Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI). METHODS: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters. RESULTS: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu). CONCLUSIONS: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation. CLINICAL TRIAL REGISTRATION: NCT00470587, http://clinicaltrials.gov/show/NCT00470587.

Anti-C1q autoantibodies are linked to autoimmune thyroid disorders in pregnant women.

Anti-C1q antibodies (anti-C1q) have been implicated in the pathogenesis of autoimmune diseases, including autoimmune thyroid disorders (AITD). The aim of this study was to evaluate the association between anti-C1q and thyroid function in pregnancy-associated AITD. In 96 pregnant women screened positive for AITD (thyroid dysfunction and/or antibodies against thyroperoxidase - TPOAb), anti-C1q were measured during the 9-11th gestational week and after delivery (median 16 months after delivery), and compared to the corresponding serum levels of thyroid hormones. As controls, 80 healthy pregnant women, 72 non-pregnant AITD patients and 72 blood donors were included. In the non-pregnant AITD group, two serum samples ≥ 6 months apart were analysed. Compared to blood donors, anti-C1q levels were substantially higher in all pregnant women analysed. In pregnancy, anti-C1q levels were higher in the TPOAb-positive women than in controls (37 versus 17·5%, P < 0·0001). Anti-C1q-positive pregnant women screened positive for AITD had higher thyroid-stimulating hormone (TSH) levels than anti-C1q-negative women (2·41 versus 1·94 mU/l, P = 0·01), and TSH correlated positively with anti-C1q (r = 0·226, P = 0·045) in the TPOAb-positive women. After delivery, serum levels of anti-C1q decreased in the positively screened TPOAb-negative women (8·8 versus 5·9 U/l, P = 0·002), but not in the TPOAb-positive ones, and they no longer correlated with TSH. Anti-C1q antibody levels increase during pregnancy in general and even more in the context of AITD, where they correlate with thyroid stimulating hormone levels.

Low prevalence of clinically high-risk women and pathological thyroid ultrasound among pregnant women positive in universal screening for thyroid disorders.

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.

Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease.

Autoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organ-specific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively anti-C1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multi-nodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of anti-C1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.

Complement component c1q and anti-c1q antibodies in theory and in clinical practice.

The complement system is a major part of the innate immunity. The first component of the classical pathway of complement activation, C1q, plays a crucial role in the clearance of immune complexes and apoptotic bodies from the organism. Autoantibodies against C1q (anti-C1q) have been found in a number of autoimmune and infectious diseases. They have been best described in patients with systemic lupus erythematosus, where they are thought to play a pathogenic role in lupus nephritis (LN). Their high negative predictive value for the occurrence of active proliferative LN, as well as their possible ability to indicate a renal flare as soon as 6 months in advance, have rendered anti-C1q antibodies a novel non-invasive tool in the detection of active LN.

[The importance of screening for thyroid dysfunction during pregnancy: pathophysiological background and practical implications]. / Význam skríninku tyreopatií u tehotných zen: patofyziologický podklad a praktické aspekty.

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 role of complement in autoimmune thyroid disorders]. / Vztah komplementu a autoimunitnich onemocnení stítné zlázy.

The complement system is a crucial part of the innate immune system. In systemic autoimmune disorders, its effects tend to be protective. On the contrary, in the autoimmune thyroid disorders (AIT) the complement actively attacks thyrocytes, which express a number of complement components as well as complement inhibitory molecules. According to the experimental studies different ways of complement activation might occur in the thyroid tissue. All ensue via the classical pathway that is started either by immune complexes containing complement activating autoantibodies against thyroid autoantigens, or by direct binding of C4 to the molecule of thyroid peroxidase (TPO); or by direct complement activation by reactive oxygen radicals. Thyrocytes are relatively resistant to the complement attack. However, sublethaly injured thyrocytes release proinflammatory cytokines and reactive oxygen radicals and thus promote the inflammatory process in the thyroid. So far, the clinical significance of the complement in the thyroid has been studied only in postpartum thyroiditis. The exact role of complement in the pathogenesis of AIT remains to be elucidated.

Serum levels of antibodies to thyroid peroxidase correlate with quantitative descriptors of thyroid ultrasound images in patients with breast cancer.

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.