Italian Association of Clinical Endocrinologists (AME) 20th National Congress

The proceedings contain 9 papers. The topics discussed include: dulaglutide and NAFLD risk reduction;correlation between plasmatic long pentraxin PTX3 and nodular thyroid disease: a preliminary report;the fructose-bisphosphate aldolase a act as autoantigen in primary autoimmune hypophysitis;cortisol deficiency in Lenvatinib treatment;side effects of mitotane treatment: a retrospective study in 35 patients with adrenocortical carcinoma in adjuvant therapy;non-functioning pituitary adenoma: do predictor factors exist?;incidence and features of adrenal crisis in a series of 133 patients with Addison's disease;serological evidence and self-reported outcomes in patients with adrenal insufficiency during the first waves of COVID-19 in the North-East Italy;and persistent effects of spironolactone after its withdrawal in patients with hyperandrogenic skin disorders.

Adjuvant Systemic Corticosteroid Therapy in Hospitalized Patients with Community-Acquired Pneumonia

The article focuses on the use of corticosteroids in the treatment of community-acquired pneumonia (CAP). Topics include the conflicting evidence on the efficacy of corticosteroids with the results of a systematic review and meta-analysis of 16 trials;and the potential benefits and risks associated with corticosteroid use which will decrease the need for mechanical ventilation, with a higher rate of hospital readmission.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care

Objective: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39;p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136;p = 0.6), antibiotic therapy (57% versus 64%;p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%;p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5];p = 0.002) and presented a higher use of vasopressors (47% versus 36%;p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%;p < 0.001) at admission, prone positioning (45% versus 36%;p = 0.04), and hydroxychloroquine (59% versus 10%;p < 0.001) and lopinavir/ ritonavir (41% versus 10%;p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%;p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave. © 2023 Associacao de Medicina Intensiva Brasileira - AMIB. All rights reserved.

Outcomes of budesonide multimatrix prescriptions in the COVID-19 pandemic

Background: Budesonide multimatrix is prescribed to treat forms of inflammatory bowel disease (IBD) during periods of relapse, and it is licensed to treat mild-to-moderate ulcerative colitis (UC). However, during the COVID-19 pandemic, there was a rise in the use of budesonide multimatrix to treat all forms of IBD after fears that systemic corticosteroid use, such as prednisolone, could increase the risk of COVID-19 severity. Methods: This audit included records of all patients who were prescribed the budesonide multimatrix Cortiment (9 mg once a day) over a year in NHS Lothian. Patients were grouped by disease activity at the point of prescription (Partial Mayo Score (PMS) less than 5 showed milder disease and above 5 showed more severe disease) and disease phenotype. The primary endpoint was response at 8 weeks from start of treatment, grouped into full response, partial response, no response and escalation. Results: The full response rate to budesonide multimatrix was 52% among all patients, but 80% in those with PMS ≤4 and only 15% in those with a PMS ≥5. By phenotype, response rates were 41% in Crohn's disease, 50% in IBD unclassified, 56% in proctitis, 56% in left-sided colitis and 51% in pancolitis. Conclusions: Budesonide multimatrix is effective to treat mild disease but is not effective in patients who are having a moderate-to-severe flare of IBD. This medication was 80% effective if the PMS was below 5, suggesting that it is very effective in mild disease.

Opinion of Brazilian physicians on the treatment of COVID-19 / Opinião de médicos brasileiros sobre o tratamento da COVID-19 / Opinión de médicos brasileños sobre el tratamiento de la COVID-19

