Higher prevalence of thyroid-specific autoantibodies (TPOAb and TgAb) is related to a higher prevalence of fractures in females: results from NHANES 2007-2010.

A retrospective analysis was conducted using data from the NHANES. Bone mineral density (BMD) was compared in different thyroid-specific autoantibodies groups. Strengths of associations were calculated by using binary logistic regression models. Higher titers of thyroid-specific autoantibodies (TgAb and/or TPOAb) may lead to decreased BMD. Higher prevalence of TgAb and TPOAb significantly associated with fractures in females but not in males. PURPOSE: Hashimoto's thyroiditis is characterized by elevated thyroid-specific autoantibodies. It is currently believed that osteoporosis is not only a disease with abnormal mineral metabolism but also with immune abnormalities. This study investigated the relationship between thyroid-specific autoantibodies and osteoporosis, including the bone mineral density (BMD) values and fractures. METHODS: A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (2007-2010). BMD was compared in different thyroid-specific autoantibodies groups. The associations between thyroid-specific autoantibodies and fractures were explored. Strengths of associations were calculated by binary logistic regression models. Candidate variables for binary logistic regression model were selected after screened in univariate analysis (variables with P < 0.05). RESULTS: A total of 3865 study participants were included in this analysis; 224 participants were TgAb positive and 356 were TPOAb positive. A total of 392 participants reported hip, spine or wrist fractures. Participants with higher prevalence of TgAb or TPOAb had lower BMD. In females, significant cigarettes use, higher prevalence of TgAb and TPOAb, and the BMD of the total femur and femoral neck were significantly associated with fractures. Higher prevalence of TPOAb was particularly associated with a higher possibility of hip or spine fractures. In males, significant cigarettes use, 25OHD3, the BMD values of the total femur, femoral neck and total spine were significantly associated with fractures. CONCLUSION: Higher prevalence of thyroid-specific autoantibodies may lead to decreased BMD. In females, higher prevalence of TgAb and TPOAb significantly associated with fractures and TPOAb especially relating to the fractures of hip and spine. Males patients with vitamin D deficiency or insufficiency associated a higher possibility of fractures.

Autoimmune Thyroiditis and Vitamin D.

Hashimoto's thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods.

In Graves' disease, thyroid autoantibodies and ultrasound features correlate with distinctive histological features.

PURPOSE: Laboratory, imaging, and pathological features of Graves' disease (GD), although well characterized, have been barely correlated each other. Aim of the study was to link laboratory and ultrasound characteristics of GD with its pathological features. METHODS: We correlated laboratory and ultrasound data at the time of diagnosis in 28 consecutive GD patients who underwent thyroidectomy with their pathological features, i.e., lymphocytic infiltration and follicular hyperplasia (both classified as mild or severe). RESULTS: Thyroid volume correlated positively with the levels of FT4 (P = 0.002, r2 = 0.42), FT3 (P = 0.011, r2 = 0.22), autoantibodies to thyroglobulin (TgAbs) (P = 0.016, r2 = 0.32), autoantibodies to thyroid peroxidase (TPOAbs) (P = 0.011, r2 = 0.34) and the extent of lymphocytic infiltration (P = 0.006 comparing mild to severe lymphocytic infiltration) but not with the levels of autoantibodies to the thyrotropin receptor (TRAbs) and to follicular hyperplasia. Compared to subjects with mild lymphocytic infiltration, those with severe lymphocytic infiltration showed higher levels of TgAbs (316 vs 0.0 IU/mL, P < 0.0001) and TPOAbs (295 IU/mL vs 14 IU/mL, P < 0.0001) and similar levels of TRAbs (7.5 vs 13 IU/mL, P = 0.68). Compared to patients with mild, those with severe follicular hyperplasia had similar levels of TgAbs (76 vs 30 IU/mL, P = 0.31) and TPOAbs (251 IU/mL vs 45 IU/mL, P = 0.26) but higher levels of TRAbs (39 vs 7.2 IU/mL, P < 0.001). CONCLUSION: In GD, TgAbs and TPOAbs levels correlate with the extent of lymphocytic infiltration, TRAbs levels with the degree of follicular hyperplasia. Thyroid volume, the main factor influencing the severity of hyperthyroidism, is related to lymphocytic infiltration and not to follicular hyperplasia.

