[Possible influence of genetic polymorphism in the area of GSTs genes on the serum PCB level]. / Mozný vplyv génového polymorfizmu v oblasti GSTs génov na sérovú hladinu polychlorovaných bifenylov (PCB).

OBJECTIVE: To find out whether the serum PCB level depends on genetic polymorphism in the area of GSTs genes. MATERIAL AND METHODS: In the group of 147 men (112 with an average age of 59.1 ± 10.1 and serum PCB level > 1,000 ng/ g lipid -  PCB1, and 35 with an average age of 56.2 ± 12.9 and serum PCB level < 700 ng/ g lipid -  PCB2), the PCR RLFP analysis of DNA was used to determine the genetic polymorphism in the area of GSTs genes. RESULTS: As regards PCB, an association was found between serum PCB concentrations and the null genotype of GSTT1 gene. Men above the median PCB levels displayed, with significantly greater frequency, the null genotype GSTT1 compared to men below the median PCB levels, both in the PCB1 set and in the PCB2 set. In the PCB1 set, the presence of the null genotype GSTT1 increased the risk of high PCB levels 11- fold, in the PCB2 set 4- fold (p < 0.001). In the PCB2 set, an association was also discovered between GSTP1 Val/ Val genotype and higher PCB levels. The risk of high PCB levels in the individuals with the Val/ Val genotype was 5- fold higher than in the carriers of the Ile allele (p < 0.001). In neither set was the GSTM1 genotype associated with serum PCB concentrations. CONCLUSION: The association between high PCB levels and the GSTT1 null and GSTP1 Val/ Val suggests that harmful effects depend not only on the intake amounts of PCB but also on the ability of the organism to detoxify these substances. Individuals living in the same environment are therefore at different risks of developing a disease when exposed to PCB. Polymorphism in the area of GSTTl gene (GSTT1 null) could be a potential genetic risk marker.

Thyroid volume, iodine intake, autoimmune thyroid disorders, inborn factors, and endocrine disruptors: twenty-year studies of multiple effects puzzle in Slovakia.

OBJECTIVE: The aim of this study was to evaluate multiple interrelations between several endogenous and exogenous effects and the thyroid volume and function in large groups of children, adolescents, and adults with a sufficient whole life intake of the iodine. SUBJECTS AND METHODS: The data were obtained either by cross sectioned or longitudinal studies in a total of 4998 children and adolescents (aged 7 to 17 years) and 2501 adults (1071 males and 1430 females aged 20-75 years). Thyroid volume (ThV) was measured by ultrasound, antibodies, and hormones by electrochemiluminiscent immunoassay, and endocrine disruptors (EDs, polychlorinated biphenyls-PCB, dichlorodiethyl-ichloroethylene-DDE, and hexachlorobenzene-HCB) by high resolution gas chromatography/mass spectrometry. RESULTS: 1. In large groups of boys and girls of age 7, 10, 13 or 17 years, the ThV was significantly higher in the 10th decile than in pooled nine lower deciles. Moreover, in 17-year old subjects significantly higher prevalence of hypoechogenicity by ultrasound, positive thyroperoxidase antibodies (TPOab), and increased thyrotropin (TSH) levels were found in the 10th decile. 2. In a small group of children, some individuals revealed consistently higher ThV during the whole 7-year follow-up period irrespective of supplementation with iodine. 3. In 325 sibling pairs of age 10-19 years, born within three years, three groups with different ThV/m2 of body surface were distinguished: Group A (183 pairs having both ThVs small), Group B (103 pairs having both ThVs large); Group C (33 pairs having one ThV small and the other one large). Similar aggregation of ThVs in three groups was observed in 13 pairs of discordant twins and 19 sibling triads in which all the siblings were born within four years. 4. In 42 concordant twins, several pairs had ThV nearly twice as high (in terms of both plain ThV or ThV/m2 of the body surface) as several other pairs of the same age which is assumed to be a result of a genetic background. 5. In large cohorts of males and females, a highly significant positive correlation was found between the ThV and high level of TPOab on one side and EDs on the other side. However, in nearly the same numbers of subjects with low TPOab, negative correlation was seen between ThV and disruptors. These observations may apparently support the synergic effect of the autoimmunity and EDs on the thyroid function. CONCLUSIONS: Several cases of an excessive thyroid growth in the iodine replenished children, adolescents, and adults may apparently result from the autoimmune thyroiditis, probably induced by immunogenic action of iodine in presumably disposed individuals. However, in some cases even simultaneous participation of EDs can not be excluded. Some observations have also suggested that excessive thyroid growth in the iodine replenished adolescent and adult population which was equally exposed to disruptors may also result from other reasons as the unfavorable hereditary background.

