RE: Intranasal corticosteroids may have systemic absorption and potential impact upon cortisol measures
References
1. Kline GA, Symonds CJ, Holmes DT. Intranasal corticosteroids may have systemic absorption and potential impact upon cortisol measures. CMAJ 2021; doi:10.1503/cmaj.78162
2. Broersen LHA, Pereira AM, Jørgensen JOL, Dekkers OM. Adrenal insufficiency in corticosteroids use: Systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100:2171–80.
3. Donaldson AM, Choby G, Kim DH, Marks LA, Lal D. Intranasal Corticosteroid Therapy: Systematic Review and Meta-analysis of Reported Safety and Adverse Effects in Adults. Otolaryngol Head Neck Surg. 2020 Dec;163(6):1097-1108.
4. Donaldson AM, Choby G, Kim DH, Marks LA, Lal D. Intranasal Corticosteroid Therapy: Systematic Review and Meta-analysis of Reported Safety and Adverse Effects in Children. Otolaryngology–Head and Neck Surgery. 2020;163(6):1087-1096.
5. Veilleux O, Lee TC, McDonald EG. Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide. CMAJ. 2017;189(37):E1188-91.
Thank you to Dr. Kline and his co-authors for their insightful comments regarding the potential risk of HPA axis suppression in certain scenarios with nasal corticosteroid (1). We agree that prescribers should be aware of possible medication interactions, in particular with CYP3A4 inhibitors. At the same time, prescribers should not shy away from prescribing these medications for the vast majority of patients with symptomatic nasal complaints as their safety profile is well established.
We would like to comment on the systematic review citing a 4% incidence of biochemical adrenal insufficiency with nasal steroid use (2). Broersen references 8 papers regarding this, but on detailed review of this paper, we could only identify 5 papers with intranasal delivery of corticosteroid, the most recent being from 2004. This also included two papers that used corticosteroid drops rather than spray, which is well-known to deliver a higher dose of corticosteroid and is not available in Canada due to the risk of HPA axis suppression.
A much more detailed review of side-effects with intranasal corticosteroid therapy in adults was published in December 2020 (3). This paper found 28 studies looking specifically at HPA suppression in adults. Of these, 23 reported no evidence of HPA axis suppression, and the 5 studies that did were with non-FDA approved methods of corticosteroid delivery (including 3 using drops). The same group published a similar systematic review in children (4), identifying 23 studies including information on HPA axis suppression. Of these studies, 17 demonstrated no evidence of HPA axis suppression. Five of the six that did note some suppression were using non-FDA approved intranasal corticosteroid drops.
Given the comorbidity of asthma with chronic rhinosinusitis and/or allergic rhinitis, it is important to keep in mind the potential additive effect of both inhaled and intranasal corticosteroid in HPA axis suppression. Indeed, one of the cases cited by Kline was on concurrent inhaled corticosteroid (5). As such, we would recommend selecting a second generation nasal corticosteroid (ciclesonide hydrofluoroalkane, mometasone furoate or fluticasone propionate) for patients on inhaled corticosteroids, and to, on occasion, re-evaluate whether the current intranasal corticosteroid dose and therapy is still required for symptom control.