Ewa Bar-Andziak

Lymphoid tyrosine phosphatase (PTPN22/LYP) variant and Graves' disease in a Polish population: association and gene dose-dependent correlation with age of onset.

Objective  Susceptibility to Graves’ disease (GD) is to a significant extent determined by genetic factors of which the best known are those associated with the HLA and the CTLA4 locus. Recently, two studies on British Caucasians reported that a single nucleotide polymorphism, 1858 C>T in PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which is a negative regulator of T‐cell activation, increases the risk of GD. The purpose of our study was to investigate whether the PTPN22‘T’ allele is associated with GD and/or its subsets, defined by clinical or genetic parameters, in a Polish population.

Polymorphism of the oestrogen receptor beta gene (ESR2) is associated with susceptibility to Graves' disease.

Objective  To investigate whether a polymorphism in the ESR2 gene (rs4986938, previously associated with endometriosis, ovulatory dysfunction and premature onset of coronary heart disease) increases the risk of Graves’ disease (GD).

Association between vitamin D concentration and levels of sex hormones in an elderly Polish population with different genotypes of VDR polymorphisms (rs10735810, rs1544410, rs7975232, rs731236)

BACKGROUND Vitamin D co-regulates the synthesis of sex hormones in part by interaction with its nuclear receptor. The aim of this study was to determine whether there is an association of vitamin D concentration vs the level of sex hormones in elderly Polish individuals with different genotypes of the vitamin D receptor (VDR) gene. MATERIALS AND METHODS Rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum sex hormone level, free estrogen index (FEI) and free androgen index (FAI) as well as vitamin D, were evaluated in 766 persons (362 women and 404 men) selected from 5695 Polish population, aged 65-90years from the PolSenior survey. RESULTS We observed that women with GG (rs731236), TT (rs7975232), BB (rs1544410) and FF (rs10735810) genotypes were characterized by a significant correlation between vitamin D vs testosterone concentration and FAI value. We found a significant correlation between testosterone level and FAI vs vitamin D concentration in men with heterozygote AG in the rs731236 polymorphism and in the GG (rs7975232), the BB (rs1544410), and the Ff (rs10735810) genotypes. CONCLUSION In elderly selected Polish population with different genotypes of VDR polymorphisms, a statistically significant relationship between vitamin D concentration vs testosterone level was observed.

Interrelation between genotypes of the vitamin D receptor gene and serum sex hormone concentrations in the Polish elderly population: the PolSenior study.

AIM Vitamin D co-regulates the synthesis of sex hormones. Therefore, the aim of this study was to determine whether the presence of certain genotypes of the vitamin D receptor gene (VDR) is associated with the serum levels of sex hormones in the elderly Polish population. MATERIALS AND METHODS The rs10735810, rs1544410, rs7975232, and rs731236 polymorphisms of VDR, the serum levels of testosterone and estradiol, as well as free estrogen index (FEI) and free androgen index (FAI) were evaluated in 360 women and 400 men aged 65-90years selected from 5695 respondents of the PolSenior survey. RESULTS Only the rs1544410 VDR polymorphism was associated with the serum levels of sex hormones. The prevalence of rs1544410 genotypes was 38% BB, 46% Bb, and 16% bb in women and 41% BB, 44% Bb, and 15% bb in men. In women the frequency of the B allele was p=0.61 and b allele q=0.39, while in men it was p=0.63 and q=0.37, respectively. We found significant differences in the serum testosterone level (p<0.0004) and FAI (p<0.0015) between the rs1544410 genotypes in women but not in men. Higher mean testosterone level and higher mean FAI were observed in women with a rare bb genotype in comparison to a common BB genotype. CONCLUSION We hypothesize that in women the increase in VDR expression associated with a rare genotype of the rs1544410 polymorphism of this gene may be associated with an increase in testosterone and FAI levels.

Vitamin D receptor gene polymorphism and cardiovascular risk variables in elderly Polish subjects

The aim of this work was to evaluate whether the FokI and BsmI polymorphisms of the VDR gene are associated with anthropometric and biochemical features of cardiovascular disease (CVD) in a Caucasian population aged over 65, participants of the Polish PolSenior study. We performed the study on randomly selected subjects: 427 women and 454 men aged over 65. Measurements of anthropometric parameters were carried out and biochemical parameters were estimated using commercial kits. VDR polymorphisms (rs10735810, rs1544410) were genotyped by PCR and FRLP. The prevalence of BsmI genotypes was 50% Bb, 23% bb, 27% BB in women and 48% Bb, 20% bb, 32% BB in men. The prevalence of FokI was 48% Ff, 22% ff, 30% FF in women and 50% Ff, 18% ff, 32% FF in men. The women bearing the rare allele b differ in homeostatic model assessment (HOMA) (p < 0.049) from women bearing common allele B, and the men differ in insulin level (p < 0.047) and HOMA (p < 0.017). There were no significant differences in anthropometric or biochemical parameters between genotypes in FokI in female and male groups. The common allele B is connected with biochemical risk factors of CVD in older Caucasian men and women.