Thyroid Disease and Systemic Lupus Erythematosus.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21-79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p < 0.05, chi-square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.

Thyroglobulin and thyroglobulin antibodies: assay-dependent management consequences in patients with differentiated thyroid carcinoma.

OBJECTIVES: International guidelines recommend fixed cut-off values for thyroglobulin (Tg). These cut-offs do not take potential assay differences into account. This study aimed to evaluate if different assays for Tg and Tg antibodies (TgAb) affect management guidance for differentiated thyroid cancer (DTC) patients. METHODS: In 793 samples derived from 413 patients with DTC, Tg and TgAb were simultaneously measured with two immunometric assays: Immulite 2000XPi and Kryptor compact plus. In addition, a qualitative measurement for TgAb interference (recovery test) was performed on the Kryptor compact plus platform. The extent to which different assays lead to different classifications of response to therapy was evaluated when applying the current cut-offs for Tg. RESULTS: Mean Tg concentrations were 37.4% lower with Kryptor as compared with Immulite. Applying guideline based cut-off values for Tg, 33 (4.7%) samples had a Tg-on concentration ≥1.0 µg/L with Immulite and <1.0 µg/L with Kryptor. Of the samples tested as TgAb+ with at least one assay (n=125), 68 (54.4%) samples showed discrepancy in TgAb status. Differences between Immulite and Kryptor measurements resulted in a change in the response to therapy classification in 94 (12.0%) measurements derived from 67 (16.2%) individual patients. CONCLUSIONS: A substantial portion of DTC patients were classified differently dependent on which Tg and TgAb assays are used, when applying the cut-off values as defined in clinical guidelines. Such differences can significantly affect clinical management. In the context of large between-method variation, the recommended Tg cut-offs in guidelines should be used with wisdom rather than as fixed cut-offs.

Effects of animal protein intake during pregnancy on autoimmune thyroiditis in pregnant women with mild iodine deficiency.

BACKGROUND: Iodine and animal protein may affect thyroid function. In the present study, we explored the association between animal protein intake and thyroid antibody status in pregnant women following universal salt iodisation. METHODS: Pregnant women were enrolled using a multistage, stratified random sampling method in Shanghai. In total, 4646 eligible women were interviewed in person. We used a validated food frequency questionnaire and food composition tables to calculate the daily intakes of protein and iodine. We collected urine samples and performed thyroid antibody tests. RESULTS: Positive thyrotropin receptor antibody (TR-Ab) rates were different among animal protein intake groups (p < 0.05). Median urinary iodine concentration (UIC) was higher in the thyroid peroxidase antibody (TPO-Ab) positive group than in the negative group (p < 0.05). The median of total protein intake, animal protein intake and UIC was higher in the TR-Ab positive group than in the negative group (p < 0.05). The median of total protein intake and UIC was higher in the TPO-Ab/TG-Ab/TR-Ab positive group than in the negative group (p < 0.05). Multivariable logistic regression results showed that insufficient iodine had a negative correlation with positive TPO-Ab and positive TR-Ab (p < 0.05). The middle third and top third animal protein intakes served as protective factors for TR-Ab (coefficient = 0.559, 95% confidence interval [CI] = 0.415-0.752, p < 0.001; coefficient = 0.0.406, 95% CI = 0.266-0.621, p < 0.001) and positive TPO-Ab/TR-Ab/TG-Ab (coefficient = 0.817, 95% CI = 0.687-0.971, p = 0.022; coefficient = 0.805, 95% CI = 0.672-0.964, p = 0.018). CONCLUSIONS: Adequate animal protein intake protects against elevated anti-thyroid antibody levels in pregnant women with mild iodine deficiency.

Histology is more ιmportant than persistent anti-Tg antibodies for progression of differentiated thyroid cancer.

