Thyroglobulin levels in COVID-19-positive patients: Correlations with thyroid function tests, inflammatory markers, and glucocorticoid use.

COVID-19 often results in generalized inflammation and affects various organs and systems. Endocrine research focused on the possible sequelae of COVID-19, with special interest given to the thyroid gland. Clinical problems such as thyroid function in non-thyroidal illness (NTI), autoimmune thyroiditis, and COVID-19-related subacute thyroiditis (SAT) quickly gained wide coverage. Thyrotoxicosis of various origins leads to the release of peripheral thyroid hormones and thyroglobulin (TG), the main glycoprotein contained within the thyroid follicular lumen. In our study, we evaluated TG levels in COVID-19-positive patients and investigated the possible relationships between TG, thyroid function tests (TFTs), and inflammatory markers. Our approach included separate subanalyses of patients who received and those who did not receive glucocorticoids (GCs). In the entire population studied, the concentration of TG tended to decrease with time (p<0.001; p1,2 = 0.025, p1,3 = 0.001, p2,3 = 0.003), and this pattern was especially clear among patients treated with GCs (p<0.001; p1,2=<0.001; p1,3=<0.001; p 2,3=<0.001). The concentration of TG differed significantly between patients treated and those not treated with GC at the second and third time points of observation (p=0.033 and p=0.001, consecutively). TG concentration did not differ between the patients with normal and abnormal TFTs. The correlations between TG, TFTs, and inflammatory markers were very limited. 19 patients had elevated TG levels, but a TFT pattern suggestive of thyrotoxicosis was not common in this group. There were no statistically significant differences between patients who met and those who did not meet the predefined combined primary endpoint.

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?

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.

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

BACKGROUND: 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. AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

Covid-induced thyroiditis.

Thyroiditis is one of the manifestations of novel Covid-19 virus. Thyroid function test (TFTs) shows typical features of hyperthyroidism. Inflammatory markers and thyroid scan give clue to the diagnosis. This report is about a 39-year-old female who presented with signs and symptoms of thyrotoxicosis along with pain in the neck, odynophagia, and intermittent fever after recovering from Covid-19 a few weeks back. She had no significant history of past medical or endocrine disease. TFTs revealed high T3 and T4 and low TSH. Thyroid scan revealed decrease uptake and ESR was 115. She was started on NSAID, steroids, and beta blocker. Four weeks later, she reverted with the resolution of symptoms and normal TFTs.

Association of thyroid dysfunction and COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis was conducted to evaluate the effect of COVID-19 on thyroid function and the role of thyroid hormones alterations in predicting the severity of COVID-19. Online databases, including Scopus, Medline/PubMed, EMBASE, Google Scholar, and Cochrane were searched up to August 2, 2022. After screening titles, abstracts, and full manuscripts, respectively, 30 reports were enrolled. The risk of bias (ROB) was evaluated using the QUADAS-2 tool. In addition, odds ratio (OR) and hazard ratio (HR) analysis for assessing the OR of abnormal thyroid function tests (TFT) in predicting the COVID-19 severity and poor outcomes. Among 30 enrolled studies, ROB of the current study is estimated low to moderate. The average number of patients in each study was 325 (range: 40-3,703), with an overall mean age of 57.6, and the female proportion of 40.4%. Overall, the pooled analysis showed that the prevalence of thyroid dysfunction among 9,707 COVID-19 cases was 15%. Among mild to moderate COVID-19 patients, 6.2% had abnormal TFT, and among patients who experienced severe to critical COVID-19, 20.8% had abnormal TFT. The pooled OR for abnormal TFT and the severity of COVID-19 obtained from 3,865 COVID-19 patients was 3.77 (2.03, 6.99). The pooled HR of TSH level of COVID-19 mortality was 1.57 (0.91, 2.72). Our results demonstrate a high prevalence of thyroid dysfunction in COVID-19, and that among patients severe cases had a 3.77-fold higher risk of abnormal TFT compared to mild to moderate COVID-19. Further studies are required to evaluate the longer-term prognostic role of thyroid dysfunction in severe COVID-19, and investigate potential therapeutic strategies.

Further understanding of thyroid function in pregnant women.

