A case of neuroblastoma in DICER1 syndrome: Chance finding or noncanonical causation?

DICER1 syndrome is an inherited disorder associated with at least a dozen rare, mainly pediatric-onset tumors. Its characterization remains incomplete. Some studies suggested that neuroblastoma (NB) may be involved in this syndrome. Here, we describe the case of a 14-year-old female presenting with a multinodular goiter (MNG) and a collision tumor composed of NB and cystic nephroma (CN). She is a carrier of a deleterious germline mutation in exon 23 of DICER1 and harbored different somatic mutations in the CN and MNG. However, no second hit was found in the NB, questioning its status as a DICER1-related tumor.

Investigation of the Mg-HCO3⁻-ATPase activity of thyroid tissue cells under various pathologies.

Distribution of the Mg²âº-dependent, HCO3⁻-stimulated ATPase (HCO3⁻-ATPase) was investigated in sub-cellular fractions of the tissue of the human thyroid gland. It was found that especially high enzymatic activity is characteristic of mitochondria and the endoplasmic reticulum. Correlation between various pathologies of the thyroid and HCO3⁻-ATPase activity was demonstrated. The activity was evaluated using the difference between active and passive ATPase. During development of the various pathologies, the sub-cellular fractions of the gland showed uneven alterations of HCO3⁻-ATPase activity. Intriguingly, the enzyme kinetic parameters are also changed, i.e. in the different pathologies both enzyme activity and its affinity towards bicarbonate ions are altered. This raises the question whether pathology is caused by, or results in, changes in the enzyme at the molecular level.

Pendred syndrome in two Galician families: insights into clinical phenotypes through cellular, genetic, and molecular studies.

CONTEXT: We studied two families from Galicia (northwest Spain) with Pendred syndrome (PS) and unusual thyroid phenotypes. In family A, the proposita had a large goiter and hypothyroxinemia but normal TSH and free T3 (FT3). In family B, some affected members showed deafness but not goiter. OBJECTIVE: Our objective was to identify the mutations causing PS and molecular mechanisms underlying the thyroid phenotypes. INTERVENTIONS: Interventions included extraction of DNA and of thyroid tissue. PATIENTS: Propositi and 10 members of the two families participated in the study. MAIN OUTCOME MEASURES: Main outcome measures included SLC26A4 gene analysis, deiodinase activities in thyroid tissue, and c.416-1G-->A effects on SLC26A4 splicing. In addition, a primary PS thyrocyte culture, T-PS2, was obtained from propositus B and compared with another culture of normal human thyrocytes, NT, by Western blotting, confocal microscopy, and iodine uptake kinetics. RESULTS: Proposita A was heterozygous for c.578C-->T and c.279delT, presented with goiter, and had normal TSH and FT3 but low FT4 attributable to high type 1 and type 2 iodothyronine deiodinase activities in the goiter. Propositus B bore c.279delT and a novel mutation c.416-1G-->A; some deaf relatives were homozygous for c.416-1G-->A but did not present goiter. The c.279delT mutation was associated with identical haplotype in the two families. T-PS2 showed truncated pendrin retained intracellularly and high iodine uptake with low efflux leading to iodine retention. CONCLUSIONS: c.279delT is a founder mutation in Galicia. Proposita A adapted to poor organification by increasing deiodinase activities in the goiter, avoiding hypothyroidism. Lack of goiter in subjects homozygous for c.416-1G-->A was due to incomplete penetrance allowing synthesis of some wild-type pendrin. Intracellular iodine retention, as seen in T-PS2, could play a role in thyroid alterations in PS.

Protein kinase Akt activity in human thyroid tumors.

