Enhancing Angioinvasion Assessment in Papillary Thyroid Cancer Via a Biomarker Panel Involving TAC, 8-OHdG, and Sortilin.

CONTEXT: Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis. OBJECTIVE: This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity, total antioxidant capacity [TAC], and sortilin), as potential indicators of angioinvasion in PTC. DESIGN: A cross-sectional study involving 50 angioinvasive patients with PTC (study group) and 30 patients with PTC with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion. SETTING: Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context. PATIENTS OR OTHER PARTICIPANTS: Participants included patients with PTC, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded. INTERVENTION(S): Serum biomarkers were measured to evaluate their association with PTC angioinvasion. MAIN OUTCOME MEASURE(S): Primary outcome measures included serum levels of 8-OHdG, total oxidative capacity, TAC, and sortilin. RESULTS: Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, whereas TAC showed a notable decrease (all P < .01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high area under the curve value (0.963) for angioinvasion discernment. CONCLUSION: Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results.

Clinical significance of oxidative stress markers as angioinvasion and metastasis indicators in papillary thyroid cancer.

Angioinvasion remains the important prognostic feature in papillary thyroid cancer (PTC) patients. Literature data indicates several markers that may be associated with oxidative stress and/or angioinvasion. Therefore, we assessed the utility of selected parameters in angioinvasion and metastasis screening in serum of PTC patients. Serum antioxidant capacity (TAC) and sirtuin 3 (SIRT3) levels were decreased (all p < 0.05) and both DNA/RNA oxidative stress damage products (DNA/RNA OSDP) and malondialdehyde (MDA) levels were increased in PTC patients with angioinvasion and metastasis (study group) when compared with PTC patients without these features (all p < 0.01). The highest screening utility in differentiation between angioinvasion and metastasis presence and absence in PTC patients was presented for DNA/RNA OSDP (AUC = 0.71), SIRT3 (AUC = 0.70), and TAC (AUC = 0.67) (all p < 0.05). Our study suggests that peripheral concentration of oxidative stress markers could be useful as angioinvasion and metastasis indicator in PTC patients.

Tears as a Source of Biomarkers in the Diagnosis of Graves' Orbitopathy.

Thyroid eye disease (TED) is a poorly understood autoimmune manifestation of thyroid diseases most commonly associated with Graves' disease. Due to a lack of specific biomarkers and uncertain signs and symptoms, Graves' orbitopathy (GO) is challenging to diagnose early and treat effectively. Nowadays, there is great interest in searching for precise molecular biomarkers for early detection, disease monitoring, and clinical management. Researchers are keen to identify novel methods to predict and diagnose diseases and to monitor patient therapeutic response. Tears, due to their direct contact with the eye and the fact that lacrimal glands can also be affected by the disease, could give new insights into the mechanisms taking place in thyroid-associated orbitopathy (TAO) and reveal potential promising biomarkers. Tear fluid offers the possibility of the non-invasive acquisition of a sample with a high protein content, thereby attracting continuously growing interest in the discovery of novel biomarkers. This article provides an up-to-date overview of the various putative tear-fluid biomarkers that have been identified. In this review, we present the potential use of tears as a diagnostic fluid and tool to investigate the mechanism of ocular diseases and discuss the future research directions in this area.

Rituximab in the treatment of Graves' orbitopathy: latest updates and perspectives.

Graves' orbitopathy (GO) is a potentially sight-threatening and disfiguring, extrathyroidal manifestation of Graves' disease. It often impairs patients' quality of life, causing severe social and psychological sequelae. Intravenous glucocorticosteroids is currently the mainstay of therapy, but the efficacy is often underwhelming and recurrence rate is high. For many years, clinicians have been searching for new methods of treatment. Rituximab (RTX) is a chimeric monoclonal antibody targeted against CD20 which is a surface antigen present on B cells. It is frequently used to treat non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, or various types of vasculitis. Numerous clinical trials employing RTX in the treatment of GO have shown promising results. RTX is currently considered to be a valid second-line treatment option in patients unresponsive to previous interventions or in disease reactivation. This review summarizes the available literature on this topic, including two largest, randomized, controlled studies. Potential benefits, as well as the limitations of RTX therapy, are discussed.

