Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving.

We report the immunohistochemical diagnosis, including TTF-1 (thyroid transcription factor 1) and Ki-67, of a rare mixed thyroid neoplasm composed of minimally invasive well differentiated follicular areas and highly aggressive undifferentiated anaplastic areas. A 75 old female presented to our clinic with a rapidly growing neck mass. Considering the dynamics of the disease and the multiple challenges presented by the patient: advanced age, tumor size, history of a longstanding goiter we decided to transfer her to the department of surgery. The intraoperative findings were an enlarged right lobe with tracheal and surrounding tissues infiltration. Total thyroidectomy, radical neck lymph nodes dissection and tracheostomy were performed. The histopathological and immunohistochemical examination revealed a coexistent anaplastic and follicular thyroid carcinoma. The proliferation index Ki-67, a cell proliferation marker, was found to be significantly higher in the anaplastic areas (30 +/- 5%) in the comparison with the follicular areas (2 +/- 1%). The evaluation of the thyroid transcription factor 1 (TTF-1) expression revealed a correlation with the tumor cells aggressiveness accordingly to the cancer areas. After a radical surgery an external adjuvant radiation was applied. The patient is alive and more than five years after diagnosis she presented an increase of the serum thyroglobulin level suggesting, probably, a recurrence of the follicular form of the cancer. According to our survey we suggest that in thyroid cancers TTF-1 and Ki-67 could provides useful information on the differentiation activities of thyroid tumor cells and may be helpful to distinguish well differentiated and undifferentiated areas in a mixed thyroid cancer.

Changes in thyroid morphology and function in children in western Poland as a result of intensified iodine prophylaxis.

AIM: To determine the changes in thyroid pathology resulting from obligatory salt iodization in a group of children aged 8-12 years from the rural and urban areas of Wielkopolska Region, Poland. POPULATION AND METHODS: The survey was conducted on 1215 children, of both sexes, 402 of whom were examined in 1992 (before salt iodization), 408 in 2000, and 405 in 2005 (after salt iodization beginning in 1996). Thyroid ultrasound, urinary iodine, FT4, FT3, TSH and antithyroid antibodies were measured. RESULTS: A significant drop in goiter cases was observed (35.4% in 1992 vs 6.3% in 2005), coupled with a marked increase of urinary iodine. There were also changes in ultrasonography and elevated levels of antibodies. CONCLUSIONS: The study proves the high efficacy of iodine prophylaxis. Despite a growing number of children with elevated antithyroid antibody titers, only a slight increase of autoimmune thyroid disorders was observed.

[Iodine prophylaxis in children population on the Wielkopolska Region area from year 1992 to 2005]. / Profilaktyka jodowa u dzieci w Regionie Wielkopolskim w latach 1992-2005.

INTRODUCTION: The aim of the study was to evaluate of efficiency of iodine prophylaxis based on obligatory model of salt iodization. MATERIAL AND METHODS: The study included 1444 children from the rural and urban area, with the proportional sex and age (8-12 years) distribution--432 children in 1992 (before salt iodization), 558 children in 2000 and 454 children in 2005 (during salt iodization from 1996). RESULTS: The prevalence of goiter detected in children population in 1992 was 40% (recount by current criteria), in 2005 was reduced to 6% (p < 0.01). Parallel, median of urinary iodine concentration increased from 44 microg/l in 1992 to 107 microg/l (p < 0.01) in 2005. The increase of incidence of autoimmunological thyroid diseases is observed, especially chronic thyroiditis. CONCLUSIONS: The study proves high efficiency of iodine prophylaxis in Wielkopolska Region, but it is still the area with mild iodine deficiency.

Radioiodine treatment of hyperthyroidism in patients with low thyroid uptake.

