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Introduction: Patients with Cushing’s syndrome (CS) represent a highly sensitive group during corona virus disease 2019 (COVID-19) pandemic. The effect of multiple comorbidities and immune system supression make the clinical picture complicated and treatment challenging. Case report: A 70-year-old female was admitted to a covid hospital with a severe form of COVID-19 pneumonia that required oxygen supplementation. Prior to her admission to the hospital she was diagnosed with adrenocorticotropic hormone (ACTH)-dependent CS, and the treatment of hypercortisolism had not been started yet. Since the patient’s condition was quickly deteriorating, and with presumend immmune system supression due to CS, we decided on treatement with intraveonus immunoglobulins (IVIg) that enabled quick onset of immunomodulatory effect. All comorbidities were treated with standard of care. The patient’s condition quickly stabilized with no direct side effects of a given treatment. Conclusion: Treatment of COVID-19 in patients with CS faces many challenges due to the complexity of comorbidity effects, immunosupression and potential interactions of available medications both for treatment of COVID-19 and CS. So far, there are no guidelines for treatment of COVID-19 in patients with active CS. It is our opinion that immunomodulating therapies like IVIg might be an effective and safe treatment modality in this particularly fragile group of patients. Introduction Dealing with corona virus disease 2019 (COVID-19) focused medical attention on several sensitive population groups. While the knowledge is still improving, some of the recognized risk factors for severe form of the disease are male sex, older age, obesity, hypertension, diabetes mellitus, and cardio-vascular disease (1). This constellation of morbidities is particularly intriguing from endocrine point of view, since they are all features of patients with Cushing’s syndrome (CS). Another relevant feature of CS is a propensity for infections due to profound immune suppression, with prevalence of 21-51%; even more so, infections are the second cause of death (31%) in CS after disease progression, and are the main cause of death (37%) in patients who died within 90 days of diagnosis (2). Immune system alterations in CS lead to depression of both innate and adaptive immune responses, favoring not only commonly acquired but also opportunistic bacterial infections, fungal infections, and severe, disseminated viral infections (3). Susceptibility to infections directly positively correlates with cortisol level, and is more frequent in ectopic ACTH secretion (EAS). Hypercortisolism hampers the first-line response to external agents and consequent activation of the adaptive response (3). Consequently, there is a decrease in total number of T-cells and B-cells, as well as a reduction in T-helper cell activation, which might favor opportunistic and intracellular infections. On the other hand, an increase in pro-inflammatory cytokine secretion, including interleukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) leads to persistent, low-grade inflammation. It is important to note that immune system changes are confirmed both during the active phase and while in remission of CS (3). In view of the aforementioned data, a few topics emerge regarding patients with CS and COVID-19. Initial clinical presentation may be altered – low-grade chronic inflammation and poor immune reaction might limit febrile response in the early phase of infection, aggravating timely diagnosis (4). Increased cytokine levels may put patients with CS at increased risk of severe course and progression to acute respiratory distress syndrome (ARDS). On the other hand, the rise in cytokine levels associated with exposure to external agents is significantly hampered, probably because of persistently elevated pro-inflammatory cytokine secretion (4, 5). Patients with CS have a possibility for prolonged duration of viral infections and risk for superinfections leading to sepsis and increased mortality risk; this is especially relevant for hospitalized patients and mandates empirical prophylaxis with broad-spectrum antibiotics (6). Both COVID-19 and CS individually represent disease states of increased thromboembolic (TE) risk, requiring additional care (6). Due to very limited data, it is still not possible to address these topics with certainty and make recommendations for optimal management of these patients. Current clinical practice guidance for management of CS during COVID-19 commissioned by the European Society of Endocrinology (ESE) emphasizes prompt and optimal control of hypercortisolism and adequate treatment of all comorbidities (7). Although individual circumstances must always be considered, we need more direct clinical experience, especially regarding the actual treatment of COVID-19 in this sensitive group. So far, there are only five published case studies of patients with CS and COVID-19, with eight patients in total (8–12). In this study, we present a patient with newly diagnosed ACTH-dependent CS who was diagnosed with COVID-19 before the initiation of specific medical treatment. Case Report A 70-year-old female was admitted to our Covid