[Medicines and thyroid gland]. / Lieky a stítna zlaza.

From their primary pharmacological effect, many drugs may also affect the thyroid gland function or the results of thyroid function tests. In addition to the drugs with a known effect on thyroid gland, including thionamides, thyroid hormones, recombinant TSH, iodine, iodide, amiodarone, lithium and heparin, novel compounds, including tyrosin-kinase inhibitors, immunomodulators and cytokines also have adverse effects on the thyroid gland. Novel drugs are then associated with new types of adverse thyroid effects.

Microsomal epoxide hydrolase polymorphisms, cigarette smoking and prostate cancer risk in the Slovak population.

Polymorphisms in tobacco carcinogen metabolizing enzymes may generate interindividual variations towards the risk of developing prostate cancer. One of these enzymes is microsomal epoxide hydrolase (EPHX1) which metabolizes polycyclic aromatic hydrocarbons, or PAH, carcinogens found in cigarette smoke. The activity of this enzyme is affected by two polymorphisms, a substitution of Tyr113 by His in exon 3 and a substitution of His139 by Arg in exon 4. The aim of this study was to use a population-based case-control study to investigate whether or not such genetic polymorphisms in EPHX1 gene can modify the relationship between smoking status and the risk of developing prostate cancer. We used restriction fragment length polymorphism, or PCR-RFLP to determine EPHX1 genotypes in subjects comprising 194 patients with histologically verified prostate cancer and 305 healthy individuals as control. We found no overall association between prostate cancer risk and functional polymorphisms of EPHX1 gene in exon 3 and exon 4. We further analysed the association between the EPHX1 genotypes and smoking. Smokers carrying the exon 3 Tyr/Tyr and Tyr/His genotypes were at no significant risk compared to non-smokers with the "rapid" Tyr/Tyr genotype. By contrast, a significant interaction of smoking and the exon 4 polymorphism was present.

Serum levels of leptin, adiponectin, retinol binding protein 4 and leptin/adiponectin molar ratio as another possible marker of insulin resistance in obese.

AIM: To determine the relationship between some adipokines and insulin resistance (IR) in obese. MATERIALS AND METHODS: 47 individuals were divided--1. according to BMI to subgroups with normal weight, overweight and obesity, 2. according to IR HOMA index to subjects with IR (IR HOMA > 1.88) and subjects without IR. Except the basic biochemical parameters, serum level of fasting insulin, leptin, retinol binding protein 4 (RBP4) (RIA), adiponectin (ELISA) and leptin/adiponectin (L/A) molar ratio were examined. RESULTS: 1. In correlation to BMI--subjects with BMI > 30 showed significantly higher level of insulin (16.1 +/- 4.1/5.9 +/- 4.1), leptin (51.9 +/- 26.4/14.7 +/- 14) and molar ratio LA (3.1 +/- 1.8/0.48 +/- 0.2) (p < 0.01) and significantly lower level of adiponectin (18.9 +/- 6.3/35.5 +/- 10.5) (p < 0.01) in comparison to both other subgroups (normal weight, overweight). There was no statistically significant difference in RBP4 level between all subgroups, although the highest level of RBP4 was observed in subjects with BMI > 30. In correlation to IR-- subjects with IR showed significantly higher BMI (35.7 +/- 5.8/24.8 +/- 2.6), insulin (15.5 +/- 7.1/4.8 +/- 1.6), leptin (47.2 +/- 29.2/15.1 +/- 13), L/A molar ratio (2.7 +/- 0.3/0.5 +/- 0.1) (p < 0.01), and RBP4 (561.6 +/- 152.5/450.9 +/- 101.7 (p < 0.05) as well. In IR subjects, serum level of adiponectin was significantly lower in comparison to subjects without IR (19.8 +/- 6.3/32.2 +/- 0.8) (p < 0.01). CONCLUSION: Decreased level of adiponectin and increased level of leptin, RBP4 and leptin/adiponectin molar ratio in obese can be also considered as a marker of developing insulin resistance (Tab. 2, Ref. 23).

Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and single nucleotide polymorphism in PSA and CYP17 gene may contribute to early diagnostics of prostate cancer.

The aim of the paper is to determine whether IGF1, IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and one-nucleotide polymorphism in PSA and CYP17 gene might contribute to early diagnostics of prostate cancer (PCa). Serum level of PSA, IGF1 and IGFBP3 in the group of 158 individuals (92 PCa and 66 controls) was examined by RIA method and IGF1/IGFBP3 was calculated. PCR RLFP method was used to examine one- nucleotide polymorphism in PSA and CYP 17 gene. The results suggest that serum level of IGF1 over 95% CI did not increase relative risk of PCa development in overall group, not even regarding to particular investigated genotypes, not even if individuals with genotype AG+A1A1, AG+A1A2, GG+A1A1 and GG+A1A2 were evaluated. Serum level of IGFBP3 under 95% CI increased PCa relative risk in overall group(chi(2) = 10,03, p= 0,001, OR 3,12, 95% CI 1,44-6,93), as well as regarding to one-nucleotide polymorphism in individuals with PSA genotype AG(chi(2) = 4,72 p= 0,029, OR 2,87, 95% CI 01,09-7,49) and CYP 17 genotype A1A1(chi(2) = 3,76 p= 0,052, OR 2,57, 95% CI 0,97-6,75). The association between frequencies of occurrence of PCa and higher IGF1/IGFBP3 molar ratio was not confirmed, nor for gene polymorphism in PSA and CYP17, however OR (chi(2) = 1,58, p= 0,208, OR 1,67, 95% CI 0,75-3,71) was more than 1, nor in combination AG+A1A1,AG+ A1A2. Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and gene polymorphism in PSA and CYP17 gene might contribute to early diagnostics of PCa. Further research is needed to prove, whether serum level of IGFBP3 in addition to PSA determines the prognosis and progression of PCa.

Effect of growth hormone replacement therapy on plasma brain natriuretic peptide concentration, cardiac morphology and function in adults with growth hormone deficiency.

OBJECTIVE: The impact of growth hormone (GH) replacement on plasma brain natriuretic peptide (BNP) in association with cardiac morphology and function in adults with growth hormone deficiency (GHD) was evaluated. SUBJECTS AND METHODS: Fifty nine adult patients with GHD (29 men, age 19-59 years) received a starting dose of 0.1-0.2 mg/day recombinant GH, which was subsequently adjusted to the 50th percentile of normal serum insulin-like growth factor (IGF-1) over a 6 month period. Plasma BNP and IGF-I levels before, 3 and 6 months after treatment were determined, as were the echocardiographic data, such as ejection fraction (EF), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass (LVM), E/A wave and deceleration time (DT). RESULTS: Mean plasma BNP levels (53.1+/-8 pg/ml) and echocardiographic parameters were within the normal range at baseline, although men had higher LVM, IVST, PWT, LVEDV and LVEDD, respectively. A significant decrease in plasma BNP was observed after 6 months (27+/-5.6 pg/ml, P<0.05). No significant changes in echocardiographic parameters were observed except for a mild tendency to increase in LVM, and a borderline decrease in DT (181+/-8.1 vs. 155+/-9 ms, P<0.01). CONCLUSIONS: Six months GH replacement therapy induced a significant decrease in plasma BNP levels despite the majority of patients having plasma BNP within the normal range at baseline. A borderline decrease in diastolic deceleration time was observed, the clinical significance of which is unclear.

[Thyroid disease in the pregnancy and congenital malformations of newborns]. / Ochorenia stítnej zl'azy matky a vrodené vývojové chyby plodu.

