Serum Antithyroglobulin Antibody Levels Are Associated with Diabetic Retinopathy among Euthyroid Type 2 Diabetes Patients: A Hospital-Based, Retrospective Study

Background. Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. Methods. This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. Results. We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05 ). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05 ). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05 ) and vice versa (33.3% vs. 18.4%, p < 0.05 ). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05 ). Conclusions. We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.

The Utility of Serum Anti-thyroglobulin Antibody and Thyroglobulin in the Preoperative Differential Diagnosis of Thyroid Follicular Neoplasm

PurposeIt is challenging to distinguish follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) before surgery due to the lack of malignant ultrasound features, the underdiagnosis by fine-needle biopsy, and the absence of definitive markers. We investigated whether thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid stimulating hormone (TSH) could help differentiate FTC from FTA.MethodsA total of 319 patients with follicular neoplasms were included. We analyzed the serum markers as continuous and categorical variables between FTC and FTA. Also, we analyzed the prevalence of FTC in different serum markers groups.ResultsThe TgAb was a risk factor of FTC. Versus the TgAb group (≤11.68 IU/mL), OR of the group (11.69-30.50 IU/mL) and the group (＞30.50 IU/mL) were 2.206 (1.114-4.369, P=0.023) and 3.247 (1.684-6.260, P＜0.001), respectively. Versus the TgAb group (≤11.68 IU/mL), the malignant prevalence of the group (＞30.50 IU/mL) was higher (13.1% vs. 32.9%, P=0.001). In TgAb (-) patients, the Tg was another risk factor of FTC. Versus the Tg group (≤38.51 ng/mL), OR of the group (＞434.60 ng/mL) was 3.836 (1.625-9.058, P=0.002); the malignant prevalence of the group (＞434.60 ng/mL) was 47.2% and higher than other groups.ConclusionsThe TgAb and Tg may have utility in the preoperative differential diagnosis of follicular neoplasm. The higher TgAb and Tg were associated with higher malignant risk. Thus, we should be cautious of preoperative TgAb and Tg in follicular neoplasm.

Two Cases of Armour Thyroid Interference in Thyroglobulin Monitoring for Thyroid Cancer

Thyroglobulin (Tg) monitoring is the biochemical standard for surveillance of recurrent differentiated thyroid cancer (DTC). Several assays are available to quantify Tg levels: immunometric assay (IMA), radioimmunoassay (RIA), and the newer liquid chromatography tandem mass spectrometry (LC-MS). It is well known that a number of entities can interfere with the accuracy of testing, and at this point in time, no one assay perfectly balances high sensitivity with low risk of interference. In this case study, we present two cases in which treatment with desiccated thyroid extract (Armour thyroid) led to a sudden elevation in Tg, which resolved when Armour thyroid was discontinued. This elevation occurred when Tg was measured with both IMA and LC-MS, which suggests direct interference from porcine Tg rather than heterophilic or thyroglobulin antibody (TgAb) interference. We suggest that patients with a history of DTC not be treated with desiccated thyroid extracts consistent with guidelines. Furthermore, more advances need to be made in the area of Tg testing to improve specificity and avoid detection of nonhuman Tg and other similar proteins.

Impact of thyroglobulin and thyroglobulin antibody assay performance on the differential classification of DTC patients

Context Measurements of thyroglobulin (Tg) and Tg antibodies are crucial in the follow-up of treated differentiated thyroid cancer (DTC) patients. Inter-assay differences may significantly impact follow-up. Objective The aim of this multicenter study was to explore the impact of Tg and Tg antibody assay performance on the differential classification of DTC patients, as described in national and international guidelines. Design Four commonly used Tg and Tg antibody assays were technically compared to reflect possible effects on patients with DTC follow-up. Storage stability at different storage temperatures was also investigated for LIAISON® and Kryptor assays, as this is an underexposed topic in current literature. Results B.R.A.H.M.S. assays yield approximately 50% lower Tg values over the whole range compared to the DiaSorin and Roche assays investigated. These differences between assays may result in potential misclassification in up to 7% of patients if fixed cut-offs (e.g. 1 ng/mL) are applied. Poor correlation was also observed between the Tg antibody assays, when the method-specific upper limits of normal are used as cut-offs. Storage of Tg and Tg antibodies was possible for three to four weeks at -20 °C and -80 °C. Calibration of the assays, however, was found to be crucial for stable results over time. Conclusions Technical aspects of Tg and Tg antibody assays, including inter-assay differences, calibration and standardization, and cut-off values, may have a significant clinical impact on the follow-up of DTC patients.