hospital due to bilateral interstitial pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Six days before she was discharged from endocrinology department of another hospital where she was hospitalized due to newly diagnosed diabetes mellitus. Her personal history was unremarkable, and she was vaccinated with two doses of inactivated COVID-19 vaccine Sinopharm BBIBP. During this hospitalization Cushingoid features were noted (moon face, centripetal obesity, thin extremities with multiple hematomas, bilateral peripheral edema), as well as diabetes mellitus (HbA1c 8.7%), arterial hypertension (BP 180/100 mmHg), hypokalemia (2.0 mmol/L), mild leukocytosis (WBC 12.9x10e9/L) with neutrophilia, and mildly elevated CRP (12.3 mg/L). Hormonal functional testing confirmed ACTH-dependent Cushing’s syndrome: morning ACTH 92.6 pg/mL (reference range 10-60 pg/mL), morning serum cortisol 1239 nmol/L (reference range 131-642 nmol/L), midnight serum cortisol 1241 nmol/L, lack of cortisol suppression in overnight dexamethasone suppression test (978 nmol/L). Pituitary MRI was unremarkable other than empty sella, and CT scan of thorax normal other than left adrenal hyperplasia. Diabetes mellitus was successfully controlled with metformin, hypertension with ACE-inhibitor, Ca-channel blocker and beta-blocker, and hypokalemia with potassium supplementation along with spironolactone. Steroidogenesis inhibitors were not available in this institution, but before referral to a tertiary care hospital she was tested for SARS-CoV-2, and the test came back positive (sample was obtained by nasopharyngeal swab). Since she was asymptomatic, with normal thoracic CT scan and stabile CRP level (9.1 mg/L), she was discharged with detailed recommendations for conduct in case of progression of COVID symptoms. Next day she started feeling malaise with episodes of fever (up to 38.2°C). Symptomatic therapy was advised in an outpatient clinic (no antiviral therapy was recommended), but 5 days later respiratory symptoms ensued. During examination, the patient was weak, with dyspnea and tachypnea (RR 22/min), afebrile (36.9°C) and with oxygen saturation (SO2) of 85% measured by pulse oximeter. Chest X-ray confirmed bilateral interstitial pneumonia with parenchymal consolidation in the right lower lung lobe, so she was referred to the COVID hospital. Laboratory analyses upon admission are presented in the Supplementary Table 1. In addition to her previous testing, elevated chromogranin A (CgA) level was verified (538.8 ng/mL, reference range 11-98.1). The patient was treated with supplemental oxygen with maximal flow of 13 l/min. For the reason of previously confirmed severe endogenous hypercortisolism, glucocorticoids were not administered. Due to limited therapeutic options and presumed further clinical deterioration, we decided to treat the patient with intravenous immunoglobulins (IVIg) 30 g iv for 5 days, starting from the 2nd day of hospitalization. We did not observe any side effects of a given treatment. In parallel, the patient received broad-spectrum antibiotics (ceftazidime and levofloxacin), proton pump inhibitor, LMWH in prophylactic dose, oral and parenteral potassium supplementation along with spironolactone. She continued with her previous antihypertensive therapy with good control of blood pressure. While the patient was on oxygen supplementation, glycaemia was controlled with short acting insulin before meals. Following given treatment, we observed clinical, biochemical (Supplementary Table 1.) and radiological improvement (Supplementary Figure 1). Oxygen supplementation was gradually discontinued. With regard to D-dimer levels and risk factors for TE events due to COVID-19 and CS, we performed color Doppler scan of lower extremities veins, and CT pulmonary angiography, but there were no signs of thrombosis. During hospital stay, there were no signs of secondary infection and cotrimoxazole was not added to the current treatment. The patient was discharged with advice to continue her prior medical therapy along with increased dose of spironolactone and initiation of rivaroxaban. She was referred to the tertiary institution for the initiation of steroidogenesis inhibitor and further diagnostics. Discussion Endogenous Cushing’s syndrome is a rare disease with an incidence of 0.7-2.4 million person-years in European population-based studies (13). Significant morbidity yields a standard mortality ratio of 3.7 (95%CI 2.3–5.3), with the highest mortality during the first year after initial presentation. COVID-19 pandemic imposes additional challenge to this fragile group of patients. Due to lack of solid experience, it is still difficult to define potential clinical course and outcome of patients with CS and COVID-19. In addition, currently there are no guidelines for management of SARS-CoV-2 infection in patients with active CS. So far, only two small case series followed patients with Cushing’s disease (CD) in various disease stages (not all were active) during COVID-19 pandemic (9, 12). Small number of SARS-CoV-2 positive cases (3/22 and 2/61) is clearly biased by shortness of analyzed period (one and a half, and three and a half months). Additionally, a small number of patients was actually tested by nasopharyngeal