Zbigniew Adamczewski

Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short‐term hypothyroidism Lack of relationship to lipoprotein abnormalities

objectives Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short‐term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins.

COX-2 expression in papillary thyroid carcinoma (PTC) in cytological material obtained by fine needle aspiration biopsy (FNAB).

BackgroundCOX-2 is an enzyme isoform that catalyses the formation of prostanoids from arachidonic acid. An increased COX-2 gene expression is believed to participate in carcinogenesis. Recent studies have shown that COX-2 up-regulation is associated with the development of numerous neoplasms, including skin, colorectal, breast, lung, stomach, pancreas and liver cancers. COX-2 products stimulate endothelial cell proliferation and their overexpression has been demonstrated to be involved in the mechanism of decreased resistance to apoptosis. Suppressed angiogenesis was found in experimental animal studies as a consequence of null mutation of COX-2 gene in mice. Despite the role of COX-2 expression remains a subject of numerous studies, its participation in carcinogenesis or the thyroid cancer progression remains unclear.MethodsTwenty three (23) patients with cytological diagnosis of PTC were evaluated. After FNAB examination, the needle was washed out with a lysis buffer and the obtained material was used for COX-2 expression estimation. Total RNA was isolated (RNeasy Micro Kit), and RT reactions were performed. β-actin was used as endogenous control. Relative COX-2 expression was assessed in real-time PCR reactions by an ABI PRISM 7500 Sequence Detection System, using the ΔΔCT method.ResultsCOX-2 gene expression was higher in patients with PTC, when compared to specimens from patients with non-toxic nodular goitre (NTG).ConclusionsThe preliminary results may indicate COX-2 role in thyroid cancer pathogenesis, however the observed variability in results among particular subjects requires additional clinical data and tumor progression analysis.

Flow cytometry in the differential diagnostics of Hashimoto’s thyroiditis and MALT lymphoma of the thyroid

INTRODUCTION A combination of traditional cytology methods with fluorescence activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB) material is considered a powerful diagnostic tool in the differential diagnosis of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT-L). The aim of this study was to demonstrate the FACS-based diagnostic process of thyroid lesions in a clinical situation where ultrasound and cytological examinations did not allow differentiation between Hashimotos thyroiditis (HT) and MALT-L. MATERIAL AND METHODS The patients analysed in this study presented significantly different clinical courses of thyroid disease: quickly enlarging painless tumour of the thyroid right lobe in the first case, and chronic HT with palpable tumour in the thyroid isthmus in the second patient. Due to the suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology results, FNAB material was obtained from all the previously examined thyroid lesions and directly subjected to FACS assessment, encompassing κ/λ light chain restriction analysis, as well as measurements of B and T cell surface antigens. RESULTS The FACS analysis of FNAB material obtained from our patients did not show any definite signs of light chain restriction. Although one of the samples showed a borderline value of κ/λ ratio (κ/λ = 0.31), further immunophenotyping confirmed clonal expansion in none of the examined thyroid regions. Histopathological findings documented the diagnosis of HT in both clinical cases. CONCLUSION We believe that FACS represents a useful and reliable complementary diagnostic measure in FNAB-based differential diagnosis of lymphoproliferative thyroid disorders.

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.

Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone

Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean ± SD) 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; p < 0.001), OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; p < 0.001), and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; p < 0.005), accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; p < 0.001). During hyperthyroidism there was a positive correlation between sclerostin and CTX (r s = 0.41, p < 0.05) and between OC and thyroid hormones (with FT3   r s = 0.42, with FT4   r s = 0.45, p < 0.05). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH.

Effect of L-thyroxine treatment on peripheral blood dendritic cell subpopulations in patients with Hashimoto's thyroiditis.

Recent reports suggested dendritic cells (DCs) to be important players in the pathogenesis of autoimmune thyroid processes in humans. However, there are virtually no data addressing the influence of thyroid autoaggression-associated disturbances of thyrometabolic conditions on DCs biology. The aim of the study was to evaluate the influence of L-thyroxine supplementation on conventional and plasmacytoid peripheral blood DCs subtypes in patients with hypothyroidism due to Hashimotos thyroiditis (HT). Eighteen patients with newly diagnosed hypothyroidism due to HT were included into the study. All patients received L-thyroxine treatment with doses adjusted to reach euthyroidism. Peripheral blood DC subtypes structure and immunoregulatory phenotype were analyzed by flow cytometry in the same patient prospectively at two time points: (i) before and (ii) 3 months after beginning of L-thyroxine treatment (hypothyroidism vs. euthyroidism, respectively). Percentage of plasmacytoid DCs in peripheral blood mononuclear cells fraction was significantly decreased in the course of L-thyroxine treatment (0.27 ± 0.19 vs. 0.11 ± 0.08; p < 0.05), whereas we did not observe any changes in the number of conventional DCs. However, the phenotypic analysis showed a significant increase of conventional DCs expressing CD86 and CD91 (64.25 ± 21.6% vs. 86.3 ± 11%; p < 0.05 and 30.75 ± 11.66% vs. 44.5 ± 13.3%; p < 0.05; respectively) in euthyroid patients. Standard L-thyroxine supplementation in HT patients exerted significant immunoregulatory effects, associated with quantitative and phenotypic changes of peripheral blood DC subpopulations.

