Variability in counselling for adrenal insufficiency in COVID-19 and beyond: a survey of rheumatology practice
Authors: Puja Mehta, Karim Meeran, Elizabeth Macphie, Afroze Abbas, Jonathan Rippin, Rachel C Jeffery, Venkat Reddy, Maria J Leandro, Coziana Ciurtin, Helen L Simpson, Sarah L Mackie
Journal: The Lancet Rheumatology (2020)

The COVID-19 pandemic has presented challenges and uncertainty for patients and physicians. Corticosteroids are the most commonly prescribed pharmacotherapy in rheumatology. Long-term corticosteroids are prescribed for many rheumatic diseases, including rheumatoid arthritis, giant cell arteritis, and polymyalgia rheumatica.1Mebrahtu TF Morgan AW Keeley A Baxter PD Stewart PM Pujades-Rodriguez M Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England.J Clin Endo Metab. 2019; 104: 3757-3767Crossref Scopus (46) Google Scholar Diabetes, hypertension, and weight gain (all poor prognostic factors for COVID-19) are widely recognised adverse events associated with long-term corticosteroid use; however, the high prevalence of glucocorticoid-induced adrenal suppression (eg, in 20 [48%] of 42 patients with rheumatoid arthritis receiving prednisolone at ≥5 mg/day for at least 6 months2Borresen SW Klose M Baslund B et al.Adrenal insufficiency is seen in more than one-third of patients during ongoing low-dose prednisolone treatment for rheumatoid arthritis.Eur J Endocrinol. 2017; 177: 287-295Crossref PubMed Scopus (45) Google Scholar) is less well known. Patients with adrenal insufficiency should be informed regarding corticosteroid sick day rules, including the risk of life-threatening adrenal crisis if corticosteroids are discontinued suddenly, or if there is insufficient stress dosing.3Rushworth RL Torpy DJ Falhammar H Adrenal Crisis.New Engl J Med. 2019; 381: 852-861Crossref PubMed Scopus (139) Google Scholar Prompt supplementary corticosteroids are required in the context of significant intercurrent infection, including COVID-19, major trauma, or surgery; and intravenous corticosteroids are needed if vomiting.3Rushworth RL Torpy DJ Falhammar H Adrenal Crisis.New Engl J Med. 2019; 381: 852-861Crossref PubMed Scopus (139) Google Scholar Despite the importance for patient safety, guidelines regarding corticosteroid sick day rules for rheumatology patients are unclear and, consequently, there is variation in practice. Most clinicians double the corticosteroid dose, but this crude rule-of-thumb can lead to undertreatment or overtreatment. Clear information for patients is particularly important during the current COVID-19 pandemic due to restricted or modified access to usual levels of health care—eg, delayed or virtual conversion of clinic appointments and difficulty accessing helplines. In September, 2020, WHO recommended corticosteroids to reduce mortality in critically ill COVID-19 patients.4WHOCorticosteroids for COVID-19, living guidance.https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1Date: 2020Date accessed: October 15, 2020Google Scholar However, worse outcomes were suggested in patients with COVID-19 not requiring supplemental oxygen. Significantly poorer outcomes were reported in patients receiving at least 10 mg/day prednisolone (n=64)5Gianfrancesco M Hyrich KL Al-Adely S et al.Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.Ann Rheum Dis. 2020; 79: 859-866Crossref PubMed Scopus (919) Google Scholar for rheumatic disease, but to the best of our knowledge, there has been no evidence of adverse outcomes attributed to supplemental stress doses of corticosteroids in COVID-19. Here we report the results of a survey evaluating corticosteroid sick day rule counselling, and highlight an educational need to prevent adrenal crisis. In March, 2020, the British Society for Rheumatology (BSR) issued shielding guidance for patients receiving long-term (>4 weeks) corticosteroids, either as high-dose monotherapy (>20 mg/day) or low-dose (≥5 mg/day) prednisolone combined with another immunosuppressant.6British Society for RheumatologyBritish Society for Rheumatology shielding guidance.https://www.rheumatology.org.uk/practice-quality/covid-19-guidanceDate: 2020Date accessed: March 28, 2020Google Scholar