swab for SARS-CoV-2 even in the presence of indicative symptoms, albeit mild. Nevertheless, all these limitations included, it seems that the prevalence of COVID-19 might be greater in patients with CD than in general population (12). This is accordant with studies on patients on exogenous glucocorticoid (GC) treatment. Overall, there is a growing body of evidence that patients on chronic GC therapy are at higher risk for SARS-CoV-2 infection and a severe course of disese, regardless of age and comorbidities (14). In many studies patients on high-dose GC therapy were at particularly high risk for a severe course of disease, so it is reasonable to assume that there is a dose-dependent effect (14). All patients except one with endogenous CS and COVID-19 presented in literature were hospitalized, with majority of them requiring oxygen supplementation, which classified them as serious cases of disease (8–12). Parameters of inflammation (namely CRP) were highly variable (from normal to elevated) and did not seem to reflect severity of COVID-19 consistently. Two patients had fatal outcome; one with postoperative hypocortisolism that required stress doses of hydrocortisone, and with terminal kidney failure as significant comorbidity; the other with suspected EAS who developed ARDS in contrast to normal CRP and absence of fever (9, 12). Based on reported cortisol levels in these patients, it seems that the severity of COVID-19 pneumonia depended on severity of hypercortisolism (8–12). A patient with probable EAS even developed ARDS, which adds to ongoing controversy regarding the risk of ARDS due to SARS-CoV-2 in patients with CS (3, 15). We ourselves have treated a severely obese female patient with active CD on pasireotide, who developed ARDS despite addition of high doses of methylprednisolone (unpublished data). Additional risk imposed by comorbidities cannot be underestimated (15, 16). This is particularly relevant for obesity, that not only hampers immune system (leading to increased levels of IL-1, IL-6, and TNF-α), but adipocytes represent a reservoir of SARS-CoV-2 thanks to ACE2 receptor, crucial for virus attachment (15). Majority of depicted patients with active CS were already medically treated for hypercortisolism but with various compliance (sometimes very poor), and two young patients have just started steroidogenesis inhibitors (metyrapone/ketoconazole). Infection with SARS-CoV-2 was treated by national protocols that were mostly based on supportive care. These protocols changed over time, so a few patients received antiviral therapy (favipiravir), and one young patient with suspected EAS was treated with methylprednisolone along with high doses of ketoconazole (10). Treatment was complicated with adrenal insufficiency (AI) in three patients (8, 11, 12). We have presented a patient with CS and rapid development of serious case of COVID-19 pneumonia that required hospital admission and oxygen support. She was febrile and had positive laboratory parameters of inflammation. Her CS was active, with very high cortisol levels, no prior medical treatment and with clinical suspicion of EAS (ACTH-dependent disease of short duration, severe hypercortisolism, hypokalemia, very high CgA, no visible pituitary tumor). With this in mind, and with regard to rapid progression of COVID-19 pneumonia, it was our opinion that the patient required treatment with quick onset and presumable immune system modulation. A logical approach to treatment of CS during COVID-19 pandemic includes meticulous therapy for comorbidities (namely antihypertensives, anti-diabetic drugs, low molecular weight heparin, etc.), and steroidogenesis inhibitors for treatment for hypercortisolemia (7). While some of these drugs demonstrate quick onset of action regarding normalization of cortisol level (and hence improve clinical comorbidities), rapid effects on immune system responses are not likely, which might be of great relevance in case of acute infection. Secondly, adrenolytic therapy increases a risk of AI, which can be even more perilous than CS in case of infection or other stress situations (8, 12, 15, 16). A modified “block and replace” approach may be considered, where addition of hydrocortisone could diminish the risk of AI (7). Still, there are a few potential pitfalls with this regimen as well. Some people fail to respond to high doses of adrenal-blocking agents due to genetic differences in the steroidogenic enzymes, since therapeutic responses to metyrapone and ketoconazole in patients with CS are associated with the polymorphism in the CYP17A1 gene (17). Additionally, there are not enough data about possible interactions between adrenolytic drugs (majority of them being metabolized through the CYP450/CYP3A4 pathway) and medications used to treat COVID-19, most of which are only just emerging (18). Special concerns, amplified with similar potential effects of SARS-CoV-2 itself as well as specific therapies are liver dysfunction (metyrapone, ketoconazole), hypokalemia (metyrapone, ketoconazole), QT-interval prolongation (ketoconazole, osilodrostat), gastrointestinal distress (mitotane, osilodrostat, etomidate) (18). Metyrapone may cause accumulation of androgenic precursors secondary to the blockade of cortisol