TPO antibody in euthyroid pregnant women and cognitive ability in the offspring: a focused review.

PURPOSE: A link between maternal thyroid dysfunction during pregnancy and the risk of cognitive and behavioral problems in the offspring has previously been established; however, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism are less clear. The present review aims to highlight the gaps in knowledge in this regard and provide a thorough assessment of relevant literature. METHOD: Related keywords searched in MEDLINE, Web of Science, and Scopus till January 2021. RESULTS: There is some evidence that neuropsychological and intellectual developments of offspring are adversely affected by maternal thyroid autoimmunity, although the results of available studies are not concordant. The tools and measurements that have been applied in different studies to assess neurodevelopment or IQ vary widely and the children born to mothers with thyroid autoimmunity have been assessed at different chronological stages of life. Such variations may explain some of the differences across studies. In addition, the definition of thyroid autoimmunity has been based on TPOAb cut points provided by manufacturers in most cases, but it is preferable to define these values based on age, trimester, and method-specific reference ranges. CONCLUSION: Well-designed studies are needed to assess verbal and non-verbal neurocognition of offspring born to mothers with autoimmune thyroid disease before or during pregnancy.

Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors.

PURPOSE: Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors. METHODS: We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response. RESULTS: Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto's thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto's thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto's thyroiditis patients with major molecular response. CONCLUSIONS: Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.

Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease.

OBJECTIVE: Hashimoto's thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations. METHODS: In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded. RESULTS: A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96. CONCLUSION: Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis.

OBJECTIVE: Thyroid hormones have important actions in the adult brain. They regulate genes expression in myelination, differentiation of neuronal and glial cells, and neuronal viability and function. METHODS: We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) to identify and verify nerve impulse transmission pathway-focused genes expression in peripheral white blood cells of patients with postoperative hypothyroidism, hypothyroidism as a result of autoimmune thyroiditis (AIT) and AIT with elevated serum an anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: It was shown that patients with postoperative hypothyroidism and hypothyroidism resulting from AIT had significantly lower expression of BDNF and CBLN1. In patients with AIT with elevated serum anti-Tg and anti-TPO antibodies, the expression of GDNF was significantly down-regulated and the expression of PNOC was up-regulated. The expression levels of MEF2C and NTSR1 were decreased in the group of patients with postoperative hypothyroidism and AIT, correspondingly. CONCLUSIONS: The results of this study demonstrate that AIT and hypothyroidism can affect the expression of mRNA nerve impulse transmission genes in gene specific manner and that these changes in gene expressions can be playing a role in the development of neurological complications associated with thyroid pathology. Detection of the transcriptional activity of nerve impulse transmission genes in peripheral white blood cells can be used as an important minimally invasive prognostic marker of the risk for developing neurological complications comorbid with thyroid pathology.

Compared with classic Hashimoto's thyroiditis, chronic autoimmune serum-negative thyroiditis requires a lower substitution dose of L-thyroxine to correct hypothyroidism.

PURPOSE: Serum-negative-chronic-autoimmune-thyroiditis (SN-CAT) is considered a milder variant of classic Hashimoto's thyroiditis (CHT). However, its prevalence remains unknown and it is still unclear whether SN-CAT behaves differently in terms of L-thyroxine (LT4) substitution treatment of hypothyroidism. Aims of this study were to estimate the prevalence of SN-CAT in a large series of hypothyroid patients and to compare LT4 requirements in hypothyroid patients with SN-CAT and CHT. METHODS: Five-hundred-eighty-one consecutive patients with primary-autoimmune-hypothyroidism were enrolled in a cross-sectional study. LT4 requirements and thyroid-volume changes were longitudinally evaluated in 49 hypothyroid patients with SN-CAT and in 98 sex and age-matched hypothyroid patients with CHT. RESULTS: In our series the prevalence of SN-CAT was 20.8%. At diagnosis, patients in the CHT and SN-CAT groups had similar male/female ratio, age and BMI, while serum TSH and thyroid-volume were significantly greater in the CHT group. In the longitudinal study, during a follow-up of 8.9 ± 4.6 years, 8 out of 49 (16.3%) SN-CAT patients developed positive tests for of circulating TPO-Ab and/or Tg-Ab. Thyroid-volume significantly decreased in CHT patients, but not in those with SN-CAT. The maximum daily substitution dose of LT4 was smaller in SN-CAT patients as compared with the CHT ones. Multivariate analysis showed that age, BMI, basal TSH and thyroid antibody status independently and significantly predicted the maximum daily substitution dose of LT4. CONCLUSIONS: SN-CAT accounts for a significant proportion of patients with autoimmune hypothyroidism. Compared with hypothyroid patients diagnosed with CHT, the SN-CAT ones require smaller doses of LT4 to correct their hypothyroidism.

