Cognitive functions and mood during chronic thyrotropin-suppressive therapy with L-thyroxine in patients with differentiated thyroid carcinoma.

BACKGROUND: Subclinical thyroid dysfunctions may cause cognitive deficits and mood disorders. Chronic TSH-suppressive therapy with L-T(4) causing subclinical hyperthyroidism has been widely used in treatment of patients with thyroid differentiated carcinoma. The impact of this therapy on cognitive functions and mood have not been systematically studied. The aim of this study was to asses executive functions, working memory, attention, and depression in patients with subclinical hyperthyroidism in the course of TSH-suppressive therapy. METHODS: Thirty-one patients with subclinical hyperthyroidism in the course of suppressive treatment with L-T(4) following the total thyroidectomy and radioiodine ablative therapy were included in the study. Cognitive functioning in patients and control group were investigated using the battery of neuropsychological tests [Wisconsin Card Sorting Test (WCST), The Oral Word Association Test (OWAT), Trail Making Test, The Stroop Color-Word Interference test and Digit span]. Psychometric evaluation was performed using 17-items the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). RESULTS: The performance on tests assessed executive functions, psychomotor speed, and attention was significantly lower in patients group. There was no differences in results of Stroop test and Digit Span forward and backwards between both groups. The intensity of depressive symptoms negatively correlated with a number of completed categories on WCST and results of OWAT. Cognitive deficits were still observed when patients with concomitant general medical conditions and depression were excluded from the analysis. CONCLUSION: Our findings provide evidence of neuropsychological impairment in patients with differentiated thyroid carcinoma treated with chronic TSH-suppressive therapy.

A systematic review of the pharmacotherapy of secondary hyperparathyroidism (SHPT) in grades 3-5 Chronic Kidney Disease (CKD).

OBJECTIVE: The data on the treatment of secondary hyperparathyroidism (SHPT) provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of SHPT treatment in (chronic kidney disease) CKD. MATERIALS AND METHODS: The Cochrane, PubMed, and Scopus databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness and side effects of calcifediol, ergocaliferol, calcitriol, paricalcitol, and cinacalcet were compared and analyzed. RESULTS: Extended-release (ER) calcifediol raised the total serum 25-hydroxyvitamin D level over the threshold of 30 ng/mL in 80% of the patients analyzed in the study. It is the level required for intact PTH (iPTH) suppression. ER calcifediol reduced the iPTH level by 30% in about 30% of the patients, whereas only 2.1% of them had hypercalcemia. Calcitriol significantly decreased the iPTH values. It was the cause of hypercalcemia in 1.7% of the patients. The reduction of the iPTH level by more than 30% was observed in 85.7% of the patients in the paracalcitol group after 48-week supplementation. Paricalcitol was the cause of hypercalcemia in 1.9% of the patients. The cinacalcet therapy resulted in the highest percentage of patients with the iPTH level within the limits recommended by the KDOQI (70-110 ng/L for stage 4 CKD and 150-300 ng/L for stage 5 CKD). 92% of the patients met the KDOQI guidelines and the mean decrease in the serum iPTH level was 68%. CONCLUSIONS: Calcifediol ER, paricalcitol, and cinacalcet significantly decreased the iPTH level in the patients under study. Paricalcitol increased the serum calcium concentration the most of all the drugs under analysis. It is noteworthy that only cinacalcet does not carry the risk of hypercalcemia.

Follicular thyroid cancer in a patient with Pendred syndrome.

We present the clinical and molecular studies of a family with Pendred syndrome, in which one affected individual developed follicular thyroid cancer. Two siblings with classic Pendred syndrome triad were operated on because of enormous multinodular goiter. Histopathology showed a follicular thyroid cancer in the male and a multinodular goiter in the female. PDS gene analysis revealed G-to-A transition in the splice donor site of intron 8 (IVS8+1G>A/c.1001+1G>A). Careful surveillance is needed in all cases of thyroid nodules in patients with Pendred syndrome, due to the high risk of malignancy.

[Treatment with L-thyroxine for differentiated thyroid carcinoma]. / Leczenie L-tyroksyna zróznicowanego raka tarczycy.