synthesis, that can virtually enhance expression of transmembrane protease serine 2 (TMPRSS2), found to be essential to activate the viral spikes, induce viral spread, and pathogenesis in the infected hosts (19). Another important issue concerns biochemical estimation of disease control (and hence risk for AI), since most commercially available assays can overestimate cortisol level in patients treated with metyrapone due to cross-reactivity with the precursor 11-deoxicortisol (7, 15). Mass spectrometry is a method of choice to overcome this problem, but it is not available in many centers. Some centers advocate titration and/or temporary halting medical therapies in the treatment of patients with CS in the context of COVID-19 infection (20). Treatement was stopped in a few patients with severe COVID-19 symptoms who were then given high dose GC for a few days with no long-term complications, and with full recovery (20). There are no data about the effect of anti-viral drugs in patients with CS and COVID-19. A special concern refers to adipose tissuse, as adipose tissue is difficult for antiviral drugs to reach. It cannot be excluded that the constant release of viral replicas from the adipose tissue reservoir may interfere with COVID-19 infection treatment, delaying its resolution and favoring a worse prognosis (15). If antiviral drugs are started, it is suggested that immunocompromised patients may require prolonged therapy (18). However, the timing is difficult in practice and candidates for antivirals are limited. Since the clinical course of COVID-19 only initially depends on viral replication, immunomodulatory therapy emerged as a valuable treatment option to control the host immune response. This became apparent ever since RECOVERY trial proved efficacy of glucocortiods (21). But this therapeutic option is fairly inapplicable in patients with active CS, since glucocorticoid treatment in chronic hypercortisolism seems to enhance immune system alterations (22). In parallel with the development of new agents, it is prudent to study the efficacy of existing therapeutic options with acceptable safety profile (20). Beside glucocorticoids, inflammation blockers, intravenous immunoglobulin and convalescent plasma were used in various settings (23). Intravenous immunoglobulin (IVIg) is a blood product prepared from the serum pooled from thousands of healthy donors, containing a mixture of polyclonal IgG antibodies, mostly IgG1 and IgG2 subclasses (24, 25). Initial rationale for its use was immunodefficiency due to hypoglobulinemia. Since then it has been shown that IVIg exerts pleiotropic immunomodulating action involving both innate and adaptive immunity and it has been used in a variety of diseases (26). In previous studies on MERS (Middle East Respiratory Syndrome) and SARS (Severe Acute Respiratory Syndrome) using IVIg showed beneficial clinical effects (25). Although pathogenesis of COVID-19 has not be fully elucidated, there is a consensus that immune-mediated inflammation plays an important role in the progression of this disease, just as it did in prior coronavirus infections (27). In this context, the actual role of IVIg in COVID-19 patients might be not to boost the immune system, but through its immunomodulatory effect to suppress a hyperactive immune response that is seen in some patients (28). So far, a limited number of studies, case series and meta-analyses demonstrate a promising potential of IVIg in patients with COVID-19. The effect was demonstrated in terms of mortality, improvement of clinical symptoms, laboratory examinations, imaging and length of hospital stay, especially in patients with moderate/severe form of the disease, and with emphasis on early administration (within 3 days of admission) (24, 25, 27–31). A recent double blind, placebo-controlled, phase 3, randomized trial tested hyperimmune intravenous immunoglobulin (hIVIg) to SARS-CoV-2 derived from recovered donors with no demonstrated effect compared with standard of care, but therapy was administered in patients symptomatic up to 12 days (32). Additional clinical trials are underway, hopefully with more guidance for proper selection of patients that might benefit from this type of treatment. Conclusion To our knowledge, this is the first case of IVIg treatment in a COVID-19 patient with CS. It is our opinion that immune-modulating properties of IVIg might present an attractive treatment option, especially in those CS patients that show rapid clinical progression and positive laboratory parameters of inflammation. While we await for new therapeutic modalities for COVID-19 and while some of the modalities remain not widely available, IVIg is more accessible, safe method, which could be rescuing in carefully selected patients. Of note, we consider our patient’s vaccinal status as an unquestionable positive contributor to the favorable outcome Data Availability Statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics Statement Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Author Contributions BP, AS, JV, TG, MJ-L, JV, VS, ZG and TA-V analyzed and interpreted the patient data. BP, AP, DI, and DJ were major contributors in writing the manuscript. All authors contributed to the article and approved the submitted version. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher’s Note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary Material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2022.889928/full#supplementary-material References 1. Hu J, Wang Y. The Clinical Characteristics and Risk Factors of Severe COVID-19. Gerontology (2021) 67(3):255–66. doi: 10.1159/000513400 PubMed Abstract | CrossRef Full Text | Google Scholar 2. 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Lancet (2022) 399(10324):530–40. doi: 10.1016/S0140-6736(22)00101-5 PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: Cushing’s syndrome, COVID-19, IVIg, hypercortisolism, immunomodulation, immunosuppression Citation: Popovic B, Radovanovic Spurnic A, Velickovic J, Plavsic A, Jecmenica-Lukic M, Glisic T, Ilic D, Jeremic D, Vratonjic J, Samardzic V, Gluvic Z and Adzic-Vukicevic T (2022) Successful Immunomodulatory Treatment of COVID-19 in a Patient With Severe ACTH-Dependent Cushing’s Syndrome: A Case Report and Review of Literature. Front. Endocrinol. 13:889928. doi: 10.3389/fendo.2022.889928 Received: 04 March 2022; Accepted: 17 May 2022; Published: 22 June 2022. Edited by: Giuseppe Reimondo, University of Turin, Italy Reviewed by: Nora Maria Elvira Albiger, Veneto Institute of Oncology (IRCCS), Italy Miguel Debono, Royal Hallamshire Hospital, United Kingdom Copyright © 2022 Popovic, Radovanovic Spurnic, Velickovic, Plavsic, Jecmenica-Lukic, Glisic, Ilic, Jeremic, Vratonjic, Samardzic, Gluvic and Adzic-Vukicevic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Bojana Popovic, popbojana@gmail.com Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. From https://www.frontiersin.org/articles/10.3389/fendo.2022.889928/full-
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Update November 22, 2020 I have not updated my patients on the COVID-19 pandemic since March. Since the last update and as of today’s date, 12.2 million Americans have been infected with COVID-19 and 256,000 Americans have died. Several of Dr. Friedman’s patients have been infected with COVID-19. Many businesses have closed and there have been major economic loses. The response to the pandemic has unfortunately been politicized and I say unfortunately because the virus doesn’t distinguish based on victim’s political party. Please see Dr. Friedman’s Letter in the Los Angeles Jewish Journal https://jewishjournal.com/letters_to_the_editor/316110/letters-lockdown-vs-no-lockdown/. Dr. Friedman completely supports efforts to limit the spread of the virus, including wearing masks, social distancing, handwashing and staying at home. Listening to government officials including the CDC is crucial. Dr. Friedman agrees with data showing gatherings are much safer outside and encourages his patients to err on the side of safety and caution. Dr. Friedman is spearheading efforts at Charles R. Drew University to be a site for a vaccine study and after some delays, it looks like his University will be a site for the Sanofi vaccine in December 2020. Dr. Friedman is very excited about the promising results from the Moderna and Pfizer trials and thinks vaccines along with mask-wearing and social distancing will curtail the pandemic, hopefully in the latter half of 2021. He does think that COVID-19 will be with us for a long time. Dr. Friedman anticipates that changes due to COVID-19, including telemedicine and working from home will remain with us after the pandemic subsides. As mentioned in the March update, patients with endocrine problems such as Cushing’s syndrome, Addison’s Disease, hypopituitarism and diabetes have slightly impaired immune systems, making them potentially susceptible for a more severe infection by COVID-19. He would recommend those patients to be especially vigilant about mask-wearing/social distancing and to get a vaccine when it comes out. He advices his patients the following: Wear masks, social distancing, handwashing and staying at home as much as possible Use delivery services for groceries, food and medications. Wash hands frequently for 20 seconds and/or use hand sanitizer several times a day Avoid air travel, public gatherings and other public places as guided by local officials Quarantine if sick or exposed. Labcorp and Quest both introduced testing for COVID-19 using nasal swabs. Several other laboratories are also performing tests. Dr. Friedman recommends PCR testing and not rapid antigen testing. For those with symptoms of Coronavirus, he recommends seeing your primary care doctor for testing. Dr. Friedman is unable to provide requisitions or swabs for this testing that should be done by their primary doctor. While Dr. Friedman was initially enthusiastic about antibody testing, he is concerned about the quality of the tests and no longer recommends it. Labcorp and Quest are both still open and Quest has a new Peace of Mind program for lab services not related to COVID-19 and for patients who are 60 years of age or older, or have other conditions that put them at greater risk for COVID-19, in which patients can come to their nearby Quest location during the first hour of each day for VIP care. Dr. Friedman encourages people to get their hormone testing done and make their followup appointments. Many patients have requested