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.

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.

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.

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.

[Iodine supply and thyroid function in the group of healthy pregnant women living in Warsaw]. / Zaopatrzenie wjod oraz czynnosc tarczycy w grupie zdrowych kobiet ciezarnych zamieszkujacych Warszawe.

UNLABELLED: Iodine deficiency and thyroid gland disorders are especially harmful for pregnant women and normal fetal development. After initiation in 1997 of obligatory iodine prophylaxis, Poland has been found since 2003 a country with sufficient delivery of this microelement. However, in the population of pregnant women, slight deficiency of this element still exists. Insufficient iodine supply results in abnormalities of thyroid hormones'biosynthesis. Simultaneously, adaptive changes, occurring in pregnancy, make the proper interpretation of hormone's assays difficult. Lack of normative data for the thyroid hormones concentration in the each pregnancy trimester for Polish population cause additional difficulties in the interpretation of these results. The aim of the study was prospective observation of iodine intake and thyroid function in healthy pregnant women supplemented with 150 pg of iodine daily MATERIALS AND METHODS: 62 healthy pregnant women living in Warsaw in the early weeks of pregnancy, confirmed by ultrasonographic examination, were included to this study. Pregnancies were singleton resulting in birth of healthy neonates. Urinary iodine concentrations (UIC), serum TSH, fT4, fT3, antyTPO, thyroid volume and morphology by the ultrasonography examination were assessed in consecutive trimesters of pregnancy. TSH level was measured in the each newborn. RESULTS: Low urinary iodine concentrations (UIC)-median 96 microg/l was found at the beginning of pregnancy Only in 14% of pregnant women UIC exceeded 150 microg/l. In spite of intended supplementation of at least 150 microg of extra iodine per day, medians of UIC in the next trimesters were 122 microg/l and 129 microg/l, respectively. TSH levels kept reference values for the 1st trimester of pregnancy in 86% of participants and in the next trimesters in 85% and 95%, respectively. Levels of fT4 were within reference range for the women in the 1st trimester. In 2nd trimester 12% and in 3rd trimester 33% of pregnant women had fT4 level below the reference value. Concentrations of fT3 were within reference values during whole pregnancy. Median thyroid volume was respectively 11.12 ml; 13.0 ml and 15.75 ml (range: 6.8-26.8 ml) in subsequent trimesters.Median neonatal' TSH level on the 3rd day of life, as a screening of thyroid insufficiency, was 1.34 mlU/l (range: 0.01-6.6 mlU/l) and in 4.41 % of newborns TSH concentrations were higher than 5 mlU/I. CONCLUSION: Despite the sufficient supply of iodine in the whole population, iodine consumption among the pregnant women is still not satisfactory. The increase of TSH values above the upper reference level for pregnant women in 15% of patients may be related to iodine deficiency. It is important to educate pregnancy planning women about this problem. Our observations confirm the importance of the recommendations that during the pregnancy every woman should receive supplementation of iodine at the minimal amount of 150 microg daily.

The reference values of sex hormones and SHBG serum levels in subjects over 65 years old - The PolSenior Study.

INTRODUCTION: Over the last decade, average life expectancy has continuously increased. There has been no data on normal sex hormone (SH) levels in a Polish elderly population. In this study, we assessed SH in the PolSenior cohort to determine normal reference ranges in relation to gender, age, and cardiovascular disease risk factors (CVDRFs). MATERIAL AND METHODS: The study was performed with 4,352 participants (2,168 men and 2,088 women), aged from 55 to over 90 years, stratified in five-year age groups. Pre-elderly subjects (55-59 years of age) served as the reference group. We assessed total testosterone (TT), estradiol (TE2) and DHEA-S (by RIA) SHBG and FSH (by IRMA) and calculated free androgen and free estrogen indices (FAI and FEI). Percentage body fat (%BF) was measured by bioelectric impedance analysis. The CVDRFs assessment included blood pressure and biochemical (blood glucose, high-density lipoproteins, triglycerides) and anthropometric (waist circumference) components of the metabolic syndrome. RESULTS: TT was low in 19.9%, normal in 78.2%, and high in 1.8% of men. TE2 was low in 94.6% of women. Age and CVDRFs significantly influenced values of SHBG, FSH, TT, FAI, FEI, and DHEA-S in men, while in women values of FSH, TT and TE2 did not change. BMI and %BF affected SH regardless of the age groups and CVDRFs. CONCLUSIONS: Our findings suggest that the reference ranges stratified by the five-year age bands seem more accurate than those given for the overall population over 60 years of age. The clinical relevance of these reference ranges increases when they are considered in relation to CVDRFs, BMI and %BF.

