Fatal Case of Possible Thyroid Crisis Induced by SARS-CoV-2 Infection: A Case Report.

Thyroid crisis is an emergency due to impaired thyroid function caused by various conditions, particularly infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that result in the dysfunction of various vital organs. We report a case of a 31-year-old Indonesian female with a 2-year history of hyperthyroidism with elevated thyroid-stimulating hormone (TSH) receptor antibodies. (TRAb) who developed thyroid crisis possibly in association with SARS-CoV-2 pneumonia, sepsis, and disseminated intravascular coagulation (DIC). Prior to admission, she was treated for her hyperthyroidism with propylthiouracil and had been in stable remission for a year. She was admitted to the Emergency Room with complaints of watery stools, icteric sclerae, jaundice, coughing, and shortness of breath. The physical examination showed a World Health Organization (WHO) performance score of 4, delirium, blood pressure within normal limits, tachycardia, tachypnea, axillary temperature of 36.7°C, icteric sclerae, jaundice, and exophthalmos. There was a 3 cm palpable nodule on the right side of the neck. Auscultation of the lungs revealed bilateral pulmonary rales. Abdominal examination noted a palpable liver and enlarged spleen. Laboratory tests showed thrombocytopenia, electrolyte imbalance, hypoalbuminemia and elevated transaminases. The thyroid function tests showed a suppressed TSH level with an elevated free thyroxine (FT4) level. The SARS-CoV-2 polymerase chain reaction (PCR) swab test was positive. Initial patient management was with supportive therapy that included favipiravir and anti-hyperthyroidism medication; however, despite these interventions, her condition continued to deteriorate and she died after a few hours. This case demonstrates no difference in therapy between patients with thyroid crises and COVID-19 or other infections. Proper and timely treatment is important for reducing mortality rates.

Study of thyroid function among COVID-19-affected and non-affected people during pre and post-vaccination.

The novel coronavirus COVID-19 has caused a global pandemic with many long-ranging effects on the physiological balance of the human body. The impact of COVID-19 on the thyroid axis remains uncertain. Our aim was to assess the long-term consequences of COVID-19 infection and its vaccination with thyroid hormones. Thirty laboratory-confirmed COVID-19-positive patients with no vaccination record, thirty COVID-19-negative patients with vaccination records, and ten healthy subjects were retrospectively, and cross-sectionally enrolled in this study. An ELISA assay was performed to evaluate thyroid function tests, including the total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). We found decreased levels of TT3, average or low plasma T4 levels, and standard or slightly decreased TSH levels in unvaccinated COVID-19-positive patients than in the healthy group, while the vaccinated COVID-19-negative group had normal thyroid hormone levels compared to controls. The correlation between TT3 and TSH levels gradually shifted from no association to a negative pattern in the unvaccinated COVID-19-positive group. Again, a highly significant negative correlation between TSH and TT3 was observed on days above 150, although a slight fluctuation was noted on day 90. This pilot study from Bangladesh shows that abnormalities in thyroid function can be observed during COVID-19 infection and after vaccination, which gradually recovers over time.

Nuclear Receptors, Ligands and the Mammalian B Cell.

Questions concerning the influences of nuclear receptors and their ligands on mammalian B cells are vast in number. Here, we briefly review the effects of nuclear receptor ligands, including estrogen and vitamins, on immunoglobulin production and protection from infectious diseases. We describe nuclear receptor interactions with the B cell genome and the potential mechanisms of gene regulation. Attention to the nuclear receptor/ligand regulation of B cell function may help optimize B cell responses, improve pathogen clearance, and prevent damaging responses toward inert- and self-antigens.

Poor Preoperative Nutritional Status, but Not Hormone Levels, Are Associated With Mortality After Cardiac Surgery.