THE AIM: The aim of this study was to compare thyroidal status of mothers who delivered newborns with morphological congenital malformations and mothers with healthy newborns. TYPE OF THE STUDY: One-time cross-sectional study. SETTING: 3rd internal clinic FN LP, Kosice. METHODS: We examined 43 mothers with newborns born with congenital malformation and 76 mothers with healthy newborns. The protocol included anamnesis, basic physical examination, ultrasonography of the thyroid, assessment of the mothers' plasma fT4, TSH and anti-TPO levels, and comparison of the birth weight and birth length of the newborns. The results were statistically processed by PC programs StatsDirect 2.6.2 and MS Excel 2000. RESULTS: The thyroid volume was significantly greater in mothers with newborns with congenital malformation as in the control group (p<0.001). The birth weight and birth length was significantly lower in newborns with malformations (p<0.0001 resp. p<0.001). We found no differences in the plasma levels of fT4, TSH and anti-TPO between these groups. CONCLUSION: Thyroid disease of the mother can contribute to the congenital malformations of the newborn although there was found no direct association between mothers' thyroid autoantibodies and creation of congenital malformations of the child, yet.

[Thyroid disease in the pregnancy and hypotrophy of newborns]. / Ochorenia stítnej zl'azy matky a hypotrofia plodu.

THE AIM: The aim of this study was to compare thyroidal status of mothers who delivered newborns with hypotrophy and mothers with healthy newborns. TYPE OF THE STUDY: One-time cross-sectional study. SETTING: 3rd internal clinic FN LP, Kosice. METHODS: We examined 56 mothers with hypotrophic newborns and 76 mothers with healthy newborns. The protocol included anamnesis, basic physical examination, ultrasonography of the thyroid, assessment of the mother's plasma fT4, TSH and anti-TPO levels, and comparison of the birth weight and birth length of the newborns. The results were statistically processed by PC programs StatsDirect 2.6.2 and MS Excel 2000. RESULTS: The thyroid volume was significantly greater in mothers with hypotrophic newborns as in the control group (p<0.001). The birth weight and birth length was significantly lower in hypotrophic newborns (p<0.0001 resp. p<0.0001). Mothers with hypotrophic newborns had significantly higher TSH levels (p<0.0001) and higher anti-TPO levels (p<0.0001) as mothers in the control group. We found no differences in the fT4 levels in these groups. CONCLUSION: Thyroid disease of the mother can contribute to the hypotrophy of the newborns.

[Serum level of retinol-binding protein 4 in obese patients with insulin resistance and in patients with type 2 diabetes treated with metformin]. / Sérová hladina retinol-binding proteinu 4 u obéznytch s inzulínovou rezistenciou a jedincov s diabetom 2. typu liecených metformínom.

OBJECTIVE: Is there a difference between the retinol-binding protein 4 (RBP4) levels in obese patients with insulin resistance (IR) without diabetes, in obese patients with type 2 diabetes mellitus (DM2T) treated with metformin and in nonobese healthy individuals? METHOD: 28 obese individuals with insulin resistance, 11 type 2 diabetes patients treated with metformin and 17 control individuals were examined for serum level of retinol-binding protein 4 using the RIA method. The results were compared within the groups and RBP4 was correlated with insulin in the IR group and the control group. OUTCOME: The highest and the lowest RBP4 levels (561.6 +/- 209 ng/ml) were recorded, respectively, for obese individuals with IR (IR HOMA 3.9) and for obese type 2 diabetics treated with metformin (391.1 +/- 133,5 ng/ml) (P < 0.01). The RBP4 level of the control group was significantly lower as compared with the obese individuals with IR (452.8 +/- 104.6 ng/ml) (P < 0.05), but insignificantly higher as compared with the obese individuals with DM2T treated with metformin (391,1 +/- 133.5 ng/ml). RBP4 in the monitored group correlated with insulin r = 0.46 (p < 0.03). CONCLUSION: The increase in RBP4 in obese individuals by GLUT4 regulation in adipocytes contributes to the development and aggravation of systemic IR. Through its effect on RBP4 expression in adipocytes, metformin may improve total insulin sensitivity in obese individuals including those with MS and delay the onset of manifest DM. RBP4 could by used as a marker of deteriorating glucose tolerance in obese individuals.