INTRODUCTION: Normal thyroid status throughout pregnancy is important for both maternal and fetal health. Despite the bulk of contemporary research honing on thyroid function in gestation and the relevant disorders, there are still gaps in our current knowledge about the etiology and treatment of thyroid diseases in pregnant women. AREAS COVERED: This article analyzes the adaptation of the thyroid gland to gestational physiological changes and attempts to explain the effect of several factors on thyroid function in pregnancy. It also stresses proper utilization and interpretation of thyroid tests during pregnancy and underlines the significance of proper screening and treatment of pregnant women aiming at favorable health outcomes. EXPERT OPINION: Appropriate strategies for diagnosing and treating thyroid disease in pregnancy are important. Laboratory thyroid testing plays a leading role, but test results should be interpreted with caution. Given the possible serious maternal and fetal/neonatal complications of thyroid disease in pregnancy, we recommend universal screening with TSH measurements of all pregnant women. Additional assessment with determination of the levels of free thyroid hormones and thyroid antibodies may be necessary under certain conditions. The economic burden of such interventions should be considered.

Thyroid Function, Inflammatory Response, and Glucocorticoids in COVID-19.

The ongoing COVID-19 pandemic calls for extensive research on various medical topics. Since the beginning of the pandemic, multiple studies investigated the impact of SARS CoV-2 on thyroid function. However, crucial data, such as trend progression over time or influence of commonly used drugs, might still be missing. We checked the thyroid function in 174 patients with PCR-confirmed COVID-19. Our research covered three separate time points of hospitalization (days 1, 4, and 10). We did not exclude patients treated with glucocorticoids but, instead, compared them with patients not treated with steroids. We correlated the results of thyroid function tests with markers of systemic inflammation. We checked if abnormal thyroid function can predict unfavorable outcomes defined as combined primary endpoint and/or secondary endpoints; the combined primary endpoint was the occurrence of death, mechanical ventilation, non-invasive ventilation, vasopressor infusion, or prolonged hospital stay, and the secondary endpoint was any of the listed events. In general, 80.46% of evaluated patients displayed abnormalities in thyroid function tests over at least one time point throughout the observation. We noticed a high prevalence of features typical for thyroid dysfunction in non-thyroidal illness (NTI). Free triiodothyronine (fT3) concentration was significantly lower in the group requiring glucocorticoids. Patients displaying abnormal thyroid function were statistically more likely to meet the predefined combined primary endpoint. We found that fT3 measured at admission could be perceived as an independent predictor of endpoint completion for all analyzed groups. Thyroid involvement is common in COVID-19. Our study supports the idea of thyroid function abnormalities being important clinical tools and allowing early recognition of possible detrimental outcomes of the disease.

Development of a prediction score (ThyroCOVID) for identifying abnormal thyroid function in COVID-19 patients.

PURPOSE: Thyroid dysfunction in COVID-19 carries clinical and prognostic implications. In this study, we developed a prediction score (ThyroCOVID) for abnormal thyroid function (TFT) on admission amongst COVID-19 patients. METHODS: Consecutive COVID-19 patients admitted to Queen Mary Hospital were prospectively recruited during July 2020-May 2021. Thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) were measured on admission. Multivariable logistic regression analysis was performed to identify independent determinants of abnormal TFTs. ThyroCOVID was developed based on a clinical model with the lowest Akaike information criteria. RESULTS: Five hundred and forty six COVID-19 patients were recruited (median age 50 years, 45.4% men, 72.9% mild disease on admission). 84 patients (15.4%) had abnormal TFTs on admission. Patients with abnormal TFTs were more likely to be older, have more comorbidities, symptomatic, have worse COVID-19 severity, higher SARS-CoV-2 viral loads and more adverse profile of acute-phase reactants, haematological and biochemical parameters. ThyroCOVID consisted of five parameters: symptoms (malaise), comorbidities (ischaemic heart disease/congestive heart failure) and laboratory parameters (lymphocyte count, C-reactive protein, and SARS-CoV-2 cycle threshold values). It was able to identify abnormal TFT on admission with an AUROC of 0.73 (95% CI 0.67-0.79). The optimal cut-off of 0.15 had a sensitivity of 75.0%, specificity of 65.2%, negative predictive value of 93.5% and positive predictive value of 28.1% in identifying abnormal TFTs on admission amongst COVID-19 patients. CONCLUSION: ThyroCOVID, a prediction score to identify COVID-19 patients at risk of having abnormal TFT on admission, was developed based on a cohort of predominantly non-severe COVID-19 patients.

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.

The potential impact of COVID-19 on thyroid gland volumes among COVID-19 survivors.

