Development Of Thyroid Dysfunction Research Articles

Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma

PurposeThyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis.MethodsPatients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study.ResultsAmong these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26–131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan–Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85–403.15) days vs 164 (95% CI 77.76–250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74–268.26) days vs 74 (95% CI 41.23–106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136–0.848), p = 0.021).ConclusionThyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis.Trial registrationThis study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.

Prevalence, Risk Factors, and Clinical and Biochemical Characteristics of Alemtuzumab-Induced Graves Disease.

Atypical Graves disease (GD) is a common complication in multiple sclerosis (MS) patients treated with alemtuzumab. We present epidemiological, clinical, and biochemical characteristics of alemtuzumab-induced GD. Retrospective follow-up study of MS patients treated with alemtuzumab from 2014 to 2020, including clinical course of GD, pregnancy outcome, and thyroid eye disease (TED). We enrolled 183 of 203 patients (90%, 68% women) treated with alemtuzumab at 4 hospitals in Norway. Seventy-five (41%) developed thyroid dysfunction, of whom 58 (77%) had GD. Median time from the first dose of alemtuzumab to GD diagnosis was 25 months (range, 0-64). Twenty-four of 58 GD patients (41%) had alternating phases of hyper- and hypothyroidism. Thyrotropin receptor antibodies became undetectable in 23 of 58 (40%) and they could discontinue antithyroid drug treatment after a median of 22 (range, 2-58) months. Conversely, 26 (44%) had active disease during a median follow-up of 39 months (range, 11-72). Two patients (3%) received definitive treatment with radioiodine, 6 (10%) with thyroidectomy. Nine developed TED (16%), 7 had mild and 2 moderate to severe disease. Four patients completed pregnancy, all without maternal or fetal complications. Patients who developed GD had a lower frequency of new MS relapses and MRI lesions than those without. GD is a very common complication of alemtuzumab treatment and is characterized by alternating hyper- and hypothyroidism. Both remission rates and the prevalence of TED were lower than those reported for conventional GD. Pregnancies were uncomplicated and GD was associated with a lower risk of subsequent MS activity.

A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.

Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction. We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in TSHB, PAX8, TPO, NKX2-5, and TSHR in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis. Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923). rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.

ПОБІЧНА ДІЯ ТЕРАПІЇ ІНГІБІТОРАМИ ИМУННИХ КОНТРОЛЬНИХ ТОЧОК НА ЩИТОПОДІБНУ ЗАЛОЗУ

Introduction. Survival of patients with advanced-stage cancers remains poor despite significant successes in targeted and chemotherapy. Immunotherapy is a systemic method of treatment that has expanded the possibilities of drug therapy for malignant tumors. Immunotherapy's side effect significantly differs from chemotherapeutic drugs and targeted therapy.
 Research rationale. One of the most common side effects is a toxic effect on the endocrine system, particularly the thyroid gland.
 Aim of the research. Conduct a systematic analysis of scientific literature on the side effects of immune checkpoint inhibitors on the thyroid gland.
 Materials and methods. A scientific search was conducted in Pubmed, Scopus, and Web of Science databases. The following search terms were used: "immune checkpoint inhibitors," "immunotherapy," "thyroid gland," and "side effects."
 Research results and discussion. Both PD-1/PD-L1 inhibitors and CTLA-4 inhibitors can cause thyroid dysfunction (hyperthyroidism or hypothyroidism). One of the meta-analyses reported no difference in the incidence of thyrotoxicity between the two drug groups. However, other meta-analyses have shown that this phenomenon is more common in patients treated with PD-1/PD-L1 inhibitors than with CTLA-4 inhibitors. In addition, scientists proved that hypothyroidism occurred statistically more often (3.8% of patients) than hyperthyroidism (1.7%). Hypothyroidism was more common in PD-1 inhibitor users than hyperthyroidism (7.0% vs. 3.2%, respectively). Patients with a history of autoimmune thyroid disease have a high risk of disease exacerbation after initiating immune checkpoint inhibitor therapy. The side effect of immune checkpoint inhibitors is developed mainly in women. The first laboratory signs of hypothyroidism are observed after 2-4 courses of immunotherapy. In most cases, the disease is asymptomatic, but in rare cases, it turns into permanent hypothyroidism and even thyroid crisis. The leading causes of destruction of the thyroid gland due to immune checkpoint inhibitors are damaged by autoantibodies or the production of thyroid-stimulating antibodies.
 Levothyroxine is prescribed at 0.8–1.6 μg/kg/day for treating hypothyroidism with clinical symptoms. For elderly patients and patients with cardiac pathology, the initial dose of the drug should be no more than 25-50 μg. Treatment with immune checkpoint inhibitors is usually continued. Treatment of thyrotoxicosis depends on the pathological mechanism that caused it. Most often, beta-blockers (atenolol and propranolol) are used to eliminate the symptoms of thyrotoxicosis. A feature of thyroiditis is its ability to transition into hypothyroidism, which can become permanent.
 Conclusions. The development of thyroid dysfunction is the most common consequence of autoimmune damage. PD-1 inhibitors are the most common cause of this condition. Usually, the disorders are asymptomatic and have the first degree of severity. Timely appointment for hormone replacement therapy allows the effective continuation of immunotherapy. However, some conditions may be refractory to such treatment, requiring steroid therapy and discontinuation of immunotherapy.