CONTEXT: Anti-thyroglobulin antibodies (anti-Tg), present in 20%-25% of differentiated thyroid cancer (DTC) patients, interfere with thyroglobulin measurements posing a challenge in the follow-up. OBJECTIVES: The aim of this study was to identify clinical-histological factors that may affect anti-Tg persistence and disease outcome in DTC with positive anti-Tg. METHODS: We retrospectively studied 234 DTC patients, with positive anti-Tg at diagnosis (females: 82.1%, age at diagnosis: 46.0 ± 14.4 yrs, median follow-up: 5 yrs (1.5-32 yrs). 221/234 (94.4%) received radioiodine (RAI) ablation. Patients were divided into two subgroups: those whose anti-Tg became undetectable (anti-Tg-NEG) and those whose anti-Tg remained positive (anti-Tg-POS) at the end of the follow-up period. RESULTS: Anti-Tg-POS patients (n = 80, 34.2%) compared to anti-Tg-NEG (n = 154, 65.8%) had more frequently lymph node infiltration (36.3% vs 20.1%, P = .01), extrathyroidal extension (ETE, 35.0% vs 22.1%, P = .04), poorly differentiated DTC and increased tumour size (P ≤ .004). They received higher total RAI dose (P < .001). In most cases, additional RAI administration and/or additional surgeries did not lead to anti-Tg elimination. These had more frequently structural disease persistence/progression compared to anti-Tg-NEG (remission: 78.8% vs 95.5%, persistence: 13.8% vs 3.9%, progression: 7.5% vs 0.6%, P < .001). In Kaplan-Meier analysis, the probability of disease progression was higher in anti-Tg-POS. In Cox proportional hazard analysis, the predictors of disease progression were size (P = .002) and ETE (P = .006). CONCLUSIONS: Worse histological features are more frequent in patients with anti-Tg persistence during follow-up. Further additional RAI administration and/or surgeries do not affect anti-Tg elimination in most cases. Anti-Tg persistence correlates with structural persistence although tumour size and extrathyroidal extension are the main predictors of disease progression.

Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma.

Background The present study was undertaken to evaluate the clinical impact of a thyroglobulin (Tg) minirecovery test (Tg-mRec) in a large series of differentiated thyroid carcinoma (DTC) patients treated and monitored homogeneously in a tertiary referral center. Methods Included were 1120 serum samples from 798 DTC patients. Tg, Tg autoantibodies (TgAb) and Tg-mrec measurements were performed on the automated Kryptor® platform and results compared to the corresponding clinical status. Results Among included samples 228 (20%) were TgAb-positive (TgAb+) and 892 (80%) TgAb-negative (TgAb-), respectively. Tg cutoff points were settled at 0.31 µg/L and 0.15 µg/L for TgAb- and TgAb+ patients, respectively, by ROC curve analysis. The diagnostic performance of serum Tg was reduced in TgAb+ compared to TgAb- patients, however, 87% of TgAb+ patients with recurrent disease and, particularly, all patients with distant metastases were correctly detected by adopting an optimized Tg cutoff for TgAb+ patients. A disturbed recovery was found in only 1% of TgAb- patients and in these cases no clinically relevant information was added by the Tg-mRec. Among TgAb+ patients with undetectable Tg and undisturbed Tg-mRec, no one had recurrent disease. However, a falsely undetectable Tg was demonstrated in two patients with recurrent disease who next to increased TgAb also had a disturbed Tg-mRec test. Conclusions There is no additional clinical benefit from performing Tg-mRec in most patients. It can however be considered in TgAb+ patients with undetectable Tg levels as it may help differentiate between patients with true negative and false negative Tg levels in the presence of such antibodies.

Thyroglobulin measurement in the management of patients with differentiated thyroid cancer.

The post-operative management of patients with differentiated thyroid carcinoma (DTC) relies on serial measurements of serum thyroglobulin. Current methodologies for thyroglobulin quantitation vary in their analytical and clinical performance. For years, thyroglobulin radioimmunoassays (RIA) and immunometric assays (IMA) have been used despite analytical interferences from anti-thyroglobulin autoantibodies (TgAb) as well as heterophile antibodies (HAb). TgAb interference limits Tg utility as a tumor marker in ∼30% of TgAb-positive patients. Consequently, additional studies are necessary to rule out persistent or recurrent disease in these patients. Recently, thyroglobulin mass spectrometry assays have been introduced as a solution to the interference problems observed in immunoassays. However, their analytical sensitivity is inferior to the high sensitivity immunoassays. The aims of this review are to: (i) review current thyroglobulin assays; (ii) discuss technical limitations of each assay; and (iii) discuss the clinical uses of thyroglobulin in serum and fine-needle aspirate biopsy washouts for the management of DTC patients. An understanding of the technical advantages and disadvantages of Tg assays is critical for clinicians and laboratorians to effectively use and interpret this test in the management of DTC patients.

Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status.

The occurrence of thyroid disorders relies on I nutrition and monitoring of all populations is recommended. Measuring I in urine is standard but thyroglobulin in serum is an alternative. This led us to assess the reliability of studies using serum thyroglobulin compared with urinary I to assess the I nutrition level and calculate the number of participants needed in a study with repeated data sampling in the same individuals for 1 year. Diet, supplement use and life style factors were assessed by questionnaires. We measured thyroglobulin and thyroglobulin antibodies in serum and I in urine. Participants were thirty-three Caucasians and sixty-four Inuit living in Greenland aged 30-49 years. Serum thyroglobulin decreased with rising I excretion (Kendall's τ -0·29, P=0·005) and did not differ with ethnicity. Variation in individuals was lower for serum-thyroglobulin than for urinary I (mean individual CV: 15·1 v. 46·1 %; P<0·01). It required 245 urine samples to be 95 % certain of having a urinary I excretion within 10 % of the true mean of the population. For serum-thyroglobulin the same precision required 206 samples. In an individual ten times more samples were needed to depict I deficiency when using urinary I excretion compared with serum-thyroglobulin. In conclusion, more participants are need to portray I deficiency in a population when using urinary I compared with serum-thyroglobulin, and about ten times more samples are needed in an individual. Adding serum-thyroglobulin to urinary I may inform surveys of I nutrition by allowing subgroup analysis with similar reliability.

Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up.

BACKGROUND: While thyroglobulin autoantibodies (TgAb) can result in false low serum thyroglobulin (Tg) immunoassay (IA) measurements, they might also be indicators of disease persistence/recurrence. Hence, accurate TgAb measurement, in addition to Tg quantification, is crucial for thyroid cancer monitoring. We compared the analytical and clinical performance of four commonly used TgAb IAs. METHODS: We measured Tg by mass spectrometry (Tg-MS) and by four pairs of Tg and TgAb IAs (Beckman, Roche, Siemens, Thermo) in 576 samples. Limit of quantitation (LOQ) and manufacturers' upper reference interval cut-off (URI) were used for comparisons. Clinical performance was assessed by receiving operator characteristics (ROC) curve analysis. RESULTS: Quantitative and qualitative agreement between TgAb-IAs was moderate with R2 of 0.20-0.70 and κ from 0.41-0.66 using LOQ and 0.47-0.71 using URI. In samples with TgAb interference, detection rates of TgAb were similar using LOQ and URI for Beckman, Siemens, and Thermo, but much lower for the Roche TgAb-IA when the URI was used. In TgAb positive cases, the ROC areas under the curve (AUC) for the TgAb-IAs were 0.59 (Beckman), 0.62 (Siemens), 0.59 (Roche), and 0.59 (Thermo), similar to ROC AUCs achieved with Tg. Combining Tg and TgAb measurements improved the ROC AUCs compared to Tg or TgAb alone. CONCLUSIONS: TgAb-IAs show significant qualitative and quantitative differences. For 2 of the 4 TgAb-IAs, using the LOQ improves the detection of interfering TgAbs. All assays showed suboptimal clinical performance when used as surrogate markers of disease, with modest improvements when Tg and TgAb were combined.

Anti-thyroglobulin antibodies do not significantly increase the risk of finding iodine avid metastases on post-radioactive iodine ablation scan in low-risk thyroid cancer patients.

OBJECTIVE: Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. METHODS: This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1-T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported, <2 mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had known distant metastases and/or extensive vascular invasion. A second group of patients (Group B) treated during the same period but without anti-Tg antibodies was selected to match group A by propensity core matching with a logistic regression model. RESULTS: Each group included 37 patients. In group A: Median age was 40 years, 86% female and 76% PTC. Median tumor size was 2 cm (0.2-3.8), 32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters in group B were not statistically different from Group A, as expected based on the selection criteria, except being less likely to have Hashimoto's thyroiditis on pathology (p < 0.001). Post-therapy scan results were compared by Chi-square test with 86% negative post therapy scan frequency in group A and 92% in group B without evidence of a difference (p = 0.45). CONCLUSION: In patients with low-risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post-therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs alone should not influence initial therapy in patients with low-risk DTC.

Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases.

It is generally believed that the detection of thyroid peroxidase antibodies (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis of Hashimoto's thyroiditis. However, limited data are available on the comparison of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's thyroiditis using sensitive immunoassays. We herein used five different current immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50), and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis, positive TgAb was significantly more frequent than positive TPOAb in kits A-D (mean ± SD of the four kits: 98.6 ± 1.7 vs 81.4 ± 2.0%). In patients with Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five kits. Patients with painless thyroiditis exhibited positive TgAb significantly more frequently than positive TPOAb in kits A-D (73.5 ± 4.1 vs 33.0 ± 3.4%). The prevalence of TgAb alone was significantly higher than that of TPOAb alone in both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb and TPOAb prevalence did not differ significantly for any disease, and TgAb distribution was different from other kits. In conclusion, the prevalence of TgAb was higher than that of TPOAb in patients with Hashimoto's thyroiditis and painless thyroiditis using commercially available kits. We suggest that TgAb immunoassay is the first choice of screening test for thyroid autoimmune abnormalities in Japan.

Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer.

PURPOSE: Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. METHODS: We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS: Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. CONCLUSIONS: Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence.

Thyroid autoimmunity: is really associated with papillary thyroid carcinoma?

The incidence of thyroid cancer has been greatly increasing. Several studies aimed to investigate biomarkers for prediction of thyroid cancer. Some of these studies have suggested that thyroid autoantibodies (TAb) could be used as predictors of thyroid cancer risk, but the correlation between TAb and PTC is still a matter of debate. The aim of this study is to evaluate thyroid autoimmunity and TAbs in patients with PTC and benign multinodular goiter (MNG) to investigate if TAbs and autoimmune thyroid disease (ATD) could predict thyroid malignancy. A total of 577 patients with thyroid papillary carcinoma (PTC) and 293 patients with benign MNG disease were enrolled postoperatively. Demographic features, thyroglobulin (TgAb) and thyroid peroxidase antibodies (TPOAb) and histologic outcome of the patients were evaluated. The prevalence of ATD and TgAb or TPOAb measurements was not statistically different in PTC and MNG groups. However, tumors were significantly smaller and tumor capsule invasion was seen less frequently in patients with PTC and ATD than without ATD. Patients without ATD had more advanced stage (TNM stage III/IV) tumors than with ATD. Only one of the 11 patients with distant organ metastasis had ATD. The present study demonstrated that the prevalence of ATD diagnosed even with histology or TAb positivity was not different in patients with PTC and MNG. However, having ATD might be associated with a better prognosis in PTC patients.

Thyroid function and thyroid autoantibodies in patients with chronic spontaneous urticaria.

INTRODUCTION: Chronic urticaria (CU) is a skin disease caused by autoantibodies against high affinity immunoglobulin E (IgE) receptor and against IgE. It is characterized by hives, erythematous wheals and redness present minimum twice a week for at least 6 weeks. It is observed that there is a strong association between CU and autoimmune diseases, such as autoimmune thyroiditis (AT). AIM: To verify the frequency of AT in patients suffering from chronic spontaneous urticaria (CSU) and to confirm the coexistence of CU and AT in the Polish population. MATERIAL AND METHODS: One hundred and forty-eight patients with CSU were included to the study. The presence of anti-thyroperoxydase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-Tg) was checked and thyrotropin (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) concentration was measured. Results were compared with outcomes in a group of 35 patients with no history of skin disease. RESULTS: Thirty-three patients were diagnosed with AT. Frequency of elevated anti-TPO (p = 0.0045) and anti-Tg (p = 0.013) levels was much higher in patients with CU. A comparison of the current study and previous ones was conducted. In a group with CU, there was a higher risk of elevated anti-TPO (OR = 6.69) and anti-Tg (OR = 6.01) levels. CONCLUSIONS: There is a statistically significant difference in the presence of AT between the patients with CU and the whole population. Doctors should consider examining patients with CU for AT. Adequate therapy and guidance for patients could be implemented at an early stage of thyroid disease and help induce remission of skin disorders.

Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival.

