Ritonavir is a protease inhibitor used in the treatment of HIV infection. It can potentiate the effect of inhaled corticosteroids, resulting in iatrogenic Cushings syndrome.
We present a case of a 21-year-old female who had acquired HIV infection at birth, who also had moderately severe asthma since childhood treated with inhaled salbutamol 100 mcg prn and fluticasone 500 mcg bd. She had twice-yearly exacerbations requiring oral steroids. She commenced a HAART regimen of ritonavir 100 mg od, atazanavir 300 mg od, DDI 250 mg od and tenofovir 245 mg od in March 2005, because her viral load was over 2000 c/ml. Three months later, she developed severe Cushings syndrome, with rapid onset of central obesity, extensive striae, muscle weakness and skin fragility, together with biochemical evidence of adrenal suppression. Her 9am serum cortisol was <6 nmol/l, 24-hour urinary free cortisol was <6 nmol/l. Short synacthen test confirmed adrenal insufficiency (0minutes: <6 nmol/l, 30 minutes: 111 nmol/l). Plasma ACTH was <5 ng/l. She also had liver impairment with a total bilirubin of 167 umol/l (conjugated bilirubin 33 umol/l) and an ALT of 95 iu/l. She was commenced on low-dose hydrocortisone support (10 mg bd). We substituted beclomethasone 200 mcg bd for fluticasone. Ritonavir was stopped and atazanavir increased to 400 mg od. Over the next 9 months, her 9am cortisol rose to 324 nmol/l and a repeat short synacthen test is awaited. Hydrocortisone was gradually withdrawn and her asthma has remained well-controlled. CD4 count is 210 c/ml, HIV viral load is <50 c/ml and total bilirubin is 70 umol/l.
Fluticasone propionate is a potent steroid that normally undergoes extensive first-pass metabolism mediated by cytochrome P450 3A4. It can cause adrenal suppression and Cushings syndrome when given in combination with potent inhibitors of cytochrome P450 such as ritonavir. This case illustrates that an alternative regime of inhaled beclomethasone and stopping ritonovir can result in regression of Cushings syndrome and recovery of adrenal function.
06 - 07 Nov 2006
Society for Endocrinology