Differentiated thyroid carcinoma (DTC) is one of malignant neoplasms with a very good prognosis and low mortality rate provided a proper therapy and its systematic monitoring is given. DTC treatment consists of surgery, radioiodine and L-thyroxine therapy. L-thyroxine therapy in DTC should be both substitutive and suppressive. Substitutive therapy consists in the removal of the lack of thyroid hormones symptoms so that the serum TSH is about 1 mU/l. Suppressive therapy consists in complete inhibition of TSH secretion by pituitary gland. This prevents from the regrowth and inhibition of carcinoma progress in patients with evident or residual neoplasmic disease. Although complete suppressive therapy (TSH less than 0.05 mU/l) is the most recommended one, in patients with low recurrence risk incomplete suppression can be used (TSH = 0.1-0.3 mU/l). Suppressive L-thyroxine doses may give side-effects such as: cardiac signs (arrhythmia, coronary or heart insufficiency), decrease in bone mineral density with osteopoenia or osteoporosis or subclinical hyperthyroidism. However, the side-effects of the suppressive L-thyroxine doses may be symptomatically treated (with beta-blockers, biphosphoniates).

[Accuracy of ultrasound-guided fine-needle aspiration biopsy in diagnosis of changes in thyroid nodular lesions]. / Skutecznosc celowanej biopsji aspiracyjnej cienkoiglowej w diagnostyce zmian guzowatych tarczycy.

The aim of this study was to compare the results of US-FNAB with definitive histological examination of thyroid nodular lesions. 590 patients who underwent surgery were reviewed (473 females, 117 males, ranging in age from 9 to 81 years, average 36 years). Histological evaluation of cytologically diagnosed benign nodules revealed nodular goiter in 407 cases (91.5%), Hashimoto's thyroiditis in 2 (0.4%), follicular adenoma in 31 (7%), papillary carcinoma in 2 (0.4%) and follicular carcinoma in 3 (0.7%). In the cytological group of follicular nodule (n = 71) histological diagnoses included: nodular goiter in 11 cases (15.5%), follicular adenoma in 36 (50.7%), papillary carcinoma in 2 (2.8%), follicular carcinoma in 20 (28.2%). The diagnosis of papillary carcinoma (n = 65) was confirmed histologically in 59 cases (90.8%), in the remaining 6 cases Hashimoto's thyroiditis and medullary carcinoma were diagnosed. In the cases diagnosed cytologically as medullary carcinoma (n = 8) histological diagnoses included: medullary carcinoma in 7 cases (87.5%). The cytological diagnosis of anaplastic carcinoma (n = 1) was confirmed histologically. These results support the value of US-FNAB in the diagnostics of thyroid neoplasms. US-FNAB performance was as follows: sensitivity 78%, specificity 97%, accuracy 92%, 2.3% of false positive and 6.1% of false negative results.

An additional restriction fragment length polymorphism at the thyroglobulin gene.

The study was aimed at the screening of human chromosomal DNA for restriction fragment length polymorphism (RFLP) at the human thyroglobulin (hTg) gene locus. The RFLP screening was performed in a typical way. As hybridization probes were used 5 Pst I fragments of hTg cDNA of the total length 5.1 kb pairs cloned in pBR 322. One not described polymorphism was found by using the probe hTg 10, (nucleotides from position 4830 to 5810 in the 3' flanking region of hTg). Restriction enzyme Msp I identified a single two allele polymorphism: A1: 3.5 kb and A2: 2.5 kb. Of 32 unrelated healthy individuals two were homozygous for 3.5 kb, one was homozygous 2.5 kb and 29 were heterozygous for both 3.5 kb. and 2.5 kb. Thus, the frequencies of the 3.5 and 2.5 kb Msp I alleles were 0.52 and 0.48 respectively.

[Anti-thyroid autoantibodies in children with insulin-dependent diabetes mellitus]. / Wystepowanie przeciwcial przeciwtarczycowych u dzieci chorych na cukrzyce insulinozalezna.

