SUN-441 - When Local Isn't Local: Systemic Complications from Intra-Articular Steroids in A Patient on Cobicistat

Cobicistat is a pharmacokinetic enhancer in the combined antiretroviral formulation Symtuza® (darunavir, cobicistat, emtricitabine, tenofovir alafenamide), which is commonly used to treat HIV. Cobicistat inhibits cytochrome P450 3A and as a result can increase serum levels of administered glucocorticoids. Glucocorticoid excess and adrenal insufficiency have been described in a few reports of patients concurrently treated with glucocorticoids and cobicistat. We present a severe case.

61-year-old man with a history of bilateral knee osteoarthritis and HIV treated with Symtuza® who presented to his PCP six weeks after he received bilateral knee triamcinolone injections. The patient initially reported markedly increased energy, insomnia and had hypomanic behavior. Several weeks later he experienced fatigue, shortness of breath, lower extremity weakness and muscle wasting. Despite advice to avoid further glucocorticoids, the patient received a second round of bilateral knee injections about three months after the first for persistent pain and inflammation. He then presented to the ED with bilateral multi-segmental pulmonary embolism treated with apixaban. He continued to experience fatigue, dizziness, and lower extremity weakness. Laboratory evaluation by his PCP at that point revealed a low afternoon cortisol of 2.0 ug/dL, ACTH of 7 pg/mL (6-50), and a serum sodium level of 131 mmol/L (135-145). Other laboratory indices were unremarkable, including TSH 1.46 uIU/mL (0.35- 4.9), free T4 1.32 ng/dL (0.6- 1.8), and potassium of 4.8 mmol/L (3.1- 5.3). Antiretroviral treatment was then switched to Biktrvy® (bictegravir/ emtricitabine/ tenofovir). Upon referral to endocrinology, testing for primary adrenal insufficiency was done including 21- Hydroxylase antibodies (negative), aldosterone 8 ng/dL and an elevated plasma renin activity 46.61 ng/mL/h (0.25- 5.82 ng/mL) thought to be due to volume depletion. Several months after the last steroid injection a cosyntropin stimulation test was done with cortisol of 9.7 ug/dL at baseline, 17.5 ug/dL at 30 minutes and 19.4 ug/dL at 1 hour, ruling out primary adrenal insufficiency. The presumptive diagnosis was glucocorticoid excess followed by secondary adrenal insufficiency due to the intensified effects of intra-articular cortisone in the context of co-occurring cobicistat administration.

In this case the cobicistat- glucocorticoid interaction appears to have caused glucocorticoid excess leading to insomnia, hypomanic behavior and possibly pulmonary embolism followed by adrenal insufficiency. Given the widespread use of inhaled and injectable steroids by patients who can also be receiving cobicistat, early recognition of this interaction can potentially prevent complications related to glucocorticoid excess and adrenal insufficiency.

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