Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity

ObjectivePrecise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death.MethodsThis retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization.ResultsOf a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death.ConclusionFT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.     

Long COVID in Patients With Mild to Moderate Disease: Do Thyroid Function and Autoimmunity Play a Role?

ObjectivePost-acute sequelae of coronavirus disease 2019 (COVID-19) or long COVID (LC) is an emerging global health issue. Fatigue is a common feature. Whether thyroid function and autoimmunity play a role is uncertain. We aimed to evaluate the prevalence and predictors of LC and the potential role of thyroid function and autoimmunity in LC.MethodsWe included consecutive adults without a known thyroid disorder who were admitted to a major COVID-19 center for confirmed COVID-19 from July to December 2020. Thyroid function tests and antithyroid antibodies were measured for all patients on admission and at follow-up. LC was defined by the presence or persistence of symptoms upon follow-up.ResultsIn total, 204 patients (median age, 55.0 years; 95 men [46.6%]) were reassessed at a median of 89 days (interquartile range, 69-99) after acute COVID-19. Of the 204 patients, 41 (20.1%) had LC. Female sex (adjusted odds ratio, 2.48; P = .018) and severe acute respiratory syndrome coronavirus 2 polymerase chain reaction cycle threshold value of <25 on admission (adjusted odds ratio, 2.84; P = .012) independently predicted the occurrence of LC. Upon follow-up, most abnormal thyroid function tests in acute COVID-19 resolved, and incident thyroid dysfunction was rare. Nonetheless, we observed incident antithyroid peroxidase (anti-TPO) positivity. Although baseline or follow-up thyroid function tests were not associated with the occurrence of LC, among 172 patients with symptomatic acute COVID-19, symptom resolution was more likely in those with positive anti-TPO upon follow-up (P = .043).ConclusionLC is common among COVID-19 survivors, with females and those with higher viral load in acute COVID-19 particularly being vulnerable. The observation of incident anti-TPO positivity warrants further follow-up for thyroid dysfunction. Whether anti-TPO plays a protective role in LC remains to be elucidated.     

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

ObjectiveTo explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsThe study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate.ResultsCompared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023).ConclusionAmong critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.     

New Insights on Effects of Glucocorticoids in Patients With SARS-CoV-2 Infection

ObjectiveSince January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients.MethodsTo review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury.ResultsIn our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs.ConclusionFor clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.     

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge.MethodsThis 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index.ResultsFasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index.ConclusionOur study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.     

Correlation of Hemoglobin A1C and Outcomes in Patients Hospitalized With COVID-19

ObjectiveDiabetes is a known risk factor for severe coronavirus disease 2019 (COVID-19). We conducted this study to determine if there is a correlation between hemoglobin A1C (HbA1C) level and poor outcomes in hospitalized patients with diabetes and COVID-19.MethodsThis is a retrospective, single-center, observational study of patients with diabetes (defined by an HbA1C level of ≥6.5% or known medical history of diabetes) who had a confirmed case of COVID-19 and required hospitalization. All patients were admitted to our institution between March 3, 2020, and May 5, 2020. HbA1C results for each patient were divided into quartiles: 5.1% to 6.7% (32-50 mmol/mol), 6.8% to 7.5% (51-58 mmol/mol), 7.6% to 8.9% (60-74 mmol/mol), and >9% (>75 mmol/mol). The primary outcome was in-hospital mortality. Secondary outcomes included admission to an intensive care unit, invasive mechanical ventilation, acute kidney injury, acute thrombosis, and length of hospital stay.ResultsA total of 506 patients were included. The number of deaths within quartiles 1 through 4 were 30 (25%), 37 (27%), 34 (27%), and 24 (19%), respectively. There was no statistical difference in the primary or secondary outcomes among the quartiles, except that acute kidney injury was less frequent in quartile 4.ConclusionThere was no significant association between HbA1C level and adverse clinical outcomes in patients with diabetes who are hospitalized with COVID-19. HbA1C levels should not be used for risk stratification in these patients.     