We studied the expression and activation of the main effector protein kinase of phosphatidylinositol-3-kinase cascade (PI3K) ­ Akt in conventionally normal tissues, benign and highly differentiated (with and without metastases) human thyroid tumors. There was a difference in the Akt1 amount in tumor tissue compared with normal tissue in papillary carcinomas and tissue of multinodular goiter. Akt expression both in tumor and conventionally normal tissues of follicular adenoma was significantly lower than in follicular carcinoma. The lowest level of Akt expression was observed in tissues of multinodular goiter. Total activity of all three isoforms of Akt1/2/3 was lower in tumors compared to conventionally normal tissue. Thus, Akt activity (according to Thr308 phosphorylation) is not associated with proliferative processes in the tumor tissue of the thyroid. Apoptosis level detected in these tissues was not associated with the protein kinase activity either. Possible mechanisms of signaling cascade PI3K/Akt inhibition in thyroid tumors are discussed.

Application of mouse monoclonal antibodies for identification of antigen regions of human thyroid peroxidase in adolescents with Graves' disease and non-toxic multinodular goiter by flow cytometry.

Thyroid peroxidase (TPO) is the major thyroid autoantigen recognized by serum autoantibodies from patients with Graves' disease (GD) or Hashimoto's thyroiditis directed to two immunodominant conformational regions termed A and B. The epitopes of human TPO have been defined using a panel of mouse monoclonal antibodies (mAbs). The aim of this study was to estimate the expression of chosen surface antigen regions of TPO (1, 18, 30, 64 epitopes) on thyroid cells in 15 patients with non-toxic multinodular goiter (NTMG) and 15 patients with GD. The thyrocytes were identified by indirect method: in the first stage we added mouse monoclonal autoantibodies specific for TPO regions and in the second stage we conjugated this complex with rabbit anti-mouse antibodies IgG (Fab')(2) with FITC. All investigations were performed by flow cytometry using Coulter EPICS XL apparatus. The percentages of thyrocytes with expression of epitopes 1, 18, 30, 64 TPO were measured in relation to the respective anti-TPO concentrations: 50-1600 microg/ml. The analysis of epitopes located in immunodominant regions (IDR) of TPO revealed higher percentages of thyrocytes in cases with GD in comparison to NTNG. The most predominant difference was observed for mAb 64 epitope (48 vs 7%, p < 0.019; 39 vs 5%, p < 0.017) at the concentration of 100-200 microg/ml mAbs. The expression of 18 epitope on thyrocytes was also statistically higher in Graves' patients than in the NTMG (14 vs 6%, p < 0.025) at concentration of 400 microg/ml mAbs. However, this expression was much less pronounced. In all the cases, the percentages of thyrocytes with epitopes 1 and 30 were in low detection (8-15% of positive cells). In conclusion, our findings suggest that the elevated expression of TPO epitopes 18 and 64 in young patients with thyroid autoimmune diseases increase stimulation and activation of thyroid cells during inflammatory reaction within the thyroid gland. In addition, predominant expression of 64 TPO epitope that recognizes B domain in GD patients could be a useful marker of the immune process in the thyroid gland.

[Cytofluorymetric evaluation of antigen regions of human thyroid peroxidase in patients with Graves' disease and non-toxic multinodular goiter using mouse monoclonal antibodies]. / Ocena cytofluorymetryczna wybranych regionów antygenowych ludzkiej tyreoperoksydazy u pacjentów z choroba Gravesa-Basedowa oraz z wolem wieloguzkowym nietoksycznym z zastosowaniem mysich przeciwcial monoklonalnych.