Multiple organochlorine pollution and the thyroid.

OBJECTIVE: Although the biological effects of major persistent organochlorinated pollutants (POPs) appear to be essentially similar, some effects which would be specific for certain substance cannot be excluded. We attempted to study the thyroid volume and thyrotropin level in the population living in the area with multiple pollution by polychlorinated biphenyls (PCBs) and pesticides (DDE and hexachlorobenzene - HCB). METHODS: A total of 454 adults was examined within the pilot field survey in 1998. Among them were 237 males (age range 19-78 years, median 47) and 227 females (age range 19-78 years, median 48). Fifteen environmentally prevalent congeners of polychlorinated biphenyls and also p,p-DDE (2,2-bis(4-chlorophenyl)-1,1-dichloroethylene), p,p-DDT (2,2-bis(4-chlorophenyl)- 1,1,1-trichloro-ethane), hexachlorobenzene (HCB) as well as alpha-, beta- and gamma-hexachlorocyclohexane (HCH) were determined in serum by high resolution gas chromatography using microelectron capture detector and microcapillary column. Thyroid volume (ThV) was measured by real time sonography using the ellipsoid method with the aid of sonographic instrument Sonoline SI-400 (Siemens, Germany). The level of TSH was estimated by supersensitive immunoradiometric method using commercial kits by Immunotech (Marseille, France). Pearsons correlation coefficients after logarithmic transformation of values and Spearmans correlation coefficients were used for statistical evaluation. RESULTS: Significant positive association (p<0.01) was found between DDE and PCB, DDE and HCB, while that between PCB and HCB was not significant. Similar positive association (p<0.01) was also found between each individual organochlorine and their sum. Significant negative association (p<0.01) was found between ThV and TSH. When using categorical PCB values either >2000 (N=208) or >3000 (N=127) ng/g lipid, significant positive association (p<0.05 and p<0.01, respectively) was found between the sum of all organochlorines (PCB+DDE+HCB) and ThV, while that between PCB and ThV (p<0.01) was found only at the PCB levels >3000 ng/g lipid. When using Spearmans correlation coefficients, significant negative association appeared between PCB and TSH (p<0.05), sum of organochlorines and TSH (p<0.05) and ThV and TSH (p<0.01). CONCLUSIONS: Although several significant positive and negative associations were found, this study, like several others, could not exactly define the participation level of individual POPs in their common toxic effects, but possibly contributed to the recognition and elucidation of some problems related to this task.

Human thyroid in the population exposed to high environmental pollution by organochlorinated pollutants for several decades.