OBJECTIVES: The authors' aim was to examine the preoperative hormone and nutritional status in patients undergoing elective cardiac surgery. DESIGN AND SETTINGS: The authors' research was a single-center, prospective, observational study (ClinicalTrials.gov: NCT03736499). PARTICIPANTS & INTERVENTIONS: The authors examined 252 patients who underwent elective cardiac surgery. Preoperative thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), prolactin, and testosterone levels were collected and analyzed after the surgery. The Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), and Prognostic Nutritional Index (PNI) were all calculated as a sum and groups. Frailty was calculated based on the modified Frailty Index-11. The primary outcome was overall mortality. MEASUREMENTS AND MAIN RESULTS: The mean age of the patients was 64.23 years (standard deviation: 11.07 years). Thirty-three patients (13.01%) died during the median follow-up time of 20.48 months (interquartile range: 18.90-22.98 months). Thyroid hormones were examined as continuous variables and also in 3 groups based on low, normal, and high hormone levels. Continuous TSH (p = 0.230), continuous fT3 (p = 0.492), and continuous fT4 (p = 0.657) were not significantly associated with total mortality. After adjustment for the European System for Cardiac Operative Risk Evaluation II and postoperative complications, the following nutritional scores were associated with total mortality: GNRI < 91 (adjusted hazard ratio [AHR]: 4.384; 95% confidence interval [CI]: 1.866-10.303, p = 0.001), the higher CONUT group (AHR: 1.736; 95% CI: 1.736-2.866, p = 0.031), and a PNI < 48 points (AHR: 3.465; 95% CI: 1.735-6.918, p < 0.001). The modified Frailty Index-11 was not associated with mortality. CONCLUSIONS: Before cardiac surgery, nutritional status should be assessed because the findings may help to decrease mortality. The hormone levels were not associated with mortality.

The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence.

Tissue hypoxia is one of the main pathophysiologic mechanisms in sepsis and particularly in COVID-19. Microvascular dysfunction, endothelialitis and alterations in red blood cell hemorheology are all implicated in severe COVID-19 hypoxia and multiorgan dysfunction. Tissue hypoxia results in tissue injury and remodeling with re-emergence of fetal programming via hypoxia-inducible factor-1α (HIF-1a)-dependent and -independent pathways. In this context, thyroid hormone (TH), a critical regulator of organ maturation, may be of relevance in preventing fetal-like hypoxia-induced remodeling in COVID-19 sepsis. Acute triiodothyronine (T3) treatment can prevent cardiac remodeling and improve recovery of function in clinical settings of hypoxic injury as acute myocardial infarction and by-pass cardiac surgery. Furthermore, T3 administration prevents tissue hypoxia in experimental sepsis. On the basis of this evidence, the use of T3 treatment was proposed for ICU (Intensive Care Unit) COVID-19 patients (Thy-Support, NCT04348513). The rationale for T3 therapy in severe COVID-19 and preliminary experimental and clinical evidence are discussed in this review.

Analysis of thyroid function in Japanese patients with coronavirus disease 2019.

Thyroid dysfunction that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is becoming increasingly recognized. However, only a few reports in Japan have addressed this issue to date. In this study, we sought to clarify whether infection with SARS-CoV-2 affected thyroid hormone levels and whether these hormones could be better predictors of prognosis in patients with coronavirus disease 2019 (COVID-19). Accordingly, we retrospectively examined 147 cases wherein thyroid hormones were measured at the time of admission among 848 Japanese patients with COVID-19 admitted to the Hyogo Prefectural Kakogawa Medical Center. All patients underwent thyroid function testing upon hospital admission. More than half (59.1%) of the patients were euthyroid. Twenty-four percent of patients had serum thyroid-stimulating hormone (TSH) levels lower than the reference range with normal serum free thyroxine (fT4) levels, and 3.4% of the patients had low TSH with high fT4 levels. Over 70% of the patients with moderate and severe COVID-19 had low serum free triiodothyronine (fT3) levels. Serum TSH and fT3 levels were inversely correlated with disease severity. The mortality rate in patients with low serum fT3 levels was significantly higher than that in those with normal serum fT3 levels.

Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses.

Background and Objective: Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs. Methods: We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results. Results: We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality. Conclusions: NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.

Patients With Autoimmune Thyroiditis Present Similar Immunological Response to COVID-19 BNT162b2 mRNA Vaccine With Healthy Subjects, While Vaccination May Affect Thyroid Function: A Clinical Study.

