TESTING A NEW FATIGUE CHECKLIST IN SLE PATIENTS FOR EVERYDAY CLINICAL PRACTICE - AN INTERIM ANALYSIS

BackgroundFatigue is a difficult subject for both physicians and patients. It is barely addressed during consultations and can therefore burden patient-physician-relations. To improve communication regarding fatigue, we developed a checklist that includes suggestions for evaluating possible causes for fatigue. In this analysis, we describe our study population and report first results 3 and 6 months after using the checklist.ObjectivesThe aims of our study are to validate the use of our newly developed fatigue checklist and to demonstrate that addressing fatigue in daily clinical practice and offering possible interventions can improve fatigue.MethodsWe recruited n=110 SLE patients with fatigue from our university hospital-based lupus reference centre in Duesseldorf. Fatigue was measured using the FSS (Fatigue Severity Scale). Our checklist included signs of depression and anxiety using the PHQ-4 (Patient Health Questionnaire), BMI (body mass index), physical activity, anemia, hypothyroidism and vitamin D deficiency. For each applicable cause, we listed possible interventions for free selection by the treating physician, such as replacement therapy (vitamin D, vitamin B12, iron, folic acid, erythropoietin), physical activity programs and psychosomatic consultations that were discussed with the patients. We re-evaluated our patients after 3 (T1) and 6 months (T2).ResultsBaseline characteristics of patients are summarized in Table 1.Table 1.BMI=body mass index, TSH=thyroidea stimulating hormone, PHQ4=patient health questionnaire (cut-off >3 points), HAQ=health assessment questionnaire, IMET= Index for measuring restrictions on social participation (higher scores point towards more restrictions on social participation), FSS=fatigue severity scale (≥4 points equal severe fatigue)N = 110n (%)Mean (SD)Age (years)49.0 (12.34)Female sex99.0 (90.0)BMI (kg/m2)25.9 (5.55)Disease duration (years)19.1 (10.05)TSH (µIU/ml)1.5 (1.05)25-OH-Vitamin D (ng/ml)39.5 (15.35)Haemoglobin (g/dl)13.0 (1.64)Sports activities>4h/week6.0 (5.5)2-4h/week18.0 (16.4)1-2h/week16.0 (14.5)<1h/week28.0 (25.5)No sport42.0 (38.2)Depression (PHQ4 score)2.3 (1.63)Anxiety (PHQ4 score)2.0 (1.71)Functional status (HAQ score)0.8 (0.49)Participation (IMET score)2.8 (2.31)Fatigue (FSS score)5.3 (1.35)After 3 and 6 months, we re-evaluated 83 patients and saw a significant reduction in fatigue measured by the FSS score (T1: mean difference estimate 0.367 and p-value <0.001;T2: mean difference estimate 0.305;p-value <0.005).Figure 1.Comparing FSS-Scores from T0, T1 and T2[Figure omitted. See PDF]ConclusionThe preliminary analysis of our study shows for the first time that incorporation of a checklist procedure into the management of patients with fatigue may improve short-term outcome after 3 and 6 months of observation. The improvement of symptoms documented in our study occurred even though the suggested exercise program and psychosomatic counseling sessions were not available for use during the current observation period because of the COVID-19 pandemic. At present, the mechanisms behind the observed effect remain unclear. Our ongoing analysis will clarify whether an additional effect on fatigue will occur after all suggested interventions resulting from the use of the checklist have been executed. Finally, it will demonstrate whether the incorporation of our checklist into routine clinical practice is capable to reduce fatigue over a prolonged time period.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.

Objective: COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods: A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results: A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P < 0.001), and 0.22 (P < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions: Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.

The prognostic utility of serum thyrotropin in hospitalized Covid-19 patients: statistical and machine learning approaches.

