Innate Immunity in Autoimmune Thyroid Disease during Pregnancy.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.

Recent data on iodine intake in Croatian schoolchildren: results of 2014-2019 survey.

BACKGROUND: Both insufficient and excessive iodine intake can lead to a broad range of disorders. A cross-sectional survey was conducted to assess iodine status in schoolchildren from Croatia. DESIGN: 957 healthy 6 to 12-year-olds were enrolled (381 from northwestern region, 190 from eastern region, 215 from north Adriatic, and 171 from central Dalmatia region). Urinary iodine concentration (UIC) was measured in spot urine samples. Thyroid volume (Tvol) was recorded by ultrasound device. Standard anthropometric measures were taken, and body surface area (BSA) was determined. Tvol medians were calculated as a function of age, sex and BSA and compared with reference values. RESULTS: Total sample size included 490 boys and 467 girls. Overall median UIC was 250.68 µg/L, with statistically significant variance in geographical regions (median UIC was 244.71 µg/L in northwestern, 208.02 µg/L in eastern, 216.07 µg/L in north Adriatic and 366.43 µg/L in central Dalmatia region). There were 10.08% of samples with UIC < 100 mcg/L while 38.24% of samples had UIC > 300 mcg/L. Age-matched Tvol medians in schoolchildren from all regions of Croatia were at the upper limits of reference values, but in north Adriatic and central Dalmatia exceeded the 97th percentile. BSA-matched Tvol was within the reference range in all regions. CONCLUSIONS: Our results demonstrate sufficient (more than adequate) iodine intake in schoolchildren of Croatia, and excessive iodine intake in central Dalmatia region. Total thyroid volumes in schoolchildren of Croatia were within the normal range, however borderline enlarged age-matched thyroid glands were observed in coastal areas.

Diagnostic Performance of 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) for Risk Stratification of Hypofunctioning Thyroid Nodules: A European Multicenter Study.

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: -19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

Risk Factors for Thyroid Cancer: What Do We Know So Far?

Thyroid cancer (TC) is the most common endocrine cancer today. The rising incidence of the differentiated papillary type cannot be entirely explained by early and meticulous diagnosis, since a proportion of large tumors has also been reported. In this review, we present the results of numerous investigations focused on possible factors causing increased TC incidence, such as chromosomal and genetic alterations, iodine intake, TSH level, autoimmune thyroid disease, gender, estrogen, obesity, lifestyle changes, and environmental pollutants. Up to now, only childhood exposure to ionizing radiation has been fully recognized as a risk factor. There is also a possibility that yet undiscovered carcinogens, especially during intrauterine life or early childhood, might be responsible for increased TC incidence as well as epigenetic changes. Therefore, more studies are necessary in order to further investigate the potential risk factors for TC and their mechanisms of action.

Glomus Tumor of the Neck Detected With 99mTc EDDA HYNIC-TOC.

A 54-year-old woman was referred to thyroid evaluation because of a lump on the left side of the neck. Ultrasound exam did not show any thyroid abnormality, but highly perfused nodule at the left common carotid artery bifurcation was found. Because of the specific location, somatostatin receptor scintigraphy with Tc EDDA HYNIC-TOC was performed, starting with perfusion images and followed with SPECT/CT imaging at 2 and 4 hours. Well-perfused nodule with intensive accumulation and no other visible pathology in the body raised suspicion of a glomus tumor, consistent with MR exam performed later. Subsequent surgical removal confirmed carotid paraganglioma.

Short-term cytolytic mediators' expression in decidual lymphocytes is enhanced by interleukin-15.

PROBLEM: We investigated whether decidual adherent cells (DAC) and interleukin (IL)-15, in comparison to interleukin (IL)-2 affect cytolytic potential of first trimester decidual lymphocytes (DL). METHOD OF STUDY: Decidual mononuclear cells were obtained by enzymatic digestion and density gradient centrifugation. Non-adherent DL were collected after 2-hr adherence and cultured for 18 or 72 hr with: IL-15 (0.5-5 ng/mL), IL-2 (100-1000 U/mL) or both of these cytokines, DAC (ratio 3:1 and 1:1) or DAC and anti-IL-15 antibody. Perforin, Fas ligand (FasL) and granzyme B were detected at mRNA level in indicated culture conditions. Cytolytic activity of DL against K-562, P815 and P815-Fas was measured by 2-hr PKH-26 cytotoxicity assay. The dynamics of perforin protein and mRNA expression were measured in DL after a contact with K-562 targets. RESULTS: Interleukin-15 enhanced perforin, FasL and granzyme B transcription after 18-hr culture and prevented perforin protein downregulation, observed after DL culture. IL-2 had similar effects. DAC sustained perforin expression in DL and anti-IL-15 monoclonal antibody abrogated this effect. DAC increased cytotoxicity of DL against K-562 which was mediated by IL-15. CONCLUSION: Interleukin-15, probably produced by DAC, upregulates cytolytic mediators' expression and perforin-mediated cytotoxicity of DL, with equal efficiency as high concentrations of IL-2.

Perforin and Fas/FasL cytolytic pathways at the maternal-fetal interface.

The immunogenetic enigma of maternal acceptance of the fetal semiallograft has been termed an immunological paradox. The first trimester decidua is heavily infiltrated with CD56(bright) CD16- uterine natural killer (uNK) cells which must be prepared to respond to potential pathogen challenges and still be able to control immune responses that allow the development of the fetus. The significant presence of cytolytic mediators, perforin and Fas/Fas ligand (FasL), at the maternal-fetal interface raises a question of their role(s) in the immunological interrelations between maternal tissues and trophoblast cells. As uNK cells in vitro lyse target cell lines (K562, P815 and P815Fas) using these effector molecules, it seems that, although immunocompetent, their cytotoxicity is not directed against trophoblast during normal pregnancy. Therefore, it is generally believed that the hormonal and Th1/Th2 cytokine balance plays an important role in the tolerance and maintenance of pregnancy. This paper gives an overview of the recent findings on the complex immunological events that occur at the maternal-fetal interface.