Applications of Metabolomics in Calcium Metabolism Disorders in Humans.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

Sphingomyelin profiling in patients with diabetes could be potentially useful as differential diagnostics biomarker: A pilot study.

PURPOSE: Autoimmune diabetes (AD) in adults includes both the classical form of type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). LADA shares clinical and metabolic features with type 1 and type 2 diabetes mellitus (T2DM). Ceramide (Cer) levels negatively correlate with insulin sensitivity in humans and animal models. However, only a few studies have focused on other sphingolipids, including sphingomyelin (SM). Therefore, we determined sphingolipids in patients with newly diagnosed diabetes as possible diagnostic biomarkers. MATERIALS AND METHODS: We evaluated sphingolipids in a cohort of 59 adults with newly diagnosed diabetes without prior hypoglycemic pharmacotherapy to distinguish diabetes mellitus types and for precise LADA definition. All patients with newly diagnosed diabetes were tested for the concentrations of individual Cer and SM species by gas-liquid chromatography. The study included healthy controls and patients with T1DM, T2DM and LADA. RESULTS: SM species were significantly altered in patients with newly diagnosed diabetes compared to healthy controls. SM-C16:0, C16:1, -C18:0, -C18:1, -C18:2, -C18:3, -C20:4, and -C22:6 species were found to be significantly elevated in LADA patients. In contrast, significant differences were observed for Cer species with saturated acyl chains, especially Cer-C14:0, -C16:0, -C18:0 (AD and T2DM), -C22:0, and -C24:0 (T1DM). Following ROC analysis, SM-C16:0, and particularly -C18:1, and -C20:4 may be supportive diagnostic markers for LADA. CONCLUSION: SM profiling in patients with newly diagnosed diabetes could be potentially helpful for differential diagnosis of LADA, T1DM, and T2DM in more challenging cases.

Cardiovascular risk factors in mild adrenal autonomous cortisol secretion in a Caucasian population.

Cardiovascular risk factors could be present in mild adrenal autonomous cortisol secretion (MACS). However, the most frequent cardiovascular risk factors in MACS have not been established. The aim of the presseent study was to analyse the difference in cardiovascular risk factors in patients with MACS in comparison to those with non-functioning adrenal tumour (NFAT). A total of 295 patients with adrenal incidentaloma were included in this retrospective study. We divided our group into those who showed suppression in 1 mg overnight dexamethasone suppression test (DST) (NFAT) (serum cortisol level ≤1.8 µg/dL) and those who did not show suppression in the DST (MACS) (serum concentration of cortisol > 1.8 µg/dL and ≤5 µg/dL). In the studied groups, we analysed the presence of cardiovascular risk factors, such as obesity, prediabetes, type 2 diabetes mellitus (T2DM), hypertension, hyperlipidaemia, chronic kidney disease and cardiovascular events. In our study, 18.9% of patients were defined as MACS. Importantly, T2DM was diagnosed in 41% of MACS vs 23% of NFAT (P < 0.01) and higher frequency of occurrence of hyperlipidaemia in NFAT (72.4%) vs MACS (53.6%) (P = 0.01) was observed. We did not observed differences in the frequency of obesity, hypertension, chronic kidney disease, prediabetes, atrial fibrillation, stroke, ST and non-ST elevation myocardial infarction and coronary angioplasty between patients with MACS and NFAT (all P > 0.05; respectively). In MACS, T2DM is more prevalent than in NFAT; hyperlipidaemia is more prevalent in NFAT. Accordingly, no differences were found in the incidence of obesity, hypertension, prediabetes, chronic kidney disease between studied groups as well as cardiovascular events.

Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer.