HOW THYROID PROFILE IS AFFECTED BY DIABETIC MELLITUS: A CROSS SECTIONAL STUDY

Background: Diabetes mellitus and thyroid illnesses are the two endocrine conditions that are seen in clinical practice the most frequently. Patients frequently have a tendency to suffer from both diabetes mellitus and thyroid dysfunction at the same time. This article illustrates why it is important to recognize the interdependent relationship that exists between thyroid illness and diabetes. Method: Present study was conducted among 193 T2DM patients. Patients’ last three month glucose level was measured by HBA1c and thyroid dysfunction evaluated by thyroid profiling. Association and prediction of different variables for developing thyroid dysfunction among diabetic patients was calculated using chi-square, t test and ROC curve. Result: Out of 193, 47 patients had thyroid dysfunction, majority 22(11.4%) had subclinical hypothyroidism. 13(6.7%) had Hypothyroidism, 6(3.1%) had subclinical Hyperthyroidism, 3(1.5%) had Hyperthyroidism and 3(1.5%) patients were euthyroid. The prevalence of established thyroid disease was higher in females 32 (68.1%). Out of 47 patients with thyroid dysfunction, 39(82.9%) patients had HBA1C >6.5%. Conclusion: Age >50 years and female gender played as risk factor for developing thyroid dysfunction among patients with T2DM. HBA1C >6.5% and TSH more than 3.65mIU/L was independent risk factor for predicting thyroid dysfunction in T2DM.

Antiseptic solutions for skin preparation during central catheter insertion in neonates.