Assessment of Insulin Infusion Requirements in COVID-19-Infected Patients With Diabetic Ketoacidosis

Background/ObjectiveCoronavirus disease 2019 (COVID-19) is thought to contribute to diabetic ketoacidosis (DKA) and worse outcomes in patients with diabetes. This study compared the cumulative insulin dose required to achieve DKA resolution in the intensive care unit among patients with type 2 diabetes and COVID-19 infection versus without COVID-19 infection.MethodsThis retrospective cohort study evaluated 100 patients—50 patients with COVID-19 in cohort 1 and 50 patients without COVID-19 in cohort 2—treated with insulin infusions for DKA at a tertiary care teaching hospital. The primary outcome was to compare the cumulative insulin dose required to achieve DKA resolution in each cohort. The secondary outcomes included time to DKA resolution, mean insulin infusion rate, and mean weight-based cumulative insulin infusion dose required to achieve DKA resolution. All endpoints were adjusted for confounders.ResultsThe mean cumulative insulin dose was 190.3 units in cohort 1 versus 116.4 units in cohort 2 (P = .0038). Patients receiving steroids had a mean time to DKA resolution of 35.9 hours in cohort 1 versus 15.6 hours in cohort 2 (P = .0014). In cohort 1 versus cohort 2, the mean insulin infusion rate was 7.1 units/hour versus 5.3 units/hour (P = .0025), whereas the mean weight-based cumulative insulin infusion dose was 2.1 units/kg versus 1.5 units/kg (P = .0437), respectively.ConclusionCOVID-19-infected patients required a significantly larger cumulative insulin dose, longer time to DKA resolution, higher insulin infusion rate, and higher weight-based insulin infusion dose to achieve DKA resolution versus non–COVID-19-infected patients with type 2 diabetes.     

Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review

ObjectiveDiabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient.MethodsA retrospective review identified 832 patients—631 inpatients and 201 outpatients—with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020. Comparisons between the outpatient and inpatient cohorts were conducted to identify risk factors associated with severity of disease determined by admission rate and mortality. Previous dipeptidyl peptidase 4 inhibitor use and disease outcomes were analyzed.ResultsRisk factors for increased admission included older age (odds ratio [OR], 1.04 [95% CI, 1.01-1.06]; P = .003), the presence of chronic kidney disease (OR, 2.32 [1.26-4.28]; P = .007), and a higher hemoglobin A1c at the time of admission (OR, 1.25 [1.12-1.39]; P < .001). Lower admission rates were seen in those with commercial insurance. Increased mortality was seen in individuals with older age (OR, 1.09 [1.07-1.11]; P < .001), higher body mass index number (OR, 1.04 [1.01-1.07]; P = .003), and higher hemoglobin A1c value at the time of diagnosis of COVID-19 (OR, 1.12 [1.01-1.24]; P = .028) and patients requiring hospitalization. Lower mortality was seen in those with hyperlipidemia. Dipeptidyl peptidase 4 inhibitor use prior to COVID-19 infection was not associated with a decreased hospitalization rate.ConclusionThis retrospective review offers the first analysis of outpatient predictors for admission rate and mortality of COVID-19 in patients with diabetes.     

Anxiety During the COVID-19 Pandemic: A Web-Based Survey of Thyroid Cancer Survivors

ObjectiveCancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors’ health care interactions and quality of life.MethodsAn anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the Thyroid Cancer Survivors’ Association, Inc website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression.ResultsFrom May 6, 2020, to October 8, 2020, 413 participants consented to take the survey; 378 (92%) met the inclusion criteria: diagnosed with thyroid cancer or noninvasive follicular neoplasm with papillary-like nuclear features, located within the United States, and completed all sections of the survey. The mean age was 53 years, 89% were women, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during the COVID-19 pandemic, as were their interactions with doctors (79%). A minority (43%) were satisfied with the information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs 56.5; P < .05) and lower for the ability to participate in social activities (46.2 vs 48.1; P < .01), fatigue (55.8 vs 57.9; P < .01), and sleep disturbance (54.7 vs 56.1; P < .01). After adjusting for confounders, higher anxiety was associated with younger age (P < .01) and change in treatment plan (P = .04).ConclusionDuring the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to treatment plans.     