The aim of this study was to estimate expression of surface antigen regions of TPO (thyroid peroxidase: #1, #18, #30, #64 epitopes) on thyroid cells in 15 patients with non-toxic multinodular goiter (NTMG) and 15 patients with Graves' disease (GD). The thyrocytes were identified by indirect method: in first stage we added mouse monoclonal autoantibodies specific for TPO regions and in second stage we conjugated this complex with rabbit anti-mouse antibodies IgG (Fab')2 with FITC. All investigations were performed by flow cytometry using apparatus Coulter EPICS XL. The percentages of thyroid cells with expression of antigen regions of TPO 1, 18, 30, 64 were measured in relationship to the responsible anti-TPO concentrations: 50, 100, 200, 400, 800, 1600 microg/ml. The analysis of the expression of epitope #64 TPO revealed insignificantly increased percentages of thyroid cells in patients with GD (73% vs 45%, ns) in comparison to NTMG at anti-TPO antibody concentration of 1600 microg/ml. In addition, we observed that reduction concentration of anti-TPO antibodies leads to the decreased percentage of thyroid cells with antigen region #64 expression. In patients with GD percentage of this cells was significantly higher (48% vs 7% p<0.019, 29% vs 56% p<0.05) in compared to the percentage of thyroid cells from patients with NTMG at concentration of 200-800 microg/ml anti-TPO antibodies. Analysis of epitopes #1 and #18 shown higher percentage of thyroid cells in GD (25% vs 20%, ns for #1 epitope) and (25% vs 13%, ns for #18 epitope) in comparison to the patients with NTMG at concentration 1600 microg/ml of anti-TPO antibodies. The percentages of thyrocytes with epitopes #1 and #18 were decreased in relation to the reduction of anti-TPO concentrations. However, in all our patients epitope #30 TPO was found only in 8% thyroid cells. We conclude that in young patients thyroid immune and nonimmune diseases predispose to elevated expression of TPO epitopes (#1, #18, #64) which suggested increase stimulation and activation of thyroid cells during inflammatory reaction within thyroid gland. Furthermore, dominance expression of #64 TPO epitope in Graves' patients which recognized B domain could be a useful marker of activity of immune process in concentration between 200-800 microg/ml of TPO antibodies.

Influence of thyroid disorders on the kidney expression and plasma activity of aminopeptidase A.

OBJECTIVE: Thyroid disorders may affect blood pressure and renal function modifying factors of the plasmatic and kidney renin-angiotensin system such as aminopeptidase A (AP A) that metabolizes angiotensin II to angiotensin III. We investigated the expression of AP A in the kidney, as well as its enzymatic activity in the plasma of euthyroid, hyperthyroid, and hypothyroid adult male rats. METHODS: Hyperthyroidism was induced by daily subcutaneous injections of tetraiodothyronine. Hypothyroid rats were obtained by administration of methimazole in drinking water. Expression of AP A was determined by Western blot analysis. Plasma AP A activity was measured fluorometrically using glutamyl-ß-naphthylamide as substrate. RESULTS: While hyperthyroid rats exhibited lower levels of plasma AP A activity than controls, the kidney of hyperthyroid animals expressed significantly higher AP A than controls and hypothyroid animals. CONCLUSIONS: A discrepancy between the high expression of AP A in kidney of hyperthyroid rats and the low activity of AP A measured in plasma and kidney of hyperthyroid animals was found. The posttranslational influence of environmental biochemical factors may be in part responsible for that divergence.

Dissociation of thyrotropin-dependent enzyme activities, reduced iodide transport, and preserved iodide organification in nonfunctioning thyroid adenoma and multinodular goiter.