The study was aimed at the assessment of frequency of occurrence of thyroid antimicrosomal and antithyreoglobuln autoantibodies in children with insulin-dependent diabetes and healthy control children. The occurrence of thyroid autoantibodies was analyzed with respect to the age and sex of children and the duration of the disease. The studied group was composed of 199 children of age between 2 and 17 years with insulin-dependent diabetes. Control group included 100 healthy children. Thyroid autoantibodies were determined by using a solid phase radioimmunoassay. Antimicrosomal antibodies were detected in 35% of diabetic children, but only in 1% of healthy children. Neither in diabetic nor in control children the occurrence of antithyreoglobulin antibodies was significant. The frequency of occurrence of antimicrosomal antibodies was not related to age of children or the duration of diabetes. The occurrence of these antibodies was significantly more frequent in girls (in 70% of cases) than in boys (30% of cases).

[Thyroid gland function in neonates with transient hyperthyrotrophinemia from a region of slight iodine deficiency]. / Czynnosc tarczycy noworodków z przemijajaca hipertyreotropinemia na obszarze nieznacznego niedoboru jodu.

The aim of this study was to evaluate thyroid gland function in neonates and babies with transient hyperthyrotrophinemia during the first twelve months of life in an attempt to establish the causes of this condition in neonates born in a region of slight iodine deficiency. Thirty-eight newborns were screened. Clinical observations and measurements of serum T3, T4, TSH levels as well as urinary iodine were conducted for one year (at the age of 2 weeks, 3-4 months, and after one year of life). The screened children showed significantly higher values of T4 (p < 0.001) in comparison with the reference value in successive follow-up examinations. High T4 values may result from an increased TBG concentration in serum, and its level should be determined in the analysed material. Other hormonal values normalized after the second weak of life. Iodine deficiency was found in 80% of the children. Our assessments concerning the causes of transient hyperthyrotrophinemia conform with previous findings. It was established that the most common causes are iodine deficiency and maternal thyroid disease. None of the screened children had goitre somatic anomalies or delayed psychomotoric development did not appear more frequently than in the general pediatric population.

Interleukin 1 beta (IL1beta) gene polymorphisms (SNP-511 and SNP+3953) in Hashimoto's thyroiditis among the Polish population.

AIM: The association between the interleukin IL1 beta gene polymorphisms SNP-511 and SNP+3953 and susceptibility to the development of Hashimoto's thyroiditis among adult Caucasian-Polish population were analyzed. PATIENTS AND METHODS: The group studied comprised of 115 unrelated patients with Hashimoto's thyroiditis (112 women and 3 men, mean age 53.3 years). All patients were euthyroid on thyroid replacement therapy, had extremely high serum anti-TPO levels and in 53 patients anti-TG levels were also increased. The control group consisted of 103 healthy blood donors without raised anti-TPO antibodies, in whom a personal and familial history of thyroid, autoimmune and inflammatory diseases was excluded. No goiter or thyroid dysfunction was found.2 polymorphisms of the IL1 beta were studied by PCR-RFLP analysis. To confirm the accuracy of the method used, randomly selected patients were analyzed by direct sequencing. RESULTS: In both groups allele frequencies were in Hardy-Weinberg equilibrium. The significant statistical differences between the frequency of C and T allele for both SNPs (C-511T and C+3953T) in the group studied and in the controls were found (p=0.0081; OR=1.846; 95% CI: 1.183-2.878 and p=0.0099; OR=1.953; 95% CI: 1.183-3.224).The frequencies of the genotype C-511C compared to C-511T and T-511T as well as C+3953C compared to C+3953T and T+3953T also differed significantly (p=0.0057; OR=2.248; 95% CI: 1.292-3.912 and p=0.0043; OR=2.338; 95% CI: 1.305-4.191) between patients and controls. CONCLUSIONS: An association between the SNPs of the IL1 beta and susceptibility to Hashimoto's thyroiditis among the group of Caucasian-Polish population studied was found.

Thyroid metastases from a breast cancer diagnosed by fine-needle aspiration biopsy. Case report and overview of the literature.