The proportion of peripheral blood Tregs among the CD4+ T cells of autoimmune thyroid disease patients: a meta-analysis.

Autoimmune thyroid disease (AITD) is characterized by a loss of self-tolerance to thyroid antigen. Tregs, whose proportions are controversial among CD4+ T cell from AITD patients (AITDs), are crucial in immune tolerance. Considering that drugs might affect Treg levels, we assumed that the differences originated from different treatment statuses. Thus, we performed a meta-analysis to explore proportions of Tregs in untreated and treated AITDs. PubMed, Embase and ISI Web of Knowledge were searched for relevant studies. Review Manager 5.3 and Stata 14.0 were used to conduct the meta-analysis. Subgroup analysis based on different diseases and cell surface markers was performed. Egger linear regression analysis was used to assess publication bias. Approximately 1,100 AITDs and healthy controls (HCs) from fourteen studies were included. Proportions of Tregs among CD4+ T cells of untreated AITDs were significantly lower than those in HCs (p = 0.002), but were not in treated patients (p = 0.40). Subgroup analysis revealed lower proportions of Tregs in untreated Graves' disease patients (GDs) (p = 0.001) but did not show obvious differences in untreated Hashimoto's thyroiditis patients (HTs) (p = 0.62). Furthermore, proportions of circulating FoxP3+ Tregs were reduced in untreated GDs (p < 0.00001) and HTs (p = 0.04). No publication bias was found. In this first meta-analysis exploring proportions of circulating Tregs among CD4+ T cells of AITDs with different treatment statuses, we found that Tregs potentially contribute to the pathogenesis of AITD but function differently in GD and HT. Remarkably, FoxP3+ Tregs, which were decreased in both diseases, might be promising targets for novel therapies.

Role of selenium and myo-inositol supplementation on autoimmune thyroiditis progression.

Previous reports indicate that selenium supplementation may be useful to reduce cell oxidative stress. In particular, selenium may decrease the level of thyroid autoantibodies in patients with Hashimoto's thyroiditis (HT). Recent studies also indicate that myo-inositol may have beneficial effects on thyroid function in patients with HT. Hence, the aim of the present study is to evaluate whether myo-inositol may enhance the protective effect of selenium on HT progression to hypothyroidism. The study was designed as observational and retrospective. Thyroid hormones were evaluated in patients with HT who were either euthyroid or subclinically hypothyroid. These patients were subdivided into three groups: untreated, treated with selenomethionine alone (Se-meth: 83 µg/day) and treated with Se-meth plus myo-inositol (Se-meth + Myo-I: 83 µg/day + 600 mg/day). Outcome evaluation was performed at baseline and after 6 and 12 months of treatment. High-resolution ultrasound of the thyroid gland was performed to evaluate changes in thyroid echoic pattern during the study. Compared to baseline, levels of thyroid-stimulating hormone (TSH) increased significantly in untreated patients but decreased by 31% and 38%, respectively, in those treated with Se-meth and Se-meth + Myo-I. Moreover, in the latter group the TSH reduction was observed earlier than in the Se-meth-treated group. Densitometric analysis of thyroid ultrasonography showed an echoic pattern improvement in both treated groups compared to untreated patients, although this difference was not statistically significant. Thus, Se-meth treatment is effective in patients with HT and its effect may be improved in combination with Myo-I through earlier achievement of TSH levels closer to physiological concentrations.

Vitamin B12 and Vitamin D Levels in Patients with Autoimmune Hypothyroidism and Their Correlation with Anti-Thyroid Peroxidase Antibodies.