Several biochemical and functional modifications demonstrated in goitrous tissues could reflect the effect of goitrogenic factors. Growth-enhancing agents, including TSH itself, have been involved in goitrogenesis. To study comparatively the variation patterns of some TSH-dependent enzymes within single goitrous tissues, we measured the activities of peroxidase (TPO), NADPH-cytochrome-c (cyt-c) reductase, and monoamine oxidase (MAO) in tissues from cold follicular adenoma and multinodular goiter. Iodide transport and organification were also evaluated. Perinodular and necropsy tissues were used as controls. The mean TPO activity measured by guaiacol as well as triiodide assays was significantly increased in multinodular goiter, whereas a nonsignificant increment was observed in cold adenoma. NADPH-cyt-c reductase and MAO were markedly increased in the two types of pathological tissues. The individual activities of the three enzymes showed dissimilar modifications within single samples and among different tissues. There was no correlation in the activities of the enzymes within single specimens from cold adenoma and multinodular goiter, except for MAO and NADPH-cyt-c reductase in multinodular goiter, for which a significant correlation was obtained. In this tissue, MAO and TPO measured by guaiacol assay were weakly correlated. TPO activity evaluated by guaiacol oxidation was correlated with that measured by triiodide formation in cold adenoma, but not in multinodular goiter. The mean iodide organification values assayed by iodotyrosine formation in the absence of exogenous H2O2 in particulate fractions from cold adenoma and multinodular goiter were within the normal range. A reduced iodide transport, evaluated as the thyroid/medium ratio, was observed in slices from these tissues. The dissociation of the three enzyme activities in single specimens from cold adenoma and multinodular goiter along with the reduced iodide transport in these tissues support the hypothesis that factors other than TSH or with TSH-like effects could be involved in the abnormal thyroid growth.

Cold follicles in a multinodular human goiter arise partly from a failing iodide pump and partly from deficient iodine organification.

To investigate whether the common cold follicles in human multinodular goiters are the consequence of a functional defect of the apical membrane peroxidase, a failure of the iodide transport system, or both deficiencies, we studied iodide accumulation and iodine organification in 30 fragments of a large multinodular goiter transplanted to nude mice and labeled with 125I. Transplants were frozen to -80 C immediately after removal to avoid diffusion of inorganic iodide. Autoradiographic assessment of over 1000 cryosections (exposed either at -20 C or after thawing and washing out unbound iodide) showed two types of cold follicles, namely those that failed to accumulate iodide and, therefore, did not organify iodine, and those that readily accumulated iodide but failed to bind it, suggesting a failure of apical membrane peroxidase. The two types of pathogenetically different cold follicles coexisted in an apparently randomly intermingled fashion throughout the whole goiter.

Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues.

The large homolog of NADPH oxidase flavoprotein LNOX2, and probably LNOX1, are flavoproteins involved in the thyroid H(2)O(2) generator. Western blot analysis of membrane proteins from normal human thyroid, using antipeptide antibodies, indicated that LNOX1,2 are 164-kDa glycoproteins and that N-glycosylated motifs account for at least 10-20 kDa of their total apparent molecular mass. Northern blot analysis of 23 different human tissues demonstrated that LNOX2 messenger RNA (mRNA) is strongly expressed only in the thyroid gland, although blast analysis of expressed sequence tags databases indicated that LNOX genes are also expressed in some nonthyroid cells. We investigated LNOX1,2 gene and protein expressions in normal and pathological human thyroid tissues using real-time kinetic quantitative PCR and antipeptide antibodies, respectively. In normal tissue, LNOX1,2 are localized at the apical pole of thyrocytes. Immunostaining for LNOX1,2 was heterogeneous, inside a given follicle, with 40-60% of positive follicular cells. Among normal and pathological tissues, variations of LNOX1 and LNOX2 mRNA levels were parallel, suggesting a similar regulation of both gene expressions. Whereas LNOX mRNAs seemed slightly affected in benign disease, the expression of protein was highly variable. In multinodular goiters, 40-60% of cells were stained. In hypofunctioning adenomas, LNOX immunostaining was highly variable among follicles, whereas sodium/iodide (Na+/I-) symporter immunostaining was decreased. In hyperfunctioning thyroid tissues, only few cells (0-10%) were weakly stained, whereas sodium/iodide symporter staining was found in the majority of follicular cells. In conclusion, LNOX proteins are new apical glycoproteins with a regulation of expression that differs from other thyroid markers.

Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients.

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.

Protein kinase patterns in hyperplastic rat thyroids and in human non-toxic nodular goitres.