Background: This is the first study, that aimed: a) to compare immune response, namely the kinetics of neutralizing antibodies (Nabs), after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) between patients with autoimmune thyroiditis and controls, and b) to investigate changes in thyroid function in healthy subjects with no history of thyroid dysfunction before and after vaccination with BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech). Methods: The entire study consisted of two sub-studies. In the first sub-study, NAbs levels after BNT162b2 mRNA vaccination were compared between 56 patients with autoimmune thyroiditis and 56 age and gender-matched healthy controls from the day of the first dose until a period of up to three months after the second dose. In the second sub-study, thyroid hormones (T3, T4, TSH) and thyroid auto-antibodies levels (anti-TG, anti-TPO) of 72 healthy subjects with no history of thyroid disease were examined before (D1) and one month after completion of the second dose (D50). Results: Among patients with autoimmune thyroiditis, the median neutralizing inhibition on D22, immediately before second dose, was 62.5%. One month later (D50), values increased to 96.7%, while three months after the second dose NAbs titers remained almost the same (94.5%). In the healthy group, median NAbs levels at D22 were 53.6%. On D50 the median inhibition values increased to 95.1%, while after three months they were 89.2%. The statistical analysis did not show significant differences between two groups (p-values 0.164, 0.390, 0.105 for D22, D50 and three months). Regarding changes in thyroid function, the mean value for T4 before vaccination was 89.797 nmol/L and one month after the second dose was 89.11 nmol/L (p-value=0.649). On D1 the mean T3 value was 1.464 nmol/L, which dropped to 1.389 nmol/L on D50 (p-value = 0.004). For TSH, mean levels were 2.064 mIU/ml on D1 and fell to 1.840 mIU/ml one month after the second dose (p-value=0.037). Despite decrease, all thyroid hormone levels remained within the normal range. No changes were found for anti-TPO or anti-TG. Conclusions: This study provided evidence that patients with autoimmune thyroiditis present similar immunological response to COVID-19 BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) with healthy subjects, while vaccination may affect thyroid function.

The Independent Association of TSH and Free Triiodothyronine Levels With Lymphocyte Counts Among COVID-19 Patients.

Background: Both lymphopenia and thyroid dysfunction are commonly observed among COVID-19 patients. Whether thyroid function independently correlates with lymphocyte counts (LYM) remains to be elucidated. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to April 2021 who had thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and LYM measured on admission. Results: A total of 541 patients were included. Median LYM was 1.22 x 109/L, with 36.0% of the cohort lymphopenic. 83 patients (15.4%) had abnormal thyroid function tests (TFTs), mostly non-thyroidal illness syndrome (NTIS). Patients with lymphopenia had lower TSH, fT4 and fT3 levels than those without. Multivariable stepwise linear regression analysis revealed that both TSH (standardized beta 0.160, p<0.001) and fT3 (standardized beta 0.094, p=0.023), but not fT4, remained independently correlated with LYM, in addition to age, SARS-CoV-2 viral load, C-reactive protein levels, coagulation profile, sodium levels and more severe clinical presentations. Among the 40 patients who had reassessment of TFTs and LYM after discharge, at a median of 9 days from admission, there were significant increases in TSH (p=0.031), fT3 (p<0.001) and LYM (p<0.001). Furthermore, patients who had both lymphopenia and NTIS were more likely to deteriorate compared to those who only had either one alone, and those without lymphopenia or NTIS (p for trend <0.001). Conclusion: TSH and fT3 levels showed independent positive correlations with LYM among COVID-19 patients, supporting the interaction between the hypothalamic-pituitary-thyroid axis and immune system in COVID-19.

Criminal of Adverse Pregnant Outcomes: A Perspective From Thyroid Hormone Disturbance Caused by SARS-CoV-2.

Nowadays, emerging evidence has shown adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean, and perinatal death, occurring in pregnant women after getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the underlying mechanisms remain elusive. Thyroid hormone disturbance has been unveiled consistently in various studies. As commonly known, thyroid hormone is vital for promoting pregnancy and optimal fetal growth and development. Even mild thyroid dysfunction can cause adverse pregnancy outcomes. We explored and summarized possible mechanisms of thyroid hormone abnormality in pregnant women after coronavirus disease 2019 (COVID-19) infection and made a scientific thypothesis that adverse pregnancy outcomes can be the result of thyroid hormone disorder during COVID-19. In which case, we accentuate the importance of thyroid hormone surveillance for COVID-19-infected pregnant women.

[Graves' Disease]. / Morbus Basedow.