Central venous catheters (CVC) are associated with potentially dangerous complications such as thromboses, pericardial effusions, extravasation, and infections in neonates. Indwelling catheters are amongst the main risk factors for nosocomial infections. The use of skin antiseptics during the preparation for central catheter insertion may prevent catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). However, it is still not clear which antiseptic solution is the best to prevent infection with minimal side effects. To systematically evaluate the safety and efficacy of different antiseptic solutions in preventing CRBSI and other related outcomes in neonates with CVC. We searched CENTRAL, MEDLINE, Embase, and trial registries up to 22 April 2022. We checked reference lists of included trials and systematic reviews that related to the intervention or population examined in this Cochrane Review. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cluster-RCTs were eligible for inclusion in this review if they were performed in the neonatal intensive care unit (NICU), and were comparing any antiseptic solution (single or in combination) against any other type of antiseptic solution or no antiseptic solution or placebo in preparation for central catheter insertion. We excluded cross-over trials and quasi-RCTs. We used the standard methods from Cochrane Neonatal. We used the GRADE approach to assess the certainty of the evidence. We included three trials that had two different comparisons: 2% chlorhexidine in 70% isopropyl alcohol (CHG-IPA) versus 10% povidone-iodine (PI) (two trials); and CHG-IPA versus 2% chlorhexidine in aqueous solution (CHG-A) (one trial). A total of 466 neonates from level III NICUs were evaluated. All included trials were at high risk of bias. The certainty of the evidence for the primary and some important secondary outcomes ranged from very low to moderate. There were no included trials that compared antiseptic skin solutions with no antiseptic solution or placebo. CHG-IPA versus 10% PI Compared to PI, CHG-IPA may result in little to no difference in CRBSI (risk ratio (RR) 1.32, 95% confidence interval (CI) 0.53 to 3.25; risk difference (RD) 0.01, 95% CI -0.03 to 0.06; 352 infants, 2 trials, low-certainty evidence) and all-cause mortality (RR 0.88, 95% CI 0.46 to 1.68; RD -0.01, 95% CI -0.08 to 0.06; 304 infants, 1 trial, low-certainty evidence). The evidence is very uncertain about the effect of CHG-IPA on CLABSI (RR 1.00, 95% CI 0.07 to 15.08; RD 0.00, 95% CI -0.11 to 0.11; 48 infants, 1 trial; very low-certainty evidence) and chemical burns (RR 1.04, 95% CI 0.24 to 4.48; RD 0.00, 95% CI -0.03 to 0.03; 352 infants, 2 trials, very low-certainty evidence), compared to PI. Based on a single trial, infants receiving CHG-IPA appeared less likely to develop thyroid dysfunction compared to PI (RR 0.05, 95% CI 0.00 to 0.85; RD -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 10 to 50; 304 infants). Neither of the two included trials assessed the outcome of premature central line removal or the proportion of infants or catheters with exit-site infection. CHG-IPA versus CHG-A The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI when applied on the skin of neonates prior to central line insertion (RR 0.80, 95% CI 0.34 to 1.87; RD -0.05, 95% CI -0.22 to 0.13; 106 infants, 1 trial, low-certainty evidence) and CLABSI (RR 1.14, 95% CI 0.34 to 3.84; RD 0.02, 95% CI -0.12 to 0.15; 106 infants, 1 trial, low-certainty evidence), compared to CHG-A. Compared to CHG-A, CHG-IPA probably results in little to no difference in premature catheter removal (RR 0.91, 95% CI 0.26 to 3.19; RD -0.01, 95% CI -0.15 to 0.13; 106 infants, 1 trial, moderate-certainty evidence) and chemical burns (RR 0.98, 95% CI 0.47 to 2.03; RD -0.01, 95% CI -0.20 to 0.18; 114 infants, 1 trial, moderate-certainty evidence). No trial assessed the outcome of all-cause mortality and the proportion of infants or catheters with exit-site infection. Based on current evidence, compared to PI, CHG-IPA may result in little to no difference in CRBSI and mortality. The evidence is very uncertain about the effect of CHG-IPA on CLABSI and chemical burns. One trial showed a statistically significant increase in thyroid dysfunction with the use of PI compared to CHG-IPA. The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI and CLABSI when applied on the skin of neonates prior to central line insertion. Compared to CHG-A, CHG-IPA probably results in little to no difference in chemical burns and premature catheter removal. Further trials that compare different antiseptic solutions are required, especially in low- and middle-income countries, before stronger conclusions can be made.

The Spectrum of Thyroid Function Tests and Autoantibodies During Hospitalization and After Six Months of Discharge in COVID-19 Patients: Does COVID-19 Trigger Autoimmunity?

ABSTRACT Objective The aim of the study was to investigate thyroid function test (TFT) results and anti-thyroid antibody titers in acutely infected COVID-19 patients, as well as the changes in TFT and autoantibody results during the 6-months recovery period among survivors. Patients and Design A total of 163 adult COVID-19 patients and 124 COVID-19 survivors were evaluated in terms of TFT (thyroid stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) and anti-thyroid antibodies (anti-thyroglobulin [anti-Tg] and anti-thyroid peroxidase [anti-TPO]). Results Thyroid dysfunction was noted in 56.4% of patients on admission, including the non-thyroidal illness syndrome (NTIS) in most cases. Presence vs. absence of thyroid dysfunction on admission was associated with significantly higher rate of severe disease (p < 0.001), while severe vs. mild-to-moderate disease was associated with significantly lower serum fT3 levels (p = 0.001). Overall, 94.4% of survivors were euthyroid at the time of 6 months post-discharge, while in some patients, the post-COVID-19 recovery period was also associated with significantly increased anti-TPO titers and the presence of new-onset or persistent subclinical hypothyroidism. Conclusion This is one of the few studies to evaluate TFT and autoantibodies over a 6-month period after recovery from COVID-19. The presence of emergent or persistent subclinical hypothyroidism and the significantly increased anti-TPO titers in some patients during the convalescence period suggest the need for follow-up for development of thyroid dysfunction and autoimmunity among COVID-19 survivors.

Thyroid dysfunction after immune checkpoint inhibitor treatment in a single-center Chinese cohort: a retrospective study.