Patient Perspectives on the Extent of Surgery and Radioactive Iodine Treatment for Low-Risk Differentiated Thyroid Cancer

ObjectiveTo understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI).MethodsAn online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked “what if” scenarios on core topics, including AS, extent of surgery, and indications for RAI.ResultsSurvey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS.ConclusionPatient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.     

Euthyroid Sick Syndrome as a Prognostic Indicator of COVID-19 Pulmonary Involvement,Associated With Poorer Disease Prognosis and Increased Mortality

ObjectiveThe prevalence of euthyroid sick syndrome (ESS) and its association with the prognosis of COVID-19 and mortality in patients with lung involvement in COVID-19 have not yet been elucidated.MethodsClinical and laboratory data of patients with COVID-19 with or without ESS were collected retrospectively and analyzed on admission. All subjects were admitted to the Department of Internal Diseases and Clinical Pharmacology at Bieganski Hospital between December 2020 and April 2021.ResultsIn total, 310 medical records of patients with COVID-19 were analyzed retrospectively. Among 215 enrolled patients, 82 cases of ESS were diagnosed. The patients with ESS had higher pro-inflammatory factor levels, longer hospitalizations, and a higher risk of requiring high-flow nasal oxygen therapy or intubation than the patients without ESS. The Kaplan-Meier curve indicated that the patients with ESS had a lower probability of survival when computed tomography showed ≤50% parenchymal involvement compared with that in patients without ESS. However, no differences in mortality were noted in those with more than 50% parenchymal involvement. The survival curve showed that ESS was associated with a higher risk of mortality during hospitalization.ConclusionESS is closely associated with a poor prognosis, including longer hospitalizations, more frequent intubation, transfer to the intensive care unit, and a higher mortality rate in patients with COVID-19. ESS is a potential prognostic predictor of survival, regardless of lung involvement in COVID-19.     

Residual Pyramidal Lobe Increases Stimulated Thyroglobulin and Decreases Endogenous Thyroid Stimulating Hormone Stimulation in Differentiated Thyroid Cancer Patients

ObjectiveTo determine the frequency of pyramidal lobe remnants after total thyroidectomy (TT) and the effect on stimulated thyroglobulin (Tg).MethodsThe study included 1740 differentiated thyroid cancer (DTC) patients who were followed up by our center. The department database was searched to identify DTC patients with residual pyramidal lobe after TT. All postoperative technetium-99m pertechnetate thyroid scintigraphy images were re-evaluated for pyramidal lobe residue. Serum stimulated Tg and thyroid stimulating hormone (TSH) levels measured within the first 6 months after TT were retrieved from the database.ResultsPyramidal lobe residue was detected in 10.4% of the patients who underwent TT. Evidence of the pyramidal lobe was present on preoperative ultrasonography in 1.6% of the patients with residual pyramidal lobe. Stimulated Tg in patients with pyramidal lobe residue was significantly higher than that in patients without residue (P = .01). Endogenous stimulated TSH in patients with residual pyramidal lobe was significantly lower than that in patients without residue (P = .036). In 5.7% of patients with pyramidal lobe residue, a TSH level of >30 mIU/L was not achieved, which was a significantly higher rate than that in patients without pyramidal lobe residue (P = .034) and is the level required for maximum radioiodine uptake.ConclusionPyramidal lobe residue was found in almost 10% of DTC patients. The pyramidal lobe is often missed on preoperative ultrasonography. Residual pyramidal lobe increased stimulated Tg and decreased endogenous stimulated TSH. Residual pyramidal lobe may complicate the follow-up of DTC patients.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

Assessment of the Effectiveness of a Protocol to Manage Dexamethasone-Induced Hyperglycemia Among Hospitalized Patients With COVID-19