The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for DEMs was found for miR-146-5p (AUC = 0.770) expression, indicating possible clinical applicability in PTC diagnosis. The combination of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) showed an AUC of 0.841. Validation by real-time quantitative polymerase chain reactions (qRT-PCRs) confirmed our findings. The introduction of an miRNA diagnostic panel based on the results of our study may help to improve therapeutic decision making for questionable cases. The use of miRNAs as biomarkers of PTC may become an aspect of personalized medicine.

MicroRNA Profile Alterations in Parathyroid Carcinoma: Latest Updates and Perspectives.

Parathyroid tumors are a genetically heterogenous group with a significant variability in clinical features. Due to a lack of specific signs and symptoms and uncertain histopathological criteria, parathyroid carcinomas (PCs) are challenging to diagnose, both before and after surgery. There is a great interest in searching for accurate molecular biomarkers for early detection, disease monitoring, and clinical management. Due to improvements in molecular pathology, the latest studies have reported that PC tumorigenesis is strongly linked to the epigenetic regulation of gene expression. MicroRNA (miRNA) profiling may serve as a helpful adjunct in distinguishing parathyroid adenoma (PAd) from PC and provide further insight into regulatory pathways involved in PTH release and parathyroid tumorigenesis. So far, only a few studies have attempted to show the miRNA signature for PC, and very few overlaps could be found between these relatively similar studies. A global miRNA downregulation was detected in PC compared with normal glands among differentially expressed miRNAs. This review summarizes changes in miRNA expression in PC and discusses the future research directions in this area.

Gas Chromatography-Mass Spectroscopy-Based Metabolomics Analysis Reveals Potential Biochemical Markers for Diagnosis of Gestational Diabetes Mellitus.

Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography-mass spectrometry (GC-MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, n = 24; aGT-GDM, n = 26; NGT, n = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α-hydroxybutyric acid (α-HB), ß-hydroxybutyric acid (ß-HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC-MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, n = 51; aGT-GDM, n = 44; and NGT, n = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8-14 gwk) who were NGT at this time, but in the second trimester (24-28 gwk) they were diagnosed with GDM. It was found that α-HB, ß-HB, and several fatty acids were associated with aGT-GDM. A combination of α-HB, ß-HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.

Body Composition and Serum Anti-Müllerian Hormone Levels in Euthyroid Caucasian Women With Hashimoto Thyroiditis.

Objective: Women with Hashimoto thyroiditis (HT) are characterized by increased incidence of infertility and disturbances in body composition. Serum anti-Müllerian hormone (AMH), which reflects functional ovarian reserve, is decreased in women with HT and it be related to body mass. The aim of the present study was to investigate the relation between serum levels of AMH and body composition in HT compared to control group. Patients and Methods: We examined 85 euthyroid women: 39 subjects with HT and 46 control women. Body composition was analysed by dual-energy X-ray absorptiometry and with bioimpedance method. Serum concentrations of AMH, leptin, TSH, thyroid hormones were assessed. Results: We observed lower serum concentration of AMH in women with HT in comparison to the control group (p=0.01), but without differences in serum concentration of leptin between studied groups (p=0.28). Women with HT were characterized by higher %body fat (p=0.01) estimated with bioimpedance method without differences in BMI, android and gynoid fat mass and visceral adipose tissue (VAT) mass estimated with DXA method when compared to the control group (all p>0.05). We found a negative relationship between serum concentration of AMH and %body fat (r=-0.38,p=0.03) in women with HT. Additionally, in HT group, the relationship between serum levels of AMH and leptin was not statistically significant (r=0.01,p=0.96). We observed a relationship between serum concentration of leptin and BMI, %body fat mass, android, gynoid and VAT mass in HT and in the control group (all p<0.01). Conclusions: Women with HT are characterized by lower levels of AMH and it is associated with higher fat mass, independently of serum levels of leptin.

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium-phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Dosimetry during adjuvant 131I therapy in patients with differentiated thyroid cancer-clinical implications.