PURPOSE: To assess the prognostic value of serum TSH in Greek patients with COVID-19 and compare it with that of commonly used prognostic biomarkers. METHODS: Retrospective study of 128 COVID-19 in patients with no history of thyroid disease. Serum TSH, albumin, CRP, ferritin, and D-dimers were measured at admission. Outcomes were classified as "favorable" (discharge from hospital) and "adverse" (intubation or in-hospital death of any cause). The prognostic performance of TSH and other indices was assessed using binary logistic regression, machine learning classifiers, and ROC curve analysis. RESULTS: Patients with adverse outcomes had significantly lower TSH compared to those with favorable outcomes (0.61 versus 1.09 mIU/L, p < 0.001). Binary logistic regression with sex, age, TSH, albumin, CRP, ferritin, and D-dimers as covariates showed that only albumin (p < 0.001) and TSH (p = 0.006) were significantly predictive of the outcome. Serum TSH below the optimal cut-off value of 0.5 mIU/L was associated with an odds ratio of 4.13 (95% C.I.: 1.41-12.05) for adverse outcome. Artificial neural network analysis showed that the prognostic importance of TSH was second only to that of albumin. However, the prognostic accuracy of low TSH was limited, with an AUC of 69.5%, compared to albumin's 86.9%. A Naïve Bayes classifier based on the combination of serum albumin and TSH levels achieved high prognostic accuracy (AUC 99.2%). CONCLUSION: Low serum TSH is independently associated with adverse outcome in hospitalized Greek patients with COVID-19 but its prognostic utility is limited. The integration of serum TSH into machine learning classifiers in combination with other biomarkers enables outcome prediction with high accuracy.

Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study.

Objectives: Graves' disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine. Methods: Serum samples collected from seventy Japanese healthcare workers at baseline, 32 weeks after the second dose (pre-third dose), and 4 weeks after the third dose of the vaccine were analyzed. The time courses of anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibody, thyroid-stimulating hormone receptor antibody (TRAb), and thyroid function were evaluated. Anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) were additionally evaluated in thirty-three participants. Results: The median age was 50 (IQR, 38-54) years and 69% were female. The median anti-spike IgG antibody titer was 17627 (IQR, 10898-24175) U/mL 4 weeks after the third dose. The mean TRAb was significantly increased from 0.81 (SD, 0.05) IU/L at baseline to 0.97 (SD, 0.30) IU/L 4 weeks after the third dose without functional changes. An increase in TRAb was positively associated with female sex (ß = 0.32, P = 0.008) and low basal FT4 (ß = -0.29, P = 0.02) and FT3 (ß = -0.33, P = 0.004). TgAb was increased by the third dose. Increase in TgAb was associated with history of the thyroid diseases (ß = 0.55, P <0.001). Conclusions: SARS-CoV-2 BNT162b2 mRNA vaccine can disrupt thyroid autoimmunity. Clinicians should consider the possibility that the SARS-CoV-2 vaccine may disrupt thyroid autoimmunity.

Association of COVID-19 vaccination before conception with maternal thyroid function during early pregnancy: A single-center study in China.

Despite the high vaccination coverage, potential COVID-19 vaccine-induced adverse effects, especially in pregnant women, have not been fully characterized. We examined the association between COVID-19 vaccination before conception and maternal thyroid function during early pregnancy. We conducted a retrospective cohort study in Shanghai, China. A total of 6979 pregnant women were included. Vaccine administration was obtained from electronic vaccination records. Serum levels of thyroid hormone were measured by fluorescence and chemiluminescence immunoassays. Among the 6979 included pregnant women, 3470 (49.7%) received at least two doses of an inactivated vaccine. COVID-19 vaccination had a statistically significant association with both maternal serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH). Compared with unvaccinated pregnant women, the mean FT4 levels were lower in pregnant women who had been vaccinated within 3 months before the date of conception by 0.27 pmol/L (ß = -0.27, 95% confidence interval [CI], -0.42, -0.12), and the mean TSH levels were higher by 0.08 mIU/L (ß = 0.08, 95% CI, 0.00, 0.15). However, when the interval from vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum FT4 or TSH levels. Moreover, we found that COVID-19 vaccination did not significantly associate with maternal hypothyroidism. Our study suggested that vaccination with inactivated COVID-19 vaccines before conception might result in a small change in maternal thyroid function, but this did not reach clinically significant levels.

Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge.

BACKGROUND: The objectives of this study were (1) to compare TSH levels between inpatients with critical versus non-critical coronavirus disease 19 (COVID-19), and (2) to describe the status of TSH levels three months after hospitalization. METHODS: We collected data on adult patients hospitalized with COVID-19 at Amiens University Hospital. We compared TSH levels between inpatients with critical (intensive care unit admission and/or death) versus non-critical COVID-19. Thereafter, survivors were invited to return for a three-month post-discharge visit where thyroid function tests were performed, regardless of the availability of TSH measurement during hospitalization. RESULTS: Among 448 inpatients with COVID-19, TSH assay data during hospitalization were available for 139 patients without prior thyroid disease. Patients with critical and non-critical forms of COVID-19 did not differ significantly with regard to the median (interquartile range) TSH level (0.96 (0.68-1.71) vs. 1.27 mIU/L (0.75-1.79), p = 0.40). Abnormal TSH level was encountered in 17 patients (12.2%); most of them had subclinical thyroid disease. TSH assay data at the three-month post-discharge visit were available for 151 patients without prior thyroid disease. Only seven of them (4.6%) had abnormal TSH levels. Median TSH level at the post-discharge visit was significantly higher than median TSH level during hospitalization. CONCLUSIONS: Our findings suggest that COVID-19 is associated with a transient suppression of TSH in a minority of patients regardless of the clinical form. The higher TSH levels three months after COVID-19 might suggest recovery from non-thyroidal illness syndrome.

Thyroid Function and COVID-19 Susceptibility and Its Severity: A Two-Sample Mendelian Randomization Study.

Several observational studies have confirmed the relationship between thyroid hormones and coronavirus disease 2019 (COVID-19), but this correlation remains controversial. We performed a two-sample Mendelian randomization (MR) analysis based on the largest publicly available summary datasets. Summary statistics with 49 269 individuals for free thyroxine (FT4) and 54 288 for thyroid stimulating hormone (TSH) were used as exposure instruments. Genome-wide association studies of susceptibility (cases = 38 984; controls = 1 644 784), hospitalization (cases: 9986 = controls = 1 877 672), and very severe disease (cases = 5101; controls = 1 383 241) of COVID-19 were used as the outcome. We used the inverse-variance weighted (IVW) method as the primary analysis, and utilized MR-Egger regression, weighted median, and robust adjusted profile score (RAPS) for sensitivity analysis. Genetic predisposition to higher serum levels of FT4 within the normal range was negatively associated with the risk of COVID-19 hospitalization (odds ratio [OR] = 0.818; 95% CI, 0.718-0.932; P = 2.6 × 10-3) and very severe disease (OR = 0.758; 95% CI, 0.626-0.923; P = 5.8 × 10-3), but not susceptibility. There is no evidence that genetically predicted circulating TSH levels are associated with COVID-19 susceptibility and severity risk. Neither apparent pleiotropy nor heterogeneity were detected in the sensitivity analysis. In summary, we found that higher FT4 levels may reduce the risk of COVID-19 severity, suggesting that thyroid function testing may be required for patients with COVID-19.

Thyrotoxicosis occurrence in SARS-CoV-2 infection: A case report.