PURPOSE: Data about the effects of COVID-19 on the endocrine system are increasing over time. In the present study, we investigated the effects of COVID-19 on the thyroid gland among COVID-19 survivors by comparing them with healthy subjects. METHODS: Adult COVID-19 survivors who were managed and followed up in the Infectious Disease clinic were asked to participate in this study. COVID-19 survivors were recruited via a convenience sampling and those who agreed to participate in this study were seen by endocrinologists for assessments. The blood tests were obtained for thyroid antibodies and thyroid function tests. Thyroid ultrasonography (USG) was done by the same physician. The ellipsoid formula was used for the calculation of thyroid gland volume. RESULTS: 64 adult COVID-19 survivors and 70 control subjects were enrolled in the study. The COVID-19 survivors were evaluated at median 5.7 months (IQR: 4-6.5) (range: 2-7 months) after acute infection. The mean thyroid gland volume was significantly lower in COVID-19 survivors (10.3 ± 3.4 mL) than in the controls (14 ± 5.3 mL) (p = 0.001). There was no significant difference in free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels between the groups. Among the twelve patients who had thyroid function evaluated in acute COVID-19, fT3 values were lower in acute COVID-19 than at the time of USG evaluation (3.04 ± 0.41 vs 3.47 ± 0.31 pg/mL), (p = 0.02). Among COVID-19 survivors, mild TSH elevation was detected in 4 (6.2%) patients and all of the other COVID-19 survivors (93.7%) were euthyroid. CONCLUSIONS: At 6 months after acute COVID, COVID-19 survivors had smaller thyroid gland volume than healthy controls, and only a few of the COVID-19 survivors had abnormal 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.

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus Infection and Thyroid Disease with Follow-Up Thyroid Function and Autoantibody Testing.

BACKGROUND Thyroiditis is an important extrahepatic association in chronic hepatitis C virus (HCV) infection. There have been reports of an association between SARS-CoV-2 infection and the onset or re-activation of autoimmune hypothyroidism. Therefore, we performed this prospective observational study of 42 patients with COVID-19 infection and a history of hepatitis C virus infection and thyroid disease with follow-up thyroid function and autoantibody testing. MATERIAL AND METHODS From April 2020 to October 2020, we performed a prospective observational study of patients with cured hepatitis C virus (HCV) infection and documented thyroid disease who became infected with SARS-CoV-2 (confirmed by SARS-CoV-2 RNA detection via reverse-transcription polymerase chain reaction [RT-PCT] from the upper respiratory tract, both nasal and pharyngeal swabs). Evaluation at 1 and 3 months after SARS-CoV-2 infection included serum determination of antithyroid antibodies (anti-thyroglobulin [anti-Tg] and antithyroid peroxidase [ATPO]), thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and evaluation of thyroid medication, with dose adjustment if required. RESULTS One-month follow-up showed that both patients with autoimmune thyroiditis as well as patients without antibodies had increased ATPO levels. Also, levels of TSH, fT3, and fT4 were significantly decreased. At 3-month follow-up, levels of ATPO were decreased in all patient groups and the levels of thyroid hormones increased to normal values. CONCLUSIONS This study supports previous reports of an association between SARS-CoV-2 infection and thyroid dysfunction associated with thyroid autoantibodies. Thyroid function tests may be considered as part of the laboratory work-up in patients with COVID-19.

Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS-CoV-2 disease.

BACKGROUND: The new coronavirus 19 disease (COVID-19) represents the current worldwide emergency. According to past evidence, a simple biomarker, such as low free triiodothyronine (fT3) levels, within the framework of euthyroid sick syndrome (ESS), might help to identify patients with unfavourable outcomes. OBJECTIVE: Evaluation of ESS significance in hospitalized mild COVID-19 patients. DESIGN: Prospective study, from 1 April 2020 to 31 May 2021. PARTICIPANTS: COVID-19 patients with mild disease at hospital admission. MAIN MEASURES: At hospital admission, eligible patients underwent a complete thyroid function evaluation. Subjects with previous thyroid disease or with thyroid-interfering medications were excluded. Levels of fT3 were correlated to biochemical markers and to patient outcome, the latter considered as favourable in the event of infection recovery and unfavourable in the event of death or transfer to an intensive care unit (ICU). KEY RESULTS: Of 600 screened patients, 506 were eligible for this study. Of those, 94 (19%) died during hospitalization and 80 (18%) required a transfer to ICU. The most frequent thyroid disorder was ESS (57%). Admission levels of fT3 were significantly lower within the unfavourable outcome subgroup (p < 0.001) and were negatively associated with several poor prognostic markers, including IL-6 (p < 0.001). In Kaplan-Meier and Cox regression analyses, fT3 was independently associated with poor outcome and death (p = 0.005 and p = 0.037, respectively). A critical fT3 threshold for levels < 2.7 pmol/l (sensitivity 69%, specificity 61%) was associated with a 3.5-fold increased risk of negative outcome (95%CI 2.34-5.34). CONCLUSION: Low fT3 levels, in the framework of ESS, resulted as being a valid predictor of unfavourable outcomes in a very early stage population of COVID-19.

