLUSION: Only long-term therapy with thyrostatic drugs leads to changes in the microscopic appearance of smears obtained by fine needle aspiration biopsy (FNAB) of the thyroid relevant to cytologic diagnosis. Thus, FNAB can be performed successfully after the onset of treatment with thyrostatics if the cytologist is informed of the time scale of treatment in each case.     

Expression of Bcl-2 family proteins in thyrocytes from young patients with immune and nonimmune thyroid diseases

The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves' disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.     

Planimetric studies on fine needle aspirates from follicular adenoma and follicular carcinoma of the thyroid

A planimetric study was performed on fine needle aspiration biopsy smears from 21 follicular thyroid adenomas, 13 follicular thyroid carcinomas and 7 nontoxic goiters. The nuclear and the cytoplasmic projected areas were measured in each smear on 50 cells with intact nuclei. The nuclear-cytoplasmic area was calculated. Significant differences in mean nuclear area were found between benign and malignant follicular neoplasms and between neoplastic cells and cells from nontoxic goiter. Planimetry of cells aspirated from follicular neoplasms permitted differentiation between carcinomas and adenomas with a high degree of statistical probability.     

Connexin-32 acts as a downregulator of growth of thyroid gland

Thyroid epithelial cells communicate through gap junctions formed from connexin (Cx)32, Cx43, and Cx26. We previously reported that reexpression of Cx32 in "gap junction-deficient" FRTL-5 and FRT thyroid cell lines induces a reduction of cell proliferation rate and an activation of expression of cell differentiation. The present study aimed at determining whether Cx32 could exert similar regulatory functions in vivo. We investigated morphological and functional characteristics of thyroid gland of Cx32-deficient mice (Cx32-KO), mice overexpressing Cx32 selectively in the thyroid (Cx32-T+), and Cx32-KO mice with a thyroid-selective Cx32 complementation obtained by crossing Cx32-KO and Cx32-T+ mice. In basal conditions, Cx32-KO mice did not present any detectable thyroid alteration, whereas Cx32-T+ mice showed a thyroid hypoplasia (20% reduction) associated with a slight increase in thyroid functional activity. Under thyrotropin stimulation (following sodium perchlorate treatment), Cx32-KO mice developed a larger goiter (< or =65% increase) than wild-type littermates, whereas Cx32-T+ mice exhibited the same thyroid hyperplasia as wild-type mice. Restoration of Cx32 expression in the thyroid of Cx32-KO mice abrogated the thyroid growth increase related to Cx32 deficiency. All together, these data show that Cx32 acts as a downregulator of growth of thyroid gland; an excess of Cx32 limits growth of thyroid cells in the basal state, whereas a lack of Cx32 confers an additional growth potential to TSH-stimulated thyroid cells.     

Does Unilateral Lobectomy Suffice to Manage Unilateral Nontoxic Goiter?

ObjectiveTo evaluate the effectiveness of ipsilateral lobectomy to treat unilateral, nontoxic, benign nodular goiter and to define predictive factors for recurrence.MethodsPatients undergoing thyroid lobectomy for unilateral, nontoxic, benign nodular goiter between 2002 and 2007 were included. Patients were excluded if coincidental thyroid cancer was detected at histopathologic examination and completion thyroidectomy was performed. Potential predictors of recurrence including age; sex; family history; preoperative volume of the thyroid gland; preoperative number, size, and ultrasonography characteristics of the nodules; duration of postoperative follow-up; postoperative use of thyroxine; and histopathologic diagnoses were recorded at baseline. Follow-up visits were scheduled every 3 months during the first year and every 6 months thereafter. Recurrent disease was defined as a hypoechogenic or hyperechogenic nodule larger than or equal to 3 mm detected in the remaining contralateral lobe during ultrasonography. Patients with a thyrotropin value greater than 5 mIU/L received thyroxine. Fineneedle aspiration biopsy was performed for nodules greater than 10 mm or for nodules with characteristics suggestive of malignancy. Reoperation was indicated if a nodule was greater than 3 cm in diameter, posed a risk of malignancy, or caused compression signs or symptoms.ResultsA total of 104 patients were included. Histopathologic diagnoses at initial operation were adenoma in 45 patients, colloidal nodular goiter in 45 patients, and chronic lymphocytic thyroiditis in 14 patients. Average duration of follow-up was 39.75 ± 21.75 months (range, 5-87 months). Recurrence was seen in 63 patients (60.6%). Histopathologic characteristics of the lobectomy material (P <.001), preoperative volume of the thyroid gland (P <.006), and multinodularity (P <.011) were significant predictors of recurrence.ConclusionsHigher preoperative thyroid volume, histopathologic characteristics of nodules, and multinodular disease are associated with an increased risk of recurrence in patients with unilateral nodular goiter. Unilateral lobectomy is an effective therapeutic option with low reoperation rates in unilateral benign thyroid disease. (Endocr Pract. 2010;16:36-41)     

