Thyroid hormones are essential both for the physiological course of pregnancy and for the optimal differentiation of the embryonic tissues and foetal brain development. Overt and subclinical hypothyroidism constitutes a frequent cause of infertility, it carries along an increased risk of spontaneous abortion and premature birth, and it may lead to an impaired foetal brain development resulting in a worse psychoneurological outcome in the progeny. The repeatedly documented high prevalence of thyroid diseases in pregnancy warrants a realization of systematic screening for thyroid dysfunction during early stage of pregnancy or better before conception whenever possible. The Czech Endocrine Society attempts to implement such a systematic screening in the Czech Republic, although the particular aspects of the screening are still discussed.

The aim of the study was to compare the structural changes in ultrasound image of the thyroid tissue in 12 women with breast cancer (BC) and 8 women with colorectal cancer (CC). MATLAB software was used to analyse the digitised images. As quantitative descriptors of thyroid ultrasound images (QDTI) were used raw grey scale values of individual image pixels (RAW) and the optimal one-dimensional discriminative texture features (F2, F6, F7). The possible relations between QDTI and thyroid laboratory parameters were tested. In the BC group serum levels of antibodies to thyroid peroxidase negatively correlated with feature RAW (multiple regression, beta coefficient -0.75, p=0.004) and positively with feature F2 (multiple regression, beta coefficient 1.44, p=0.04). In the BC group RAW negatively correlated with serum levels of tumour marker CA 15-3 (Pearson's correlation coefficient, r=-0.714, p=0.00917). No such correlations were found in CC group. The correlations between QDTI and serum levels of antibodies to thyroid peroxidase in patients with BC show that the positivity of antibodies to thyroid peroxidase is probably accompanied with structural changes in the thyroid tissue.

BACKGROUND It is controversial whether screening program for thyroid disorders in pregnancy should be universal or targeted case-finding. To evaluate the relationship between history, laboratory parameters and thyroid ultrasound (TUS) in pregnant women positive in universal screening. SUBJECTS AND METHODS The screening included investigation of serum TSH (thyroid stimulating hormone) and TPOAb (antithyroperoxidase antibodies) in 5,520 unselected pregnant women in the 9-11th gestational week. In 822 the screening was positive: abnormal TSH (> 3.67 or < 0.06 mIU/l) and/or positive TPOAb (> 143 kIU/l). 200 consecutive women with positive screening were included it the study. RESULTS 41 women (21%) had transient gestational hyperthyroidism (TGH) and 159 (79%) had a thyroid pathology: 10 (5%) overt hypothyroidism; 76 (38%) subclinical hypothyroidism, 7 (3.5%) overt hyperthyroidism and 66 (33%) euthyroid TPOAb positivity. After exclusion of TGH, only 74/159 (47%) women were classified as high-risk for thyroid disease according to their history. There were no significant clinical and laboratory differences between the high- vs. low-risk women, except for higher proportion of FT4<75th percentile (P=0.008) and larger thyroid volume in the high-risk group (P=0.04). Finally, only 66/126 (52%) of TPOAb-positive pregnant women had autoimmune pattern in TUS in comparison with 41/49 (84%) TPOAb-positive non-pregnant control women of comparable age (P<0.001). CONCLUSIONS Less than half of the positively screened pregnant women can be classified as high-risk and almost half of them had not autoimmune pattern in TUS. High- and low-risk pregnant women have similar clinical and laboratory characteristics.