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.

Thyroid dysfunction and thyroid autoimmunity in a large unselected population of elderly subjects in Poland - the 'PolSenior' multicentre crossover study.

INTRODUCTION: Data on the thyroid function of a randomly chosen elderly population was collected during a multicentre study performed in Poland (PolSenior) in 2007-2010. MATERIAL AND METHODS: The population of 4,190 participants under study was divided into six age subgroups of > 65 to > 90 years of age and a younger group aged between 55 and 59 years. Assessment of thyroid function was based on hormonal measurements. RESULTS: Concentrations of both TSH and fT(4) were significantly higher in females than in males. No differences in TSH and fT(4) concentrations between different age groups were found. Thyroid dysfunction was revealed in more than 10% of participants, hypothyroidism in 7.95%, and hyperthyroidism in 2.95%. Both types of dysfunction were more prevalent in women, and in more than 80% both dysfunctions were subclinical. In 1,542 participants, concentrations of TPOAb were measured. Increased TPOAb was revealed in 19% of the cohort and the prevalence of thyroid autoimmunity was higher in women and also more often found in participants with hypothyroidism. CONCLUSIONS: Cross sectional survey revealed thyroid dysfunctions in over 10% of non selected elderly population. No age related differences were found in TSH concentrations, TPOAb positivity and prevalence of thyroid dysfunctions.

Insulin-like factor 3 -- a new hormone related to polycystic ovary syndrome?

INTRODUCTION: The aim of this study was to find a correlation between insulin-like factor 3 (INSL3) and androgens: androstenedione (A), free testosterone (fT), and total testosterone (T), in two groups of polycystic ovary syndrome (PCOS) women: those with a body mass index (BMI) lower than 25 kg/m(2) and those with a BMI higher than 25 kg/m(2). The association between INSL3 and other serum parameters: luteinising hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and glucose and insulin were also investigated. MATERIAL AND METHODS: The study group comprised 37 PCOS women aged 27 ± 4 years. The control group consisted of 34 healthy, premenopausal women (aged 24.2 ± 1.2) with regular menses and no signs of hyperandrogenism. There were 27 PCOS women of normal weight (BMI < 25 kg/m(2)), and ten overweight individuals (BMI ≥ 25-30 kg/m(2)). Correlations between level of INSL3 and LH, FSH, T, fT, A, DHEA-S, SHBG, metabolic tests, height, weight, and WHR (waist-to-hip ratio) were also investigated. RESULTS: PCOS women showed non-significantly higher levels of INSL3 compared to the healthy controls (64.6 ± 27.7 and 62.7 ± 20.0 ng/mL, respectively). However, we identified very strong correlations between INSL3 and androstenedione (r = 0.48, p = 0.0115), and free (r = 0.44, p = 0.0108) and total testosterone (r = 0.46, p = 0.0057) in the PCOS subgroup with a BMI of < 25 kg/m(2). There was no statistically significant correlation between INSL3 and LH in any subject of the PCOS group, nor between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR. CONCLUSIONS: We found a positive correlation between INSL3 and androgens in PCOS women, especially those with a BMI of < 25 kg/m(2). This may play a key role in PCOS pathophysiology.