extra supply of their medications. However, most insurances do not allow this and carefully monitor medication use. Dr. Friedman recommends patients to use a mail-order pharmacy and sign up for auto-refills so that they get a consistent supply of their medications. Except for patients sick with COVID-19, patients should not up-dose hydrocortisone Dr. Friedman has restarting in person visits on the last Tuesday of each month and continues to see patients via telemedicine on the other Tuesday nights. Please visit goodhormonehealth.com for more information or to schedule an appointment. Dr. Friedman’s staff will still be doing in person growth hormone stimulation tests on Tuesday night in an isolated and sanitized clinic setting. Dr. Friedman especially encourages patients to eat healthy and exercise (especially being outside) including walking, hiking, biking, aerobic videos yoga or pilates at home, during this stressful period. Dr. Friedman encourages patients to get their flu vaccine and the COVID-19 vaccine when available. Everyone should pray that the pandemic ends soon. Dr. Friedman wishes everyone to stay healthy
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Dexamethasone, a cheap and widely used steroid, has become the first drug shown to be able to save lives among Covid-19 patients in what scientists hailed as a “major breakthrough”. Results of trials announced on Tuesday showed dexamethasone, which is used to reduce inflammation in other diseases, reduced death rates by around a third among the most severely ill Covid-19 patients admitted to hospital. The results suggest the drug should immediately become standard care in patients with severe cases of the pandemic disease, said the researchers who led the trials. “This is a result that shows that if patients who have Covid-19 and are on ventilators or are on oxygen are given dexamethasone, it will save lives, and it will do so at a remarkably low cost,” said Martin Landray, an Oxford University professor co-leading the trial, known as the RECOVERY trial. “It’s going to be very hard for any drug really to replace this, given that for less than 50 pounds ($63.26), you can treat eight patients and save a life,” he told reporters in an online briefing. His co-lead investigator, Peter Horby, said dexamethasone was “the only drug that’s so far shown to reduce mortality - and it reduces it significantly.” “It is a major breakthrough,” he said. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.” There are currently no approved treatments or vaccines for Covid-19, the disease caused by the new coronavirus which has killed more than 431,000 globally. Saving ‘countless lives’ The RECOVERY trial compared outcomes of around 2,100 patients who were randomly assigned to get the steroid, with those of around 4,300 patients who did not get it. The results suggest that one death would be prevented by treatment with dexamethasone among every eight ventilated Covid-19 patients, Landray said, and one death would be prevented among every 25 Covid-19 patients that received the drug and are on oxygen. Among patients with Covid-19 who did not require respiratory support, there was no benefit from treatment with dexamethasone. “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients,” Horby said. Nick Cammack, a expert on Covid-19 at the Wellcome Trust global health charity, said the findings would “transform the impact of the Covid-19 pandemic on lives and economies across the world”. “Countless lives will be saved globally,” he said in a statement responding to the results. The RECOVERY trial was launched in April as a randomised clinical trial to test a range of potential treatments for Covid-19, including low-dose dexamethasone and the malaria drug hydoxycholoroquine. The hydroxychloroquine arm was halted earlier this month after Horby and Landray said results showed it was “useless” at treating Covid-19 patients. Global cases of infection with the novel coronavirus have reached over 8 million, according to a Reuters tally, and more than 434,000 people have died after contracting the virus, the first case if which was reported in China in early January. From https://www.cnbc.com/2020/06/16/steroid-dexamethasone-reduces-deaths-from-severe-covid-19-trial.html
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Presented by Jamie J. Van Gompel, M.D., B.S., Professor in Neurosurgery and Otolaryngology specializing in endoscopic/open skull base focusing on Pituitary tumors as well as Epilepsy at the Mayo Clinic in Rochester, Minnesota, USA and Garret W. Choby, M.D., a fellowship-trained rhinologist and endoscopic skull base surgeon practicing at the Mayo Clinic. Objectives: - Understand the additional considerations that are key to performing endonasal surgery during the COVID pandemic - Identify the practice changes that are allowing pituitary surgery to proceed safely - Characterize the nasal cavity and nasopharynx as a reservoir for the coronavirus - Identify the risk of undergoing pituitary surgery during the Covid -19 pandemic Register Now! After registering you will receive a confirmation email containing information about joining the Webinar. Date: Monday, May 11, 2020 Time: 4:00 PM Pacific Daylight Time - 5:15 PM Pacific Daylight Time