The Effect of Diagnostic Absorbed Doses from 131I on Human Thyrocytes in Vitro

Background: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called “thyroid stunning”. We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). Materials and Methods: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. Results: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. Conclusions: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the “thyroid stunning” reduces the NIS protein synthesis.

Lateral spread of heat during thyroidectomy using different haemostatic devices

INTRODUCTION The presented study is an attempt to comprehensively analyze the lateral spread of heat during thyroidectomy. Obtained results may be valuable in other surgical disciplines in which thermal analysis is difficult or impossible. OBJECTIVE The aim of the study was to evaluate the temperature distribution in the operating field during thyroidectomy performed with the use of modern haemostatic instruments, and to define the safety margin for the investigated devices. MATERIALS AND METHODS Ninety-three patients were thyroidectomised due to thyroid neoplasm. During all the operations the thermovisual measurements were carried out along with continuous intraoperative neuromonitoring of the recurrent laryngeal nerve (CIONM). Investigated patients were divided into 5 groups, named according to the applied haemostatic technique: LigaSure (N=17); ThermoStapler (N=20); Focus (N=19); SonoSurg (N=17) and Monopolar (N=20). RESULTS At maximal performance settings, the highest working temperature was observed for the ThermoStapler, while the lowest temperature was recorded for the Monopolar. Safety margin and working time were increased in Focus and SonoSurg, compared to LigaSure and ThermoStapler. The differences in the necrosis thickness were negligible. The largest distance of the midline of the active blade from isotherm of 42ºC observed in the study was 5.51 mm; none of investigated devices used at a bigger distance had influence on the morphology of the electric signal of CIONM. CONCLUSION The thermo-visual camera allows non-invasive, safe, and real-time monitoring and analysis of temperature distribution in the operation area during thyroidectomy. Proposed minimal safety margin for the analysed devices is 5.51 mm.

Continuous intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve is sufficient as the only neuromonitoring technique in thyroidectomy performed because of benign goitre

INTRODUCTION Recently, intraoperative neurophysiological neuromonitoring (IONM) of recurrent laryngeal nerves (RLN) has been evolving quickly. This evolution touched many aspects of the technique, leading to continuous stimulation of the RLN with real time analysis of the electrical signal. OBJECTIVE The aim of the study was to estimate the value of continuous intraoperative neuromonitoring (CIONM) as the only technique for intraoperative neuromonitoring in thyroidectomy performed because of benign goitre. MATERIAL AND METHODS The study comprised 80 women qualified for thyroidectomy due to nodular goitre. The patients were divided into 4 groups depending on the technique used for RLN integrity verification: group 1 - thyroidectomy with CIONM; group 2 - thyroidectomy with direct, intermittent stimulation of RLN and vagus nerve (NX); group 3 - both CIONM and intermittent stimulation of RLN and NX; group 4 - thyroidectomy without any IONM. RESULTS Mean operation time did not differ significantly among the groups with IONM, but was significantly longer in comparison to group 4, as well as the operations cost. In the analysed groups there was no significant difference in complication ratio. CONCLUSION CIONM with RLN visualization in thyroidectomy performed because of benign goitre is as safe as other methods of IONM and gives a continuous confirmation of the electrical integrity of the loop NX-RLN-vocal folds during almost the entire procedure. There is a clinical need for the development of external stimulation of NX (transdermal or trancranial), particularly for minimally invasive techniques in which access to NX is limited (i.e. transoral thyroidectomy).

Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country

Introduction Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). Material and methods A group of 603 children (316 girls and 287 boys), aged 6–14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. Results The median UIC in 1994 (45.5 μg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 – 101.1 μg/l, 2010 – 100.6 μg/l, 2016 – 288.3 μg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10–6 m; this value was higher than at other time points (2.73 × 10–6 m in 1999, 2.73 × 10–6 m in 2010, and 2.70 × 10–6 m in 2016). Conclusions Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.