Objetivo: Investigar a opinião de médicos brasileiros sobre o tratamento precoce da COVID-19 com hidroxicloroquina/ cloroquina e azitromicina em pacientes com suspeita clínica e sobre o tratamento com corticoterapia na fase inflamatória da doença. Métodos: Trata-se de uma pesquisa de opinião, com amostragem por conveniência, com médicos atuantes no Brasil. A coleta dos dados ocorreu no período de 26 de maio a 8 de junho de 2020 (13 dias), por meio de um formulário Google, disponibilizado publicamente nas redes sociais e aplicativos de comunicação. Realizou-se uma análise descritiva dos dados, teste de independência, teste T Student e modelo de regressão logística com análise multivariada. Resultados: A pesquisa contou com 1.020 médicos participantes, com média de 21,9 anos de formado. 72,4% dos participantes apresentaram-se a favor do tratamento precoce com hidroxicloroquina/cloroquina e azitromicina e 89,7% dos médicos apresentaram-se favoráveis ao uso da corticoterapia para o tratamento da fase inflamatória da COVID-19. Constatou-se também que participantes com maior idade, com residência médica, atuantes nas regiões Nordeste e Norte possuíam mais chances de serem favoráveis aos tratamentos. Por outro lado, profissionais especialistas em medicina intensiva, infectologia e pneumologia, além de atuantes nas unidades de terapia intensiva, mostraram-se mais desfavoráveis. Conclusão: A maioria dos médicos investigados nesta pesquisa de opinião mostrou-se a favor do tratamento precoce apresentado e do uso da corticoterapia no tratamento da COVID-19. Já os especialistas em medicina intensiva, infectologia e pneumologia e profissionais atuantes nas Unidades de Terapia Intensiva mostraram-se mais desfavoráveis.

Objective: To investigate the opinion of Brazilian physicians on the early treatment of COVID-19 with hydroxychloroquine/ chloroquine and azithromycin in patients with clinical suspicion and on the treatment with corticosteroid therapy in the inflammatory stage of the disease. Methods: This is an opinion survey conducted with a convenient sample of physicians working in Brazil. Data were collected from May 26 to June 8, 2020 (13 days) through Google forms made publicly available on social media and chat applications. Data underwent descriptive analysis, independence test, Student t-test, and a logistic regression model using multivariate analysis. Results: The survey included 1020 physicians with a mean of 21.9 years since graduation. 72.4% of the participants were in favor of early treatment with hydroxychloroquine/chloroquine and azithromycin and 89.7% of the physicians were in favor of using corticosteroid therapy to treat the inflammatory stage of COVID-19. We also observed that older participants, those who completed medical residency, and those working in the Northeast and North regions were more likely to be in favor of the treatments. On the other hand, professionals specialized in intensive care medicine, infectious diseases and pneumology and working in intensive care units were more opposed. Conclusion: Most physicians in this opinion survey were in favor of the early treatment presented and the use of corticosteroid therapy in the treatment of COVID-19. But specialists in intensive care medicine, infectious diseases and pulmonology, and professionals working in Intensive Care Units were more opposed to them.

Objetivo: Investigar la opinión de médicos brasileños sobre el tratamiento precoz de la COVID-19 con la hidroxicloroquina/ cloroquina y la azitromicina en pacientes con sospecha clínica y bajo el tratamiento de corticoterapia en la fase inflamatoria de la enfermedad. Métodos: Se trata de una investigación de opinión con la muestra de conveniencia realizada con médicos de Brasil. La recogida de datos se dio en el periodo entre 26 de mayo y 8 de junio de 2020 (13 días) a través de un formulario Google que ha estado disponible públicamente en las redes sociales y los aplicativos de comunicación. Se realizó un análisis descriptivo de los datos, la prueba de independencia, la prueba T Student y el modelo de regresión logística con el análisis multivariado. Resultados: La investigación tuvo 1.020 médicos participantes, con la media de 21,9 años de término del grado. El 72,4% de los participantes se presentaron a favor del tratamiento precoz con la hidroxicloroquina/cloroquina y la azitromicina y el 89,7% de los médicos se presentaron favorables a la utilización de la corticoterapia para el tratamiento de la fase inflamatoria de la COVID-19. Se constató también que los participantes de más edad, con el curso de residencia medica y que eran de las regiones Noreste y Norte del país eran más favorables a los tratamientos. Los profesionales especialistas de la medicina intensiva, la infectologia y la neumología, además de actuaren en las unidades de cuidados intensivos parecieron más desfavorables. Conclusión: La mayoría de los médicos investigados de esa investigación de opinión se mostró favorable al tratamiento precoz presentado y a la utilización de la corticoterapia para el tratamiento de la COVID-19. Los especialistas de la medicina intensiva, la infectología y la neumología y los profesionales de las Unidades de Cuidados Intensivos se presentaron más desfavorables a los tratamientos.