Patterns of cAMP-dependent protein kinases and cAMP-independent histone and casein kinases of hyperplastic rat thyroid glands and of human nodular non-toxic goitres have been analysed in two subcellular compartments, cytosol and particulate fraction. In hyperplastic rat glands the different compartmentalization of the two cAMP-dependent isoenzymes was preserved and the pattern of cAMP-independent protein kinases was not changed qualitatively, but the activities of the three classes of protein kinases were enhanced to different degrees: the highest increase was observed for the cAMP-dependent enzymes and the lowest for the cAMP-independent casein kinases. Analysis of individual peaks of cAMP-dependent kinases showed selective stimulation of the cytosolic Type II form and independent control of the Type I activity in the two subcellular compartments. Among cAMP-independent protein kinases only two histone kinase peaks were selectively enhanced; other kinase entities were changed to a lesser degree. During the involution of hyperplastic glands, a transient but differential enhancement of nearly all kinases was noted at first, which was followed later by a strong decrease, more or less rapid, of almost all kinase activities. In the regressed glands, neither the thyroid weight nor the pattern of different kinase entities corresponded to those of control, untreated glands, indicating that some of the protein kinase alterations in hyperplastic tissues are partly irreversible. In spite of great similarities, human and rat goitre tissues are not identical. The most important difference was the loss of compartmentalization of the cAMP-dependent isoenzymes in human tissue. The different ratios of the light and heavy peaks of cytosolic cAMP-independent histone kinases was the second characteristic which distinguished human and rat glands.

Cathepsin B activity and protein levels in thyroid carcinoma, Graves' disease, and multinodular goiters.

Cathepsin B (CB) is involved in the hydrolysis of thyroglobulin (Tg) and thought to be regulated by thyroid stimulating hormone (TSH) in the normal thyroid. Our analyses of 91 thyroid tissues from 71 patients with Graves' disease (GD), multinodular goiter (MNG), papillary carcinoma (PC), or follicular carcinoma (FC), demonstrated a 2-fold increase in expression of CB in GD and an average increase of 1.5-fold in MNG (varying from 10-fold below normal to 6-fold above normal in MNG nodules), as might be predicted by the altered functional status of thyroid follicular cells in those diseases. However, CB activity was not downregulated in conjunction with the known "blocking effect" of malignancy on many thyroid functions, but rather increased on average 9-fold in papillary carcinomas (n = 33), and also showed a marked increase in 2 follicular carcinomas. Activity measurements were confirmed by CB protein detection on Western blot with moderately increased CB protein levels demonstrated in GD, variable expression in nodules of MNG, and markedly increased protein expression in carcinomas. In all diseased states, increased protein was detected primarily as overexpression of the 27 kd heavy chain of 2-chain mature CB and less frequently as overexpression of 31 kd single-chain mature CB. However, an additional 35 kd protein form was noted in 3 of 9 PCs, 1 of 2 FCs, and 1 of 4 GD cases but in none of 10 MNG cases. In conjunction with elevated CB activity plus additional protein bands on Western blots, altered patterns of CB immunohistochemical staining were observed, irrespective of the type of thyroid disease, suggesting certain common changes in CB expression, posttranslational processing, and vesicular trafficking. In summary, GD and MNG thyroid tissues demonstrated altered CB expression in keeping with predicted functional changes in thyroid follicular cells, while increased CB expression in carcinomas indicated a more pathological role for CB in thyroid cancers, possibly related to the processes of invasion or metastasis.

Thyroid peroxidase activity in human nodular goiters.

1. Thyroid peroxidase (TPO, iodide-oxidation) activity was evaluated in nodular and paranodular tissue samples from 27 patients with nodular goiter (19 "cold" and 8 "hot" nodules), and compared to 11 diffuse toxic goiter and 9 normal thyroid tissue samples. 2. In terms of U/g digitonin solubilized protein, TPO activity was increased in hot nodules (P less than 0.05), although not as much as in diffuse toxic goiters (P less than 0.01). 3. The mean TPO activity of tissues paranodular to a cold nodule was not different from that of normal thyroids. 4. Both the highest and the lowest TPO activities were found in cold nodules, but their mean value did not differ from those of their paranodular tissues or normal thyroids. 5. Inter-tissue variability was significantly increased (P less than 0.01) in cold nodules and in tissues paranodular to a hot nodule. 6. These data show that heterogeneity both within and among tissues contributes to the wide range of TPO activity detected in nodular goiters.

