Cushing Syndrome and Severe Adrenal Suppression Caused by Fluticasone and Protease Inhibitor Combination in an HIV-Infected Adolescent

Abstract

A 14-year-old female with perinatally acquired HIV on boosted protease inhibitor (PI) therapy with atazanavir and ritonavir rapidly developed cushingoid features with excessive weight gain and moon facies within 2 weeks of receiving inhaled fluticasone/salmeterol for asthma treatment. Soon after discontinuing PIs and inhaled steroid, she required hospitalization for dyspnea, headache, muscle weakness, and extreme fatigue requiring hydrocortisone replacement therapy for presumed adrenal insufficiency. Cushing syndrome and adrenal suppression were very likely caused by elevated steroid systemic concentrations resulting from the cytochrome p450 interaction between the protease inhibitors and fluticasone. The Naranjo probability scale score of 5 suggests that the event was probably drug related. This is the first case report of fluticasone and PI-induced Cushing syndrome and adrenal suppression in a pediatric patient without a history of recent or concomitant treatment with systemic steroid therapy. Additionally, this case is unique as it is the most rapid (<2 weeks) presentation documented, thus far. Health care professionals should be conscious of this important drug-drug interaction in HIV-infected children and adolescents and be aware that rapid onset of hypercortisolism and adrenal suppression are possible.

Endocrinopathies in Children Infected with Human Immunodeficiency Virus

“…Ritonavir's use in children infected with HIV taking inhaled glucocorticoids for pulmonary disease may cause severe cortisol excess (iatrogenic Cushing syndrome) and adrenal insufficiency with the discontinuation of the inhaled glucocorticoid ( Table 1). [9][10][11] Prescribers should be aware of this interaction, particularly given the widespread use of inhaled glucocorticoids in the pediatric population.…”

Iatrogenic Cushing's Syndrome in HIV-Infected Patients Receiving Ritonavir and Inhaled Fluticasone: Description of 4 New Cases and Review of the Literature

“…On the other hand, chest physicians or general practitioners who may have to treat HIV-infected patients receiving ART with inhaled steroids are not aware of the pharmacokinetic properties of RTV and may not be familiar with RTV-associated drug-drug interactions. This partly explains why iatrogenic Cushing's syndrome is still occurring despite a recommendation in 1999 with more than 30 cases having reported since [8][9][10][11][12][13][14][15][16][17][18][19][20][21] ( Table 1).…”

Anterior Pituitary Failure

“…Multiple sources of exogenous glucocorticoids have been implicated in causing adrenal insufficiency, including oral, inhaled [84,85], topical [86] and injections [87]. Concomitant retroviral therapy for HIV infection may exacerbate the suppression [87,88]. Recovery from adrenal insufficiency during glucocorticoid withdrawal can be prolonged, with some cases extending as long as 18 months after the therapeutic regimen.…”