Introduction: Coronavirus Disease 2019 (COVID-19) is predominantly manifested as respiratory distress. There are growing reports of extrapulmonary clinical manifestations of COVID-19 in addition to the respiratory symptoms. COVID-19 has been associated with the thyroid function through Angiotensin-converting enzyme 2 (ACE2), the central mechanism through Thyroid Stimulating Hormone (TSH), and direct replication of the virus. Case presentation: A 26-year-old woman presented with complaints of palpitation and abdominal pain for three days. Because the symptoms were worsening, she was brought to the emergency room. Her temperature was 37.9 °C without any symptoms of cough, coryza, sneezing, nor headache. Physical examination revealed tremor, tachycardia with 162 beats per minute (bpm), excessive sweating, hyperreflexia of patellar reflex, and no prominent lump in the neck. Electrocardiography (ECG) showed supraventricular tachycardic rhythm (SVT) and 150 J cardioversions were performed. The ECG converted to sinus rhythm, regular, with 120 bpm. Thyroid function tests showed an elevated fT4 level (>7.77 ng/dL) and low TSH level (<0.005 µIU/mL). Chest X-ray showed slight cardiomegaly without prominent abnormality in the lungs that was confirmed with thoracic computerized tomography. The result of the rapid antigen test for COVID-19 was positive and confirmed with polymerase chain reaction testing. She was then treated in the intensive isolation room with remdesivir, anti-hyperthyroid, and supportive therapy. As her condition improved, she was shifted to a non-intensive isolation room and was discharged from the hospital at day 7. Discussion: COVID-19 could present as a thyroid crisis as the initial clinical manifestation. Clinicians should be aware that presentation of thyroid dysfunction in a patient without previous endocrine disease could be due to COVID-19 infection. Early recognition, anti-hyperthyroid therapy, and following isolation procedures for COVID-19 are required in the emergency condition.

THYROXIN AND THYROID-STIMULATING HORMONE CHANGES IN PATIENTS WITH COVID-19

Objective: Whether COVID-19 has any effect on thyroid function is still up for debate. The aim of this study was to assess thyroid function in COVID-19 patients. Materials and methods: Clinical signs, laboratory results, and computed tomography scans of the chest of patients followed up in our hospital due to COVID-19 infection, who did not have a known history of thyroid disease, were analyzed retrospectively. Prior to the initiation of treatment for COVID-19 infection, a total of 131 patients who underwent thyroid function tests and 70 healthy volunteers were included in the study as the control group. Serum free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels of COVID-19 and control groups were measured and compared. Results: When compared with the healthy control group, within the normal range, COVID-19 patients had a significantly lower TSH level and significantly higher fT4 level (p=0.001, p<0.001, respectively). When each group was compared with the control group in terms of clinical severity, it was found that TSH levels were significantly lower in the critical case group (p< 0.001), and fT4 levels were significantly higher in all levels of clinical severity of COVID-19 (mild to critical) (p<0.001, p<0.001, p=0.001, and p=0.006, respectively). Conclusion: Although TSH and fT4 levels were within the normal range in COVID-19 infection, they changed significantly. This suggests that the changes in thyroid function tests in COVID-19 did not have any clinical significance, but caution should be exercised for the transition to thyrotoxicosis in patients with borderline thyroid function tests. © 2022 A. CARBONE Editore. All rights reserved.

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.

A 33-year-old man with COVID-19 presented with subacute thyroiditis: A rare case report and literature review.

We report the first case of the novel coronavirus disease 2019 (COVID-19) presenting with subacute thyroiditis in Ghaemshar, Mazandaran Province, Iran. In our patient, with the initiation of corticosteroid therapy, the symptoms of subacute thyroiditis gradually disappeared with a slow increase in thyroid-stimulating hormone (TSH) and the gradual elimination of thyrotoxicosis. This case shows that decreased TSH and persistent thyrotoxicosis may make the patient's condition worse. Managing this complication can take several weeks and can be complicated.

Thyroid Function Abnormalities in COVID-19 Patients.

Purpose: The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods: Eighty-four hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were retrospectively enrolled in this study, among which 22 cases had complete records of thyroid hormones. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls. Results: We found that levels of total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were lower in COVID-19 patients than healthy group (p < 0.001). Besides, TSH level in COVID-19 patients was obviously lower than non-COVID-19 patients (p < 0.001). Within the group of COVID-19, 61.9% (52/84) patients presented with thyroid function abnormalities and the proportion of thyroid dysfunction was higher in severe cases than mild/moderate cases (74.6 vs. 23.8%, p < 0.001). Patients with thyroid dysfunction tended to have longer viral nucleic acid cleaning time (14.1 ± 9.4 vs. 10.6 ± 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. Conclusion: Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be partially explained by nonthyroidal illness syndrome.

A Case of Post-COVID-19 Subacute Thyroiditis.