SARS-CoV-2-correlated ASGR1 is a novel potential marker for the treatment and identification of multiple human cancers

Objectives: Cancer patients are reported to be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the COVID-19 (the Corona Virus Disease 2019) patients with cancer suffer from certain serious complications. ASGR1 has been recently identified as a novel receptor of SARS-CoV-2 in human cells;however, there are limited studies on ASGR1 in various human cancers. Method(s): This study utilized a comprehensive analysis of COVID-19-related ASGR1 in multiple human cancers based on 18,589 multi-center samples. Using Wilcoxon rank-sum analysis, a difference in ASGR1 expression between cancer and control tissues was detected. Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were utilized to determine the correlation between ASGR1 expression and the clinical parameters of cancer patients. The immune relevance and potential mechanisms of ASGR1 in various cancers were also investigated. Result(s): Abnormal ASGR1 mRNA expression was observed in 16 of 20 different cancers (e.g., it was upregulated in colon adenocarcinoma but downregulated in cholangiocarcinoma;P < 0.05). ASGR1 was related to prognosis, e.g., overall survival, in 14 cancers (P < 0.05), such as adrenocortical carcinoma. The gene was also found to be a potential marker that can be utilized to distinguish eleven cancers from controls with moderate to high accuracy (e.g., the area under the curve for cholangiocarcinoma = 1.000). ASGR1 expression was related to DNA methyltransferases, mismatch repair genes, immune checkpoints, levels of tumor mutational burden, microsatellite instability, neoantigen count, and immune infiltration levels in certain cancers (P < 0.05). The gene plays a role in multiple cancers by affecting four signaling pathways, such as cytokine-cytokine receptor interaction. Cancer patients with high ASGR1 expression are sensitive to 25 drugs, including ulixertinib. Conclusion(s): SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers. Copyright © 2022 E-Century Publishing Corporation. All rights reserved.

Suicide attempt and severe depression in a patient with COVID-19, the possible effect of therapeutic regimes

Coronavirus disease 2019 (COVID-19) has different manifestations including neurologic manifestations. Lack of a suit-able therapeutic regime and administration of a variety of treatments could worsen disease manifestations. Some medical interventions besides the high level of stress and quarantined conditions could induce severe depression and even suicide attempts. Here we presented a 42-year-old man without a history of psychiatric disorders that had been admitted to the clinic due to worsening of his dyspnea. After history taking and physical examination, he had been hospitalized and interferon, corticosteroids, and other conservative treatments had been started. According to his clinical manifestations, the doses and medications had been changed the next days. On the morning of his seventh day of hospitalization he had several suicidal attempts which were not successful and after changes in his medications, starting antidepressant drugs, and visiting his family members he had been discharged without the idea of suicide and depressed mood. This report showed the important role of medical staff in monitoring the mental health of COVID-19 patients as there are many risk factors for them to develop psychiatric disturbance. They should be aware of the possible effect of drugs in the alternat-ing mood of patients and even causing suicidal thoughts. We also suggest increasing the level of tryptophan sources in meals of patients and administration of selective serotonin reuptake inhibitors in patients with signs of depression after further studies.