Association of different pathologic processes of the thyroid gland in fine needle aspiration samples

OBJECTIVE: To evaluate the possible significant association between different pathologic processes of the thyroid gland. STUDY DESIGN: From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, a total of 1,330 cases were aspirated involving two or more palpable nodules. In 103 (1%) cases, two different pathologic processes were cytologically diagnosed. Statistical analysis was performed through four two-tailed chi 2 tests to evaluate the following events: (1) mononodularity and multinodularity vs. neoplasms, (2) colloid goiter and neoplasms, and (3) all neoplasms vs. colloid goiter and lymphocytic thyroiditis. All tests were performed using < .05 as the probability level. RESULTS: Simultaneous pathologic processes observed were: goiter and chronic lymphocytic thyroiditis (32), goiter and Hashimoto's thyroiditis (21), goiter and subacute granulomatous thyroiditis (8), goiter and follicular neoplasm (9), and goiter and papillary carcinoma (14). In 12 cases we found goiter and Hürthle cell tumor, goiter and medullary thyroid carcinoma (2), papillary thyroid carcinoma and Hashimoto's thyroiditis (2), Graves' disease and lymphocytic thyroiditis (2), and follicular neoplasm and lymphocytic thyroiditis (1). Statistical analysis showed significant association between multinodularity and neoplasms (P < .001), while the association between goiter and any type of neoplasia was not statistically significant. All the neoplasms taken together were associated with lymphocytic thyroiditis and goiter (P < .005). CONCLUSION: While there may be no statistically significant associations between the individual pathologies, it seems that having one pathology increases the risk of developing another. All the palpable nodules in the same gland should be investigated by fine needle aspiration in order to improve diagnostic sensitivity and to identify occult neoplasms.     

乳头状甲状腺癌中线粒体DNA突变的研究

该文探究了线粒体DNA(mtDNA)突变与甲状腺癌的发生发展的相关性,评估了mtDNA拷贝数对甲状腺癌的诊断价值。根据对结节性甲状腺肿、滤泡状甲状腺腺瘤和乳头状甲状腺癌3组病人的mtDNA全基因测序和单倍型分型结果,统计3组病人mtDNA突变率及单倍型的差异,分析乳头状甲状腺癌病人的mtDNA突变率与临床资料的联系,最后通过荧光定量PCR检测3组病人的组织和血液样本中mtDNA的拷贝数。结果显示,乳头状甲状腺癌患者mtDNA的复合体I亚基编码区和tRNA编码区的突变率明显高于结节性甲状腺肿,在乳头状甲状腺癌患者中线粒体单体型M相对于单体型N有更低的淋巴结转移率,荧光定量PCR结果显示,甲状腺腺瘤和甲状腺癌组织中的mtDNA拷贝数明显高于结节性甲状腺肿,而在血液标本中,两者的mtDNA拷贝数均低于结节性甲状腺肿。这些结果表明,mtDNA拷贝数的变化和复合体I亚基编码区的突变可能作为甲状腺癌诊断的生物指标,而线粒体单体型N可能可以作为乳头状甲状腺癌恶性变化的预警指标。     

Role of Bamboo-Shoot in the Pathogenesis of Endemic Goiter in Manipur,North East India

ObjectiveEndemic goiter is prevalent in the iodine-sufficient region of Manipur, India. Bamboo shoot (BS), a goitrogenic plant food, are consumed regularly in the area. The objective of this study was to examine the role of BS in the pathogenesis of endemic goiter.MethodsGoiter prevalence, urinary iodine, and thiocyanate (SCN) excretion in school children, iodine content in drinking water, and the household consumption of salt fortified with iodine were measured. To confirm the goitrogenic potential of BS, its progoitrogenic constituents were fed to rats as part of an iodine-sufficient diet, after which the animals' thyroid gland morphology and functional status were assessed.ResultsGoiter prevalence was 31% in 4852 children, and the median urinary I and SCN levels were 176.3 μg/L and 0.962 ± 0.190 mg/dL, respectively. Of the households assessed, 90% consumed salt fortified with adequate iodine. Progoitrogenic constituents were high in BS from Manipur. Increased thyroid weight, hypertrophy and hyperplasia of follicular cells, decreased thyroid peroxidase activity, and low serum thyroxine (T₄) and triiodothyronine (T₃) levels were observed in BS-fed rats.ConclusionNearly one third of the studied participants had palpable goiter, despite a successful salt iodine fortification program. SCN from BS causes goiter in iodine-sufficient experimental animals. Similar ingestion in study participants was confirmed and is the likely cause for the persistence of endemic goiter in the Manipur region. (Endocr Pract. 2013;19:36-45)     