Subacute thyroiditis is usually a self-limiting inflammatory condition. The clinical presentation varies from person to person, but usually includes neck pain or discomfort and a painful diffuse goiter. There is at times a transient episode of hyperthyroidism followed by euthyroidism and sometimes hypothyroidism. We describe the case of a previously healthy 29-year-old female presenting with symptoms consistent with subacute thyroiditis. The patient had recently recovered from a mild episode of COVID-19 infection. Labs and imaging were consistent with the clinical diagnosis of subacute thyroiditis. The patient was provided symptomatic treatment with prednisone and atenolol and had an uneventful recovery.

Graves' Thyrotoxicosis Following SARS-CoV-2 Infection.

OBJECTIVE: Graves' disease is an autoimmune thyroid disease that is thought to develop following environmental exposure in patients with genetic predisposition. Our objective is to present the first report of Graves' disease onset immediately following recovery from mild coronavirus disease 2019 (COVID-19), a close temporal occurrence that should be studied further. METHODS: We describe the clinical course and laboratory features, including thyroid function studies, antibody testing, and polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2. RESULTS: A 21-year-old woman with prediabetes, obesity, asthma, and gastroesophageal reflux disease presented to the emergency department reporting 3 days of tachycardia, palpitations, anxiety, and shortness of breath. Laboratory investigation revealed a thyroid-stimulating hormone level of 0.01 (0.30-5.00) mcIU/mL with a free thyroxine level of 3.8 (0.6-1.6) ng/dL, prompting endocrinology consultation. On physical examination, she had mild diffuse thyromegaly without tenderness and a history, which included hypothyroidism in her mother. Antibody testing results demonstrated thyroid-stimulating immunoglobulin and thyrotropin receptor antibody levels of 2.6 (<1.3) thyroid-stimulating immunoglobulin index and 17 (0.00-1.75) IU/L, respectively. Sixteen days before presenting to the ED, she was diagnosed with COVID-19 by polymerase chain reaction test after reporting typical symptoms, including fever. Infectious symptoms resolved within 10 days. She achieved clinical and laboratory improvements with a combination of methimazole and beta blocker therapy. CONCLUSION: This case documents the occurrence of Graves' thyrotoxicosis following mild symptomatic COVID-19. Whether the preceding infection is coincidental or contributed to GD development requires definitive studies. This presentation may align with the theory of a viral link in the development of autoimmune thyroid disease in those with genetic predisposition.

Delayed Onset of Central Hypocortisolism in a Patient Recovering From COVID-19.

OBJECTIVE: The objective of this report is to highlight the possible but little-known association between coronavirus disease 2019 (COVID-19) and delayed onset of central hypocortisolism, which may be of significant clinical importance. METHODS: We describe a patient who developed new-onset central hypocortisolism in the convalescent phase of mild COVID-19, which has not been previously reported. RESULTS: A 47-year-old man with recent COVID-19 upper respiratory tract infection developed new-onset persistent dyspepsia and eosinophilia for which multiple investigations were normal. He was eventually diagnosed with central hypocortisolism, as evidenced by 8 AM cortisol level of 19 nmol/L (normal, 133-537 nmol/L) and adrenocorticotropic hormone of 7.1 ng/mL (normal, 10.0-60.0 ng/mL). He was started on hydrocortisone, which led to resolution of both dyspepsia and eosinophilia. At the same time, an interesting thyroid function trend was observed-an initial increase in both free thyroxine and thyroid stimulating hormone was followed by temporary central hypothyroidism before subsequent spontaneous recovery. On follow-up 3 weeks later, the patient remained hypocortisolemic. CONCLUSION: COVID-19 may be associated with the delayed onset of central hypocortisolism in its convalescent phase. Although various mechanisms are possible, hypothalamic-pituitary activation during systemic illness, followed by a rebound decrease in activity after recovery, is consistent with the clinical course and thyroid function trend in this patient. It is essential that physicians consider endocrinopathies in the differential diagnosis of such cases, given the risk of life-threatening adrenal crises and their possible contribution to persistent symptoms following recovery from COVID-19.