Measuring salivary androgens as a useful tool in the diagnosis of polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the commonest endocrinopathies. Clinically it can present as oligo-/amenorrhoea, hyperandrogenism and/or fertility problems. MATERIAL AND METHODS: The study involved 60 women admitted to the Department of Internal Medicine and Endocrinology at the Medical University of Warsaw. The initial evaluation, including case history and two-dimensional vaginal ultrasound, was performed by gynaecologists. All hormonal investigations (fT, free testosterone; bioT, bioavailable testosterone; T, total testosterone; T EQ, free testosterone by equilibrium dialysis; A, androstenedione; A EQ, free androstenedione by equilibrium dialysis; salA, salivary androstenedione; salT, salivary testosterone) were performed. Anthropometrical data, excess facial and body hair, acne, and menstrual cycle frequency were also assessed. RESULTS: Increased levels of T, fT, T EQ and A were noted in 20.0%, 89.8%, 100% and 28.3% of women, respectively. A very high correlation was found between salivary androstenedione and free androstenedione estimated by EQ in plasma (p < 0.05, r = 0.67), and total androstenedione in plasma (p < 0.05, r = 0.71). Correlation between salT and T was r = 0.31, p < 0.05 and salT and T EQ was r = 0.26, p = 0.04. Correlation between salA/salT and T, A in plasma (respective values r = 0.39 and r = 0.28, p < 0.01) and between salA/salT and A EQ, T EQ (respectively r = 0.34 and r = 0.48, p < 0.01) was evident. CONCLUSIONS: SalA/salT ratio may be a good indicator of hyperandrogenism in women. We also confirm that measurement of androstenedione in plasma may be useful in making a diagnosis of PCOS.

Suppurative thyroiditis caused by Salmonella enteritidis.

Bacterial thyroiditis is a rare disease, and one of which the clinical symptoms and signs are frequently misleading. On the other hand, prompt diagnosis is crucial for successful treatment. We report the case of an 82 year-old man with diabetes mellitus type 2 and a history of steroid treatment who presented with severe odynophagia and dysphagia associated with fever, chills, sore throat and right ear pain. Based on the clinical picture, radiological studies, thyroid cytology, blood and thyroid aspirate culture, suppurative thyroiditis caused by Salmonella enteritidis was diagnosed. The patient was successfully treated with antibiotics and surgical drainage.

[Management of thyroid diseases during pregnancy]. / Postepowanie w chorobach tarczycy u kobiet w ciazy.

The management of thyroid disorders during pregnancy is one of the most frequently disputed problems in modern endocrinology. It is widely known that thyroid dysfunction may result in subfertility, and, if inadequately treated during pregnancy, may cause obstetrical complications and influence fetal development. The 2007 Endocrine Society Practice Guideline endorsed with the participation of the Latino America Thyroid Association, the American Thyroid Association, the Asia and Oceania Thyroid Association and the European Thyroid Association, greatly contributed towards uniformity of the management of thyroid disorders during pregnancy and postpartum. Despite the tremendous progress in knowledge on the mutual influence of pregnancy and thyroid in health and disease, there are still important areas of uncertainty. There have been at least a few important studies published in the last 3 years, which influenced the thyroidal care of the expecting mother. It should also be remembered that guidelines may not always be universally applied in all populations with different ethnical, socio-economical, nutritional (including iodine intake) background or exposed to different iodine prophylaxis models. The Task Force for development of guidelines for thyroid dysfunction management in pregnant women was established in 2008. The expert group has recognized the following tasks: development of the coherent model of the management of thyroid dysfunction in pregnant women, identification of the group of women at risk of thyroid dysfunction, who may require endocrine care in the preconception period, during pregnancy and postpartum - that is in other words, the development of Polish recommendations for targeted thyroid disorder case finding during pregnancy, and the development of Polish trimester-specific reference values of thyroid hormones. Comprehensive Polish guidelines developed by the Task Force are to systematize the management of the thyroid disorders in pregnant women in Poland.

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 Cushing's syndrome due to a left adrenal tumour, underwent laparoscopic adrenalectomy followed by hydrocortisone replacement. Spontaneous delivery occurred at the 37/38(th) 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.

Insulinoma in a patient with MEN 1 syndrome--9-year follow-up: case report.