BACKGROUND: The aim of the study was to analyze the effectiveness of radioactive 131I in hyperthyroid patients with confirmed lowered iodine uptake as compared to patients with an uptake of over 30%. MATERIAL AND METHODS: We retrospectively analyzed 53 consecutive patients aged from 29 to 84 (mean age 60 years) suffering from hyperthyroidism caused by Graves' disease or toxic nodular goitre. The patients were divided into 2 sub-groups: the 1st with a maximum iodine uptake of 18.7 +/- 3.2% (range, 11-23%) - 24 patients; the 2nd with a maximum iodine uptake of 27.1 +/- 2.1% (range, 24-30%) - 29 patients. The control group consisted of 50 patients treated with 131I with an iodine uptake of over 30%. Each patient was evaluated before, and 6 months after, treatment for fT3, fT4 and TSH with ECLIA; TRAb with RIA; ultrasound with a 7.5 MHz linear probe. The volume of the thyroid gland was determined using the Gutekunst method. All these factors underwent statistical analysis and were considered along with the results of clinical examinations. RESULTS: Clinical remission of hyperthyroidism was evident in 79.3% of both sub-groups, in total (83.3% and 75.3%, respectively). TSH was normalized in 62.3% of these patients (54.2% and 69.0%, respectively). The mean range of TSH levels increased from 0.081 microU/ml to 4.0 microU/ml after therapy; that is, from 0.087 microU/ml to 4.97 microU/ml in the 1st sub-group and from 0.076 microU/ml to 3.3 microU/ml in the 2nd sub-group. The volume of the thyroid gland was uniformly significantly lower, with a mean range of 40.5 ml before treatment and 21.7 ml afterwards. The results seen in both sub-groups were similar; only age and dose of radioiodine were slightly higher in the 1st, while mean uptake was higher in the 2nd. By comparison of these results to those of the control patients, we observed that the values of TSH, as well as thyroid volume and evidence of clinical remission, reflected those found in the control group. The mean dose of 131I was lower in the control group, that is 11.3 m Ci, as compared to the sub-groups as a whole, specifically, 15.7 mCi. The mean age of patients in the control group was slightly less than that of the study group (50.8 and 60, respectively). CONCLUSIONS: 1. The results of the treatment of patients with a low iodine uptake are similar to the results obtained in the group of patients with iodine uptake above 30% and therefore low iodine uptake should not be a contraindication for isotope I-131 therapy. 2. Additionally, we have demonstrated that a statistically significant decrease in thyroid volume is observed in all patients after the iodine isotope treatment which indirectly proves the effectiveness of the prescribed treatment, and that low thyroid iodine uptake is more frequently observed in elderly patients and in patients treated with iodine or anti-thyroid drugs.

[Soluble forms of adhesion molecules sELAM-1 and sICAM-1 in Graves disease and toxic nodular goiter]. / Rozpuszczalne formy czasteczek adhezyjnych sELAM-1 i sICAM-1 w chorobie Gravesa i Basedowa i wolu guzowatym nadczynnym.

Intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) are playing a significant role in an inflammatory process. In patients with autoimmune disorders of thyroid gland an increased expression of ICAM-1 and ELAM-1 was found in thyroid and also in orbital tissue in presence of active ophthalmopathy. Reports concerning concentrations of adhesion molecules soluble forms (sELAM-1 and sICAM-1) in sera of patients suffered from different thyroid gland diseases are controversial. The aim of the project was an estimation of levels of adhesion molecules soluble forms in sera of patients with Graves' disease (GD) and toxic nodular goiter (TNG). In the presented research work sICAM-1 and sELAM-1 were determined in 149 subjects (aged 17-69 years) divided to following groups: group 1--16 hyperthyroid GD patients with active ophthalmopathy (GO) (10 females and 6 males); group 2--25 euthyroid GD patients with GO (17 females and 8 males); group 3--41 hyperthyroid GD patients without GO (22 females and 16 males); group 4--36 patients with TNG (20 females and 16 males) and control group (group 5)--31 healthy subjects (16 females and 16 males). sICAM-1 and sELAM-1 serum concentrations were determined using highly sensitive enzyme linked immunosorbent assay (ELISA). In comparison with control group (group 5) in groups 1--3 significant increase of sICAM-1 and sELAM-1 concentrations was found (p < 0.001). The highest values for both adhesion molecules were demonstrated in the group of hyperthyroid GD patients with GO (group 1) as well as in group of euthyroid GD patients with GO (group 2). In group 1 the values were higher than those in group 2. Lower concentrations were present in group of GD patients with hyperthryroidism without symptoms of GO (group 3). The lowest adhesion molecules concentrations in four examined groups were present in sera of patients with TNG (group 4). The level of sICAM-1 in this group was higher than that in control group, but the difference was not statistically significant (p < 0.01), on the contrary sELAM-1 concentration was markedly elevated in comparison with group 5 (p < 0.002). From the obtained results it may be concluded that elevated sICAM-1 and sELAM-1 concentrations in sera of GD patients are dependent on autoimmunological factors, presence of inflammatory changes in the orbital tissue as well as on hyperthyroidism. Nonautoimmune hyperthyroidism has also influence on increase of sICAM-1 and sELAM-1 levels.

