Endocrine Abstracts

Background: CYP3A4 is the most prevalent cytochrome P450 (CYP) enzyme in the liver, and is used by the majority of medications for their metabolism and elimination from the body. The inhibition of CYP3A4 can result in the accumulation of drug concentrations increasing the risk for possible toxicity. We report a case of iatrogenic Cushings’s syndrome secondary to impaired CYP3A4 metabolism of triamcinolone by coadministration of darunavir/cobicistat, with resultant secondary hypoadrenalism on conventional synthetic ACTH testing.

Case: A 54 year old woman presented with one week history of increasing neck and face swelling associated with fatigue. Past medical history included HIV infection. Her medication included darunavir/cobicistat with dolutegravir. 2 weeks previously she received an intracapsular injection of triamcinolone acetonide (equivalent to hydrocortisone 200mg) for hip pain. On examination she appeared Cushingoid with a round face, facial plethora and buffalo hump. Despite the clinical picture random cortisol was <40 nmol/L with 30 minute cortisol post ACTH 165 nmol/L. 24 hour urine cortisol was 85 nmol. We were unable to measure serum triamcinolone concentrations. The clinical picture was explained by exogenous steroid interference from triamcinolone. Due to persistent symptoms her antiretrovirals were temporarily changed to facilitate metabolism of triamcinolone. She required several doses of hydrocortisone to cover intercurrent illness. Recovery of endogenous HPA axis was observed 10 weeks after the initial injection.

Discussion: Iatrogenic Cushing’s syndrome secondary to the antiretroviral ritonavir is well recognised. We describe a case related to an additional antiretroviral, cobicistat, which is known to be a strong inhibitor of the CYP3A4 metabolism. This case highlights the importance of taking a robust drug history and considering potential drug interactions in patients on antiretroviral treatment. This is particularly important as not all electronic medicines systems will have access to specialist prescribing records, that sit outwith standard primary care prescribing systems.