Laparoscopic treatment of Cushing’s syndrome in a woman in late pregnancy – a case presentation

Hypercortisolaemia during pregnancy constitutes a serious threat to life of the mother and fetus and may be associated with adrenocortical carcinoma. The objective of this study is to present the usefulness of laparoscopic procedures in treating adrenal tumours in such cases. One 21-year-old woman, 24 weeks pregnant, with hypertension and Cushings syndrome due to a left adrenal tumour, underwent laparoscopic adrenalectomy followed by hydrocortisone replacement. Spontaneous delivery occurred at the 37/38th week of gestation. At 3 months postpartum the function of the remaining adrenal gland was found to be normal. Similarly, imaging tests, abdominal CT scan and chest X-ray revealed no abnormalities. Pregnancy is not a contraindication for performing complicated laparoscopic procedures unless they are planned in advance and done by an experienced team.

Enzymatic activity of type 1 iodothyronine deiodinase in selected liver tumors.

Introduction Type 1 iodothyronine deiodinase (D1) converts thyroxin (T4) into tri-iodothyronine (T3). Strong evidence indicates that thyroid hormone metabolism is disturbed in neoplasms such as thyroid and breast cancer. However, there is limited data concerning the function of the D1 enzyme in liver tumors. We aimed to estimate the enzymatic activity of D1 in two different common liver tumors. Material and methods We obtained 20 tumor samples from patients who had undergone a liver resection. Of the tissue samples, there were 13 benign lesions of focal nodular hyperplasia (FNH) and 7 malignant lesions of hepatocellular carcinomas (HCC). The D1 activity was assessed by measuring the amount of radioactive iodine released in reaction to D1-catalysed deiodination. Groups were compared by the Mann-Whitney non-parametrical test for independent trials, and the Kruskal Wallis test. Results The enzymatic activity of D1 was not significantly altered in the FNH group (median = 536 fmol/mg of protein/min; p = 0.972) and HCC group (367 fmol/mg; p = 0.128) when compared to matched normal liver parenchyma controls (546 fmol/mg and 556 fmol/mg, respectively). Conclusions Liver parenchyma expresses high levels of D1. The results clearly revealed that D1 activity was not significantly different between benign and malignant tumors (FNH and HCC) compared to healthy liver parenchyma cells.

Reference Values for TSH and Free Thyroid Hormones in Healthy Pregnant Women in Poland: A Prospective, Multicenter Study

Objectives: The diagnosis and treatment of thyroid diseases in pregnant women remains a challenge. Various medical associations recommend establishing the reference intervals for thyroid hormones by a local laboratory. Considering differences within geophysical, socioeconomic conditions, and iodine prophylaxis in various populations, it is advisable to assess reference intervals for thyroid hormones specific to a region of residence. The objective was to assess trimester-specific reference intervals for TSH, fT3, and fT4 for pregnant women in the Polish population. Methods and Results: We conducted a prospective study in 4 centers representing different regions of Poland (Krakow, Warsaw, Poznan, and Bialystok). Our study included consecutive, healthy pregnant women (172 patients), with an age range of 27-47 years. All women had a negative history for thyroid diseases, normal thyroid peroxidase antibody levels, and proper iodine prophylaxis. All newborns had TSH levels in the appropriate reference range. Serum TSH, fT3, fT4, and thyroid-peroxidase antibodies were measured in each trimester. The reference intervals were calculated using the percentile method, as recommended by the International Federation of Clinical Chemistry. The reference values calculated were 0.009-3.177, 0.05-3.442, and 0.11-3.53 mIU/L for TSH; 3.63-6.55, 3.29-5.45, and 3.1-5.37 pmol/L for fT3; and 11.99-21.89, 10.46-16.67, and 8.96-17.23 pmol/L for fT4 in consecutive trimesters of pregnancy. Reference intervals for pregnant women when compared to the general population showed a lower concentration of TSH in every trimester of pregnancy and lower fT4 in the 2nd and 3rd trimesters. Conclusions: Using appropriate trimester-specific reference intervals may improve care of pregnant women by preventing misdiagnosis and inadequate treatment.

Subclinical hypothyroidism in population of aging Polish women and men over 65yrs old and cardiovascular risk factor, endogenous vitamin D levels and its gene receptor polymorphisms – PolSenior Study

Clinical consequences of subclinical hypothyroidism (SH) are still controversial, especially in aging persons. Recently the pleiotropic action of vit. D, also the influence on immune system, was shown and discussed. On the basis of randomly selected 723 women and men (382 men) over 65 yrs old from PolSenior Study we developed the frequency of SH in Polish aging population, and we compared the metabolic profile of cases with SH in comparison to healthy controls according to cardiovascular risk factors (CRF). The serum vit. D and its receptor (VDR) gene polymorphisms Fok-I and Bsm-I in both these groups were estimated. The elevated serum TSH level (over 4.5 mU/ml) with FT4 range: 10.3-25.7 pmol/l and elevated anti-TPO over 20.0 mU/ml showed 7.9% of women and 4.4% of men. The CRF profile: waist circumference, BMI, serum total cholesterol, HDL and LDL cholesterol, triglycerides, fasting glucose, insulin and HOMA were comparable in both groups. Also the endogenous vit. D serum levels were comparable between the group of patients with elevated anti-TPO and elevated or decreased TSH in comparison to controls with euthyroidism. However the analysis of Fok-I and Bsm-I polymorphisms of VDR and thyroid immune status showed higher frequency of recessive genotype bb in person with elevated TSH and anti-TPO (p=0.0334). Conclusions: aging people with subclinical hypothyroidism don’t present higher risk for CVD. The relation between vit. D and its receptor gene polymorphisms and thyroid immune status needs further study.