Arkadiusz Zygmunt

Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid gland.

Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole‐3‐propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylothiouracil (PTU)—a thyrostatic drug—have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA + 4‐HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3—injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3‐related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3.

Evaluation of selective embolization of thyroid arteries (SETA) as a preresective treatment in selected cases of toxic goitre.

Backgroundin recent years, an increasing interest in the application of selective embolization of thyroid arteries (SETA) in the treatment of thyroid diseases is observed. In the present report, we analyse the value, safety and possible indications for preresective SETA in cases of large toxic goitres.Patients and methodthe study group comprised 10 patients with large toxic goitre (thyroid volume 254 ± 50 mL), including one patient with cervicomediastinal goitre and one patient with anti-thyroid drug intolerance in state of overt thyrotoxicosis. All the patients underwent SETA of the superior and/or inferior thyroid arteries, followed by thyroidectomy, performed up to thirty-six hours after SETA (23.1 ± 11 h). After embolization, selective angiographies of thyroid arteries were performed to ensure that the targeted arteries had been completely occluded.Results and conclusionin all the patients, SETA decreased blood flow through the thyroid. Preresective SETA reduced blood loss during and after thyroidectomy and decreased the operating time, but the differences were too small to justify routine applications of preresective SETA as an adjunct to surgical treatment of toxic goitre. On the other hand, SETA is a safe and minimally-invasive technique, which may become an attractive option for quick preparation to surgery in selected patients with toxic goitre, who present anti-thyroid drug intolerance or refuse radioactive iodine treatment.

Assessment of cyclooxygenase-1 and 2 gene expression levels in chronic autoimmune thyroiditis, papillary thyroid carcinoma and nontoxic nodular goitre

IntroductionThe cyclooxygenases are a group of enzymes catalyzing the formation of prostaglandins from arachidonic acid. Cyclooxygenase-1 (COX-1) is a constitutive form, thought to be a “housekeeping gene”, with constant levels of expression in most tissues. COX-1 expression in the thyroid gland, except for medullary thyroid carcinoma, has not been a subject of much interest. Cyclooxygenase-2 (COX-2) can be expressed in response to various stimuli, such as mitogens, hormones, cytokines, growth factors. The product of COX-2 activity has been implicated in carcinogenesis.Recent studies have shown that up-regulation of COX-2 is associated with numerous neoplasms. Hereby, we present a study analysing COX-1 and COX-2 expression in papillary thyroid carcinoma (PTC), Hashimoto thyroiditis (HT) and nontoxic nodular goitre (NNG) in fine needle aspiration biopsy (FNAB) washouts and in postoperative tissue.Material and methodsCytological specimens from 120 patients (105 females and 15 males) have been studied, including patients with HT, PTC and NNG. Moreover, we have examined postoperative tissue specimens from 51 patients with PTC and NNG.The methods of molecular analysis have included extraction of total RNA from FNAB cytological material and postoperative tissues, spectrophotometric assessment of the RNA purity, cDNA synthesis in reverse transcription reaction and an analysis of genes expression data by real-time PCR.ResultsThe performed analysis has revealed statistically significant higher expression level of the COX-2 gene in PTC group, in comparison with HT and NNG groups (in both cytological and postoperative material).In PTC patients, COX-2 gene expression levels in the material obtained by FNAB were similar to those in the postoperative thyroid tissue.No correlations between COX-2 gene expression level and TNM staging in PTC samples have been observed.There were no correlations between COX-2 expression and anti-TPO antibodies level, or patient’s sex or age in the studied groups. Also, there were no correlations of COX-1 gene expression level among PTC, HT and NNG groups.ConclusionsOur results suggest that COX-2 gene does not participate in the mechanisms involved in molecular association of HT with PTC. However, in case of PTC itself, it may play some role in neoplastic transformation.

Hepatitis and the polyglandular autoimmune syndrome, type 1

Autoimmune polyglandular syndrome, type 1 (APS-1) is a rare syndrome. Here we present a case report of a 24-year-old female patient who complained of progressive weakness. While autoimmune hepatitis was diagnosed, no improvement of biochemical parameters was obtained after immunosuppressive treatment. Hypoparathyroidism and adrenocortical failure were identified. Her health status clearly improved once proper control of the calcium-phosphate metabolism was obtained and after the administration of substitution hydrocortisone doses, leading to full normalization of biochemical liver tests. The reported case illustrates a rare form of APS-1 failure, in which the diagnosed autoimmune hepatitis was only the first symptom.