Summary Interactions between cytokines play an important role in the development of thyroid autoimmunity. Using enzyme-linked immunosorbent assay we investigated serum concentrations of soluble interleukin-2 receptor (sIL-2R), interferon-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10, CD30, monokine induced by interferon-gamma (MIG), cytotoxic T lymphocyte antigen-4 and markers of apoptosis decoy receptor 3 and Bcl-2 in 28 patients with hyperthyroid Graves' disease (GD), 24 patients with untreated Hashimoto's thyroiditis (HT) and 15 healthy controls. TNF-alpha, IL-10 and sIL-2R were higher in GD compared with HT and controls (TNF-alpha: 8.79 in GD versus 2.54 pg/ml in HT, P = 0.01; IL-10: 10.00 versus 3.10 versus 3.10 pg/ml, P(1)< 0.001, P(2)= 0.005; sIL-2R: 1.26 versus 0.64 versus 0.46 ng/ml, P < 0.001). MIG and CD30 were higher in HT compared with controls (649.22 +/- 262.55 versus 312.95 +/- 143.35 pg/ml, P = 0.037, 6.57 +/- 2.35 versus 3.03 +/- 1.04 U/ml, P = 0.036 respectively). In GD sIL-2R decreased when the euthyroid state was achieved (1.31 +/- 0.64 versus 0.260 +/- 0.11, n = 12, P < 0.001). sIL-2R correlated positively with free thyroxine (FT4)(R = 0.521, P = 0.000) and negatively with thyroid stimulating hormone (TSH)(R =-0.472, P = 0.00132). MIG correlated negatively with FT4 (R =-0.573, P = 0.00234) and positively with TSH (R = 0.462, P = 0.0179). The results suggest that serum concentrations of sIL-2R and MIG are related to thyroid function rather than to activation of autoimmunity.

Review of contemporary theories and hypothesis concerning chronic lymphycytic thyroiditis is presented. The origin of the disease depends on various factors: genetics, immunological conditions, cytokins, iodine supply, hormones, TSH and its receptors, apoptosis activation and inhibition. The environmental conditions include goitrogens, selenium, polutants and other still unknown factors. Whether the disease will be accompanied with goiter, nodules or thyroid atrophy with functional disorder is still not evident.

The authors review the most common situation concerning oncological patients with concomitant thyroid disease. In case of unknown origin of metastasis and nodular goitre the ultrasound examination with fine needle aspiration biopsy confirms or excludes the thyroid origin. The euthyroid sick syndrome is often diagnosed in oncological patient as a consequence of oncological disease and it doesn't mean hypothyroidism. If oncological patients prove to have a thyroid functional failure the endocrinologist must correct the function as fast as possible to enable oncological treatment. There is no evidence that chemotherapy can influence the thyroid function, but radiotherapy can cause thyroiditis with later hypofunction. The interferon therapy causes thyroid dysfunction in 10% of patients and the recommendation to examine not only TSH and FT4 but also thyroid antibodies is warranted. Lymphoma of the thyroid gland occurs most often on the basis of lymphocytic thyroiditis and lymphocytic thyroiditis may be a risk factor for papillary carcinoma of the thyroid as well. Women with breast carcinoma were proved to have lymphocytic thyroiditis with minor thyroid hypofunction more often than the corresponding group of women with colon cancer or control group of healthy women. In case of renal tumor (Grawitz), breast or lung carcinoma the thyroid can be attacked with metastasis, and ultrasound with fine needle biopsy can reliably differentiate between primary or secondary thyroid involvements. The thyroid can be involved in some diseases: multiple endocrine neoplasia, Carney, Cowden and Gardner's syndromes.

The aim of the study was to compare the prevalence of autoimmune thyroid diseases in three groups of women (66 with breast cancer (CaB), 68 with colorectal cancer (CaC) and 49 without oncological diseases as a control group). Serum levels of thyroid-stimulating hormone (TSH), free thyroxin (fT4), antibodies to thyroglobulin (TGB-ab) and thyroperoxidase (TPO-ab) and tumor markers CEA, CA 15-3 and CA 19-9 were investigated in all subjects by using the chemiluminiscence method. In contrast to Graves' disease (no observed case), autoimmune thyroiditis was diagnosed in 24.2 % women with CaB (4.5 % euthyroid and 19.7 % with subclinical or overt hypothyroidism), compared to 16.7 % in women with CaC (2.0 % euthyroid and 14.7 % with subclinical or overt hypothyroidism) and 16.2 % controls (4.0 % euthyroid and 12.2 % with subclinical or overt hypothyroidism). Serum levels of TGB-ab were higher in the group with breast cancer as compared to those with colorectal cancer and the control group (medians: 35.80 vs. 31.75 vs. 27.70, p<0.001). Similarly, the percentage of positive TGB-ab and TPO-ab serum levels was higher in women with breast cancer as compared to those with colorectal cancer and the control group. The results of the study support the controversial theory that there is an increased prevalence of autoimmune thyroiditis in women with breast cancer.