The Impact of Interferon Beta-1b Therapy on Thyroid Function and Autoimmunity Among COVID-19 Survivors.

Background: Some studies have indicated that interferon (IFN) may be valuable in COVID-19. We aimed to evaluate the impact of short-term IFN on incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adults without known thyroid disorder admitted to Queen Mary Hospital for COVID-19 from July 2020 to January 2021 who had thyroid function tests (TFTs) and anti-thyroid antibodies measured both on admission and at three months. Results: 226 patients were included (median age 55.0 years; 49.6% men): 135 were IFN-treated. There tended to be more abnormal TFTs upon reassessment in IFN-treated patients (8.1% vs 2.2%, p=0.080). 179 patients (65.4% IFN-treated) had a complete reassessment of anti-thyroid antibodies. There were significant increases in titres of both anti-thyroid peroxidase antibodies (anti-TPO: baseline 29.21 units [IQR: 14.97 - 67.14] vs reassessment 34.30 units [IQR: 18.82 - 94.65], p<0.001) and anti-thyroglobulin antibodies (anti-Tg: baseline 8.23 units [IQR: 5.40 - 18.44] vs reassessment 9.14 units [IQR: 6.83 - 17.17], p=0.001) in the IFN-treated group but not IFN-naïve group. IFN treatment (standardised beta 0.245, p=0.001) was independently associated with changes in anti-TPO titre. Of the 143 patients negative for anti-TPO at baseline, 8 became anti-TPO positive upon reassessment (seven IFN-treated; one IFN-naïve). Incident anti-TPO positivity was more likely to be associated with abnormal TFTs upon reassessment (phi 0.188, p=0.025). Conclusion: IFN for COVID-19 was associated with modest increases in anti-thyroid antibody titres, and a trend of more incident anti-TPO positivity and abnormal TFTs during convalescence. Our findings suggest that clinicians monitor the thyroid function and anti-thyroid antibodies among IFN-treated COVID-19 survivors, and call for further follow-up studies regarding the clinical significance of these changes.

Insights from a Prospective Follow-up of Thyroid Function and Autoimmunity among COVID-19 Survivors.

BACKGROUND: The occurrence of Graves' disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. METHODS: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. RESULTS: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. CONCLUSION: Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Normal Adrenal and Thyroid Function in Patients Who Survive COVID-19 Infection.

CONTEXT: The COVID-19 pandemic continues to exert an immense burden on global health services. Moreover, up to 63% of patients experience persistent symptoms, including fatigue, after acute illness. Endocrine systems are vulnerable to the effects of COVID-19 as many glands express the ACE2 receptor, used by the SARS-CoV-2 virion for cellular access. However, the effects of COVID-19 on adrenal and thyroid gland function after acute COVID-19 remain unknown. OBJECTIVE: Our objectives were to evaluate adrenal and thyroid gland function in COVID-19 survivors. METHODS: A prospective, observational study was undertaken at the Clinical Research Facility, Imperial College NHS Healthcare Trust, including 70 patients ≥18 years of age, at least 3 months after diagnosis of COVID-19. Participants attended a research study visit (8:00-9:30 am), during which a short Synacthen test (250 µg IV bolus) and thyroid function assessments were performed. RESULTS: All patients had a peak cortisol ≥450 nmol/L after Synacthen, consistent with adequate adrenal reserve. Basal and peak serum cortisol did not differ according to disease severity or history of dexamethasone treatment during COVID-19. There was no difference in baseline or peak cortisol after Synacthen or in thyroid function tests, or thyroid status, in patients with fatigue (n = 44) compared to those without (n = 26). CONCLUSION: Adrenal and thyroid function ≥3 months after presentation with COVID-19 was preserved. While a significant proportion of patients experienced persistent fatigue, their symptoms were not accounted for by alterations in adrenal or thyroid function. These findings have important implications for the clinical care of patients after COVID-19.

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects.

BACKGROUND: Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS: To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS: SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION: Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection.

OBJECTIVE: Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. METHODS: We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3-7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. RESULTS: The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. CONCLUSIONS: Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.