Detrimental Effects of Increasing Iodine Supply: Iodine-Induced Hyperthyroidism, Following Iodine Prophylaxis

This chapter discusses the epidemiology and etiology of iodine-induced hyperthyroidism (IIH), which follows normalization of iodine supply. The thyroid gland seems to be well adapted to incidents of iodine intake in very high amounts. Still, there is evidence showing that increased intake of iodine may induce clinically relevant problems in some susceptible subjects. These effects are optimally identifiable at population level, as individual responses vary depending on many other factors that are difficult to control. One of the main undesirable consequences of increased iodine intake in a population is a higher incidence of hyperthyroidism. The elevated incidence of IIH, which follows normalization of iodine supply, is transient. The greater the iodine deficiency, the more numerous and clinically more difficult are the cases of hyperthyroidism, which occur after correction of the iodine supply. In fact, IIH, which follows iodine supply normalization, can be viewed as an outcome of iodine deficiency. The deeper the iodine deficiency, the more numerous and more difficult are the IIH cases, which occur after the correction of iodine supply. Also, children form the group that benefits the most from iodine prophylaxis. Some effects of prolonged iodine deficiency, such as the presence of autonomous nodules in the thyroid, seem to be irreversible.

An assessment of the effectiveness of iodine prophylaxis in pregnant women — analysis in one of reference gynaecological-obstetric centres in Poland

INTRODUCTION Iodine deficiency in pregnant women, even of a mild degree, may have adverse effects on both the mother and the foetus. Despite the obligatory model of functioning iodine prophylaxis in Poland, the iodine supply in women during pregnancy and physiological lactation is insufficient. Therefore, those groups should take additional iodine supplementation at a dose of 150-200 μg/day. The aim of this study was to examine the effectiveness of iodine prophylaxis in pregnant women in Poland. MATERIAL AND METHODS The assessment of iodine supply, urine iodine concentration (UIC) in the spot urine sample, as well as levels of TSH, fT4, thyroid antibodies, and thyroid volume, was performed at one time point in 115 women (7 in the 1st trimester, 61 in the 2nd trimester, and 47 in the 3rd trimester). RESULTS Only 45.2% of women were taking additional amounts of iodine at any time of pregnancy, and the median ioduria was 79.6 μg/L, which pointed to an insufficient supply of iodine. The percentage of women using iodine supplementation increased with the length of pregnancy, which indicates that the recommendations are implemented too late. In women who took iodine supplementation, ioduria was significantly higher than in those not applying iodine supplementation (median 129.4 μg/L vs. 73.0 μg/L; p < 0.001); however, this was still below recommended values. CONCLUSIONS The effectiveness of iodine prophylaxis in pregnant women in Poland, evaluated on the basis of the analysis of randomly chosen sample, is not satisfactory in terms of compliance with the recommendations and, possibly, the quality of supplementation.

Iodine prophylaxis in pregnant women in Poland - where we are? (update 2015)

Introduction of the model of iodine prophylaxis based on the consumption of iodized salt in 1997 has eliminated the iodine deficiency in Poland. However, in accordance with the current recommendations, all women who are planning to be pregnant or are pregnant or breastfeeding should receive an additional dose of iodine at 150–200 mcg / day because of the increased bodys need for iodine during this period. Studies show that only part of women in Poland conduct a proper iodine prophylaxis and it is often initiated in the second and third trimester of pregnancy. The authors try to analyze the possible causes of this situation, pointing out what could be done to increase the degree of compliance with iodine prophylaxis during pregnancy and physiological lactation in Poland.