BACKGROUND: This study was designed to investigate the vitamin D (vit-D) and vitamin B12 (vit-B12) levels and their correlation with anti-thyroid peroxidase (anti-TPO) antibodies in patients with autoimmune hypothyroidism. METHODS: A total of 130 patients diagnosed with autoimmune hypothyroidism were included in the study retrospectively. The patients were divided into two groups as those having vit-B12 levels below 200 pg/mL (n = 60) and vit-B12 levels equal to or above 200 pg/mL (n = 70). These two groups were compared in terms of age, sex, thyroid-stimulating hormone (TSH), free-T4 (FT4), vit-D, and anti-TPO. The correlation between vit-B12 and anti-TPO levels was also investigated in these groups. Patients were then divided into four groups according to their vit-D levels. Patients with normal vit-D levels (25[OH]D >30 ng/mL; n = 5), those with vit-D insufficiency (20-30 mg/mL; n = 9), those with vit-D deficiency (10-20 ng/mL; n = 43), and those with severe vit-D deficiency (<10 ng/mL; n = 73). These four groups were compared in terms of age, gender, TSH, FT4, vit-B12, and anti-TPO levels. In addition, the correlation between levels of vit-D and anti-TPO was also investigated. RESULTS: We found that vit-B12 deficiency and vit-D deficiency were associated with autoimmune hypothyroidism, and that there was a negative correlation between vit-B12 and vit-D levels and anti-TPO antibodies in these patients. CONCLUSION: In patients with autoimmune hypothyroidism, vit-D and vit-B12 deficiency should be investigated at the time of diagnosis and periodically on follow-ups.

Autoimmune Thyroid Disease is Associated with a Lower Prevalence of Diabetic Retinopathy in Patients with Type 1 Diabetic Mellitus.

Background and objectives: The aim of the study was to assess the correlation of autoimmune thyroid diseases (AITD) in patients with diabetes mellitus type 1 (DM1) with the occurrence of diabetic retinopathy (DR). Materials and Methods: The inclusion criteria for the study were: type 1 diabetes diagnosed on the basis of WHO criteria lasting at least a year, presence of AITD for at least a year, and age over 18 years. The control group consisted of patients without diagnosed AITD (DM1noAITD), selected according to age, BMI and DM1 duration. Anthropometric parameters, metabolic risk factors such as glycated hemoglobin (HbA1c), lipids and blood pressure, thyroid status and the presence of DR were assessed. Results: The study involved 200 patients with type 1 diabetes aged 36 ± 12 years, 70 men and 130 women. Patients from the study group (DM1AITD) had significantly lower creatinine concentration, significantly lower systolic blood pressure (SBP), glycated hemoglobin (HbA1c) percentage and triglyceride (TG) concentration, and higher high-density lipoprotein (HDL-cholesterol) concentration than the control group (DM1noAITD). There was a significantly lower chance of non-proliferative diabetic retinopathy (NPDR) among DM1AITD than in the control group. Conclusions: Patients with DM1 and AITD were metabolically better balanced, as evidenced by a significantly lower SBP, percentage of HbA1c and TG, as well as significantly higher HDL-cholesterol in this group. Patients with DM1 and AITD were significantly less likely to have NPDR than the control group.

Vitamin D Status and Thyroid Autoantibodies in Autoimmune Thyroiditis.

A lack of vitamin D seems to be related to autoimmune diseases including autoimmune thyroiditis (AIT). This study intends to determine the correlation between improvement of 25-hydroxyvitamin D [25(OH)D] levels and AIT in patients from an outpatient endocrine clinic in Frankfurt, Germany. This study included 933 patients with thyroid peroxidase antibodies (anti-TPO-Ab) ≥34 kIU/l, including most patients with clear AIT due to a concurrent sonographic evidence of reduced echogenicity. We performed clinical evaluation and laboratory analysis at five points in time within two years retrospectively. Due to a high dropout rate within the observation period, we excluded the last two time points from analysis. Data from 933 AIT patients revealed 89% having vitamin D deficiency or insufficiency [25(OH)D <75 nmol/l] with a median 25(OH)D level of 39.7 nmol/l. At baseline, a weak inverse correlation between 25(OH)D and anti-TPO-Ab was observed during winter (rs=-0.09, p=0.048*), but not during summer time (p>0.2). We discovered 58 patients having initially a 25(OH)D level < 75 nmol/l (median: 40.2 nmol/l), which improved over time to a 25(OH)D level ≥ 75 nmol/l (median: 83.2 nmol/l, p<0.0005***). Simultaneously, the median anti-TPO-Ab level showed a significant decrease of 25% from 245.8 to 181.3 kIU/l (p=0.036*). A significant reduction of the median anti-TPO-Ab level of 9% was also observed in the control group, which consisted of patients having constantly a 25(OH)D level <75 nmol/l. The result may suggest that in particular patients with 25(OH)D levels < 75 nmol/l benefit from an increase of 25(OH)D levels ≥ 75 nmol/l. Further prospective randomized controlled clinical trials are needed to finally evaluate if vitamin D has immunmodulatory effects in AIT.