DIAGNOSIS: The diagnosis of Graves' disease is mainly based on ultrasonography and laboratory diagnostics. This includes the determination of the TSH value and the peripheral thyroid hormones. TSH receptor antibody (TRAb) measurement is highly sensitive and specific for the detection of Graves' disease (GD) and helps to distinguish from autoimmune thyroiditis (AIT). However, as recent studies show, some may AIT patients may also reveal TRAb. THERAPY: Current guidelines recommend primarily the use of thiamazol/carbimazole in GD. Due to the comparatively higher hepatotoxicity, propylthiouracil is not recommended as first line therapy. In case of relapse during 12 up to 18 months of antithyroid drug therapy or after a frustrating attempt at cessation, definitive therapy should be considered. Alternatively, in accordance with the current recommendations of the European Thyroid Association, drug therapy may be continued for up to 12 months after initial diagnosis. PREGNANCY: The treatment of active GD during pregnancy is problematic due to diaplacental crossing of peripheral thyroid hormones, TSH receptor stimulating antibodies and antithyroid drugs. According to current guidelines, PTU is recommended during the first 16 weeks of pregnancy, whereas for the 2nd and 3 rd trimester no special recommendations are given. After that, you can choose which antithyroid drug might be used. The aim of antithyroid drug therapy during pregnancy is to achieve a suppressed TSH value together with normal or slightly increased fT4 while using lowest effective dose of antithyroid drug. IMMUNE CHECKPOINT INHIBITORS (ICI): The most common endocrine side effect with this therapy is thyroid dysfunction. Hyperthyroidism; occur most frequently in combination therapy (CTLA-4 / anti-PD-1 therapy) ICI mainly causes destructive thyroiditis with lymphocytic infiltration; GD is absolutely rare in this context and only few cases are described.

How to investigate human health effects related to exposure to mixtures of per- and polyfluoroalkyl substances: A systematic review of statistical methods.

BACKGROUND: Humans are exposed to several per- and polyfluoroalkyl substances (PFAS) daily; however, most previous studies have focused on individual PFAS. Although attention to effects of exposure to mixtures of PFAS has grown in recent years, there is no consensus on the appropriate statistical methods that can be used to assess their combined effect on human health. OBJECTIVES: We aim to perform a comprehensive review of the statistical methods used in the existing studies which evaluate the association between exposure to mixtures of PFAS and any adverse human health effect. METHODS: The online databases PubMed, Embase and Scopus were searched for eligible studies, published during the last ten years (last search performed on April 08, 2021). Covidence software was used by two different reviewers to perform a title/abstract screening, followed by a full text revision of the selected papers. RESULTS: A total of 3640 papers were identified, and after the screening process, 53 papers were included in the current review. Most of the studies were published between 2019 and 2021 and were conducted mainly in North America and Europe; more than half of the studies (28 out of 53) were conducted on mother and child pairs. WQS (Weighted Quantile Sum) Regression and BKMR (Bayesian Kernel Machine Regression) were used in 36 out of 53 papers to model mixtures' effects. Health outcomes included in the studies are immunotoxicity (n = 8), fetal development (n = 7), neurodevelopment (n = 9), reproductive hormones (n = 6), thyroid hormones (n = 7), outcomes related to metabolic pathways (n = 16). CONCLUSION: Studies on human exposure to PFAS as complex mixtures and health consequences have substantially increased in the last few years. Based on our findings, we propose that addressing risk from PFAS mixtures will likely require combinations of approaches and implementation of constantly evolving statistical methods. Specific guidelines and tools for quality assessment and publication of mixture observational studies are warranted.

Possible Contributions of Nongenomic Actions of Thyroid Hormones to the Vasculopathic Complex of COVID-19 Infection.

BACKGROUND: Integrin αvß3 is a cell membrane structural protein whose extracellular domain contains a receptor for L-thyroxine (T4). The integrin is expressed in rapidly dividing cells and its internalization is prompted by T4. The protein binds viruses and we have raised the possibility elsewhere that action of free T4 (FT4)-when he latter is increased in the nonthyroidal illness syndrome (NTIS) known to complicate COVID-19 infecction-may enhance cellular uptke of SARS-CoV-2 and its receptor. OBJECTIVE: Because T4 also acts nongenomically via the integrin to promote platelet aggregation and angiogenesis, we suggest here that T4 may contribute to the coagulopathy and endothelial abnormalities that can develop in COVID-19 infections, particularly when the lung is primary affected. DISCUSSION AND CONCLUSIONS: Elevated FT4 has been described in the NTIS of COVID-19 patients and may be associated with increased illness severity, but the finding of FT4 elevation is inconsistent in the NTIS literature. Circulating 3,5',3'-triiodo-L-thyronine (reverse T3, rT3) are frequently elevated in NTIS. Thought to be biologically inactive, rT3in fact stimulates cancer cell proliferation via avb3 and also may increase actin polymerization. We propose here that rT3 in the NTIS complicating systemic COVIF-19 infection may support coagulation and disordered blood vessel formation via actin polymerization.

Assessment of thyroid function of newly diagnosed SARS-CoV-2 infected patients in Nigeria.