ObjectiveWell-controlled glucose levels (ie, 70-180 mg/dL) have been associated with lower mortality from COVID-19. The addition of dexamethasone to COVID-19 treatment protocols has raised concerns about the potential negative consequences of dexamethasone-induced hyperglycemia.MethodsWe developed a protocol to guide the management of dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19. Two of the 4 medical teams managing patients with COVID-19 at a tertiary center in Saudi Arabia used the protocol and the other 2 teams continued to manage hyperglycemia at the discretion of the treating physicians (protocol and control groups, respectively). The glycemic control and clinical outcomes in 163 patients hospitalized with COVID-19 and dexamethasone-induced hyperglycemia between July 5th and September 30th, 2020, were retrospectively compared between the 2 groups.ResultsCompared to the control group, the protocol group had higher proportions of patients with well-controlled glucose across all premeals and bedtime glucose readings throughout the hospital stay. The differences in glycemic control between the 2 groups were statistically significant for fasting glucose on days 4, 5, and the discharge day; prelunch glucose on the discharge day; predinner glucose on days 3, 5, and the discharge day; and bedtime glucose on day 1 (all P < .05). After adjusting for age, sex, nationality, body mass index, Charlson score, and diabetes status, patients in the protocol group were more likely to have well-controlled glucose levels compared with those in the control group. Moreover, the in-hospital mortality was significantly lower in the protocol group (12.93%) compared to the control group (29.93%) (P < .01).ConclusionThe implementation of a protocol to manage dexamethasone-induced hyperglycemia in hospitalized patients with COVID-19 resulted in more patients achieving well-controlled glucose levels and was associated with lower mortality from COVID-19.     

Increased Incidence and Severity of New Graves Disease Diagnoses in Youth During the COVID-19 Pandemic

ObjectiveGraves disease (GD), an autoimmune disease of the thyroid, is likely caused by a combination of genetic predisposition and environmental triggers. Recent data suggest that COVID-19 may be associated with the development of autoimmune disease. The aim of this study was to assess the incidence and characteristics of new GD diagnoses in youth prior to and during the COVID-19 pandemic.MethodsWe performed a retrospective chart review of all new GD diagnoses in patients aged 0 to 18 years diagnosed at a tertiary care pediatric hospital between January 1, 2018, and December 31, 2021.ResultsOver a 4-year period, 51 patients had been diagnosed with new-onset GD. We observed an increased incidence in new-onset GD during the pandemic compared with that in the 2 prior years (P = .01). During the pandemic period, heart rates (P = .03) as well as systolic (P = .005) and diastolic (P = .01) blood pressures were higher at initial evaluation, patients more frequently reported palpitations (P = .03) and tremors (P = .04), and an increased proportion of patients required beta-blockade treatment at diagnosis (P = .002). The percentage of patients requiring thionamide treatment and thionamide doses had been similar over time.ConclusionWe identified an increase in new-onset pediatric GD diagnoses during the COVID-19 pandemic. In addition, youths had increased severity of symptoms and more frequently required beta-blockade treatment at diagnosis. Further study of the relationship between COVID-19 and autoimmune thyroid disease is needed.     

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study

ObjectiveAlthough the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up.MethodsIn this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons.ResultsThis study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease.ConclusionApplying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.     

Bradyarrhythmias in patients with COVID-19: A case series

Novel coronavirus disease (COVID-19) can have variety of cardiac manifestations; however, less is known about the prevalence, clinical characteristics and outcomes of bradyarrhythmias in patients with COVID-19. In the present case series of bradyarrhythmia in patients with COVID-19, we report complete heart block requiring intervention in 5 patients and sinus node dysfunction in 2 patients.     

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017

BackgroundExternal beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California.MethodsA population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT.ResultsAmong the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05).ConclusionsThe use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

A cytokine super cyclone in COVID-19 patients with risk factors: the therapeutic potential of BCG immunization

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a ‘Cytokine Super Cyclone’. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of ‘trained immunity’ in early protection against SARS-CoV2.