Celiac disease is a chronic illness of the small bowel caused by gliadin intolerance in genetically predisposed subjects. The aim of this study was to investigate serum levels of IgA and IgG antigliadin antibodies, IgA antiendomysial antibodies, and IgA anti-tissue transglutaminase antibodies in 169 patients with autoimmune thyroid diseases, i.e. chronic thyroiditis and Graves' disease. Antiendomysial antibodies were positive in 2 out of 169 persons (1.18%), IgA antigliadin antibodies in 15.98%, IgG antigliadin antibodies in 51.48%, and IgA anti-tissue transglutaminase in 14.79%. The prevalence of positivity was higher compared to the 1312 control blood donors described in our previous study (Vancíková et al. 2002)(p<0.05). Patients with chronic thyroiditis treated with a high replacement dosage of levothyroxin (125-200 microg daily) had higher serum levels of IgA antigliadin antibodies in comparison with patients treated with a lower dosage (50-100 microg daily)(medians: 13.00 vs. 19.69, p=0.033). We found a negative correlation of IgA anti-tissue transglutaminase antibodies and total calcium serum levels (r =-0.480, p=0.0236, n=22). We can conclude that in persons with autoimmune thyropathy there is a high prevalence of positive antigliadin, anti-tissue transglutaminase and antiendomysial antibodies. Latent celiac disease may lead to impaired resorption of therapeutically administered levothyroxine, calcium, or other substances.

This article describes three cases of undiagnosed hypothyroidism in a developed stage which manifest themselves with myopathic syndrome (myalgia, muscular fatigue, and higher serum levels of creatine kinase, aminotranferases, and lactate dehydrogenase) without the "classic" symptoms of hypothyroidism. In addition, two of the three patients were receiving hypolipidemic drugs for secondary hyperlipoproteinemia, which could have affected the development of the myopathy. Emphasis is placed on the description of atypical symptoms of hypothyroidism and the necessity of endocrinological examination in each case of myopathy with indefinite etiology.

Diseases of the thyroid gland involve many areas of medicine. The impairment of thyroid gland function affects 4-5% of younger population and more than 10% of the senior population (in ratio of 6-8 women to every man). Thyroid gland defects are mostly of autoimmune origin. The development of various kind of autoimmune disease in specific cases can be anticipatedd or diagnosed in their early stages. This article emphasizes certain connections of autoimmune thyroid gland diseases with diabetology, dermatology, and .. hematology.

Statins are an effective treatment for the prevention of cardiovascular diseases and used extensively worldwide. However, myotoxicity induced by statins is a common adverse event and a major barrier to maximising cardiovascular risk reduction. The clinical spectrum of statin induced myotoxicity includes asymptomatic rise in creatine kinase concentration, myalgia, myositis and rhabdomyolysis. In certain cases, the cessation of statin therapy does not result in the resolution of muscular symptoms or the normalization of creatine kinase, raising the possibility of necrotizing autoimmune myopathy. There is increasing understanding and recognition of the pathophysiology and risk factors of statin induced myotoxicity. Careful history and physical examination in conjunction with selected investigations such as creatine kinase measurement, electromyography and muscle biopsy in appropriate clinical scenario help diagnose the condition. The management of statin induced myotoxicity involves statin cessation, the use of alternative lipid lowering agents or treatment regimes, and in the case of necrotizing autoimmune myopathy, immunosuppression.

Thyroid dysfunction has a great impact on lipids as well as a number of other cardiovascular risk factors. Hypothyroidism is relatively common and is associated with an unfavorable effect on lipids. Substitution therapy is beneficial for patients with overt hypothyroidism, improving lipid profile. However, whether subclinical hypothyroidism should be treated or not is a matter of debate. On the other hand, hyperthyroidism can be associated with acquired hypocholesterolemia or unexplained improvement of lipid profile. Overall, thyroid dysfunction should be taken into account when evaluating and treating dyslipidemic patients.