Thyroid dysfunction is a common adverse event after immune checkpoint inhibitor (ICI) therapy. The clinical manifestations of thyroid immune-related adverse events (irAEs) are variable and the underlying mechanisms remain unclear. To identify the clinical and biochemical characteristics of Chinese patients with ICI-related thyroid dysfunction. We retrospectively reviewed patients with carcinoma who received ICI therapy and underwent evaluation of thyroid function during hospitalization at Peking Union Medical College Hospital between January 1, 2017 and December 31, 2020. Clinical and biochemical features were analyzed in patients who developed ICI-related thyroid dysfunction. Survival analyses were performed to determine the effect of thyroid autoantibodies on thyroid abnormalities and the impact of thyroid irAEs on clinical outcomes. The cohort included 270 patients with a median follow-up of 17.7 months; 120 (44%) of these patients developed thyroid dysfunction on immunotherapy. The most common thyroid irAE was overt hypothyroidism (with/without transient thyrotoxicosis), which occurred in 38% of patients (n = 45), followed by subclinical thyrotoxicosis (n = 42), subclinical hypothyroidism (n = 27), and isolated overt thyrotoxicosis (n = 6). The median time to first clinical presentation was 49 days (interquartile range 23, 93) for thyrotoxicosis and 98 days (interquartile range 51, 172) for hypothyroidism. In patients treated with PD-1 inhibitors, hypothyroidism was strongly associated with younger age (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.29-0.67; P < 0.001), previous thyroid disease (OR 4.30, 95% CI 1.54-11.99; P = 0.005), and a higher baseline thyroid-stimulating hormone level (OR 2.76, 95% CI 1.80-4.23; P < 0.001). Thyrotoxicosis was only associated with the baseline thyroid-stimulating hormone (TSH) level (OR 0.59, 95% CI 0.37-0.94; P = 0.025). Thyroid dysfunction after initiation of ICI therapy was associated with better progression-free survival (hazard ratio [HR] 0.61, 95% CI 0.44-0.86; P = 0.005) and overall survival (hazard ratio 0.67, 95% CI 0.45-0.99; P = 0.046). Anti-thyroglobulin antibody positivity increased the risk of thyroid irAEs. The occurrence of thyroid irAEs with diverse phenotypes is common. Distinct clinical and biochemical characteristics suggest heterogeneity among different subgroups of thyroid dysfunction, which requires further research to explore the under mechanism.

Immune Checkpoint Inhibitor-induced Thyroid Disorders: A Single Center Experience.

Immune checkpoint inhibitors (ICI) foster T lymphocytes to fight cancer, but they can also trigger immune-related adverse events (irAE) in various organs, including thyroid dysfunction that can manifest itself in terms of both hyperthyroidism and hypothyroidism or subclinical disease. Based on previous observations, this study evaluated the impact of oncological immunotherapy on the development of thyroid dysfunction in a cohort of patients treated with ICI at our institution. We collected 10 cases of thyroid irAE that emerged from 24 cancer patients treated with immunotherapy, belonging to a cohort of 120 patients who were sent to our clinic by the Oncology Department of our institution, between December 2016 and March 2020. From the analysis of the data, thyroid irAEs emerged after a median time of 9 weeks, and they occurred mainly in females. Regardless of the initial presentation (thyroiditis with thyrotoxicosis, hypothyroidism, or worsening of the previous subclinical hypothyroidism), later all patients developed persistent hypothyroidism which required hormone replacement therapy with levothyroxine. This finding was confirmed by a statistically significant increase in the median value of TSH (thyroid-stimulating hormone) between the pre-ICI treatment and subsequent phases and, for the first time, by a reduction in the median value of the thyroid volume estimated by neck ultrasound, a sign of destructive thyroiditis. Our results confirm that patients undergoing immunotherapy should be monitored for potential thyroid dysfunction with biochemical assessments and changes in thyroid volume estimated by ultrasound could be helpful in the diagnostic work-up.

Iodinated Contrast Administration and Risks of Thyroid Dysfunction: A Retrospective Cohort Analysis of the U.S. Veterans Health Administration System.