Cone-Beam Computed Tomography Guided Percutaneous Cryoablation to Treat Bone Metastases Due to Endocrine Tumors: A Preliminary Analysis of a Prospective Clinical Trial

Objective: To assess the efficacy and safety of CBCT-guided percutaneous cryoablation of bone metastases due to endocrine tumors. Outcomes included reduction of skeletal-related events and pain control. Method(s): This is a prospective, single arm, tertiary single-center study. Inclusion criteria included age >18 years;ECOG 0-3;mean life expectancy >one month;biopsy-proven bone metastases <7.0 cm in diameter from thyroid, adrenal and neuroendocrine tumors, with pain, hypercalcemia or at risk to develop fracture or spinal cord compression. Prior to ablation, all patients were evaluated by a pain specialist and a brief pain inventory (BPI) was obtained. Follow-up was carried out weekly for the first 8 weeks and then at 3, 6, 12 and 24 months when a BPI was obtained and observation of skeletal-related events. Result(s): This is an interim analysis of 17 patients,12 women and 5 men, mean age of 64.2+/- 12.3 years. Ten patients had papillary thyroid cancer (58.8%), 5 medullary thyroid cancer (29.4%) and 2 with adrenocortical cancer. A total of 24 lesions were treated (21 sessions);current mean follow-up time: 11.1+/- 7.3 months.Cementoplasty was carried out in three lesions;mean size lesions were 3.3 +/- 1.3 cm. Only one mild adverse event was observed (transient sciatic neuropraxia). From the group of patients included with bone pain (N= 14), a mean pre-procedural BPI was 8.3 +/- 2.1 (10 being highest score). After procedure, all patients had reduction of the pain score;complete pain relief was observed in 6 (31.6%) patients within 1-week and the other patients reported a significant reduction of BPI score: mean 2.8+/- 3.3 (1-week);0.9 +/- 1.8 (6-months). Eleven (64.7%) patients achieved complete ablation;radiation therapy was required in 2 patients and no patients required additional surgery. Pathologic fracture was observed in 2 treated lesionswhich recovered spontaneously within 1month. Six non-procedure related deaths were reported during follow-up (oncologic disease progression n = 5;Covid-19 infection n = 1);Discussion/Conclusion: Cryoablation proved to be safe and effective to treat bone metastases due to endocrine tumors, providing a rapid and durable pain palliation, local disease control, and should be considered an option to improve patient care in selected cases.

[Current and future therapeutic options for COVID-19]

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

NIGHT SWEATS IN AN ELDERLY FEMALE

CASE: 74 year old woman with history of anxiety, depression, and nonsecretory adrenal adenoma presented with two months of progressive night sweats. Initially, she described waking up damp all over, but without needing to change her sheets. Her weight had been stable, and she denied recent travel. Her recent health changes included starting sertraline and receiving the Moderna COVID vaccines. Her other medications included atorvastatin and lisinopril. Her vital signs were all within normal range and her physical exam was unremarkable. Night sweats described were mild, so work up began with checking a CBC with differential and a TSH level. Initial labs were normal. However, the patient called a week later with night sweats that were worsening. She also recalled being treated for tuberculosis at age fifteen. This prompted additional bloodwork including Quantiferon, ACTH, androstenedione, estradiol, testosterone, progesterone, and DHEAS levels, as well as urine catecholamines and metanephrines. Additionally, it was noted sertraline could be a potential cause of night sweats. The dose was halved with the goal to taper off and discontinue the medication. All lab results came back within normal limits, so CT scans of the chest/ abdomen/ pelvis were ordered, and blood cultures collected. Imaging showed an unchanged adrenal adenoma and blood cultures had no growth. Ultimately, after five months of symptoms, her night sweats completely resolved five weeks after stopping sertraline. IMPACT/DISCUSSION: When working up night sweats, first, the severity of symptoms should be determined and medications reviewed. Mild night sweats with no associated red flag symptoms (weight loss, lymphadenopathy, and fever) do not need immediate or extensive work up. Further work up is essential in the setting of any red flag symptoms. Without a clear etiology, the work up includes the following items: chest radiography along with bloodwork including Quantiferon test, CBC, TSH, HIV serology, and CRP. If these results are normal then a CT of the chest, abdomen, and pelvis could be obtained as well as a bone marrow biopsy. Little evidence exists to guide an exact order of workup for night sweats, so it remains the clinician's responsibility to determine which tests to prioritize. Classes of medications that tend to cause night sweats are cholinergics and anti-depressants. Anti-depressants most associated with night sweats include TCAs and SNRIs. Sertraline has been implicated as a cause of night sweats, but little data exists as to how often this occurs and how often severe presentations like the one described occur. Given that selective serotonin reuptake inhibitors are a first line treatment in depression, recognizing this adverse effect is important in primary care and could prevent unnecessary extensive work ups for night sweats. CONCLUSION: -An initial step in evaluating persistent night sweats should be medication review -Many antidepressants including sertraline can have night sweats as an adverse effect.

