Beclometasone but not fluticasone modulates PDGFD expression in the H295R adrenal cell line.

BackgroundAdrenal suppression is a clinically concerning side effect of inhaled corticosteroid (ICS) treatment in patients with asthma. Increased susceptibility to ICS-induced adrenal suppression has previously been identified in those with the rs591118 polymorphism in Platelet Derived Growth Factor D (PDGFD). The mechanism underpinning this relationship is not known.MethodsH295R cells were genotyped for rs591118 using a validated Taqman PCR allelic discrimination assay. H295R cell viability was determined after treatment with beclometasone and fluticasone (range 0-330 μM). Cortisol was measured in cell culture medium using competitive enzyme immunoassay.ResultsPDGFD protein expression in H295R cells was confirmed using Western blotting. When ACTH and forskolin were added to H295R cells, a reduction in PDGFD expression was seen which was then restored by incubation with prochloraz, a known inhibitor of steroidogenesis.A dose-dependent, decrease in PDGFD expression was observed with beclometasone (over a 24 h incubation period) but not with beclometasone incubations beyond 24 hour nor with fluticasone (at 24 or 48 hours).ConclusionsH295R cells express PDGFD protein which can be modulated by incubation with steroidogenesis agonists and antagonists and additionally with exogenous beclometasone.

Occurrence of Adrenal Suppression in Patients Having Sepsis in Indian Population and Impact of Corticosteroid Supplementation on Its Overall Survival

Objective Our aim was to estimate the occurrence of adrenal suppression in critically ill patients with septic shock who have got admission in intensive care unit and to evaluate the effectiveness of hydrocortisone in these patients in relation to mortality of patient, development of septic shock, and effect on total leucocyte count. Methods Serum cortisol was measured in 120 patients with sepsis. Patients with decreased cortisol level were split in to two groups (group A and B). Group A received 50 mg of hydrocortisone 6 hourly and group B was given matching placebo. At day 7, serum cortisol level was estimated for both A and B groups. The results were calculated and compared with relation to incidence of adrenal insufficiency, development of septic shock, effect on total leucocyte count, and survival at 28 days. Results The occurrence of adrenal suppression in patients having sepsis in our study was 44 out of 120 patients, that is, 36.6%. After supplementation of corticosteroid for 7 days the mean value of serum cortisol of group A was 40.38 ± 8.44 µg/dL and group B was 24.30 ± 6.47 µg/dL (p < 0.001). At day 7, in group A, 22.7% developed septic shock, whereas in group B, 36.4% developed septic shock (p < 0.001). In group A and B, mortality rate of the patients at 28 days was 18.2 and 22.7%, respectively. Conclusion Hydrocortisone supplementation in critically ill patients with low random basal serum cortisol level with sepsis does not significantly improve the overall survival.

Safety of topical corticosteroids in atopic eczema: an umbrella review

ObjectiveAn umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.MethodsEmbase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool).Results38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2–4 weeks).Key findingsTCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased.TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).ConclusionsWe found no evidence of harm when TCS were used intermittently ‘as required’ to treat flares or ‘weekend therapy’ to prevent flares. However, long-term safety data were limited.PROSPERO registration numberCRD42018079409.

Adrenal suppression from exogenous glucocorticoids: Recognizing risk factors and preventing morbidity

Adrenal suppression (AS), a potential side effect of glucocorticoid therapy (including inhaled corticosteroids), can be associated with significant morbidity and even death. In Canada, adrenal crisis secondary to AS continues to be reported in children. Being aware of symptoms associated with AS, understanding the risk factors for developing this condition, and familiarity with potential strategies to reduce risks associated with AS, are essential starting points for any clinician prescribing glucocorticoids.

Audit on Steroid Replacement in Confirmed or Suspected COVID-19 Patients With Adrenal Insufficiency or Adrenal Suppression in a District General Hospital

Aim: In response to new updated guidance from Society For Endocrinology April 2020, this Audit was conduct to assess the adequacy of steroid replacement in confirmed or suspected COVID-19 patients with adrenal insufficiency or adrenal suppression admitted to Bedford District General Hospital. In steroid dependent patients (Addison’s disease, adrenal insufficiency, pituitary steroid insufficiency, use of long term steroids for other conditions - 5mg or more of prednisolone (or equivalent doses) daily for longer than 4 weeks) admitted to hospital very unwell with confirmed or suspected COVID recommendations is to start on Hydrocortisone 100 mg per IV injection followed by continuous IV infusion of 200 mg hydrocortisone/24h (alternatively 50 mg every 6 h per intravenous or IM bolus injection). Method: Retrospect data collection on Patients admitted in May 2020 to Bedford Hospital with suspected or confirmed COVID 19 disease with adrenal insufficiency or on long term steroid use. Those patients should be started on Hydrocortisone 100 mg per IV injection followed by continuous IV infusion of 200 mg hydrocortisone/24h (alternatively 50 mg every 6 h per intravenous or IM bolus injection). Results: In May 2020, 295 patients admitted under the medical team in Bedford Hospital with confirmed or suspected COVID-19. Only 12 patients met the inclusion criteria, one patient with a diagnosis of Addison disease and the remaining 11 patients on long term steroids. None of these patients were managed as per updated guidelines. 6 patients had less than the adequate dose, they were started on prednisolone 30-40mg. 4 patients dose of oral steroids was only doubled, 1 patient received the same dose of oral steroid and the only confirmed Addison had higher dose of hydrocortisone. Moreover, In June 2020, The RECOVERY Outcome trial results showed that Dexamethasone 6mg for 10 days reduces the death by one third in hospitalised patient with severe respiratory complications of COVID-19. Dexamethasone 6mg is 12 times the physiological required steroid dose, this is equivalent to 240mg hydrocortisone, which is adequate for steroid replacement in patients with adrenal insufficiency or suppression. Conclusion: In view of these results and the outcome of the RECOVERY Trial, Local trust guidelines updated, indicated that any patient with Adrenal insufficiency or suppression including those on long term steroids very unwell admitted to the hospital should receive Dexamethasone if requiring oxygen or Hydrocortisone if not requiring oxygen. Recommendation of changes included teaching sessions delivered to doctors, posters on updated guidelines distributed in major areas in hospital and trust guidelines updated on the intranet.