Presence of Anti-Thyroid Antibodies Correlate to Worse Outcome of Anti-NMDAR Encephalitis

ObjectiveTo investigate the characteristics and prognosis of anti-NMDAR encephalitis with the prevalence of anti-thyroid antibodies (ATAbs).MethodsThe clinical data of anti-NMDAR encephalitis patients admitted to Xuanwu Hospital from January 2012 to August 2018 was prospectively analyzed, and the patients were followed up for 24 months.ResultsA total of 120 patients were enrolled, of which 34.2% (41/120) were positive for ATAbs. The antibodies were more frequent in patients with severe disease compared to the non-severe group (51.4% vs. 25.6%, P=0.008). In addition, prevalence of ATAbs correlated with a higher incidence of disturbed consciousness, autonomic dysfunction, central hypoventilation and mechanical ventilation. The ATAbs-positive patients were also more likely to receive intravenous gamma immunoglobulin and immunosuppressor compared to the ATAbs-negative cases (P=0.006; P=0.035). Although the presence of ATAbs was associated with longer hospital stays and worse prognosis at 6 months (P=0.006; P=0.038), it had no impact on long-term patient prognosis. Positive status of anti-thyroglobulin antibody was an independent risk factor for worse prognosis at 6 months [odds ratio (OR)= 3.907, 95% CI: 1.178-12.958, P=0.026].ConclusionATAbs are prevalent in patients with anti-NMDAR encephalitis, especially in severe cases, and correlate with poor prognosis and impaired short-term neurological recovery.

КОРЕЛЯЦІЙНИЙ ЗВ’ЯЗОК МІЖ КІЛЬКІСТЮ СD3+ ТА СD4+-ЛІМФОЦИТІВ ТА РІВНЕМ ЕКСПРЕСІЇ МОНОКЛОНАЛЬНИХ АНТИТІЛ ДО ТИРОГЛОБУЛІНУ, TTF-1 ТА KІ-67 У ЩИТОПОДІБНІЙ ЗАЛОЗІ ЩУРІВ ЗА УМОВ ПРЕНАТАЛЬНОЇ ДІЇ АНТИГЕНУ

Резюме. Останнім часом невплинно зростає рівень захворюваності дітей та підлітків із патологією щитоподібної залози, особливо автоімунного генезу. Розвитку таких станів сприяє імунологічний фон, який формується під дією антигенів, у тому числі й інфекційного генезу як пре-, так і постнатально. Тож постає питання про те, як впливають різні класи лімфоцитів на фолікулярні тироцити за умов пренатальної дії тиреоїднеспецифічного антигену, про інтенсивність впливу й векторність взаємодії. Мета дослідження – за допомогою коефіцієнта кореляції Пірсона встановити наявність й інтенсивність взаємодії між імуногістохімічно визначеними СD3+ та СD4+- лімфоцитами й імуноморфологічною експресією тиреоїдспецифічних антитіл до тироглобуліну, TTF-1 та Ki-67. Матеріали і методи. Досліджували щитоподібні залози щурів лінії Вістар у віці від 1 до 60 діб після народження (162 тварини): перша група – інтактні тварини (норма); друга група – контроль, тваринам вводили внутрішньоутробно 0,9 % розчин NaCl; третя група – експериментальним тваринам вводили стафілококовий анатоксин, очищений адсорбованою рідиною (10–14 одиниць зв’язування в 1 мл, розведених 10 разів) внутрішньоутробно на 18 день вагітності. Гістологічні зрізи товщиною 4 мкм фарбували гематоксиліном та еозином, імуногістохімічно використовуючи моноклональні антитіла СD3 (5В2), CD4 (5B4), Thyroglobulin Antibody (1D4) (Tg Ab) та TTF-1 (8G7G3/1), Ki-67 (Ki-67) фірми Santa Cruz Biotechnology, Inc. та дофарбовування гематоксиліном Майєра. Морфометрію проведено з використанням мікроскопа Carl Zeiss «Primo Star» з використанням камери AxioCam, комплекс морфометричних досліджень виконували за допомогою програми Zeiss Zen (2017). Розрахунок коефіцієнта кореляції Пірсона (r) проводили за допомогою програми Microsoft Office Excel, 2010. Результати. Встановлена наявність й інтенсивність взаємодії між імуногістохімічно визначеними СD3-, СD4-, TTF-1- та Ki-67-позитивними клітинами, а також імуногістохімічною експресією тироглобуліну, які інтенсивно змінюються в період з 11 до 30 доби життя після пренатальної дії стафілококового анатоксину на організм та значно відрізняються від таких показників у інтактній і контрольній групі. До 60 доби коефіцієнти кореляції за вищезазначеними показниками значно не відрізняються у всіх групах експериментальних тварин. Висновки. Встановлено наявність корелятивного взаємозв’язку між між CD4+-лімфоцитами та TTF-1 позитивними клітинами. В інтактних тварин цей зв’язок після народження помірний і до 60-ї доби майже не змінюється. В експериментальних тварин, на відміну від інтактних, ступінь зв’язку зростає до 60-ї доби. Взаємозв’язок між TTF-1+ тироцитами й ступенем експресії антитіл до тироглобуліну (r(TTF-1:TG)) експериментальних тварин вищий, ніж у інтактних, і залишається таким до 60-ї доби життя. Ступінь взаємозв’язку між Т-лімфоцитами та проліферуючими клітинами (r(CD3:Ki-67)) після народження більший в експериментальних тварин, і поступово підвищується до 30 доби. Ступінь взаємозв’язку між CD3+-лімфоцитами й ступенем експресії антитіл до тироглобуліну (r(CD3:TG)) після народження більший в інтактних тварин, але поступово зменшується, порівняно з експериментальними, у яких була зворотна тенденція. Отже, кількісний та класовий склад Т-лімфоцитарного пулу щитоподібної залози впливає на загальну та спеціалізовану проліферацію та синтетичну активність тироцитів, що в динаміці є адаптивною реакцією у відповідь на пренатальну дію стафілококового анатоксину.