[Practical recommendations for screening and management of functional disorders of the adrenal cortex in cases of SARS-CoV-2 infections]. / Praktische Empfehlungen zum Screening und Management von Funktionsstörungen der Nebennierenrinde bei einer akuten SARS-CoV-2-Infektion.

Diseases of the adrenal cortex require particular attention during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Firstly, SARS-CoV­2 infections can give rise to extrapulmonary manifestations and cause endocrine disorders, particularly in the adrenal cortex. Furthermore, patients with pre-existing insufficiency of the adrenal cortex or hypercortisonism are particularly at risk from a severe infection such as SARS-CoV­2, to suffer from additional complications or a more severe course of a SARS-CoV­2 infection with a higher mortality. Especially in hemodynamically unstable patients with a SARS-CoV­2 infection, diseases of the adrenal glands should also be considered in the differential diagnostics and if necessary clarified, if this is not already known. Prolonged treatment of patients with a SARS-CoV­2 infection with regimens containing high doses of glucocorticoids can also result in a secondary adrenal insufficiency. In order to address these special aspects, some practical recommendations for the diagnostic and therapeutic management of functional disorders of the adrenal glands in patients with a SARS-CoV­2 infection are therefore presented.

Strongyloides Hyperinfection Syndrome Following Corticosteroid Therapy in a Patient with COVID-19 infection: A Case Report

Strongyloides stercoralis (S. stercoralis) is a helminth, which infects humans widely in tropical and subtropical countries. This parasitic infestation usually does not produce symptoms in humans;however, severe and life-threatening forms of this infection can occur in immunocompromised individuals. Patients with Coronavirus disease 2019 (COVID-19) with concurrent immunosuppressive therapy are at risk of developing Strongyloides hyperinfection syndrome (SHS). We present a 70-yearold male with a history of high-dose dexamethasone therapy due to severe COVID-19 who was referred to our hospital with chest discomfort, nausea, and anorexia. Histological assessment of the gastric and duodenal mucosae revealed numerous eggs and filariform larvae of S. stercoralis indicative of SHS. Ivermectin and albendazole were administered to the patient. Following the treatment, the patient's symptoms improved. Clinicians must be aware of the risk of SHS, especially in S. stercoralis endemic countries before and during corticosteroid therapy for COVID-19 because early diagnosis and appropriate treatment can significantly reduce mortality in these patients.

Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

OBJECTIVE: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children. METHODS: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized. RESULTS: 30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44). CONCLUSIONS: Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed.

Tuberculosis

Tuberculosis (TB) is a communicable, airborne infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). A quarter of the world's population is infected with TB, affecting all age groups. Infection with MTB results in latent or active disease. Latent infection is associated with a 10% lifetime risk of developing active disease, but this is much higher in those with concurrent immunosuppression. Despite being both preventable and curable, TB remains the leading cause of global death from a single infectious agent. Active disease most commonly affects the lungs but can spread to cause extrapulmonary disease anywhere in the body. Over half of individuals in the UK now present with features of extrapulmonary TB, those with HIV being at particular risk. In all cases, obtaining samples for TB culture is absolutely vital. Standard treatment is with quadruple therapy for 6 months, extended in TB meningitis and often TB bone infection. Adjunctive corticosteroids have proven benefit in TB meningitis and TB pericarditis, and can be considered in other circumstances, such as paradoxical reactions to starting treatment in miliary TB. Despite recent gains in diagnosing and treating TB cases worldwide, the global COVID-19 pandemic is likely to have significantly affected recent progress.