Effects of selenium and vitamin C on the serum level of antithyroid peroxidase antibody in patients with autoimmune thyroiditis.

PURPOSE: Selenium (Se), an essential trace element, has been implicated in pathogenesis of autoimmune thyroiditis (AIT). Most studies attributed the immune modulating effects of Se to its antioxidant properties. However, there is insufficient evidence to support the use of selenium supplementation or other antioxidants in patients with AIT. This clinical trial was designed to investigate the impact of Se and vitamin C supplementation on antithyroid peroxidase antibody (TPO-Ab) level in patients with AIT. METHODS: One hundred and two subjects aged 15-78 years were randomized into three groups. Group one (GI) (n = 38) was treated with 200 µg/day sodium selenite, group two (GII) (n = 36) received 500 mg vitamin C/day, and group three (GIII) (n = 28) received placebo over a 3-month period. Thyroid stimulating hormone (TSH), TPO-Ab, antithyroglobulin antibody (Tg-Ab) and Se concentrations were once measured before treatment and at the end of the study. RESULTS: After 3 months, TPO-Ab concentrations decreased within Se and vitamin C-treated groups, but did not change in the placebo subjects. In this regard, there was no significant difference between the groups. We also did not find any statistically significant difference in TSH and Tg-Ab levels within and between the groups. At the end of the study, Se level was significantly higher in GI compared with GII and GIII. CONCLUSION: Our findings supported the hypothesis of antioxidant beneficial effects of Se in AIT. However, it was not superior to vitamin C, regarding its effects on thyroid-specific antibodies.

Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases.

BACKGROUND: Patients with autoimmune thyroid diseases (ATD) such as Graves' disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as antinuclear antibodies (ANA) and rheumatoid factor (RF). AIM: To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients' epidemiological and treatment profiles. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. METHODS: A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profiles were obtained through chart review. These patients were followed for the mean period of 5 years, between 2010 and 2015. RESULTS: Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%), and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR 3.89; 95% CI 1.1-13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. CONCLUSION: We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of 5 years.

Assessment of serum selenium concentration in patients with autoimmune thyroiditis in Poznan district.

Autoimmune thyroiditis (AIT) is characterised by infiltration of lymphocytes and destruction of thyroid gland. It results from the interaction of genetic predisposition and environmental triggers. Among environmental factors some infections, medications and inadequate micronutrients supply like selenium (Se) deficiency are believed to play a role. AIM: The aim of our study was to assess the serum selenium concentration in patients with AIT and healthy volunteers in the Polish population living in the Poznan district, and to compare our results with similar trials conducted on other European AIT groups. MATERIALS AND METHODS: Fifty three patients with AIT were included in the study. Elevated thyroperoxidase antibodies and/or thyroglobulin antibodies concentration and abnormalities typical for AIT in the thyroid ultrasound were the inclusion criteria. A control group consisted of 36 healthy, age and sex-matched volunteers. RESULTS: The median Se concentration was 56.67 µg/L in the AIT group and 39.75 µg/L in the controls (p>0.05). Decreased Se concentration was observed in 62% of the patients and in 72% of the controls (p=0.47). There was no statistically significant difference in Se status in AIT group when compared to the other Polish, German, Austrian, Dutch and Greek populations with AIT. Significantly higher values were observed in Italian and Greek study when compared to present results in AIT group. CONCLUSIONS: No association between selenium status and prevalence of autoimmune thyroiditis in Polish population living in Poznan district was noticed. Nevertheless determination of the normal serum Se concentration for European populations is necessary. Further studies with enlarged studied groups should be implemented.