The role of phosphoinositide 3-kinase subunits in chronic thyroiditis

BackgroundThe risk of neoplastic transformation in patients with chronic thyroiditis (Hashimoto’s thyroiditis – HT) is slightly increased. Genetic background of this observation is still unclear. PI3K isoforms are linked with inflammatory and neoplastic processes, thus they appear to be interesting subjects of a research in this respect. The aim of our study was to assess the PIK3CA, PIK3CB, PIK3CD and PIK3CG genes expression levels in HT.MethodsFollowing conventional cytological examination, 67 thyroid FNAB specimens, received from patients with HT, were quantitatively evaluated regarding PIK3CA, PIK3CB, PIK3CD and PIK3CG expression levels by real-time PCR in the ABI PRISM ®7500 Sequence Detection System.ResultsThe performed analysis has revealed significantly higher expression levels (RQ) of PIK3CD, PIK3CG and PIK3CA genes in comparison with PIK3CB gene (p<0.05) and significantly higher gene expression level of PIK3CD in comparison with PIK3CA (p<0.05).ConclusionThe observed increased PIK3CD, PIK3CG genes expression in HT is probably related to lymphocyte infiltration commonly seen in this condition, however, the role of increased PIK3CA gene expression in the multi-step carcinogenesis process cannot be excluded.

The influence of liver and pancreas surgery on the thyroid function

BackgroundNowadays, the increasing number of oncologic patients with liver or pancreatic tumours are subjected to surgical treatment, as it can provide a long-term survival or sometimes cure. As a result, numerous new clinical questions regarding metabolic disturbances in these patients have been arisen. Among others, the impact of the pancreas and liver surgery extent in relation to the thyroid function remains to be elucidated.Materials and methodsThe study comprised 51 patients (25 men and 26 women, mean age ± SD 61.6 ± 10.4 yrs, mean ± SD) with pancreatic or liver tumours, qualified for abdominal operation. Serum levels of FT3, FT4 and TSH were measured on the day before (time “0”) and on the 1st, 3rd and 5th day after surgery in two (2) subgroups reflecting the extent of surgery: twenty seven (27) patients (14 men and 13 women, mean age ± SD 61.5 ± 11.8 yrs) after major surgery (Whipple’s surgery, right and left hemihepatectomy, segmentectomy of the liver, distal pancreatectomy, total duodenopancreatectomy) and twenty four (24) patients (11 men and 13 women, mean age ± SD 61.8 ± 8.9 yrs) after minor, palliative surgery (exploratory laparotomy, gastroenterostomy, triple by-pass, liver tumour embolization, hepaticojejunostomy). Additionally, the obtained results were analyzed in relation to the type of the disease (pancreatic surgery vs liver surgery).ResultsMean serum FT3 level decreased significantly during the study in major and minor surgery subgroups (p<0.001, in both) in comparison to the baseline values, accompanied by stable serum concentrations of TSH (NS) and FT4 (NS). The above decreasing tendency in FT3 concentrations was similar in both subgroups (NS), the same as were unchanged levels of TSH (NS) and FT4 (NS). Mean FT4 concentration on the 3rd and 5th day after major surgery was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.002, p=0.032, respectively). Similarly, mean FT3 concentration on the 3rd day in minor surgery subgroup was lower in pancreatic tumour patients in comparison to liver tumour patients (p=0.015).DiscussionOur findings have confirmed essential reduction of FT3 values after abdominal surgery, independently of surgery extent. Additionally, pancreatic tumour patients are more likely to have lower FT3 and FT4 levels after surgery when compared to liver tumour patients.

Relationship between urine lipid peroxidation, anthropometric parameters and parameters associated with goitre formation in school-age children

Introduction Oxidative stress has been implicated in the normal ageing process and the pathogenesis of several diseases, including goitre. The aim of the study was to evaluate the relationship between urine lipid peroxidation (LPO) and anthropometric parameters as well as the parameters associated with goitre formation in children. Material and methods The subjects included 172 healthy children (93 girls and 79 boys) aged 8–15, divided into 4 age groups – group I (8–9 years), group II (10–11 years), group III (12–13 years) and group IV (14–15 years) – and into 2 groups based on the BSA: the BSA-1 group (≤ 0.55 m2) and the BSA-2 group (> 0.55 m2). Results The value of LPO was the highest in group I but the difference between the groups was not statistically significant (p = 0.074). In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 ±6.90 nmol/ml and 10.79 ±4.86 nmol/ml, respectively; p = 0.023). We found a weak, negative linear correlation between LPO and age (r = –0.216; p < 0.005), body mass (r = –0.153; p < 0.05), height (r = –0.152; p < 0.05) and BSA (r = –0.151; p < 0.05). Conclusions Anthropometric parameters of school-age children independently of age are negatively associated with oxidative damage to membrane lipids, whereas factors promoting goitrogenesis do not contribute to this process.