Can aldosterone increase Interleukin-6 levels in CoViD-19 pneumonia

Background: Several evidence have identified the role of Interleukin- 6 (IL-6) in the cytokine storm induced by CoViD-19 pneumonia. Interestingly, the correlation between the serum levels of IL-6 and the plasma aldosterone has already been demonstrated in patients affected by primary aldosteronism (PA). Therefore, we suppose that aldosteronism may increase IL-6 levels in CoViD-19. Presentation of the case:We report a case of a 47-year-old female CoViD-19 patient who had developed severe pneumonia complicated by Guillain-Barre syndrome (GBS). The blood test revealed high levels of IL-6 (serum IL-6: 402 pg/mL) and of its soluble receptor (soluble IL-6 receptor >1900pg/mL) and she required mechanical ventilation for severe hypoxemia. Furthermore, evidence of right adrenal adenoma, resistant hypertension, severe hypokalemia and high serum levels of aldosterone with high aldosterone/renin ratio were also consistent with diagnosis of PA. Thus, tocilizumab and spironolactone were administered with rapid improvement in clinical condition. Finally, she was diagnosed with acute motor sensitive neuropathy and began the rehabilitation phase. Conclusions: Increased aldosterone levels in PA may be associated with more severe forms of CoViD-19 by stimulating IL-6 production. This association could have a synergic effect in development of complications such as GBS. Increased aldosterone activity/levels could be involved in CoViD-19 patients with secondary aldosteronism. Further studies are needed to.

Corticosteroid Therapy in Management of Myocarditis Associated with COVID-19; a Systematic Review of Current Evidence.

INTRODUCTION: Myocarditis in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seems to be associated with a higher mortality rate. This study aims to summarize the latest evidence on whether the use of corticosteroids in patients with myocarditis associated with COVID-19 is necessary. METHODS: We performed an extensive search using a combination of search terms in PubMed, Europe PMC, ProQuest, EBSCOhost, and Google Scholar up to January 2021. Full-text articles that met the predefined inclusion criteria were included in the present study. RESULTS: The full-texts of 18 articles have been reviewed. Thirteen out of the eighteen (72%) patients who got corticosteroid administration experienced major clinical improvements during follow-up while the other five (28%) were experiencing uneventful events. The mean age of the reported patients was 47.8±13.2 years. There was no gender predominance. Most of the reported cases were from USA (39%) followed by Spain, China, and UK (11% each), while Brazil, Colombia, France, Belgium, and Italy contributed one case each. Various corticosteroids were used but the most commonly applied were methylprednisolone (89%), hydrocortisone (5.5%), and prednisolone (5.5%). The most common route of administration among the studies was intravenous administration and the duration of treatment varied between one and fourteen days. CONCLUSION: A review of the currently available literature shows that with the use of corticosteroid agents in treating myocarditis associated with COVID-19, favorable outcomes are attainable. Well-established randomized clinical trials are needed to evaluate the efficacy and safety of using corticosteroids in this condition.

A reassessment about included studies and certainty of evidence on a systematic review and meta-analysis of steroid for patients with acute respiratory distress syndrome.

We comment on the study by Hirano et al. about the effect of steroids in patients with acute respiratory distress syndrome. It might be necessary to include only the existing randomized control trials and to reassess the certainty of evidence about the primary outcomes.

COVID-19, adrenal gland, glucocorticoids, and adrenal insufficiency.

The current Coronavirus disease outbreak requires that physicians work in collaboration with other physicians especially in intensive care and emergency units. To fight against this new disease, whose pathogenesis, effects, and results have not been clearly demonstrated, especially in patients with the pre-existing chronic disease, requires special expertise and perspectives. Due to the need for dynamic glucocorticoid treatment at different stages of the disease in patients with adrenal insufficiency, the existence of reports indicating that "coronavirus disease 2019" also affects the adrenal reserve, and the use of glucocorticoids also in advanced stages in patients with Coronavirus disease require this issue to be emphasized with precision. Herein, treatment of the pre-existing adrenal insufficiency in patients with actual Coronavirus disease and the effects of the this critical disease on the adrenal gland have been reviewed.