OBJECTIVE: To study possible effects of long-time exposure of chemical factory employees and population of surrounding polluted area to polychlorinated biphenyls and pesticides on the thyroid volume and function as compared to the population from the area of background pollution. METHODS: A total of 461 adults consisting of 239 men and 222 women was examined and divided into four groups according to their permanent domicile as related to the level of environmental pollution, e.g. SR (area of background pollution, n = 207), SI (slightly polluted area, n = 59), MI (polluted city of Michalovce, n = 94) and CH (employees of chemical factory subjected to high PCB exposure, n = 101), combined first three groups being also called LPA (less polluted areas, n = 360). Thyroid volume (ThV) and echogenicity were measured by real time sonography. The level of polychlorinated biphenyls (PCB) and pesticides (hexachlorbenzene--HCB, DDE (2,2'-2-bis(4-chlorobiphenyl)- 1,1-dichloroethylene), p,p'-DDT (2,2'-bis(4-chlorophenyl)- 1,1,1-trichloroethane) and alpha-, beta- and gamma-hexachlorcyclohexane--HCH) was estimated by congener specific analysis using HP 5890 gas chromatograph with a 63Ni electron capture detector. Serum levels of thyrotropin (TSH) and thyroid peroxidase antibodies (anti-TPO) were measured by specific sensitive immunoassays. RESULTS: The association of very high PCB level (e.g. 7300 +/- 871 ng/g lipid; mean +/- S.E.) with increased ThV (e.g. 16.3 +/- 0.73 ml) in CH has been found, the values being significantly higher than these of 360 subjects in LPA (e.g. 2045 +/- 147 ng/g, p < 0.001 for PCB and 14.0 +/- 0.32 ml, p < 0.001 for ThV). In 23 subjects from CH with PCB level > 10000 ng/g the ThV was 18.7 +/- 2.32 ml, while that in 251 subjects from LPA with PCB level of < 2000 ng/g was 13.8 +/- 0.35 ml (p < 0.05). In addition, ThV as well as PCB levels were strikingly increasing with age. In parallel with PCB levels, also the levels of other organochlorines estimated (namely these of DDE) were increasing. Although the participation of these substances in the development of adverse effects cannot yet be defined, it cannot be excluded. The association of increased levels of episodic congener PCB 101 with increased ThV appeared to be more pronounced than that of stable congeners PCB 153 and 180. Finally, significant increase in the frequency of thyroid hypoechogenicity by ultrasound, ThV > 20.0 ml and thyroperoxidase antibodies in CH area was observed as compared to LPA. CONCLUSIONS: Several associations of high PCB and pesticides level with characteristics of thyroid disorders (e.g. increased thyroid volume, frequency of hypoechogenicity and frequency of positive thyroperoxidase antibodies level in blood) were observed in the area with heavy industrial pollution by PCB.

Selected hormones levels in individuals with endothelial dysfunction and insulin resistance.

AIM: To determine possible differences in selected serum hormones levels related to endothelial function and insulin sensitivity. METHODS: Ghrelin, insulin, serotonin, growth hormone, IGF-1, leptin and adiponectin serum levels were determined in a group of 83 adults (40 women, 43 men) with a mean age 49.4+/-4.6 years. Total ghrelin, insulin and serotonin levels were measured using RIA, growth hormone and leptin using IRMA and human adiponectin was measured using ELISA. Results were associated with BMI, calculated as kg/ m2, endothelial function, determined by ultrasound measured flow mediated vasodilatation of brachial artery, and with insulin resistance, calculated by IR HOMA index. RESULTS: We found no difference in age comparing subjects with (ED+) and without (ED-) endothelial dysfunction, neither comparing subject with (IR+) and without (IR-) insulin resistance. In individuals ED+ and IR+ a higher BMI, serum leptin and insulin levels and lower ghrelin, growth hormone and adiponectin levels were found. Subject with ED presented with a higher serum serotonin level compared to subjects without ED. This difference was not found in individuals with and without IR. CONCLUSION: Lower ghrelin, growth hormone and adiponectin levels along with higher insulin and leptin levels may contribute to the progression of endothelial dysfunction and insulin resistance.

[The thyroid gland in women during the reproductive age]. / Stítna zl'aza u zien v reprodukcnom veku.

OBJECTIVE: To find out thyroid volume and its functional status in women in reproductive age as well as possible correlation between thyroid size and functional status and age and residential location of women. DESIGN: Project can be characterized as an epidemiological study and consists of three separate observations. SETTING: 1st Internal Clinic, UPJS, Kosice, Medical Faculty, Slovakia. METHODS: 347 women from different regions of Eastern Slovakia (160 aged 20-29 and 187 aged 30-40) were measured thyroid volume via ultrasonography and thyroid functional status by RIA TSH and anti TPO examinations. Urinary iodine was examined in 70 cases. In this part of the study correlation between thyroid size and functional status and age and residential location of women were determined. Four days after delivery thyroid volume in 99 women was measured. The volume was correlated with the number of previous pregnancies. Thyroid volume was correlated with residential location and number of pregnancies of 77 women that had not delivered in the previous year. RESULTS: Women aged 20-29 years had thyroid volume smaller than women aged 30-40 (8.78 ml/10.66 ml; p < 0.01). The size of thyroid gland was not only affected by age but also by residential location. The largest thyroid glands and increased level of anti TPO antibodies in both age groups were found in women from agricultural regions and regions close to chemical factory. The women with anti TPO antibodies had increased level of TSH as well as more frequently changed echogenity of thyroid gland. Median of urinary iodine was 13.2 micrograms/dl in both age groups and indicated sufficient iodine intake in the observed area. The volume of thyroid gland four days after delivery did not exceed 22 ml in 89.9% of cases. Significant difference in size of thyroid gland depending on number of previous deliveries was not only observed in women 4 days after delivery but also in those that had not delivered during previous year. The largest volumes were measured in secundiparous mothers. CONCLUSION: Polluted environment affects the size and functional status of thyroid gland. Environment can via this negative impact on thyroid gland influence fertility, pregnancy and fetus development in women in reproductive age.