Pituitary resistance to thyroid hormone--a case report

Pituitary resistance to thyroid hormone is a very rare cause of hyperthyroidism. It is characterized by normal, or elevated TSH concentration with high concentration of T3 and T4. Here, we present a case of a 24-year-old woman who suffered from mild thyrotoxicosis and diffuse goiter for several years. She had elevated fT3 and fT4 with slightly elevated TSH concentration. Pituitary adenoma was excluded as magnetic resonance imaging showed normal pituitary gland, alpha subunit was within normal range and TSH concentration increased after TRH administration. Sonography revealed normoechogenic, slightly enlarged thyroid gland. Previously, she was given thiamazole, but without any significant amelioration. Thus, the diagnosis of the syndrome of pituitary resistance to thyroid hormone was established. The patient was given bromocriptine at a dose of 10 mg per day. After 2 months of treatment she achieved a state of constant euthyrosis and following next few months thyroid volume diminished.     

Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.

Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.     

Relationship of biochemical and morphological changes in rat thyroid and proton spin-relaxation of the tissue water.

The effect was studied of biochemical and morphological changes induced by antithyroid substances (PTU, C10(-4)) on proton spin-relaxation properties of rat thyroid gland. It was found that thyroid stimulated by PTU (0.05%) or C10(-4) (1.0%) exhibit marked morphological changes (hyperplasia and epithelial hypertrophy) with alteration of the soluble iodoprotein pattern (content and composition.). Both relaxation times spin-lattice (T1) and spin-spin (T2) were increasing with the lenght of treatment with antithyroid drugs. Reversibility of the process was noted in accordance with biochemical and morphological data. The relaxation rate (formula: see text) for thyroid tissue water was in positive correlation with the suluble protein concentration and particularly with the TG content in the gland. There was no difference in relaxation times between normal thyroid and gland of rats treated chronically with excess iodide. The observed difference in T1 between normal glands and glands of PTU,-C10(-4)--treated rats was comparable with that found in cases of human thyroid cancer. This finding is of importance when the diagnostic potential of NMR in the detection of malignancy is considered. In conclusion, a strong correlation was found between microstructural and biochemical changes of the thyroid gland and proton magnetic relaxation of tissue water. The striking difference between the proton spin-relaxation times in normal and in goiter thyroid glands of rats suggests that pulsed NMR spectroscopy could be a method for evaluation of some disturbances in thyroid gland.     

Function of the serotoninergic system of the thyrotoxic thyroid

The state of serotoninergic system in thyrotoxic and euthyroid gland were compared. It was shown that in patients with hyperthyroidism (diffuse toxic goiter) serotonin and 5-hydroxytryptophan content, velocity and the latter uptake were augmented. The authors stress the role of the delay in serotonin oxidative deamination as one of the reasons for increased serotonin content in thyrotoxic thyroid gland. Possible ways of increasing intrathyroid serotonin accumulation and its role in the development of thyroid hyperfunction are discussed.     

Competition can maintain genetic but not environmental variance in the presence of stabilizing selection

A population in which there is stabilizing selection acting on quantitative traits toward an intermediate optimum becomes monomorphic in the absence of mutation. Further, genotypes that show least environmental variation are also favored, such that selection is likely to reduce both genetic and environmental components of phenotypic variance. In contrast, intraspecific competition for resources is more severe between phenotypically similar individuals, such that those deviating from prevailing phenotypes have a selective advantage. It has been shown previously that polymorphism and phenotypic variance can be maintained if competition between individuals is "effectively" stronger than stabilizing selection. Environmental variance is generally observed in quantitative traits, so mechanisms to explain its maintenance are sought, but the impact of competition on its magnitude has not previously been studied. Here we assume that a quantitative trait is subject to selection for an optimal value and to selection due to competition. Further, we assume that both the mean and variance of the phenotypic value depend on genotype, such that both may be affected by selection. Theoretical analysis and numerical simulations reveal that environmental variance can be maintained only when the genetic variance (in mean phenotypic value) is constrained to a very low level. Environmental variance will be replaced entirely by genotypic variance if a range of genotypes that vary widely in mean phenotype are present or become so by mutation. The distribution of mean phenotypic values is discrete when competition is strong relative to stabilizing selection; but more genotypes segregate and the distribution can approach continuity as competition becomes extremely strong. If the magnitude of the environmental variance is not under genetic control, there is a complementary relationship between the levels of environmental and genetic variance such that the level of phenotypic variance is little affected.