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- Page navigation anchor for RE: Intranasal corticosteroids may have systemic absorption and potential impact upon cortisol measuresRE: Intranasal corticosteroids may have systemic absorption and potential impact upon cortisol measures
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 chi...
Show MoreCompeting Interests: Leigh Sowerby reports receiving personal fees from Mylan, GSK and Sanofi, and grants from GSK, Roche and AstraZeneca, outside of the submitted work. No other competing interests were declared.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.
- Page navigation anchor for Intranasal corticosteroids may have systemic absorption and potential impact upon cortisol measuresIntranasal corticosteroids may have systemic absorption and potential impact upon cortisol measures
In their recent review of intranasal corticosteroids, the authors claim that there is no correlation with hypothalamic-pituitary-adrenal suppression(1). However, there are scenarios for which this is not always true and therefore, some additional details may be useful. In support of their claim, the authors have only cited a review article which, in turn, cites another review article and other small older studies. Most studies looking at this question have had major design flaws in their 1) very small numbers, 2) use of presently out-dated and less accurate cortisol assays, 3) collection of adrenal tests as an exploratory secondary endpoint, 4) lack of differentiation between different types, doses and durations of glucocorticoids and 5) lack of clinically relevant data.
A 2015 systematic review and meta-analysis of primary data, using appropriate inclusion, exclusion and stratification criteria has shown that nearly 4% (0.5-28.9%) of intranasal steroid users can show adrenal suppression when defined biochemically(2). The risk is likely increased with longer duration of use and with higher doses but is likely less than what is seen with inhaled steroids, for asthma treatment. However, in combination with medications that inhibit cytochrome p450 3A4 (CYP3A4 inhibitors) which will slow systemic glucocorticoid metabolism, intranasal steroids may even cause Cushing’s syndrome(3)(4) with rebound adrenal insufficiency after discontinuation(5) emphasizing their poten...
Show MoreCompeting Interests: None declared.References
- James Fowler, Leigh J Sowerby. Using intranasal corticosteroids. CMAJ 2021;193:E47-E47.
- 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.
- Hillebrand-Haverkort ME, Prummel MF, Ten Veen JH. Ritonavir-induced Cushing’s syndrome in a patient treated with nasal fluticasone [15]. AIDS. 1999;13:1803.
- Chen F, Kearney T, Robinson S, Daley-Yates PT, Waldron S, Churchill DR. Cushing’s syndrome and severe adrenal suppression in patients treated with ritonavir and inhaled nasal fluticasone [3]. Sex Transm Infect. 1999;75:274.
- Veilleux O, Lee TC, McDonald EG. Rebound adrenal insuficiency afer withdrawal of ritonavir in a 65-year-old man using inhaled budesonide. CMAJ. 2017;189(37):E1188-91.