Background: Iodine-induced thyroid dysfunction is a potential risk among susceptible individuals. Iodinated contrast media is a common source of an acute iodine load used in the health care setting and is frequently required for diagnostic computed tomography scans, coronary angiograms, and other radiologic studies. However, the epidemiologic risks of iodine-thyroid dysfunction have not been fully established in the United States. Methods: This population-based retrospective cohort study used the U.S. Veterans Health Administration database between 1998 and 2021 and included adults aged ≥18 years with a serum thyrotropin (TSH) measurement. Multivariable logistic regression was used to ascertain the risk of incident thyroid dysfunction (defined by repeated measurements of serum thyroid function) following iodine exposure, adjusting for age, sex, race/ethnicity, baseline serum TSH concentration, and duration between baseline and follow-up TSH concentration. Results: The cohort was composed of N = 4,253,119 veterans (mean ± SD = 63.5 ± 14.3 years; 92.9% men; 65.6% non-Hispanic Whites) with 8,729,155 corresponding pairs of serum TSH measurements, from which there were 499,897 TSH pairs with intervening iodine exposure. Thyroid dysfunction occurred in 4.8% of those pairs who had received iodine contrast and 3.6% of those without iodine exposure. Iodinated exposure was associated with an increased risk of thyroid dysfunction (odds ratio [OR] = 1.39, 95% confidence intervals [CI] = 1.37-1.41, p < 0.001) and consistent for all types of serum thyroid dysfunction (overt or subclinical hypo-/hyperthyroidism). Men were at higher risk for the development of thyroid dysfunction than women (men: OR = 1.42, 95% CI = 1.40-1.44; women: OR = 1.16, 95% CI = 1.11-1.21; p-for-interaction <0.001). Conclusions: In this largest analysis of U.S. adults to date, iodine exposure was associated with only clinically small absolute increased risks of thyroid dysfunction, particularly in men. These findings suggest that screening of thyroid function following iodinated contrast administration should be targeted to high-risk individuals.

Tumor PD-L1 expression and molecular profiling are not associated with immune checkpoint inhibitor-induced thyroid dysfunction in advanced NSCLC patients.

Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), however are frequently associated with thyroid immune-related adverse events (IRAEs). We investigated the association between patient characteristics, tumor PD-L1 expression and molecular profile with the development of thyroid IRAEs in NSCLC patients. Methods: Single center, retrospective study including 107 NSCLC patients treated with PD-1/PD-L1 inhibitors from April 2016 to July 2020. All patients were euthyroid at baseline with at least two TSH measurements post-treatment initiation. The primary outcome was the difference in tumor PD-L1 expression in patients who developed any thyroid IRAEs versus those who remained euthyroid. Additional outcomes included development of overt thyroid dysfunction, the association of specific molecular alterations with thyroid IRAEs, and onset of thyroid IRAEs as a function of tumor PD-L1 expression. Results: Overall, 37 (34.6%) patients developed any thyroid dysfunction and 18 (16.8%) developed overt thyroid dysfunction. Tumor PD-L1 staining intensity was not associated with thyroid IRAEs. TP53 mutation was less likely to be associated with any thyroid dysfunction (p < 0.05) and no association was found between EGFR, ROS, ALK or KRAS mutations. There was no association between PD-L1 expression and time to develop thyroid IRAEs. Conclusion: PD-L1 expression is not associated with the development of thyroid dysfunction in advanced NSCLC patients treated with ICIs, suggesting that thyroid IRAEs are unrelated to tumor PD-L1 expression.

Thyroid dysfunction with atezolizumab plus bevacizumab after lenvatinib in hepatocellular carcinoma: A case series

Atezolizumab plus bevacizumab is the recommended first-line treatment for unresectable hepatocellular carcinoma, based on guidelines from the Barcelona Clinic Liver Cancer prognosis and treatment strategy. However, atezolizumab plus bevacizumab may be used after administration of lenvatinib. Here, we present four patients who developed thyroid dysfunction after second-line treatment with atezolizumab plus bevacizumab, but not after lenvatinib alone. The patients were treated with lenvatinib and/or atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma at Showa University Northern Yokohama Hospital. Of patients treated with only lenvatinib or atezolizumab plus bevacizumab, 2/18 (11%) and 4/15 (27%) developed thyroid dysfunction, respectively. All four patients treated with atezolizumab plus bevacizumab after lenvatinib developed hypothyroidism after 2-14 doses of atezolizumab plus bevacizumab. Three patients developed Grade 2 symptoms and were treated with levothyroxine sodium. In patients with hepatocellular carcinoma, the incidence of thyroid dysfunction may be higher among patients treated with atezolizumab plus bevacizumab after lenvatinib than those treated with lenvatinib or atezolizumab plus bevacizumab alone.

The role of systemic immune activation in the development of thyroid dysfunction in COVID-19

The research of cytokine-induced thyropathies in the midst of continuing coronavirus infection (COVID-19) pandemic is a very important and urgent problem. On the one hand, COVID-19 is often accompanied by a massive overproduction of cytokines, so we can expect an enhanced cytokines effects impact on the thyroid gland. On the other hand, it is possible that biological therapy with tocilizumab, which has a powerful immunosuppressive effect, plays a protective role to the development of cytokines-induced thyropathies amidst COVID-19. The results of the study should be the starting point for understanding the mechanisms of possible compromise of thyroid function during COVID-19. The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, FT3 and FT4 values, and patient survival. This retrospective, single-center study included 122 patients hospitalized at the National Medical Research Center for Endocrinology with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, FT3, FT4, antibodies to thyroid peroxidase, antibodies to the TSH receptor (AT-recTSH). The markers of the inflammatory process were assessed: interleukin-6, C-reactive protein, the degree of lung tissue damage according to multispiral computed tomography of the lungs, the percentage of blood oxygen saturation (SpO2), the treatment outcomes. Five (4%) patients were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with interleukin-6 (r=-0.221; p=0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p=0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. This study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate.