The activity of radioiodine (131I) used in adjuvant therapy for thyroid cancer ranges between 30 mCi (1.1 GBq) and 150 mCi (5.5 GBq). Dosimetry based on Marinelli's formula, taking into consideration the absorbed dose in the postoperative tumour bed (D) should systematise the determination of 131I activity. Retrospective analysis of 57 patients with differentiated thyroid cancer (DTC) after thyreidectomy and adjuvant 131I therapy with the fixed activity of 3.7 GBq. In order to calculate D from Marinelli's formula, the authors took into account, among other things, repeated dosimetry measurements (after 6, 24, and 72 h) made during scintigraphy and after administration of the therapeutic activity or radioiodine. In 75% of the patients, the values of D were > 300 Gy (i.e. above the value recommended by current guidelines). In just 16% of the patients, the obtained values fell between 250 and 300 Gy, whereas in 9% of the patients, the value of D was < 250 Gy. The therapy was successful for all the patients (stimulated Tg < 1 ng/ml and 131I uptake < 0.1% in the thyroid bed in follow-up examination). Dosimetry during adjuvant 131I therapy makes it possible to diversify the therapeutic activities of 131I in order to obtain a uniform value of D.

Thyroid carcinoma with atypical metastasis to the pituitary gland and unexpected postmortal diagnosis.

SUMMARY: Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient's case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual. LEARNING POINTS: The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes. Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy. This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.

Pituitary adenoma and apoplexy during GnRH agonist treatment for IVF - case report.

In vitro fertilization is commonly used for treating infertility. One stage of this process is controlled hyperstimulation of the ovaries, achieved by administering gonadotropins. There are several stimulation protocols utilized that increase the number of ovarian follicles during IVF. The most common protocol employs desensitization - the inhibition of follicle-stimulating hormone and luteinizing hormone secretion by the pituitary gland. This is achieved by administering a gonadotropin-releasing hormone (GnRH) analog that is agonistic for the GnRH receptor. However the use of a this drug during therapy carries a risk of complications. This case report deals with a rare case of a woman who underwent pituitary tumor growth as a result of the treatment of GnRH analog.

The interferon-induced helicase C domain-containing protein 1 gene variant (rs1990760) as an autoimmune-based pathology susceptibility factor.

PURPOSE: Autoimmune diseases are a group of complex diseases localized in multiple organ systems, with a wide spectrum of symptoms and still unclear causes. The aim of the present study was to analyse a possible association of three autoimmune disabilities - Multiple sclerosis (MS), LADA diabetes and Graves' disease (GD) with single nucleotide polymorphism (SNP; rs1990760) in the IF IH1 gene (also known as a melanoma differentiation-associated protein 5 - MDA5) within the Polish population. An additional goal was also to look for a correlation between this polymorphism and different clinical patient-related factors. MATERIALS AND METHODS: The study population consisted of four groups of 944 unrelated Polish origin Caucasian patients - 324 with GD, 171 with MS, 49 with LADA diabetes and 400 healthy subjects as a control group. The SNP analysis was performed using the allelic discrimination technique. RESULTS & CONCLUSIONS: There were significant associations of risk T allel of the analyzed polymorphism with all studied autoimmune diseases (GDOR = 1.34, p = 7.02e-03; MSOR = 1.36, p = 2.17e-02; LADA - OR = 3.36, p = 8.73e-07). We also found that the frequency of CT and TT genotypes of the rs1990760 IFIH1 gene only in females (with LADA, GD, MS) was significantly higher than those in the female control group (47%, 41% vs 44%, 34%; p = 1.32e-03, p = 4.39e-04; OR = 2.08, 95%CI: (1.33-3.28), OR = 2.29, 95% CI: (1.44-3.65) respectively). Our research has shown significant differences regarding some clinical features (BMI, TRAb, TSH, HbA1C, anti-GAD antibodies) and age at the beginning of the studied autoimmune disabilities. This study showed an association of rs1990760 polymorphism in the IFIH1 gene in the development of GD, LADA diabetes and MS within the Polish population. To our knowledge, this is the first study to investigate the relationship between IFIH1 polymorphisms and the risk of the development of MS and LADA in Poland.

Interleukin-6 and Interleukin-15 as Possible Biomarkers of the Risk of Autoimmune Diabetes Development.

