Hypothalamic-pituitary-adrenal axis suppression by inhaled or nasal corticosteroids in HIV-infected patients

Femke Besemer, Cornelis Kramers, Kees Brinkman, Ad R M M Hermus, Antonius E van Herwaarden, David M Burger, Femke Besemer, Cornelis Kramers, Kees Brinkman, Ad R M M Hermus, Antonius E van Herwaarden, David M Burger

Abstract

Background Inhaled or nasal corticosteroids can cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Early detection is important because this suppression can be associated with significant morbidity. Objective To explore the adverse effect of hypothalamic-pituitary-adrenal suppression by local corticosteroids in HIV-infected patients. Method Ambulatory HIV-infected patients were selected if they used both antiretroviral treatment and inhaled or nasal corticosteroid. Suppression of hypothalamic-pituitary-adrenal axis was defined as a morning plasma cortisol below 80 nmol/L or a cortisol below 550 nmol/L during a 250 mcg adrenocorticotropic hormone-stimulation test. Results Twelve patients were tested; four of them were taking a CYP3A4 inhibitor. All patients had a normal morning plasma cortisol. Suppression of the hypothalamic-pituitary-adrenal axis during the ACTH stimulation test was identified in three of the twelve patients. None of these three individuals were taking a CYP3A4 inhibitor. Conclusion Hypothalamic-pituitary-adrenal axis suppression is frequently identified in patients on inhaled or nasal corticosteroids. CYP3A4 inhibitors such as ritonavir or cobicistat may increase the chance of this adverse effect. In this study we did not identify HPA axis suppression in patients taking CYP3A4 inhibitors. This may be related to the fact that 2 of these 4 patients used beclomethasone, a corticosteroid not metabolized by CYP3A4.ClinicalTrials.gov Identifier NCT02501486.

Keywords: Adrenal insufficiency; Antiretroviral therapy; Drug interactions; Inhaled corticosteroid; Nasal corticosteroid.

Conflict of interest statement

KB serves on advisory boards for Viiv, Gilead, MSD and Janssen. The other authors have no conflict of interest.

References

    1. Broersen LH, Pereira AM, Jorgensen JO, Dekkers OM. Adrenal insufficiency in corticosteroids use: systematic review and meta-analysis. J Clin Endocrinol Metab. 2015;100(6):2171–2180. doi: 10.1210/jc.2015-1218.
    1. Foisy MM, Yakiwchuk EM, Chiu I, Singh AE. Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIVMed. 2008;9(6):389–396.
    1. Saberi P, Phengrasamy T, Nguyen DP. Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management. HIV Med. 2013;14(9):519–529. doi: 10.1111/hiv.12039.
    1. Albert NE, Kazi S, Santoro J, Dougherty R. Ritonavir and epidural triamcinolone as a cause of iatrogenic Cushing's syndrome. Am J Med Sci. 2012;344(1):72–74. doi: 10.1097/MAJ.0b013e31824ceb2b.
    1. Endert E, Ouwehand A, Fliers E, Prummel MF, Wiersinga WM. Establishment of reference values for endocrine tests. Part IV: adrenal insufficiency. Neth J Med. 2005;63(11):435–43.
    1. Ueland GA, Methlie P, Oksnes M, Thordarson HB, Sagen J, Kellmann R, et al. The short cosyntropin test revisited: new normal reference range using LC–MS/MS. J Clin Endocrinol Metab. 2018;103(4):1696–1703. doi: 10.1210/jc.2017-02602.
    1. Boyd SD, Hadigan C, McManus M, Chairez C, Nieman LK, Pau AK, et al. Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone. J Acquir Immune Defic Syndr. 2013;63(3):355–61. doi: 10.1097/QAI.0b013e31829260d6.
    1. Elliot ER, Theodoraki A, Jain LR, Marshall NJ, Boffito M, Baldeweg SE, et al. Iatrogenic Cushing's syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies. Clin Med (Lond) 2016;16(5):412–418. doi: 10.7861/clinmedicine.16-5-412.

Source: PubMed

3
Iratkozz fel