INTRODUCTION: Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant inherited endocrine disease characterized by pancreatic, parathyroid, and anterior pituitary tumours. Hypercalcaemia due to parathyroid tumours is usually the first manifestation of MEN 1. Pancreatic islet tumours occur less frequently, among them gastrinomas and insulinomas are the most prevalent. Prolactinomas are a relatively common pituitary presentation of the syndrome. The gene causing MEN 1 is localized in chromosome 11q13 and encodes a protein named menin, which interacts with various proteins involved in transcriptional regulation, cell division, and DNA repair. Various mutations in the menin gene have been described, but so far no strong correlation between genotype and phenotype has been found. CASE REPORT: We report a case of a 31-year-old man, a lawyer, who was diagnosed with MEN 1 syndrome in 1999 at the age of 21 when he was operated because of prolactinoma and hyperparathyroidism. In 2000 insulinoma was suspected and eventually multifocal lesions in the pancreas were revealed. However, the patient did not agree to be operated on. Since then he has been followed up and has been treated with diazoxid. We observed gradual progression of the disease, but the patient remains in relatively good condition. CONCLUSIONS: Careful screening for MEN 1 is important in young patients with pituitary tumours. Regular follow up is crucial even after surgical treatment. The presented patient developed gradual enlargement of insulinomas and reoccurrence of hyperparathyroidism as well.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency - management in adults.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive hereditary diseases. The impairment of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), adrenal hyperplasia, and excessive androgen synthesis. The syndrome is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase deficiency. The clinical manifestations of CAH in adults result from adrenocortical and adrenomedullary insufficiency, hyperandrogenism, and the adverse effects of glucocorticosteroids used for the treatment of the condition. Non-classic CAH may sometimes be asymptomatic. In patients with classic CAH obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia are more often seen than in the general population. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. Long-term glucocorticosteroid treatment is also a known risk factor for osteoporosis. Patients with CAH require constant monitoring of biochemical parameters (17a-hydroxyprogesterone [17-OHP] and androstenedione), clinical parameters (body mass, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females, and minimise the adverse effects of glucocorticosteroid treatment. Patients with classic CAH require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic CAH require monitoring: treatment is not always necessary. Medical care for patients with CAH should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.

The enzymatic activity of type 1 iodothyronine deiodinase (D1) is low in liver hemangioma: a preliminary study.

Type 1 iodothyronine deiodinase (D1) is a crucial enzyme which converts the prohormone thyroxine (T4) into active tri-iodothyronine (T3). There has been strong evidence that the metabolism of thyroid hormones is disturbed in some neoplastic tissues such as thyroid, renal, and breast cancer. However, there are few available data about D1 enzyme activity in benign tumors such as hemangioma, which is the most common primary liver tumor. Hence this study aimed to determine the enzymatic activity of D1 in hemangiomas in relation to healthy liver tissue. Seven tumors and healthy control tissues were obtained from patients who had liver resection due to hemangioma. The activity was assessed by measurement of radioactive iodine released by deiodination catalyzed by D1. It was found that D1 activity was significantly lower in the hemangiomas than in the healthy surrounding tissue (p = 0.0017). The results indicated that thyroid hormones play important roles not only in the regulation of cell metabolism, but also in cell growth, division, and apoptosis. The active form T3 acts through its nuclear receptors and influences the up- and down-regulation of target genes. Healthy liver tissue expresses a high level of D1, but disturbed D1 activity may result in changes in the local concentration of T3 which may impair gene transcription. These finding demonstrate a low enzymatic activity of D1 in liver hemangioma and suggest an as yet unknown role of thyroid hormones in this type of benign liver tumor.