INTRODUCTION: the outbreak and rapid spread of the novel SARS-CoV-2, the causative agent of the coronavirus disease 2019 (COVID-19), has evolved into an unprecedented global pandemic. The infection impairs several human organs and systems, however, it is not clear how it affects thyroid function. The study therefore aimed at measuring plasma levels of thyroid hormones and Hs-CRP in COVID-19 patients and apparently healthy uninfected controls to assess the possible effect of SAR-CoV-2 infection on thyroid function. METHODS: in this cross-sectional study carried out between May-August 2020, 90 consenting participants comprising 45 COVID-19 patients and 45 apparently healthy uninfected controls were recruited. Plasma FT3, FT4, TSH and Hs-CRP were measured using Enzyme Linked Immunosorbent Assay (ELISA) method. Data was analysed using SPSS version 20 and statistical significance set at p < 0.05. RESULTS: the mean plasma FT3 and TSH concentrations were significantly higher in COVID-19 patients compared to controls (p < 0.001, p < 0.001 respectively). Euthyroidism was observed in all uninfected controls, whereas 35 (77.8%) COVID-19 patients were euthyroid. Sick euthyroid and subclinical hypothyroidism was observed in 7 (15.6%) and 3 (6.7%) COVID-19 patients, respectively. CONCLUSION: though there was a preponderance of euthyroidism among COVID-19 patients, significantly higher mean plasma levels of TSH and FT3, sick euthyroid syndrome and subclinical hypothyroidism observed among some COVID-19 patients may be indicative of disease-related thyroid function changes. Hence, there is need to pay attention to thyroid function during and after treatment of COVID-19.

Correlation between inflammatory parameters and pituitary-thyroid axis in patients with COVID-19.

PURPOSE: Inflammation plays a critical role in the progression of COVID-19. Nonthyroidal illness syndrome (NTIS) has been increasingly recognized in affected patients. We aim to evaluate the correlation of thyroid hormones with markers of inflammation and association with disease outcome in hospitalized patients with COVID-19, and in two profiles of NTIS (low T3-normal/low FT4 vs. low T3-high FT4). METHODS: consecutive patients admitted to a nonintensive care unit for COVID-19 were recruited. Infection was mild in 22%, moderate in 27.1% and severe in 50.8%; 7.41% died. T4, T3, FT4, FT3, and their ratios (T3/T4, FT3/FT4) were correlated with albumin, ferritin, fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer. RESULTS: Fifty five patients (50.9% men, median age 56 years) were included. Albumin correlated positively with T3 and hormones ratios, but negatively with FT4. T3, FT3, T3/T4, and FT3/FT4 correlated inversely with ferritin, fibrinogen, ESR, CRP, LDH, and D-dimer. FT4 showed direct correlation with fibrinogen and ESR. T3/T4 was lower in severe compared to mild/moderate disease [7.5 (4.5-15.5) vs. 9.2 (5.8-18.1); p = 0.04], and lower in patients who died than in those discharged [5 (4.53-5.6) vs. 8.1 (4.7-18.1); p = 0.03]. A low T3/high FT4 profile was associated with lower albumin, higher ferritin, and severity. CONCLUSION: In this cohort, thyroid hormones correlated with inflammation and outcome. T3 and T3/T4 correlated inversely with inflammatory markers; a low T3/T4 ratio was associated with severity and poor prognosis. Patients with low T3 but high FT4 had higher ferritin, lower albumin, and more severe disease at presentation.

Association of hypothyroidism with acute COVID-19: a systematic review.

OBJECTIVE: There is an increasing body of literature on the impact of COVID-19 on the pituitary-thyroid axis. Therefore, we conducted a systematic review to assess the prevalence of hypothyroidism in patients with COVID-19. METHODS: A literature review was conducted using LitCOVID for study selection in PubMed and MEDLINE till May 2021. All relevant original articles evaluating thyroid dysfunction were included and information regarding the prevalence of hypothyroid disease in COVID-19 was retrieved from the eligible articles. RESULTS: Out of 32 articles, six articles qualified for the final analysis which included 1160 patients. There was significant heterogeneity among the included articles. Most of the patients had lower mean triiodothyronine (T3) and normal or low thyroid-stimulating hormone (TSH). Increased TSH ranged from 5.1% to 8% while low T3 was present in up to 28% of the patients. In these studies, the prevalence of altered thyroid hormones was significantly more in COVID-19 patients as compared to control groups. A positive correlation between low mean T3 and clinical severity of COVID-19 was reported. CONCLUSION: This systematic review reveals a significant proportion of hypothyroidism associated with COVID-19. Therefore, routine assessment of thyroid function is warranted in hospitalized COVID-19 patients.