IMPORTANCE OF ISOLATED GESTATIONAL HYPOTHYROXINEMIA IN THE DEVELOPMENT OF OBSTETRIC AND SOMATIC PATHOLOGIES.

The isolated hypothyroxinemia of pregnancy (IHP) has gained specific attention in the specialized literature during the recent years as the possible factor impeding the intellectual development of fetus and increasing the risk of complications related with pregnancy, delivery and perinatal period. Aim of the study was to define the importance of isolated hypothyroxinemia in the development of obstetric and somatic pathologies in outpatient population of pregnant females. The study of prospective design was performed at the base of "David Gagua Clinic" Ltd. Based on hospital referral we selected the pregnant patients who were diagnosed for isolated hypothyroxinemia in the 1st trimester of pregnancy by clinical-laboratory studies. 104 pregnant females with isolated hypothyroxinemia were included in the main group, and 58 pregrant females of reproductive age who were not identified to have thyroid pathology by screening studies were included in the control group,. The questionnaire used in the study process included the retrospective medical history data, demographic findings, information about premorbid background, genetic burden of somatic pathology, social-economical factors (including education level, living conditions, economic income, family environment etc.) and concomitant somatic pathology. In addition, it included the clinical and para-clinical study data and pregnancy follow-up findings. The test studies for thyroid status were performed every trimester and after one month postpartum. The software packages Microsoft Excel (2010) and SPSS/v.12 was used for statistical treatment of data. The digital data is presented by M±STD, where M is the arithmetic mean and STD is the standard deviation of arithmetic mean. To define the confidence interval for the indices and their relation, we calculated 2 and p, whose critical value was defined to be 0.05. Based on analysis of the acquired data, we found out that pregnant females with isolated hypothyroxinemia were more statistically demonstrating asthenia, dry skin, increased hair loss and fragile nails, and from somatic disorders - pregnancy-associated vomiting and anemia. From concomitant diseases, allergic disorders (18.2%), primary dysmenorrhea (27.8%), spontaneous abortions (25%) were taking the highest incidence rate and other obstetric complications (premature delivery, late delivery) were higher in the main group, though statistically significant difference was not demonstrated. It must be noted that isolated hypothyroxinemia in the studied cohort was mostly found in 1st trimester of pregnancy, whereas according to the literature data, the latter is demonstrated more frequently in the second or third trimester. The above mentioned makes us consider that the iodine deficit in the cohort of pregnant females studied by us was probably present before pregnancy as well and maybe with even higher extent. Thus, the isolated hypothyroxinemia developed in the very first trimester of pregnancy still has its negative impact on the pregnancy course and outcome, despite of applied treatment. According to performed studies and their results, for the prevention of obstetric and perinatal complications, its important to administer iodine preparations together with folic acid at pregravid stage in addition to complete elimination of diet abnormalities, plan the pregnancy in stable normothyroxinemia conditions and at positive energetic balance. In addition, its desirable to perform the repeated thyroid status evaluation in the first trimester of pregnancy and timely administration of adequate therapeutic measures in case of finding any pathology.

Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease.

The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = -0·86, P < 0·05). The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with  > 70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.

Papillary Thyroid Cancer and Coexisting Autoimmune Thyroiditis.