Staining for dipeptidyl aminopeptidase IV activity in nodular thyroid diseases.

OBJECTIVE: To determine the effectiveness of staining for dipeptidyl aminopeptidase IV (DAP IV) activity in thyroid nodular diseases. STUDY DESIGN: Imprint smears were made in 76 cases of papillary carcinoma, 10 of follicular carcinoma, 32 of follicular adenoma and 48 of adenomatous goiter after surgery, and staining for DAP IV activity was performed in all cases. RESULTS: All papillary carcinomas stained positively, and most adenomatous goiter cases were negative. Follicular carcinoma and follicular adenoma cases exhibited various degrees of positivity, though the former tended to be stained more than the latter. Of the total 166 cases of thyroid nodules, 53 showed negative staining; of those 53, all except 1 were benign. Follicular carcinoma cases that had vascular invasion tended to show a high DAP IV staining pattern, but no statistically significant difference between it and follicular carcinoma that did not show vascular invasion was found. CONCLUSION: DAP IV activity staining might reveal malignant potential and could have some value in the preoperative diagnosis between thyroid nodular diseases. The DAP IV method is a reliable indicator of benign disease if negative results are obtained.

Immunohistochemical assessment of peroxidase-like immunoreactivity in the thyroid gland and its correlation with biochemical assay.

BACKGROUND: Peroxidase content has been recently evaluated in normal thyroid and in different thyroid disorders by biochemical, histochemical, ultrastructural and immunocytochemical methods. Nevertheless immunocytochemical detection of thyroid peroxidase in thyroid samples conventionally processed for histology has never been done using a commercially available antibody, neither its correlation with the biochemical activity on adjacent samples. METHODS: In this study we have analyzed normal thyroid tissue (3 patients), follicular adenoma (2 patients) and multinodular goiter (2 patients) conventionally processed for histology and stained by immunocytochemistry (Avidin Biotin System) using a polyclonal (rabbit) antibody for horseradish peroxidase (Serotec). Biochemical assay was performed on adjacent samples according to Hosoya method. RESULTS: Normal thyroid showed peroxidase immunoreactivity in the majority of follicular cells; neoplastic cells of adenomas were variably stained. Biochemical assay showed positive correlation with ICC ranging from 20.4 micrograms/mg/prot a in multinodular goiter to 42.12 in normal thyroid, up to 122 of follicular adenoma. CONCLUSIONS: Peroxidase content in the thyroid gland may be of clinical interest in several thyroid diseases, and in this study we have demonstrated that thyroid peroxidase can be detected by ICC in routinely processed thyroid samples using a commercially available antibody.

[Plasminogen activators of urokinase and tissue types and their inhibitor (PAI-1) in cytosol fraction in thyroid diseases]. / Aktivatory plazminogena urokinaznogo i tkanevogo tipov i ikh ingibitor (PAI-I) v tsitozol'noi fraktsii pri zabolevaniiakh shchitovidnoi zhelezy.

Enzyme immunoassay (ELISA) was used to estimate the levels of plasminogen activators of urokinase (uPA) and tissue (tPA) types and one of their inhibitors (PAI-I) in the cytosolic fraction of the thyroid in 129 patients with malignant and benign tumors and various non-cancer diseases of the gland. Tumors from patients with thyroid cancer displayed the lowest levels of tPA and the highest levels of uPA and PAI-I, while those from patients with benign thyroid diseases, including adenoma, had high concentrations of tPA and relatively low levels of uPA and PAI-I in the tissue of the diseased organ. At the same time, the lowest levels of uPA and PAI-I were found in patients suffering from toxic goiter with and without adenomatosis. In terms of uPA and PAI-I levels, patients with nodular colloidal goiter were intermediate between those with toxic goiter and adenoma, on the one hand, and those with thyroid cancer, on the other.