[Prognostic role of adhesion molecules sELAM-1 and sICAM-1 in glucocorticoid therapy of active ophthalmopathy]. / Rola prognostyczna rozpuszczalnych form czasteczek adhezyjnych sELAM-1 i sICAM-1 w kortykoterapii oftalmopatii naciekowej.

Inflammatory process is connected with the increased expression on cells of adhesion molecules, also including intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1). In active ophthalmopathy (GO) this process, of various severity, is progressing in orbital tissue. This is reflected by the increase in blood of these molecules soluble forms. The aim of the project was to study sELAM-1 and sICAM-1 concentrations in sera of patients with GO in the course of Graves' disease (GD) gratified to glucocorticoid therapy, as well as the analysis of this treatment influence on both adhesion molecules with taking into consideration their prognostic role in an applied treatment. The analysis included 25 subjects with eye changes in the class at least 2c (ATA). The duration of GO did not exceed 2 years. Patients received 3 i.v. "pulses" of methyloprednisolone (1 g/d, every second day), followed by oral administration of prednisone during 3 months (60 mg/d, with gradual dose reduction). The blood was taken before treatment, next day after the last methyloprednisolone infusion, after 2 week of prednisone therapy and after completing of glucocorticoid treatment. As a result of the applied therapy 15 subjects obtained clinical improvement (group 1A), on the contrary 10 persons did not gain positive effects after finishing prednisone (group 1B). Before starting the treatment sICAM-1 and sELAM-1 levels in group 1A were lower than those in group 1B. After methyloprednisolone therapy sICAM-1 and sELAM-1 concentrations declined in both groups. This was related in the most of patients to clinical improvement, which occurred at that time. After 2 weeks of prednisone application concentrations of both adhesion molecules were still decreased. After completing of glucocorticoid therapy in patients with clinical improvement (group 1A) sICAM-1 concentration remained suppressed, in the range of concentrations present in sera of healthy subjects (group 2). In patients without clinical response (group 1A), with gradual recurrence of inflammatory symptoms together with reduction of prednisone dose sICAM-1 concentration increased again to values comparable to initial levels. sELAM-1 concentration in group 1A still did not markedly change after completing of glucocorticoid therapy, on the contrary--in group 1B the level of this adhesion molecule slightly increased. These values, in contradistinction to sICAM-1, did not drop during therapy to concentrations characteristic for normal range. According to the results it may be concluded, that clinical improvement after glucocorticoid therapy is connected with lower adhesion molecules concentrations before treatment. Glucocorticosteroids are causing decrease of sICAM-1 and sELAM-1 concentrations in patients with GO in the grade dependent on the dose of medication, on the contrary changes in sELAM-1 concentration are less significant. Maintenance of decreased sICAM-1 concentration during glucorticoid therapy is a positive prognostic factor.

A study of thyroglobulin concentration in the thyroid and serum of patients with different thyroid disorders.

Knowledge concerning the structure and quality of thyroglobulin (Tg) has great significance for the better understanding of the pathogenesis of different thyroid diseases. The localization of the Tg gene and studies of its structure by molecular biological techniques make possible precise investigations of its expression. The aim of our study was to evaluate Tg content in the thyroids and Tg concentrations in the serum of 108 patients suffering from benign or malignant thyroid disorders. The method of investigation was isolating total protein from thyroid tissues obtained during surgery and determining Tg content in the thyroid extracts and Tg concentrations in serum. The Tg concentrations in serum and in thyroid protein extracts were evaluated by fluoroimmunometric assay. Statistical analysis was carried out with the help of the computing programmes.