Evaluation of Thyroglobulin Antibody Normalization in Papillary Thyroid Cancer Patients Receiving High-Dose I-131 Therapy

Purpose: Thyroglobulin antibody (TgAb) elevation after I-131 ablation may be difficult to evaluate in cases of recurrence, especially in high-risk patients. This study aimed to evaluate factors contributing to TgAb normalization in papillary thyroid cancer patients receiving high-dose I-131 therapy. Methods: From September 2009 to June 2012, 98 papillary thyroid cancer patients treated with 150 mCi radioactive iodine (RAI) were retrospectively enrolled. Early (3 day) and Delayed (7 day) post-RAI neck counts and reduction ratios were measured and correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum thyroglobulin (<0.1 ng/mL) and TgAb (<10 IU/mL) were defined as having successful ablation.Results: Thirty-five patients (35.7%) had thyroiditis and 28 (28.6%) achieved ablation success. The thyroiditis group had lower neck counts in both Early and Delayed whole-body scans (WBS), and higher reduction rates than the thyroiditis-absent group. In the ablation success group, Early and Delayed neck counts were significantly higher and the reduction rate of RAI was lower than those in the ablation failure group (p < 0.05). In multivariable analysis, Delayed neck count was the only significant factor for predicting ablation failure (odds ratio = 54.37, 95% confidence interval = 1.33-14.32; p = 0.015).Conclusion: I-131 uptake in the remnant thyroid gland and thyroiditis are factors that indicate TgAb normalization and ablation success in thyroid cancer patients receiving high-dose I-131 therapy.

Longitudinal Change of Postoperative Serum Anti-thyroglobulin Antibody Levels in Patients Without Total Thyroidectomy and Remnant Ablation

Background: There is little information regarding postoperative thyroglobulin antibody (TgAb) changes in patients without a total thyroidectomy and ablation. This study aimed to analyze the longitudinal change of TgAb levels in patients with remnant thyroid.Methods: The study group were patients who had undergone a non-total thyroidectomy for a thyroid tumor from 1996 to 2018. The median follow-up period was 3.5 years (1–7.5 years). Eligible patients had a combined serum Tg and TgAb measurement at least three times biannually. We excluded patients with thyroid dysfunction at the initial diagnosis or with papillary carcinoma who had persistent or any recurrence of disease. Results: A total of 222 patients were enrolled. In the preoperative analysis, 42 (30%) patients had positive TgAb values, and 98 were negative (70%). Seventeen years after the operation, a TgAb value over 1000 IU/ml was not seen. The positive TgAb ratio was stable for 12 years (20%–30%); however, its positivity gradually increased from 13 years onward to 53.8%. The number of patients with consistently negative and positive TgAb values was 151 (68.0%) and 48 (21.6%), respectively. The number of patients with a mixture of positive and negative TgAb values was 10 (4.5%). The number of patients who changed from positive to negative values was six (2.7%) and, inversely, seven (3.2%). Conclusions: We found positivity of TgAb after surgery gradually increases over about 10 years in patients with normal remnant thyroid. We should measure both serum Tg and TgAb values concurrently for the patients with remnant thyroid tissue throughout.