Histological findings often display an association between papillary thyroid carcinomas (PTC) and autoimmune thyroiditis (AIT) and so differ significantly from follicular thyroid carcinomas (FTC). The aim of this interdisciplinary, retrospective study was to evaluate the association of AIT in patients with PTC and FTC and a control group of benign nodular goiters. One hundred thyroidectomies with histologically confirmed differentiated thyroid carcinomas, 67 with PTC and 33 with FTC, were submitted for examination. The two control groups consisted of 60 patients with euthyroid nodular goiter, displaying no signs for malignancy (no surgery) and 100 patients (second control group) with surgery of a benign nodular goiter. Controls were collected to obtain data about the incidence of significantly increased TPOAbs in the first group and of lymphocytic infiltrates (LI) in the second group. High TPOAbs were found in 35% (23/67) of patients with PTC. LI were detected by histology in 48% (32/67) of PTC. Ten patients (10/32) of this group showed the clinical and histological manifestation of a classic AIT with diffuse dense LI as well as diffuse hypoechogeneity in ultrasonography. In 7/32 cases, the histological report described focal dense LI (fAIT) and in 15/32 cases scant scattered LI. AIT and fAIT, together 25% of all PTC (17/67), showed germinal centers and can therefore be characterized as chronic autoimmune thyroiditis. In this group, high TPOAb could be detected in 94% (16/17). Scan scattered LI without germinal centers (15/32) do not represent a fAIT, although TPOAb are high in 47% (7/15). The younger age group (<45 years) showed significantly more often high TPOAbs (p<0.023) in comparison with the age-group older than 60 years. In contrast to PTC, only 4/33 (12%) patients with FTC had high TPOAb levels. We conclude that in contrast to benign euthyroid goiters and to FTC, different degrees of LI are often associated with high TPOAb levels and seem to be significantly increased in PTC, particularly prominent in younger age. There is a high coincidence between LI and high TPOAb levels. In the presence of hypoechoic thyroid nodule, signs of thyroid autoimmunity such as the presence of high TPOAbs, lymphocytic infiltration in cytology, and/or characteristic ultrasonic features, are arguments that might favor the decision for surgery if a cytologically indeterminate thyroid nodule is found and focal autonomy is excluded by szintiscan.

IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM WHILE IN THERAPY WITH TABLET L-T4, THE LIQUID L-T4 FORMULATION IS MORE EFFECTIVE IN RESTORING EUTHYROIDISM.

OBJECTIVE: Levothyroxine (L-T4) is the standard therapy of hypothyroidism. Our purpose was to compare the effectiveness of the L-T4 liquid formulation with respect to L-T4 tablet in hypothyroid patients without malabsorption or drug interference. Twenty-one subjects with high thyroid-stimulating hormone (TSH) values under therapy with L-T4 tablets were switched to liquid L-T4 at the same dosage given 30 minutes before breakfast. RESULTS: TSH values significantly declined 2 months after from the switch to liquid L-T4, reaching the normal range in most cases. In 15 (of the 21 patients) who switched back to tablets, TSH increased again to the hypothyroid range. Since the liquid L-T4 formulation resulted in better TSH level control, all patients were finally treated with the liquid L-T4, and TSH, free tri-iodothyronine and free thyroxine were evaluated again after 6 and 12 months, resulting in normal ranges in all subjects. CONCLUSIONS: The change from tablets to liquid oral formulation normalized serum TSH levels, while switching back to tablets caused thyrotropin levels to worsen. These results suggest that the liquid L-T4 formulation is more effective than tablets in controlling TSH levels in hypothyroid patients in the absence of malabsorption, gastric disorders, or drug interference. ABBREVIATIONS: BMI = body mass index FT3 = free tri-iodothyronine FT4 = free thyroxine L-T4 = levothyroxine PPIs = proton-pump inhibitors TSH = thyroid-stimulating hormone.

Correlation of thyroid antibodies with TSH, T3 and T4 hormones in patients diagnosed with autoimmune thyroid disorders.

The serum concentrations of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies are directly correlate in the induction and diagnosis of autoimmune thyroid disorders (AITDs). Therefore, the evaluation of serum anti-TPO and anti-TG antibodies in relation to thyroid function test parameters including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). This evaluation would be helpful in early diagnosis of abnormal thyroid function and associated autoimmune thyroid diseases. In this cross-sectional study, the serum anti-TPO, anti-TG, T3, T4 and TSH levels of 311 suspected patients of autoimmune thyroid disorders and 40 control subjects were evaluated. The data were presented as mean, ± standard deviations of the mean. Pearson correlation and chi-square tests were used to assess the correlation coefficients and significance in the contingency tables. The thyroid function test parameters in normal and AITDs suspected patients were significantly different in correlation to elevated serum levels of anti-TPO antibody. A significant association was detected between female gender and elevated levels of anti-TPO (P value = 0.047). A higher percentage of women showed elevated levels of anti-TG, but it was not statistically significant (P value= 0.107). The findings of the study reveal a strong correlation between thyroid function test and thyroid antibodies levels, elaborating the clinical importance of thyroid antibodies in clinical examination and follow-up of patients with autoimmune thyroid disorders.

Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased Risk for Developing Hypothyroidism in Autoimmune Thyroiditis.

Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.