Iatrogenic Cushing Syndrome and Secondary Adrenal Insufficiency Due to an Interaction Between Fluticasone and Ritonavir

Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction. Several case series have been described.-Fluticasone is the one with the greatest potential risk of producing iatrogenic adrenal insufficiency given its pharmacokinetic characteristics. Clinical Case: 44-year-old woman diagnosed with HIV (human immunodeficiency virus) category B3 diagnosed in 1989; multiple antiretroviral treatments. Severe lipodystrophy Also HCV genotype IA. Bronchial asthma since 2000. A treatment with fluticasone 1 inh / 24h, salbutamol on demand, darunavir 800 mg / day and ritonavir 100 mg / day. He had known lipodystrophy since 2001 and the abdominal perimeter was controlled, showing an increase in it. Likewise, she presented progressive proximal weakness in the lower limbs, with increased hair, capillary fragility and alopecia, which is why she was referred to Endocrinology. Moderate hirsutism, muscle atrophy were observed and in the analytical study: normal FSH and LH. Testosterone 0.05 ng / ml (0.1–0.9), ACTH 1.0 pg / ml (7.2–63.3), Cortisol am 0.65 µg / dl (4.30–22.40). Urinary free cortisol 3.74 µg / 24h (36–137). A Synacten Test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and a diagnosis of iatrogenic independent ACTH Cushing Syndrome associated with secondary adrenal insufficiency. With this diagnosis, he was referred to the pulmonology clinic for a change from inhaled corticosteroid to beclomethasone and replacement treatment with hydroaltenesone was started. Three months later, he was admitted for a fever after stopping hydroaltesone. It was restarted, antibiotic treatment was prescribed, and she was discharged home with a new regimen of antiretrovirals (raltegravir, tenofovir, and abacavir). Clinical Lesson: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 enzyme CYP3A4, which is inhibited or enhanced by a multitude of drugs, including ritonavir. As it is not metabolized, there is an increase in circulating levels, causing a decrease in ACTH secretion and therefore a suppression of the adrenal gland with its insufficiency and cushing syndrome. In our case and usually, the initial signs are difficult to detect due to their overlap with lipodystrophy associated with protease inhibitors. Although there is no agreement in the literature: the options are the replacement of fluticasone with another corticosteroid that is not a CYP3A4 substrate such as beclomethasone and the replacement of ritonavir with another antiretroviral (as in our case) or the reduction of the dose of fluticasone. It is recommended to avoid the initiation of fluticasone in patients receiving ritonavir. Substitution treatment with a progressive reduction in dose is performed with hydroaltesona. Most cases resolve in 9–12 months.