From naturally occurring goitrogens to the effects of anthropogenic endocrine disruptors on the thyroid in Slovakia.

The objective is to describe the effect of mandatory and well monitored prophylaxis of endemic goitre in Slovakia with the use of iodised salt for past 50 years and previous experimental attempts to assess a possible participation of naturally occurring goitrogens in the etiology of goitre. Previous observations by others showed a striking decrease of goitre prevalence in schoolchildren as early as few years after starting the prophylaxis in Slovakia and this success has been confirmed by a European study conducted by others in mid nineties. In the meantime, however, massive industrialisation of Slovakia and environmental negligence of the administration resulted in heavy airborne and mainly waterborne pollution of the food chain in certain areas around large chemical factories by industrial waste including polychlorinated biphenyls (PCB). Since Slovakia has been recently evaluated as an iodine replete country as based on the findings of the low thyroid volume by ultrasound and high urinary iodine, it became possible to evaluate the participation of factors different from iodine deficiency in the thyroid growth. Recent field surveys including an extensive international study PCBRISK repeatedly showed highly increased blood PCB level in subjects living in the polluted area and, at the same time, increased thyroid volume by ultrasound, increased frequency of positive thyroid antibodies and impaired glucose tolerance. (Ref. 59)

Thyroid function and cholesterol level: paradoxical findings in large groups of population with high cholesterol food intake.

OBJECTIVE: To compare the levels of serum cholesterol with thyroid function as estimated by the level of thyrotropin and free thyroxine with possible participation of thyroperoxidase antibodies in large number of adults examined within large field surveys focused on the evaluation of thyroid status of Slovak rural population. SUBJECTS AND METHODS: Serum level of cholesterol and thyrotropin (TSH) was estimated in a total of 2786 adults. In addition, in 2038 of them also the level of free thyroxine (FT4), total triiodothyronine (TT3), cholesterol, triglycerides and phospholipids was measured. The levels of TSH, anti-TPO and FT4 were estimated by supersensitive electrochemiluminiscent immunoassay using the automatic system Elecsys (Roche, Switzerland). RESULTS: A total of 2786 adults was stratified into 7 groups according to the range of TSH level as related to generally recognized level of thyroid function, e.g. 1. TSH <0.10 mU/L (overt hyperthyroidism, N=41), 2. TSH 0.11-0.30 mU/L (overt or subclinical hyperthyroidism, N=149), 3. TSH 0.31-2.50 mU/L (normal level, N=1750), 4. TSH 2.51-4.50 ("high normal" level, N=607), 5 TSH 4.51-6.50 (mild or incipient subclinical hypothyroidism, N=137), 6. TSH 6.51-10.00 mU/L (mild hypothyroidism, N=50), 7. TSH 10.01-99.00 mU/L (severe hypothyroidism, N=53). The average levels of cholesterol in all groups were very similar ranging from 5.53 to 6.17 mmol/L and no interrelations with TSH level were found. In addition, no considerable differences between these groups were found when considering the levels of medians, upper quartiles and 90th percentiles of individual groups. When male and female subjects were divided into age groups according to the decades, an age dependent increase of cholesterol level was found in both sexes. The fraction of 2038 subjects was divided into the same TSH related groups as defined above. Similarly as above, no considerable differences in cholesterol, triglycerides and phospholipids level were observed. However, the levels of FT4 and TT3 were significantly decreasing with the increase of TSH level which confirmed the continuing decrease of thyroid function. The frequency of positive anti-TPO in subjects with TSH >6.5 mU/l (71/86 = 82.5%) was significantly higher than that in subjects with TSH <6.5 mU/l (468/1952 = 23.9%). CONCLUSIONS: No difference in the level of cholesterol and triglycerides was found in large groups of rural adults from Slovakia with various thyroid function as estimated by the level of TSH, FT4, TT3 and anti-TPO. It is assumed that this interrelation resulted from very high cholesterol intake due to inappropriate general nutritional status of rural population resulting from the consumption of unhealthy foods.