Cancer immunotherapy induces a variety of autoinflammatory responses, including those against the thyroid gland, which can be exploited to predict clinical outcomes. Considering the paucity of information about thyroid autoimmunity in patients receiving cancer vaccines, we designed our study to assess the development of thyroglobulin antibodies (TgAbs) in patients treated with GVAX (vaccine made of a tumor cell type transfected with GM-CSF) and/or ipilimumab and correlated seroconversion with survival. Using both in house and commercial ELISA assays, we measured TgAbs in patients with pancreatic (No. = 53), prostate (No. = 35) or colon (No. = 8) cancer, before and after treatment with GVAX only (No. = 34), GVAX plus ipilimumab (No. = 42) or ipilimumab (No. = 20), and correlated their levels with patient's survival, disease status and T-cell surface markers. Antibodies to thyroperoxidase, myeloperoxidase, proteinase 3, insulin and actin were also measured. TgAbs specifically developed after GVAX, independent of the underlying cancer (81% in prostate, 75% colon cancer and 76% pancreatic cancer) and co-administration of ipilimumab (75% in GVAX only and 78% in GVAX plus ipilimumab). This TgAbs seroconversion could be detected mainly by the in house assay, suggesting that the thyroglobulin epitopes recognized by the antibodies induced by GVAX are different from the epitopes seen in the classic form of Hashimoto thyroiditis. Notably, TgAbs seroconversion was associated with significantly prolonged survival (p = 0.01 for pancreas and p = 0.005 for prostate cancer). In conclusion, GVAX immunotherapy induces the appearance of TgAbs that recognize a unique antigenic repertoire and associate with prolonged survival.

Influence of Thyroglobulin (Tg) Autoantibodies on Tg levels Measured by Different Methodologies: (IMA, LC-MS/MS and RIA).

CONTEXT: Serum thyroglobulin (Tg) measured by Immunometric assays (IMA) is prone to underestimation due to Tg autoantibody (TgAb) interference, often prompting reflex Tg measurement by liquid chromatography/tandem mass spectrometry (MS) or radioimmunoassay (RIA). OBJECTIVE: IMA, MS and RIA methodologies were used to measure serum Tg in TgAb-negative (TgAb-) and TgAb-positive (TgAb+) patients with either distant metastatic thyroid cancer (DTC) or hyperthyroidism (HY) - patients in whom a detectable serum Tg would be expected. CONCLUSIONS: 1) Between-method Tg variability necessitates method continuity when monitoring the Tg trends of TgAb- DTC patients. 2) The presence and concentration of TgAb appeared to have a lowering effect on serum Tg measured by all methodologies (IMA, MS and RIA). 3) Since the reliability of Tg measured in the presence of TgAb is often uncertain, the TgAb trend (measured by the same method) may be a useful surrogate DTC tumor marker.

The Ratio of Peripheral Blood Natural Killer Cells is not a Solid Surrogate Immune Index in Unexplained Recurrent Miscarriage.

Background: Immunotherapies targeting peripheral natural killer (pbNK) cells in unexplained recurrent miscarriage (uRM) remain controversial. We hypothesized that the change in pbNK cell count might be a result of innate immune responses rather than a cause. Objective: To explore whether the pbNK count is significantly different in women testing positive than those testing negative for commonly studied autoimmune markers. Methods: Peripheral blood samples were collected from 302 eligible patients with uRM for the antinuclear antibody (ANA) testing determined by the enzyme-linked immunosorbent assay (ELISA), anti-thyroid peroxidase antibody (TPO-Ab) testing and anti-thyroglobulin antibody (Tg-Ab) testing determined by the chemiluminescent immunoassay, and pbNK cell testing determined by flow cytometry. The patients were divided into two groups according to the pbNK normal range, and the comparative analysis entailed an examination of the prevalence rates of autoantibodies within the high pbNK group and the normal pbNK group, followed by a comprehensive investigation into the potential correlations between autoantibodies and pbNK cells. Results: There was a positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356-19.159), while there was a negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111-0.773). TPO-Ab-positive patients had a higher pbNK cell count compared with TPO-Ab-negative patients, while ANA-positive patients had a lower pbNK cell count compared with ANA-negative patients. Conclusion: The change in pbNK cell count may be a consequence of immune responses, and there should be careful consideration in applying it as an immunotherapeutic index.