OBJECTIVE The relationship of cardiovascular disease (CVD) with plasma cholesteryl ester transfer protein (CETP) levels is controversial. We determined whether plasma cholesteryl ester transfer (CET), reflecting CETP-mediated transfer of cholesteryl esters from endogenous HDL towards apolipoprotein B-lipoproteins, predicts incident CVD. METHODS A prospective nested case-control study was carried out in 114 men who developed CVD and 105 controls. Participants did not use lipid lowering drugs at baseline. Plasma CET was assayed using an isotope method. RESULTS Plasma CET was 19% higher (P=0.030), whereas CETP mass was unaltered (P=0.30) in cases vs. controls. Plasma CET predicted CVD (age-adjusted hazard ratio (HR): 1.20 (95% CI 1.02-1.46, P=0.028), but incident CVD was unrelated to CETP mass (HR: 0.88 (95% CI 0.73-1.07), P=0.20). Plasma CET still predicted CVD after additional adjustment for total cholesterol/HDL cholesterol, triglycerides and non-lipid risk markers (HR: 1.22 (95% CI 1.02-1.46, P=0.031). CONCLUSION Plasma CET rather than CETP mass may be a determinant of cardiovascular risk.

INTRODUCTION: Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Low-density lipoprotein cholesterol (LDL-C) reduction has been demonstrated to decrease CVD-related morbidity and mortality. However, several patients do not reach LDL-C target levels with the currently available lipid lowering agents, particularly statins. Lipid and non-lipid parameters other than LDL-C may account for the residual CVD risk after adequate LDL-C lowering with statins. AREAS COVERED: This review focuses on the efficacy and safety of emerging drugs aiming at high-density lipoprotein cholesterol (HDL-C) elevation (i.e., recombinant or plasma-derived wild-type apolipoprotein (apo) A-I, apo A-I mimetic peptides, reconstituted mutant HDL, partially delipidated HDL and cholesterol ester transfer protein inhibitors), microsomal triglyceride transfer protein inhibitors and antisense oligonucleotides. EXPERT OPINION: Several lipid modifying agents in development may potently reduce the residual CVD risk. Ongoing and future studies with clinical outcomes will clarify their efficacy in clinical practice.

Dyslipidemia in metabolic syndrome (MS), called the atherogenic triad, includes elevated levels of plasma triglycerides (TGs), low levels of HDL-cholesterol (HDL-CH), and the presence of small dense low-density lipoproteins (sdLDLs) with normal or slightly elevated LDL-CH levels. Insulin resistance drives the increase in the three main sources of TG for VLDL synthesis: fatty-acid flux from adipose tissue, de novo lipogenesis, and uptake of remnant lipoproteins. Overproduction of VLDL, predominantly triglyceride-rich large VLDL1 particles, induces the cascade of events which lead to abnormalities of other plasma lipoproteins. The accumulation of VLDL in plasma and decreased activity of lipoprotein lipase (LPL) impair the catabolism of chylomicrons. Moreover, hyperinsulinemia induces increased intestinal production of chylomicrons. These factors cause augmented postprandial lipemia. Hepatic overproduction of VLDL leads to an increased level of VLDL remnants in plasma. Highly atherogenic sdLDLs are generated from VLDL1 particles by the action of LPL, cholesterol ester transfer protein (CETP), and hepatic lipase (HL). In the presence of hypertriglyceridemia, accelerated CETP-mediated lipid transfer generates TG-enriched HDL particles. This enhances HDL catabolism mediated by HL and endothelial lipase (EL). The assessment of risk of atherosclerotic cardiovascular disease in MS related to low HDL-CH and the presence of sdLDL particles may be improved by the incorporation of measurements of apolipoproteins (apo)-B and apoA-I into clinical practice. In addition, the concentration of non-HDL-CH may be useful in quantifying apo-B-containing atherogenic lipoproteins.

Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.