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Presented by Jamie J. Van Gompel, M.D., B.S., Professor in Neurosurgery and Otolaryngology specializing in endoscopic/open skull base focusing on Pituitary tumors as well as Epilepsy at the Mayo Clinic in Rochester, Minnesota, USA and Garret W. Choby, M.D., a fellowship-trained rhinologist and endoscopic skull base surgeon practicing at the Mayo Clinic. Objectives: - Understand the additional considerations that are key to performing endonasal surgery during the COVID pandemic - Identify the practice changes that are allowing pituitary surgery to proceed safely - Characterize the nasal cavity and nasopharynx as a reservoir for the coronavirus - Identify the risk of undergoing pituitary surgery during the Covid -19 pandemic Register Now! After registering you will receive a confirmation email containing information about joining the Webinar. Date: Monday, May 11, 2020 Time: 4:00 PM Pacific Daylight Time - 5:15 PM Pacific Daylight Time
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Endocrinologists have underlined the importance that physicians consider "a stress dose" of glucocorticoids in the event of severe COVID-19 infection in endocrine, and other, patients on long-term steroids. People taking corticosteroids on a routine basis for a variety of underlying inflammatory conditions, such as asthma, allergies, and arthritis, are at elevated risk of being infected with, and adversely affected by, COVID-19. This also applies to a rarer group of patients with adrenal insufficiency and uncontrolled Cushing syndrome, as well as secondary adrenal insufficiency occurring in hypopituitarism, who also rely on glucocorticoids for day-to-day living. In the event of COVID-19, all of these individuals may be unable to mount a normal stress response, and "in the case of adrenal suppression...such patients may run into severe difficulties, particularly if on intensive care units," warns Paul Stewart, MD, University of Leeds, UK, and editor-in-chief of the Journal of Clinical Endocrinology & Metabolism (JCEM). As such, it is vitally important to recognize that "Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case," Stewart and colleagues emphasize in a newly published editorial in JCEM. They note this advice must be considered alongside World Health Organization (WHO) guidance against prescribing therapeutic glucocorticoids to treat complications of COVID-19, based on prior experience in patients with acute respiratory distress syndrome, as well as those affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The key difference here is not to use pharmacologic doses of glucocorticoids as treatment for COVID-19 (where they have no effect), but rather to prevent death from adrenal failure by using "stress" doses of replacement glucocorticoid, Stewart explained to Medscape Medical News. "No patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months)...should die without consideration" for a stress dose of replacement glucocorticoid therapy. "The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months) by whatever route should die without consideration for parenteral glucocorticoid therapy," the editorialists write. He advises using physiological stress doses of hydrocortisone (50-100 mg intravenously tid). Specific Advice for Adrenal Insufficiency: Follow Sick Day Rules A separate statement by the American Association of Clinical Endocrinologists (AACE) also emphasizes that it is particularly important for patients with adrenal insufficiency to follow advice from the Centers for Disease Control and Prevention (CDC) or similar guidance on preventing COVID-19 infection, including social distancing and frequent hand washing. Such patients should continue to take medications as prescribed and ensure they have appropriate supplies of oral and injectable steroids, ideally for 90 days, AACE advises. And if there is a shortage of hydrocortisone, the statement advises patients ask a pharmacist or physician about replacement hydrocortisone with different doses that might be available. Stewart agrees that patients with adrenal insufficiency need to be hypervigilant, but says that "if they do become ill, for the most part they are well counseled to respond appropriately to intercurrent infections." Nevertheless, it is "invaluable to reiterate 'sick day rules'" for suspected COVID-19 infection. "Any patient who develops a dry continuous cough and fever should immediately double their daily oral glucocorticoid dose and continue on this regimen until the fever has subsided." If a patient still deteriorates on this regimen, develops diarrhea or vomiting, or is unable to take oral glucocorticoids for other reasons, they should contact their physicians or seek urgent medical care to receive parenteral treatment with a glucocorticoid. J Clin Endocrinol Metab. Published online March 31, 2020. Position statement For more diabetes and endocrinology news, follow us on Twitter and Facebook. From https://www.medscape.com/viewarticle/928072?nlid=134869_3901&src=wnl_newsalrt_200404_MSCPEDIT&uac=295048SY&impID=2335560&faf=1&fbclid=IwAR1zZe6fqDS3tKuHUYoFpbvBMkQYJ4JN59RzC93xdzVcGGkJIz5bnmmE4LY