AIM: Intrathyroid metastases are uncommon in cytology practice. We report a case of metastatic lesion in the thyroid from breast carcinoma which was recognized in a fine-needle aspiration (FNA) biopsy and confirmed by immunohistopathology. In addition, we provide an overview of the literature describing similar cases. STUDY DESIGN: The patient was a 54-year old woman with a large, multinodular goiter and bilaterally enlarged lymph nodes in the supraclavicular areas. Fourteen years earlier she had undergone radical mastectomy followed by chemio- and radiotherapy due to a breast carcinoma. RESULTS: FNA of the thyroid nodules showed a metastatic breast carcinoma and was followed by total strumectomy and lymphadenectomy. Histological reassessment of the surgical thyroid specimens as well as the neck lymph nodes revealed multiple breast metastases. This was strongly confirmed by immunohistochemical examinations, which revealed a positive staining for: CKMNF 116, CK7, CEA as well as for ER, PgR and HER2, and a negative staining for: CK20, thyroglobulin, TTF1, calcitonin, and chromogranin. CONCLUSION: Every new aggregate in the thyroid in patients with even a long-term history of cancer should be considered as potentially metastatic until proved otherwise. FNA could be helpful in the diagnosis of thyroid metastatic lesion, but it should be confirmed by immunohistopathology.

The associations between iL-18 serum levels and the prevalence of metabolic syndrome in Polish men over the age of 40 according to other selected inflammatory indices and androgens: comparison of NCEP with IDF criteria.

BACKGROUND: The frequency of MS increases with age and augments the cardiovascular risk. The criteria for distinguishing MS constantly evolve. The aim of the study was to estimate the reciprocal links between low-grade inflammation, selected serum androgens and prevalence of MS, according to NCEP and IDF criteria, in Polish men over the age of 40. MATERIALS AND METHODS: A sample of 160 men was randomly selected from men at the age of 40, 50, 60 and 70, residing in the rural south-western region of Poland. IL-18 and CRP, transferrin, α (1)-antichymotrypsin, dehydroepiandrosterone and its sulfate as well as free-testosterone levels were evaluated. RESULTS: The prevalence of MS was 37.5% using NCEP criteria and 46.25% employing IDF indices. Patients with MS diagnosed according to criteria proposed by NCEP and IDF exhibit a similar hormonal and immunological profile. Age was positively correlated with CRP (r=0.231; p<0.0005), and α (1)-ACT (r=0.191 p<0.05) and negatively with transferrin (r=-0.27; p<0.001), but not with IL-18 plasma levels. Both adrenal androgens were negatively correlated with age: DHEA r=-0.489; p<0.001 and DHEAS: r=-0.553; p<0.001 respectively, in contrast to free-testosterone. People suffering from MS have shown a significantly higher level of IL-18 and CRP. The number of MS components identified (according to NCEP) is positively correlated only with IL-18 serum levels (r=0.226; p=0.043). CONCLUSIONS: Inflammatory parameters were better than a deficit of androgens in identifying men suffering from MS. However, the best correlation with the number of MS components was revealed by IL-18 plasma levels.

Quality of life, depressive symptoms and anxiety in hyperthyroid patients.

PURPOSE: The aim of the study was to evaluate quality of life and to assess frequency and severity of depressive and anxiety symptoms in hyperthyroid patients. MATERIAL AND METHODS: Forty-seven hyperthyroid patients (38 female, 9 male, mean age 51.4 +/- 13.0; 25-Graves disease, 22 - nodular goitre) and fifty-eight sex- and age-matched controls (40 female, 18 male, mean age 49.6 +/- 16.0) were studied. Quality of life was assessed by means of WHO QuoL Questionnaire. Psychometric evaluation included assessment of depressive symptoms (Hamilton Depression Rating Scale and Beck Depression Inventory) and anxiety level (State and Trait Anxiety Inventory--STAI). RESULTS: Patients presented significantly decreased perception of quality of life and health state, and scored worse in physical domain and global score of WHO QuoL. Nineteen patients showed depressive symptoms, remaining 28 were euthymic. Level of anxiety did not differ significantly between the patients group and controls. Free thyroxine plasma level correlated with psychological domain of QuoL. Depression severity correlated with anxiety (STAI 2). Anxiety as a state marker influenced psychological and environmental domains and global score of quality of life questionnaire. CONCLUSIONS: The influence of hyperthyroidism on the quality of life was observed. Depressive symptoms are frequent in hyperthyroidism, occurring in 40% hyperthyroid patients. We found also the association between the anxiety level and the quality of life.

[Electrophoretic and enzymatic analysis of glycosaminoglycans in the blood serum of patients with hyperthyroidism]. / Analiza elektroforetyczna i enzymatyczna glikozoaminoglikanów w surowicy osób z nadczynnoscia tarczycy.