Further studies of blood levels of some tumor markers in the area polluted by polychlorinated biphenyls and control population.

The levels of beta2-microglobulin (beta2-m), alpha-fetoprotein (AFP) and thyroglobulin (TG) were measured in the serum of 245 employees of chemical factory formerly producing polychlorinated biphenyls (PCB) consisting of 54 males (age range 24-65 years, median 45) and 191 females (age range 20-69 years, median 45). The control population consisted of 636 adults from control areas of northwest and east Slovakia. The frequency of beta2-microglobulin levels lower than 1.6 microg/ml in 242 employees of chemical factory was 76.8% (186/242) which was three times higher (P<0.001) than 24.4% (155/635) in 636 controls. Still more remarkable difference was obtained when using the cut/off level of 1.2 microg/ml, the frequency of such values in the employees being 45.4% (110/242) vs. 4.4% (28/635) in the controls. In contrast, no difference in alpha-fetoprotein levels was observed between the employees and the controls, the respective frequency of these < 5.0 ng/ml being 87.6% (212/242) vs. 86.2% (389/451) and these < 10.0 ng/ml being 100.0% (242/242) vs. 97.8% (441/451). Similarly, the frequency of normal thyroglobulin levels < 50.0 ng/ml) did not differ, being 95.6% (174/182) in the employees and 87.9% (87/99) in the controls. Most of a total of 20 cases with thyroglobulin level > 50.0 ng/ml showed sonographicaly enlarged and multinodular thyroid with focal or diffuse hypoechogenicity, three of them showed solitary nodule with a diameter > 10 mm. Although the decreased levels of beta2-microglobulin might be somehow related to the modulation of immune system, more plausible explanation appears to be the possible impairment of renal tubules by PCB similar to that caused by heavy metals resulting in increased urinary excretion of beta2-microglobulin and decrease of its blood level.

[Effect of nitrates on active transport of iodine]. / Ovplyvnenie aktívneho transportu jódu nitrátmi.

Active iodine transport into the thyrocyte is catalyzed by the transmembrane transport protein Na+/J- symport (NIS) Nitrates can expel iodine from the bond with this transport protein which was found not only in the thyrocyte membrane but also in the cell membrane of the gastric mucosa. The weight of the thyroid gland in mg was significantly greater even when calculated in relation to body weight in the NIT group of rats who were given for 6 days nitrate by gastric tube (100 mg/kg/day) as compared with controls (CON) 17.56 +/- 8.4, 0.07 +/- 0.03/12.10 +/- 9.57, 0.05 +/- 0.03, P < or = 0.01. A lower thyroid activity in per cent calculated per 1 mg of its weight (1.39 +/- 1.0/2.22 +/- 0.9, P < or = 0.01), a higher activity in blood before removal of the thyroid gland (8.54 +/- 4.09/5.45 +/- 2.78) and a lower one after removal of the thyroid gland (1.09 +/- 0.05/0.21 +/- 0.10) before oral administration of I131 in group NIT, suggests a negative effect of nitrates on active iodine transport not only at the level of the thyrocyte but also possible interaction with iodine at the level of the digestive tract. A significantly higher serum level of TT3 in group NIT (0.66 +/- 0.27/0.44 +/- 0.21, P < or = 0.01 regardless of the TSH serum level (2.31 +/- 1.83/2.64 +/- 1.52) and T4 (22.72 +/- 8.2/25 +/- 11.0) suggests a qualitative change in thyroid hormone production in favour of T3 caused even by short-term nitrate administration.