ODP468 Checkpoint Inhibitor Immunotherapy- related Thyroid Disorders and Iodine Contrast Studies

Abstract Introduction Checkpoint Inhibitor Immunotherapy (CII) has been linked to multiple endocrinopathies. Thyroid dysfunction is more frequently associated with anti-PD-1 and anti-PD-L1 monoclonal antibody use, yet there are no good predictors for the development of thyroid complications after immunotherapy treatment. Iodinated contrast studies have been related to the development of thyroid dysfunction, and are frequently used in the oncology patient population for surveillance of malignancy and response to treatment. Methodology and Results We conducted a retrospective observational study to identify any potential association between the development of thyroid dysfunction and exposure to iodinated contrast studies in patients receiving CII. A chart review was conducted from 2012-2020. Data analysis was performed using Chi-square. Using ICD codes, 236 patients with new thyroid dysfunction after initiation of CII, and no alternative etiology for the thyroid dysfunction, were included. Out of these, 162 (68.6%) patients developed hypothyroidism, 71 (30%) developed thyrotoxicosis initially and subsequently developed hypothyroidism, and 3 (1.27%) developed hyperthyroidism. Of the total patients who developed thyroid dysfunction following CII, 145 vs.91 patients received ≥3 contrast studies, (p. 0. 0004). Discussion These findings suggest that there is an association with the use of three or more iodinated contrast studies and the development of thyroid dysfunction in patients receiving CII. More research is needed to identify additional predictors that could be utilized in clinical practice for earlier detection of patients at risk of developing CII related thyroid dysfunction. Conclusion Thyroid dysfunction following the use of CII, namely anti-PD-1 and anti-PD-L1 therapies, remains prevalent; however, it has been difficult to identify who is most at risk for this complication. This is the first study examining exposure to iodinated contrast and its potential contribution to CII thyroid endocrinopathy, and it warrants further investigation. Presentation: No date and time listed

PSAT235 The Role of Systemic Immune Activation in the Development of Thyroid Dysfunction in COVID-19

