Endocrine Abstracts (2017) 49 EP74 | DOI: 10.1530/endoabs.49.EP74

Iatrogenic Cushing syndrome and suprarenal secondary insufficiency due to interaction between fluticasone and ritonavir

Suarez Gutierrez Lorena1, Veiguela Blanco Brenda2, Dieguez Felechosa Lorena2, Manjon Miguelez Laura1, Riestra Gonzalez Maria2, Antuña García Nuria2, Diaz Fernandez Maria Jesus2 & Casal Alvarez Florentino2

1Hospital Universitario Central De Asturias, Oviedo, Spain; 2Hospital De Cabueñes, Gijon, Spain.

Introduction: The interaction between corticosteroids and protease inhibitors (PIs) is a clearly described drug interaction.

Case report: A 44-year-old woman diagnosed with HIV category B3 diagnosed in 1989; severe lipodystrophy. In addition , HCV genotype IA. Bronchial asthma since 2000. Treatment with fluticasone 1 inh/24 h, salbutamol on demand, darunavir 800 mg/day and ritonavir 100 mg/day. He had known lipodystrophy since 2001 and the abdominal perimeter was monitored, aiming to increase it. Likewise, it presented progressive proximal weakness in lower limbs, with increased hair, hair fragility and alopecia reason why it is referred to Endocrinology. Moderate hirsutism, muscular atrophy and in the analytical study: normal FSH and LH are objectified. 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/24 h (36–137). A Synacten test is performed: Basal 0.52; 30 min 2.33; 60 min 2.84 with ACTH 1 and was diagnosed as having an independent iatrogenic Cushing ACTH syndrome associated with secondary adrenal insufficiency. With this diagnosis he is referred to the pulmonology department for corticosteroid replacement. Inhaled and substitution treatment was initiated with hydrocortisone and went home with a new antiretroviral regimen (raltegravir, tenofovir and abacavir)

Discussion: Fluticasone is a synthetic steroid that is cleared by the cytochrome P450 CYP3A4 enzyme, which is inhibited or potentiated by a multitude of drugs, including ritonavir. As it is not metabolized, an increase in circulating levels leads to a decrease in the secretion of ACTH and therefore a suppression of the adrenal gland with insufficiency of the same and cushing syndrome.

The options are the substitution of Fluticasone by a non-substrate of CYP3A4 such as beclomethasone and the substitution of ritonavir for another antiretroviral. Most cases resolve in about 9–12 months.