AIM: The aim of our study was to assay circulating interleukin-15 (IL-15) and interleukin-6 (IL-6) levels and insulin resistance measured by two different methods in newly diagnosed autoimmune diabetes (AD) patients, their I° relatives, and healthy controls. MATERIAL AND METHODS: The group studied consisted of 54 patients with AD (28 with Latent Autoimmune Diabetes in Adults (LADA) and 26 with type 1 diabetes (T1D)), 70 first-degree relatives, and 60 controls. IL-6, IL-15, and anti-islet antibodies concentrations were measured by ELISA method. Homeostatic model assessment-insulin resistance (HOMAIR) and estimated glucose disposal rate (eGDR) were calculated. RESULTS: The patients with AD had significantly higher IL-15, IL-6, and HOMAIR and lower eGDR than the controls (p < 0.001, respectively) and first-degree relatives (p < 0.001, respectively). Significantly higher IL-15 and IL-6 were shown in the relatives with positive Ab as compared to the relatives without antibodies (p < 0.001, respectively) and the controls (p < 0.001, respectively). IL-15 negatively correlated with eGDR (r = -0.436, p = 0.021) in LADA and positively with HOMAIR in LADA and T1D (r = 0.507, p < 0.001; r = 0.4209, p < 0.001). CONCLUSIONS: Significantly higher IL-15 and IL-6 concentrations, HOMAIR, and markedly lower eGDR in newly diagnosed AD patients and first-degree relatives with positive anti-islet antibodies might suggest the role of these pro-inflammatory cytokines and insulin resistance in the pathogenesis of autoimmune diabetes. IL-15 and IL-6 might be used as biomarkers of the risk of autoimmune diabetes development, in particular IL-15 for LADA. Both methods of IR measurement appear equally useful for calculating insulin resistance in autoimmune diabetes.

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.

Endocrine autoimmunity in patients with Latent Autoimmune Diabetes in Adults (LADA) ­ association with HLA genotype.

INTRODUCTION: Latent autoimmune diabetes in adults (LADA) is a slow-developing form of autoimmune diabetes, characterised by the presence of type 1 diabetes-associated autoantibody and presentation at diagnosis similar to patients with type 2 diabetes. The aim of this study was to determine the prevalence of auto-antibodies related to endocrine autoimmune diseases in patients with LADA and to assess their association with HLA genotype. MATERIAL AND METHODS: We evaluated the presence of anti-thyroglobulin (ATG), anti-thyroid peroxidase (ATPO), anti-tissue transglutaminase IgA (ATTA), and anti 21 hydroxylase (A21H) in 70 patients with LADA, 69 with Type 2 diabetes, and in 50 healthy controls HLA genotype was assed in subpopulation of sluclied subjects. RESULTS: The presence of ATPO (28.6 vs. 10%); ATG (28.6 vs. 14%) was higher in patients with LADA in comparison to healthy controls and ATPO in comparison to patients with type 2 diabetes (38.6 vs. 17.4 %). In patients with LADA the presence of autoimmune thyroid autoantibodies was associated with newly diagnosed subclinical hypothyroidism; almost 7% of patients presented with high TSH. The presence of A21H (2.86 vs. 5.8 vs. 6.1%) and ATTA (2.86 vs. 4.3 vs. 6.0%) was not different between groups. Patients with high TSH level were positive for DQA1*0301 and DRB1*04 HLA genotype: DQB1*0201 and DQB1*02 were higher in patients positive for ATTA. CONCLUSIONS: Patients with LADA have higher prevalence of thyroid autoimmune diseases. In patients with LADA similarly to type 1 genotype DQA1*0301 seems to CONFER susceptibility to thyroid autoimmunity, and DQB1*0201 to celiac disease.

High Serum IgG4 Concentrations in Patients with Hashimoto's Thyroiditis.

Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT) may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb), anti-TSH receptor antibodies, TNF-α, TGF-ß1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10) were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb (P=0.02) than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (P=0.01). Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis.