Iatrogenic Cushing Syndrome and Secondary Adrenal Insufficiency Related to Concomitant Triamcinolone and Ritonavir Administration

Abstract

Triamcinolone is a long-acting glucocorticoid medication that can be responsible for transient suppression of the hypothalamicpituitary-adrenal (HPA) axis. This physiologic alteration may persist for weeks after repeated or even single localized injection of this agent. However, when this glucocorticoid agent is given to patients receiving the HIV protease inhibitor (PI) ritonavir (RTV), inhibition of their shared cytochrome P450 3A4 degradation pathway leads to an increased bioavailability of triamcinolone, with subsequent heightening and prolongation of the glucocorticoid serum levels. In those instances, iatrogenic Cushing syndrome may ensue. The authors encountered such an event in an HIV-infected patient on chronic treatment with an antiretroviral regimen containing RTV. The patient's clinical presentation and laboratory investigations confirmed a diagnosis of Cushing syndrome and secondary adrenal insufficiency. This was believed to have occurred in close association following cervical vertebral column facet joint injections with triamcinolone acetonide for cephalagia deemed related to cervical spine disease. The discontinuation of the RTV-boosted PI therapy alone, promoting the clearance of the elevated triamcinolone serum levels and restoration of HPA homeostasis, proved successful in this patient. For this case, the authors review the published English medical literature relating to this uncommon phenomenon.

Corticosteroid and Cortisol Serum Levels Following Intra‐articular Triamcinolone Acetonide Lumbar Facet Joint Injections

“…Methods: The study cohort included 5 patients undergoing fluoroscopically guided intra-articular lumbar facet joint injections at a pain medicine specialty clinic. Blood was collected prior to the injections and on days 1,2,4,6,8, 14,21,28,35, and 42 following the injections.…”

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

“…Another review identified 13 reports of Cushing's syndrome secondary to triamcinolone injection use in combination with ritonavir. Patients in the review had received a total of one or two doses of the medication, and symptoms usually began 2 or 3 weeks (range 4-42 days) after treatment [24]. In symptomatic patients, CYP3A4 inhibitors and corticosteroids should be stopped.…”

Iatrogenic Cushing’s syndrome due to drug interaction between glucocorticoids and the ritonavir or cobicistat containing HIV therapies

“…All of these patients were injected with triamcinolone, except one who was injected with methylprednisolone. [8][9][10][11][26][27][28][29][30] A retrospective review reported an 11% event frequency, with the biggest risk factor being two or more injections within 6 months. 26 Interestingly, a recent randomised controlled trial demonstrated no efficacy advantage of triamcinolone over methylprednisolone for knee osteoarthritis (in a non-HIV population).…”