[Congenital adrenal hyperplasia due to 21-hydroxylase deficiency--management in adults]. / Wrodzony przerost nadnerczy z niedoboru 21-hydroksylazy--problemy i postepowanie u doroslych.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive hereditary diseases. The impairment of cortisol synthesis leads to excessive stimulation of the adrenal glands by adrenocorticotropic hormone (ACTH), adrenal hyperplasia, and excessive androgen synthesis. The syndrome is characterised by a considerable correlation between the genotype and the phenotype with the type of CYP21A2 gene mutation affecting the severity of 21-hydroxylase deficiency. The clinical manifestations of CAH in adults result from adrenocortical and adrenomedullary insufficiency, hyperandrogenism, and the adverse effects of glucocorticosteroids used for the treatment of the condition. Non-classic CAH may sometimes be asymptomatic. In patients with classic CAH obesity, hyperinsulinaemia, insulin resistance, and hyperleptinaemia are more often seen than in the general population. These abnormalities promote the development of metabolic syndrome and its sequelae, including endothelial dysfunction, and cardiovascular disease. Long-term glucocorticosteroid treatment is also a known risk factor for osteoporosis. Patients with CAH require constant monitoring of biochemical parameters (17a-hydroxyprogesterone and androstenedione), clinical parameters (body mass, waist circumference, blood pressure, glucose, and lipids), and bone mineral density by densitometry. The principal goal of treatment in adults with CAH is to improve quality of life, ensure that they remain fertile, reduce the manifestations of hyperandrogenisation in females, and minimise the adverse effects of glucocorticosteroid treatment. Patients with classic CAH require treatment with glucocorticosteroids and, in cases of salt wasting, also with a mineralocorticosteroid. Radical measures, such as bilateral adrenalectomy, are very rarely needed. Asymptomatic patients with non-classic CAH require monitoring: treatment is not always necessary. Medical care for patients with CAH should be provided by reference centres, as the management of such patients requires collaboration between an endocrinologist, diabetologist, gynaecologist, andrologist, urologist, and psychologist.

Association of polymorphism in genes encoding kappaB inhibitors (IkappaB) with susceptibility to and phenotype of Graves' disease: a case-control study.

BACKGROUND: Genes related to the nuclear factor-kappaB (NF-kappaB), a key transcription factor involved in regulation of immune responses, are interesting candidates for association studies in autoimmune disorders. The aim of this study was to investigate an association of polymorphisms in two genes encoding NF-kappaB inhibitors: IKBL (encoding inhibitor of kappaB-like) and NFKBIA (encoding kappaB inhibitor alpha), withsusceptibility to and phenotype of Graves' disease (GD). METHODS: A population-based, case-control association study comprising 481 patients with GD and 455 healthy controls was performed. We analyzed 3 single nucleotide polymorphisms (SNPs) in IKBL [promoter region -62T/A substitution (rs2071592), intron 1 C/T substitution (rs2071591) and exon 4 T/C substitution (rs3130062)] and 3 SNPs in NFKBIA [G/A substitution in 3' untranslated region (rs696) and two promoter region polymorphisms -297C/T (rs2233409) and -826C/T (rs2233406)] by the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: The two SNPs in IKBL (rs2071592 and rs2071591) were in a strong linkage disequilibrium (D' = 0.835) and the AT haplotype was associated with susceptibility to GD (p < 10-4, OR = 1.61 [95%CI:1.21-2.14]). Moreover subgroup analysis revealed a gen-gen interaction between the investigated IKBL haplotype and HLA-DRB1*03 allele (p < 10-4). The investigated NFKBIA SNPs were not associated with susceptibility to GD. However, when correlated with phenotype, the -297T (rs2233409) and -826T (rs2233406) alleles were associated with the development of clinically evident ophthalmophaty (p = 0.004, pc = 0.07, OR = 1.65 [95%CI: 1.18-2.38] and p = 0.002, pc = 0.036, OR = 1.67 [95%CI: 1.20-2.36], respectively). CONCLUSION: Our results suggest that SNPs in genes encoding NF-kappaB inhibitors may contribute to the development and clinical phenotype of GD.

First isolation of Clostridium difficile PCR-ribotype 027/toxinotype III in Poland.

Of 175 Clostridium difficile strains isolated from patient hospitalized in one academic hospital in Warsaw between 2005-2006, one isolate belonged to PCR-ribotype 027/toxinotype III. This isolate had tcdA, tcdB, binary toxin genes (cdtA and cdtB), a 18-bp deletion and a 1 bp deletion at 117 position in the tcdC gene. Antimicrobial susceptibility tests revealed high level resistance to erythromycin, moxifloxacin and gatifloxacin. This is a first report of the 027 strain of C. difficile in Poland.