[Antibodies against thyroid gland peroxidase and thyroglobulin in various thyroid diseases]. / Pajzsmirigy peroxidáz enzim és thyreoglobulin elleni autoantitestek elöfordulása különbözö pajzsmirigy betegségekben.

Autoantibodies to thyroperoxidase (anti-TPOAb) and thyroglobulin (anti-TgAb) were measured in 564 patients with various thyroid disorders and in 59 healthy subjects using chemiluminometric immunoassay. The frequency of elevated titers was 8.6% in healthy subjects, 76.2% in patients with untreated hyperthyroidism and diffuse goiter, 80.7% in patients with relapse of hyperthyroidism. 83.4% of patient with hyperfunction changed spontaneously to hypothyroidism and 71.5% of patients with hypothyroidism and goiter had antibodies above the normal range. Unexpectedly low prevalence of autoantibodies were detected in patients with primary myxoedema without goiter (48.2%) and in patients with endocrine ophthalmopathy and euthyroidism (33.2%). In the subgroup of patients with hyperthyroidism under methimazole treatment we found an incidence of positivity of 56% and the mean of positive values was lower compared with the untreated ones. In 42.8% of patients with hyperthyroidism and diffuse goiter treated successfully by methimazole, surgery or radioiodine elevated concentrations of antibodies could be detected, however they were in remission for more than five years. 197 (82.4%) of the patients with positive antibody titers showed higher concentrations to peroxidase compared with thyroglobulin. 57.9% of serum samples positive for anti-TPOAb were negative for anti-TgAb, whereas 9.4% of samples positive for anti-TgAb were anti-TPOAb negative. The diagnosis of thyroid autoimmunity could generally be based on measurement of anti-TPOAb with additional measurement of anti-TgAb in special cases.

[Morphological characteristics of nodular goiters in Latvia]. / Morfologicheskie osobennosti uzlovykh zobov v Latvii.

Examinations of nodular forms of euthyroid and thyrotoxic strumas established direct relationshps between the level of hydrolytic and oxidative-reductive enzymes under study and the ultrastructural organization of the tissue. A marked decrease of the functional activity in nodes of euthyroid goiter was found whereas high functional activity was observed in nodes of thyrotoxic strumas.

Abnormalities of apoptosis of the thyroid gland cells from extratumoral microfollicular tissue.

AIM: The aim of this study was to evaluate the frequency of existence of thyroid extratumoral normo- and microfollicular tissue in patients with thyroid carcinoma and peculiarities of apoptosis in mentioned tissue. MATERIALS AND METHODS: Using samples of normo- and microfollicular thyroid tissue it was determined the content of fragmented DNA and intensity of stimulated internucleosomal DNA fragmentation; activities of caspase-3 and cysteine lysosomal cathepsins. RESULTS: It was found that normofollicular tissue is observed more often in patients with nodal euthyroid goiter but microfollicular tissue is more common for patients with carcinoma. Extratumoral microfollicular tissue was found in the thyroid of patients above 50 years old mostly, and more rarely in young ones. The fragmented DNA concentration in microfollicular tissue was lower by a factor of 3.5 and intensity of stimulated internucleosomal DNA fragmentation was also decreased. Activity both of cathepsin B in lisosomes and caspase-3 in lysates of such tissue was also decreased. CONCLUSIONS: The decrease of intensity of spontaneous apoptosis and the absence of its modulation/induction following proapoptotic factors in extratumoral microfollicular thyroid tissue may be considered as a respond of the thyroid gland tissue to an existence of carcinoma.