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With the novel COVID-19 virus continuing to spread, it is crucial to adhere to the advice from experts and the Centers for Disease Control and Prevention (CDC) to help reduce risk of infection for individuals and the population at large. This is particularly important for people with adrenal insufficiency and people with uncontrolled Cushing’s Syndrome. Studies have reported that individuals with adrenal insufficiency have an increased rate of respiratory infection-related deaths, possibly due to impaired immune function. As such, people with adrenal insufficiency should observe the following recommendations: Maintain social distancing to reduce the risk of contracting COVID-19 Continue taking medications as prescribed Ensure appropriate supplies for oral and injectable steroids at home, ideally a 90-day preparation In the case of hydrocortisone shortages, ask your pharmacist and physician about replacement with different strengths of hydrocortisone tablets that might be available. Hydrocortisone (or brand name Cortef) tablets have 5 mg, 10 mg or 20 mg strength In cases of acute illness, increase the hydrocortisone dose per instructions and call the physician’s office for more details Follow sick day rules for increasing oral glucocorticoids or injectables per your physician’s recommendations In general, patients should double their usual glucocorticoid dose in times of acute illness In case of inability to take oral glucocorticoids, contact your physician for alternative medicines and regimens If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist Monitor symptoms and contact your physician immediately following signs of illness Acquire a medical alert bracelet/necklace in case of an emergency Individuals with uncontrolled Cushing’s Syndrome of any origin are at higher risk of infection in general. Although information on people with Cushing’s Syndrome and COVID-19 is scarce, given the rarity of the condition, those with Cushing’s Syndrome should strictly adhere to CDC recommendations: Maintain social distancing to reduce the risk of contracting COVID-19 If experiencing fever, cough, shortness of breath or other symptoms, call both the COVID-19 hotline (check your state government website for contact information) and your primary care physician or endocrinologist In addition, people with either condition should continue to follow the general guidelines at these times: Stay home as much as possible to reduce your risk of being exposed When you do go out in public, avoid crowds and limit close contact with others Avoid non-essential travel Wash your hands with soap and water regularly, for at least 20 seconds, especially before eating or drinking and after using the restroom and blowing your nose, coughing or sneezing If soap and water are not readily available, use an alcohol-based sanitizer with at least 60% alcohol Cover your nose and mouth when coughing or sneezing with a tissue or a flexed elbow, then throw the tissue in the trash Avoid touching your eyes, mouth or nose when possible From https://www.aace.com/recent-news-and-updates/aace-position-statement-coronavirus-covid-19-and-people-adrenal
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Dr. Theodore Friedman will host an important webinar on Coronavirus Information for Endocrine Patients Many patients have asked Dr. Friedman what do during the Coronavirus Pandemic. He will give candid answers from his view as an Endocrinologist. He will also talk about new telehealth opportunities for his patients. Sunday • April 5 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m505da5a10afe3aeea456e162414c17b9 OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 807 657 124 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: hormones For more information, email us at mail@goodhormonehealth.com
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Along with all of you, NADF is monitoring this outbreak by paying close attention to CDC and FDA updates. We have also asked our Medical Advisor to help answer your important questions as they come up. We asked Medical Director Paul Margulies, MD, FACE, FACP to help us with this question: Question: Does Adrenal Insufficiency cause us to have a weakened immune system and therefore make us more susceptible? Response: Individuals with adrenal insufficiency on replacement doses of glucocorticoids do not have a suppressed immune system. The autoimmune mechanism that causes Addison’s disease does not cause an immune deficiency that would make one more likely to get an infection. The problem is with the individual’s ability to deal with the stress of an infection once it develops. Those with adrenal insufficiency fall into that category. When sick with a viral infection, they can have a more serious illness, and certainly require stress dose steroids to help to respond to the illness. If someone with adrenal insufficiency contracts the coronavirus, it is more likely to lead to the need for supportive care, including hospitalization. This information from the CDC Website provides important information regarding Prevention & Treatment. You can find this information here: https://www.cdc.gov/coronavirus/2019-ncov/about/prevention-treatment.html From https://www.nadf.us/
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