Using intranasal corticosteroids

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 potential for systemic absorption.

While adverse clinical sequelae may be uncommon, it is particularly worth noting that in modern lab medicine, use of more specific cortisol immunoassays or mass spectrometry can show a very low basal cortisol level when measured in a patient using intranasal or inhaled steroids particularly in patients receiving highly active antiretroviral therapy or azole antifungals. It is a common mistake to interpret this as “adrenal insufficiency” in need of replacement therapy; rather it is simply evidence that the synthetic glucocorticoid does indeed have systemic absorption and may be suppressing the basal HPA axis. Based upon a low serum cortisol measured while the patient is actively using exogenous glucocorticoids in any form, one cannot determine whether this leads to suppression, delayed recovery or clinical adrenal insufficiency after glucocorticoid discontinuation. Intranasal steroids may have systemic absorption with impact upon the native HPA axis and therefore the decision of when or how to stop such medications should keep this in mind, particularly among persons treated with CYP3A4 inhibitors.