Abstract Background The research of cytokine-induced thyropathies in the midst of continuing COVID-19 pandemic is a very important and urgent problem. This work is based on the hypothesis that the hyperactivation of the immune system during COVID-19 is accompanied by a massive production of proinflammatory cytokines, and this could lead to thyroid gland disruption. Aim The primary endpoint is to assess the relationship between the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (T3f), and free thyroxine (T4f) with the inflammatory process markers. The secondary endpoint is the identification of an association between TSH, T3f, T4f values, and patient survival. Materials and Methods This retrospective, single-center study included 122 patients hospitalized at the National Endocrinology Research Centre with a clinical and laboratory analysis of COVID-19 and bilateral polysegmental viral pneumonia. To assess the functional status of the thyroid gland all patients underwent observation of the TSH, T3f, T4f, AT-TPO, and AT-recTSH. Additionally, the markers of the inflammatory process were assessed in all patients, including: interleukin-6 (IL-6). Results Five patients (4%) were found with subclinical thyrotoxicosis. Serum TSH values were inversely correlated with IL-6 (r: -0.221; p = 0.024). Analysis of the level of hospital mortality, stratified by TSH, revealed statistically significantly lower TSH values in the group of deceased patients (p = 0.012). The median TSH in surviving patients was 1.34 [0.85; 1.80], for the deceased 0.44 [0.29; 0.99]. Based on the hypothesis that the immunosuppressive effect of genetically engineered biological therapy may have a protective role against thyroid damage in the development of cytokine storm, a comparative analysis of TSH values in two groups of patients with cytokine storm was performed (p=0.080). Conclusion Our research shows that the trigger of thyropathies in coronavirus infection is most likely thyroid tissue damage by the proinflammatory cytokines. In addition to the pathophysiological aspects of thyrotoxicosis, this study shows some specific clinical aspects regarding the clinical relevance in patients with thyrotoxicosis and COVID-19, namely, the high hospital mortality rate. The results obtained indicate a high risk of developing cytokine-induced thyropathies in patients with COVID-19. In support of the hypothesis of thyroid tissue damage being caused by pro-inflammatory cytokines, the differences in detected TSH values rose to the level of a statistical trend in 2 groups of patients with cytokine storm (i.e., patients who received tocilizumab therapy, and patients who received symptomatic therapy). Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Anti-PD-1 Immunotherapy Changed the Spectrum of Thyroid Dysfunction during Radiotherapy in Patients with Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated their efficacy in a variety of malignancies, including nasopharyngeal carcinoma (NPC). Thyroid dysfunction is among the most common immune-related adverse event. However, presently we have a paucity of data on thyroid dysfunction associated with PD-1 blockade in non-metastatic NPC. This study aimed to study the incidence and pattern of immune-related thyroid dysfunction in non-metastatic NPC during radiotherapy <h3>Materials/Methods</h3> From January 1, 2019 to December 31, 2021, 165 pairs of non-metastatic NPC patients matching by propensity score matching (PSM) method to balance prognostic factors were included in this study: 165 cases in control group received conventional treatment (introduction chemotherapy and concurrent chemoradiotherapy), 165 cases in immunotherapy group received conventional treatment and anti-PD-1 immunotherapy before completion of radiotherapy. Thyroid function test and antithyroid antibodies were assessed prospectively before each immunotherapy cycle, beginning before the first treatment. Incidence and clinical pattern of thyroid dysfunction, and association with anti-thyroid antibodies was evaluated. <h3>Results</h3> In control group, 51 patients (30.91%) had thyroid dysfunctions. Among them, 12 patients had hypothyroidism (23.53%), 39 had thyrotoxicosis (76.47%) and none had biphasic hypothyroidism. In immunotherapy group, 47 patients (28.49%) had thyroid dysfunctions. Among them, 24 patients had hypothyroidism (51.06%), 18 had thyrotoxicosis (38.31%) and 5 had biphasic hypothyroidism (10.63%), a distinct pattern only observed in patients received immunotherapy. The positive rates of antithyroid peroxidase antibody (A-TPO) were similar between two groups, 12.12% in control group and 12.73% in immunotherapy group (<i>P</i> = 1). A-TPO was positive in 12 of 47 patients who developed thyroid dysfunction, compared with 11 of 118 who did not (25.53% vs 9.32%, <i>P</i> = 0.014). Especially, all patients with biphasic hypothyroidism had positive A-TPO, and the onset of A-TPO was earlier than that of transient hyperthyroidism. In patients with positive A-TPO and hypothyroidism or thyrotoxicosis, the A-TPO onset coincided with onset of thyroid dysfunction. <h3>Conclusion</h3> In non-metastatic NPC patients, thyroid dysfunction is common during treatment. Hypothyroidism and thyrotoxicosis are the most frequent presentations. Compared with conventional treatment, anti-PD-1 immunotherapy changed the spectrum of thyroid dysfunction but not the incidence. Patients who received anti-PD-1 immunotherapy developed a distinct pattern of thyroid dysfunction, biphasic hypothyroidism. The early elevation of A-TPO without aberrant TSH and FT4 may be a predictive marker for biphasic hypothyroidism. Our result suggested that thyroid functions should be under regular and intensive surveillance in clinical practice of anti-PD-1 immunotherapy in non-metastatic NPC patients.

Association between rheumatoid arthritis and thyroid dysfunction: A meta-analysis and systematic review.

ObjectiveRheumatoid arthritis (RA) is an autoimmune disorder. Multiple studies have investigated the risk of thyroid dysfunction in patients with RA but have reached conflicting conclusions. This systematic review aimed to determine whether patients with RA are at higher risk of thyroid dysfunction.MethodsWe comprehensively reviewed online literature databases, including PubMed, Scopus, Embase, and the Cochrane Library, from their respective inception dates to March 25, 2022. Studies that provided data on at least one case of thyroid dysfunction in RA patients and their controls were included. Based on these data, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for thyroid dysfunction in RA and non-RA patients.ResultsTwenty-nine studies met the inclusion criteria, involving a total of 35,708 patients with RA. The meta-analysis showed that, compared with non-RA patients, RA patients had an increased risk of developing thyroid dysfunction, particularly hypothyroidism (OR 2.25, 95% CI 1.78–2.84). Subgroup analysis suggested that study type and sample source of control group were the source of heterogeneity.ConclusionsPatients with RA are at increased risk of developing thyroid dysfunction, especially hypothyroidism. Routine biochemical examination of thyroid function in RA patients should be strengthened. Larger prospective studies are needed to explore the causal relationship between RA and thyroid dysfunction, and to investigate the impact of thyroid dysfunction on RA disease activity, drug efficacy, and medication safety.Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42022331142.