Diabetes mellitus type 2 is reaching epidemic proportions in western societies. The treatment of diabetic dyslipidemia to prevent cardiovascular disease is of increasing clinical and scientific interest. In the pathogenesis of this disease plasma triglycerides play a central role. Triglyceride rich particles by themselves are not considered atherogenic; however, they are hydrolysed to chylomicron and VLDL remnant particles. Furthermore, mediated by cholesteryl ester transfer protein (CETP), atherogenic small dense LDL particles (sdLDL) emerge, and HDL cholesterol decreases. All these factors yield into a significantly increased atherogenesis and cardiovascular risk. Weight reduction and low fat diets have shown positive effects in general, but a specific therapy to treat diabetic dyslipidemia is still missing. Studies so far have failed to show a reliable benefit for fibrates and for nicotinic acid. Thus, statin therapy to decrease LDL cholesterol to target is the essential treatment for diabetic dyslipidemia to reduce cardiovascular risk. Other lipid lowering drugs can be added optionally.

Tetrahydroquinoline A is a potent inhibitor of the cholesterol ester transfer protein (CETP), a target for the treatment of low HDL-C and atherosclerosis. Low HDL-C has been identified as a key risk factor for cardiovascular disease in addition to high LDL-C, the target of the statin drugs. Tetrahydroquinoline A inhibits partially purified CETP with an IC(50) of 39nM. The preparation of a series of potent inhibitors of CETP designed around a 1,2,3,4-tetrahydroquinoline platform will be discussed.

Reverse cholesterol transport (RCT) is a complex process ensuring the efflux of cholesterol from peripheral cells and its transport back in the liver for its metabolism and biliary excretion. Cholesterol efflux results by the interaction of a cellular free cholesterol and phospholipid transporter, the ABC-AI, with lipid poor apoAI, endowed HDL particles. The free cholesterol taken up by HDL is then esterified by lecithin:cholesterol acyltransferase (LCAT) and the hydrophobic cholesteryl esters are retained into the core of HDL, so that new cholesterol molecules can be translocated on the HDL surface. The generated cholesteryl esters are partially transferred to triglyceride rich apoB containing lipoprotein through a nonenzymatic process mediated by cholesteryl ester transfer protein (CETP) in exchange for triglyceride. The hepatic uptake of the cholesterol released from peripheral cells may thus proceed via an HDL-receptor, the SR-BI and through the LDL receptor route. Hepatic lipase (HL) facilitates the selective uptake of cholesteryl esters by the hepatocytes by exerting a lipolytic effect and a ligand-binding effect, bridging the lipoprotein particles to the heparan sulfate proteoglycans on cells surface and allowing the transcytosis of cholesteryl esters. Studies on genetically modified animals and on humans with severe genetic deficiencies demonstrated that abnormalities of the various components of RCT would accelerate atherogenesis. Clinical studies revealed that the development of coronary artery disease (CAD) may by delayed by increased HL activity in patients with familial hypercholesterolemia (heterozygotes), while in hypertriglyceridemic patients an increased plasma CETP and HL levels would favor the generation of less lipidated HDL and of small dense atherogenic LDL particles.

Systemic lupus erythematosus (SLE) is an independent risk factor for atherosclerosis, placing children and adolescents with SLE at great risk for developing cardiovascular sequelae, including myocardial infarction, in adulthood. Dyslipidemia and other traditional cardiac risk factors occur frequently in pediatric SLE and are often under-recognized and under-treated. Two dyslipidemia patterns are evident in pediatric SLE. Active disease is characterized by elevated triglycerides (TG) and low high density lipoprotein (HDL). With SLE treatment HDL and TG often normalize, while total cholesterol and low density lipoprotein (LDL) rise. The complex pathophysiology of dyslipidemia in SLE involves cytokines, autoantibodies, disease activity, medications, diet, and physical activity level, as well as other factors. Routine screening for dyslipidemia with fasting lipid profiles is indicated for children and adolescents with SLE. If lipoprotein levels are abnormal, first line therapy involves diet and exercise interventions for a minimum of six months. For persistent dyslipidemia, several pharmacologic therapies are available. Hydroxychloroquine, a common treatment for SLE, can improve lipid profiles and should be considered for all patients with SLE. Statins and bile acid sequestrants are typically added first for dyslipidemia, while niacin and fibrates are reserved for refractory disease and optimally prescribed in a multidisciplinary lipid clinic. Future research is needed to further illuminate the mechanisms of dyslipidemia in pediatric SLE with well designed clinical trials to determine the safest and most effective interventions to correct lipid profiles and prevent atherosclerosis.