An effect of hyperthyroidism on the composition and levels of glycosaminoglycans in the blood serum was studied. Glycosaminoglycans isolated from 1-ml blood samples were assayed with the following techniques: carbazole, electrophoretic and enzymatic. Separation and assay of particular GAG were made with bidirectional electrophoresis. Isomers of the remaining chondroitin sulphates were assayed enzymatically. Electrophoretograms of GAG in blood serum of healthy women have shown two fractions: low sulphate chondroitin sulphate and chondroitin-4-sulphate. The same fractions of GAG were found in blood serum of the female patients with hyperthyroidism. Mean concentration of GAG in the blood serum of hyperthyroid patients increased by 51%: low sulphate chondroitin sulphate and chondroitin-4-sulphate concentrations increased by 22% and 190% respectively. Chondroitin sulphates in the blood serum of both groups were degraded to unsaturated disaccharides not containing sulphur and unsaturated 4-sulphate disaccharides. Concentrations of unsaturated 4-sulphate and unsaturated sulphur-free disaccharides increased by 71% and 17% in hyperthyroidism. Observed changes in the blood serum GAG concentrations reflect changes in the connective tissue metabolism in hyperthyroidism.

[Human leukocyte antigen (HLA) complex and anti-thyroidal antibodies in Graves' disease]. / Uklad HLA a przeciwciala przeciwtarczycowe w chorobie Gravesa-Basedowa.

The study aimed at: 1) assessing occurrence of HLA-A, HLA-B and HLA-C antigens in patients with Graves' disease in comparison with control group of healthy individuals; 2) determining relationship between circulating serum antimicrosomal and antithyroglobulin antibodies and selected HLA complex antigens. Human leukocyte antigens A, B, and C were detected with serological technique using cytotoxicity test. Thyroidal antimicrosomal and antithyroglobulin antibodies were titrated with radioimmunological solid phase technique while anti-membrane antibodies with immunoenzyme technique. The study involved 50 patients with Graves' disease and 50 healthy individuals. HLA-B8, HLA-B15, HLA-B35, and HLA-Cw3 antibodies were detected more frequently in patients with Graves' disease than in the healthy individuals. Antimicrosomal and antithyroglobulin antibodies were detected in the same group in 76% and 58% of patients, respectively whereas anti-membrane antibodies in 92% of patients. Comparison of the occurrence of thyroidal antimicrosomal and antithyroglobulin antibodies with the presence of HLA-B8, HLA-B35, HLA-B15, and HLA-Cw3 antigens did not show statistically significant correlation between these two parameters.

[Occurrence of various autoantibodies in autoimmune diseases]. / Czestosc wystepowania róznych autoprzeciwcial w autoimmunologicznych chorobach tarczycy.

The study aimed at determining the incidence of autoantibodies occurrence in the course of autoimmunological diseases of the thyroid gland and in healthy population. Autoantibodies against various structures were assayed, including: cellular nuclei, smooth muscles, mitochondria, biliary tubules, parietal cells, reticular fibres, striated muscles as well as thyroglobulin and thyroid microsomes. The study involved 63 patients with autoimmunological diseases of the thyroid gland (35 patients with Graves-Basedow disease and 28 patients with Hashimoto's disease) and 30 healthy individuals. Thyroid antimicrosomal and antithyroglobulin antibodies were assayed with RIA in stable phase whereas the remaining antibodies--with multifunctional indirect immunofluorescence test. The obtained results are the following: antimicrosomal antibodies were present in 68.3% cases while antithyroglobulin antibodies in 76.2% of the examined patients with autoimmunological diseases of the thyroid gland. Immunofluorescence tests performed in the same group have shown antinuclear antibodies in 13% of cases, antibodies against smooth muscles in 28.6%, antimitochondrial antibodies in 1.6%, antibodies against biliary tubules in 3.4%, antibodies against parietal cells in 11.1%, antibodies against reticular fibres in 7.9%, and antibodies against striated muscles in 9.5% of cases. Antinuclear antibodies, antibodies against smooth muscles, and antibodies against both thyroidal microsome and thyroglobulin (in 3.3%) were the only antibodies found in the control group.