Vitamin D categories and postpartum thyroid function in women with hypothyroidism.

ObjectiveTo analyze the related factors of the postpartum thyroid function in women with overt hypothyroidism (OH)/subclinical hypothyroidism (SCH) and explore the effects of vitamin D categories.MethodsThyroid hormones, thyroid autoantibody, and serum 25OHD levels were continuously recorded from the first trimester of pregnancy (T1) to the 12th postpartum month. Logistic regression analysis and Cox regression analysis were used to screen the related factors of postpartum thyroid function, and the Latent Class Growth Model was performed to analyze the trajectory characteristics of serum 25OHD levels.ResultsTotally, 252 pregnant women with OH/SCH were enrolled in the study. In the 12th month postpartum, 36.5% of the patients improved thyroid function, 37.3% continued hypothyroidism, and 26.2% developed thyroid dysfunction. Vitamin D sufficiency, positive TPOAb, and positive TgAb in T1 were independent prognostic factors of postpartum thyroid function. Vitamin D sufficiency in T1 was illustrated as an independent factor of the improved postpartum thyroid function, but the protective effect for the developed postpartum thyroid dysfunction was only confirmed in TPOAb-positive patients. Cox regression analysis further confirmed the effects of vitamin D categories. Notably, the high-level 25OHD trajectory during pregnancy and postpartum could predict improved postpartum thyroid function and decrease the risk of developed postpartum thyroid dysfunction.ConclusionAppropriate vitamin D nutrition during pregnancy and postpartum may be beneficial to postpartum thyroid function.

Influence of selenium deficiency on the development of thyroid disorders - a literature review

Introduction and purpose: Selenium is essential for the proper course of many physiological and biochemical processes in the human body. It plays a large role in ensuring proper immunoendocrine function. The organ with the greatest amount of selenium per gram of tissue is the thyroid gland. This element builds enzymes involved in antioxidant processes - peroxidase, as well as deiodinases involved in the metabolism of thyroid hormones. There are scientific reports showing a beneficial effect of selenium supplementation in autoimmune diseases of the thyroid gland. The aim of this study is to summarize the current knowledge on the relationship between selenium deficiency and the development of thyroid dysfunction. Description of the state of knowledge: There is a correlation between selenium deficiency and the functioning of the thyroid gland. It has been shown that selenium levels are often lowered in patients with autoimmune thyroiditis. Research shows that selenium supplementation may lower TPOAb and TgAb antibody levels in patients with Hashimoto's disease. In patients with Graves' orbitopathy, administration of selenium resulted in delayed progression of orbitopathy and less disease severity. There are reports that supplementation with this element may also increase the effectiveness of antithyroid drugs in patients with Graves-Basedow disease. There was also an association between selenium deficiency and the development of goiter and thyroid nodules. Conclusions: Selenium plays an important role in the proper functioning of the thyroid gland. Although the specific role of selenium in the pathogenesis of thyroid disease is still under investigation, there are numerous reports saying that its deficiency may affect it. More research is needed on the relationship between selenium concentration and the regulation of thyroid function, because introducing it into the treatment regimen of thyroid disorders may give hope for better therapeutic effects.

Adverse perinatal conditions and the developmental origins of thyroid dysfunction-Lessons from Animal Models.

Nutritional, hormonal, and environmental status during development can predispose the individual to obesity and endocrine diseases later in life, an association known as metabolic programming. In general, weight loss or gain are seen in thyroid disorders, and thyroid function can be affected by body adiposity. In addition, hyper- and hypothyroidism can be related to metabolic programming. Our aim was to gather evidence that regardless of the type or critical window of metabolic imprinting, offspring exposed to certain adverse perinatal conditions have a higher risk of developing thyroid dysfunction. We reviewed literature data that relate insults occurring during pregnancy and/or lactation to short- and long-term offspring thyroid dysfunction in animal models. Few studies have addressed the hypothalamic-pituitary-thyroid axis and thyroid dysfunction related to metabolic programming. The literature shows that under- and overnutrition, exposure to endocrine disruptors, early weaning, maternal thyroid disease and maternal high-fat diet can induce alterations in offspring thyroid function in a sex-dependent manner. Based on the few available data, mainly in rodent models, we can conclude that diet, hormones, and environmental contaminants are related to the developmental origins of later thyroid dysfunction by interrupting the normal maturation of the thyroid gland.