Endocrine Abstracts

Section 1: Case history: A 50-year-old woman presented to the HIV clinic after suspecting adverse effects following two intra-articular triamcinolone injections to her left hip, administered three and seven months prior. She complained of ongoing leg pain, generalised weakness and lethargy. Her past medical history included HIV infection, mild asthma for which she took inhalers only and had never required oral steroids. Her antiretroviral medications included dolutegravir, darunavir and ritonavir. Her asthma was treated with inhaled beclomethasone and formoterol twice daily for five years. On examination She had increased facial fat, prominent supraclavicular and dorsocervical fat pads, dark abdominal striae and central adiposity with slim arms and legs. On neurological examination she had proximal weakness of the lower limbs.

Section 2: Investigations: A Short Synacthen Test showed a cortisol level that was undetectable at baseline (RR 160-550 nmol/l), 167 nmol/l 30 mins after administering tetracosactide (RR >450 nmol/l) and 244 nmol/l after 60minutes (RR >600 nmol/l).

Section 3: Results and treatment: She was diagnosed with iatrogenic Cushing’s disease and secondary adrenal insufficiency (SAI) following a known interaction between triamcinolone and the CYP450 inhibitor ritonavir. She commenced 4 mg prednisolone once daily. Ritonavir was stopped immediately and darunavir was switched to Triumeq, which does not inhibit CYP450, aiming to facilitate hepatic clearance of triamcinolone.

Section 4: Conclusions and points for discussion: Ritonavir is an HIV protease inhibitor which is primarily used as a ‘booster’ for other antiretroviral agents. It is a highly potent inhibitor of hepatic cytochrome P450 3A4 (CYP3A4) activity. When given at subtherapeutic doses, ritonavir increases the concentration of other antiretrovirals given in conjunction with it, allowing for decreased dosages and increased dose intervals. However, as exogenous steroids are primarily metabolised via the CYP3A4 pathway, significant interactions with ritonavir may occur. It is now well known that this interaction can cause iatrogenic Cushing’s disease and sometimes SAI which occurs due to ACTH suppression by excess non-metabolised exogenous steroids. Patients on CYP3A4 inhibitors such as ritonavir require careful consideration regarding prescribing of new drugs and potential drug interactions. Practitioners should be aware of potential interactions with glucocorticoids in all forms. Following a diagnosis of iatrogenic Cushing’s disease in such cases, prompt assessment for SAI is indicated with a low threshold for commencing steroid replacement in patients who are symptomatic. This is particularly crucial for those who have had depot injections, where the exogenous steroid can not be withdrawn.