The shielding guidance identified categories of patients as clinically vulnerable, who were advised to take extra precautions during the first peak of the pandemic in England. Some clinicians and patients elected to delay starting or increasing corticosteroids for inflammatory flares, due to perceived safety concerns and to avoid needing to shield. Anecdotally, we became aware of safety incidents (adrenal crises) after discontinuation of long-term corticosteroids or inadequate dose increments with concomitant COVID-19 (unpublished). In April, 2020, the BSR updated their advice to reflect endocrinology consensus guidelines on prevention of adrenal crisis for COVID-19.7Arlt W Baldeweg SE Pearce SHS Simpson HL Endocrinology in the time of COVID-19: management of adrenal insufficiency.Eur J Endocrinol. 2020; 183: G25-G32Crossref PubMed Scopus (70) Google Scholar These guidelines stated that hospitalised patients on long-term corticosteroids with COVID-19 should receive intravenous corticosteroids; in the community, patients taking 5 mg to 20 mg prednisolone daily should take 10 mg prednisolone twice daily and patients taking more than 20 mg should continue their usual dose, but in divided doses.7Arlt W Baldeweg SE Pearce SHS Simpson HL Endocrinology in the time of COVID-19: management of adrenal insufficiency.Eur J Endocrinol. 2020; 183: G25-G32Crossref PubMed Scopus (70) Google Scholar The twice-daily prednisolone dose (to mimic the stress response7Arlt W Baldeweg SE Pearce SHS Simpson HL Endocrinology in the time of COVID-19: management of adrenal insufficiency.Eur J Endocrinol. 2020; 183: G25-G32Crossref PubMed Scopus (70) Google Scholar), is an unfamiliar frequency of administration in rheumatology practice. We conducted an online survey, via the BSR (electronic newsletter and social media), between May 16, and July 16, 2020, to assess corticosteroid sick day rule counselling and to improve visibility of the COVID-19-specific corticosteroid guidelines. We aimed for a sample size of 100 respondents, which was selected as a reasonable compromise between generalisability of the results and feasibility. Although the survey was done during the peak of the first wave of the COVID-19 pandemic, there was rapid engagement, with the target of 100 responses achieved within a short period of time. Respondent characteristics reflected the BSR professional body, as the majority of respondents were consultants. Of 100 respondents (93 physicians and seven specialist nurses), only 50% always or usually counselled patients about corticosteroid sick day rules, and 28% did this rarely or never. The timing and content of education was variable (results in appendix). The majority counselled patients when starting (45%) and tapering (42%) corticosteroids, and advised not to discontinue corticosteroids suddenly (85%) and to increase doses with intercurrent infection (72%). Although 74% prescribed a variable regimen, 15% advised patients to self-titrate without contacting a medical professional. Despite recognising that infection might warrant increased corticosteroid doses, 69% of clinicians changed their usual management with COVID-19 (52% would reduce the corticosteroid dose, 10% would not increase, and 7% would advise a lower than usual increment), 10% would give the same advice (as per any other infection), and only 13% followed the recent endocrinology guidance. The majority (74%) would refer someone with suspected adrenal insufficiency for endocrinology consultation without doing any investigations themselves; the remaining showed variability in timing and testing for adrenal insufficiency. After being directed to the endocrinology COVID-19-specific guidelines,7Arlt W Baldeweg SE Pearce SHS Simpson HL Endocrinology in the time of COVID-19: management of adrenal insufficiency.Eur J Endocrinol. 2020; 183: G25-G32Crossref PubMed Scopus (70) Google Scholar 71% changed their management and 16% stated that they had not read the guidance. To our knowledge, this is the first evaluation of corticosteroid sick day rules in rheumatology, which are highly relevant, given that many patients with rheumatic disease receive long-term prednisolone. Patients receiving long-term prednisolone are more vulnerable to infection and might have poorer outcomes with COVID-19;5Gianfrancesco M Hyrich KL Al-Adely S et al.Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.Ann Rheum Dis. 2020; 79: 859-866Crossref PubMed Scopus (919) Google Scholar however, approximately half might have adrenal insufficiency and are at risk of adrenal crisis with significant intercurrent infection, as highlighted by the UK National Patient Safety Alert.8National Patient Safety AlertSteroid Emergency Card to support early recognition and treatment of adrenal crisis in adults.https://www.england.nhs.uk/wp-content/uploads/2020/08/NPSA-Emergency-Steroid-Card-FINAL-2.3.pdfDate: 2020Date accessed: September 21, 2020Google Scholar Patients with primary adrenal insufficiency on replacement corticosteroids exhibit greater knowledge of sick day rules than patients receiving corticosteroids for non-endocrine immunosuppressive indications, and therefore rheumatology patients might be at higher risk of adrenal crisis.9Salehmohamed MR Griffin M Branigan T Cuesta M Thompson CJ Patients treated with immunosuppressive steroids are less aware of sick day rules Than those on endocrine replacement therapy and may be at greater risk of adrenal crisis.Ir J Med Sci. 2018; 187: 69-74Crossref PubMed Scopus (12) Google Scholar Our results show variation in practice. Despite acknowledging that intercurrent infection might necessitate corticosteroid dose increment, most clinicians said they would reduce the dose with COVID-19. This highlights a significant unmet educational need among rheumatologists. This unmet need is an immediate and critical patient safety issue, given a global second wave of COVID-19 and the advent of seasonal influenza. We also call for specific guidance and clinician training to better manage patients taking long-term corticosteroids, to standardise sick day rule counselling across specialties, including issuing the steroid emergency card7Arlt W Baldeweg SE Pearce SHS Simpson HL Endocrinology in the time of COVID-19: management of adrenal insufficiency.Eur J Endocrinol. 2020; 183: G25-G32Crossref PubMed Scopus (70) Google Scholar and patient information leaflets.10Leeds NHS TrustPatient information leaflet for COVID-19, long-term steroids and adrenal insufficiency for rheumatology patients.https://www.leedsth.nhs.uk/assets/be1c37f891/Instructions_For-online-distribution_Final-Design2.pdfDate: 2020Date accessed: November 25, 2020Google Scholar Consideration should be given to the type and severity of stressors (eg, infection, surgery, and trauma). Guidelines published in May, 2020,11Woodcock T Barker P Daniel S et al.Guidelines for the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency: guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK.Anaesthesia. 2020; 75: 654-663Crossref PubMed Scopus (91) Google Scholar recommend perioperative stress-dosing, despite limited evidence. Supplemental steroid dosing during times of physiological stress is considered the safest approach. Guidance is also needed for the evaluation of adrenal insufficiency in patients taking long-term prednisolone. CC, HLS, and SLM contributed equally. PM is a Medical Research Council (MRC)-GlaxoSmithKline (GSK) EMINENT clinical training fellow with project funding outside the submitted work. PM receives co-funding by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. PM has served on an advisory board for SOBI, outside the submitted work. VR reports grants from Roche (Basel) outside the submitted work and funding support from MRC. SM reports non-financial support from Roche (co-investigator on a grant), Sanofi (advisory board and consultancy), GSK (local investigator on GSK-sponsored study), and travel expenses for conference attendance from Roche, outside the submitted work; and Patron of the UK charity, PMRGCAuk. This report presents independent research supported by the NIHR Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. All other authors declare no competing interests. We thank all respondents of the survey and the British Society for Rheumatology for disseminating the survey. Download .pdf (.22 MB) Help with pdf files Supplementary appendix