Endocrine Abstracts

JOINT890

The complex pharmacological interaction between ritonavir, a protease inhibitor frequently used in HIV infection that acts through the inhibition of the cytochrome P450, and fluticasone produced a significant increase in the systemic concentrations of the latter, consequently generating iatrogenic Cushing’s syndrome.

Clinical case: In 2022 a 42-year-old male with a history of chronic persistent asthma and HIV on ritonavir treatment was referred to by Pulmonology for presenting weight gain with truncal obesity, severe skin pain predominantly in recent and acute reddish stretch marks, edema in the lower limbs, asthenia and severe low back pain.

Personal history: In 2018 the patient was diagnosed with HIV, starting treatment with darunavir/ritonavir 800/160 mg and dolutegravir 50 mg/day evolving to undetectable viral load; he had grade II obesity and severe and persistent asthma. In July 2022 he presented worsening asthma and was treated with meprednisone 40 mg for 7 days, budesonide/formoterol 100 mg 2 puffs twice a day, montelukast 1 tablet/day at night, salmeterol/fluticasone 500/500 (Seretide diskus) 3 times a day and tiotropium 18 mg/day. The physical examination showed arterial hypertension (160/100 mmHg), heart rate: 100/bpm, rounded face, fatty hump, fat in the supraclavicular spaces, bilateral rhonchi, severe abdominal obesity, painful wide dark red striae. Although the findings were suggestive of Cushing’s syndrome, the discontinuation of inhaled fluticasone was complicated due to the severity of the respiratory condition. Diagnostic studies confirmed suppression of the adrenal axis, MRI showed lumbodorsal vertebral compression fractures: T7-T10 and L4 and evidence of osteoporosis in the bone mineral density. After stabilizing the asthmatic condition, the dose of corticosteroids was reduced: salmeterol/fluticasone 25/250 mg 1 puff twice a day, budesonide was discontinued and hydrocortisone 10 mg/day was indicated. The antiretroviral medication had to be changed for Dolutegravir/Tenofovir/Lamivudine; the patient improved Cushing syndrome symptoms; zoledronic acid was prescribed for the secondary osteoporosis.

Conclusions: Cushing syndrome triggered by inhaled corticosteroids is very rare, that is why we started to investigate the possible interaction between fluticasone and HIV medication. We found that ritonavir was the drug which produced a severe increase of fluticasone half-life causing a dramatic syndrome. This case highlights the need for effective communication between health professionals, multidisciplinary management, and knowledge of drug interactions in unique clinical situations.