Iatrogenic Cushing’s syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir

Abstract

The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

Iatrogenic Cushing's Syndrome Due to Pharmacokinetic Interaction of Intra-Ocular Corticosteroids and Lopinavir/Ritonavir in an HIV-Infected Adolescent: A Case Report

“…Patients who develop Cushing's syndrome may require replacement therapy with corticosteroids and gradual tapering with special consideration of the potential use of "stress dose" replacement steroids in times of acute illness or trauma. Iatrogenic Cushing's syndrome and secondary adrenal suppression have recently been reported in adult patients receiving ritonavir with a single intraarticular or epidural injection of triamcinolone acetonide [13][14][15][16]. Duration of hypothalamic pituitary axis suppression was from 5-8 months in these case reports, suggesting the persistence of systemic triamcinolone plasma concentrations and prolonged suppression of adrenal function.…”

“…Even short-term corticosteroid therapy has been associated with iatrogenic Cushing's syndrome and adrenal suppression in HIV-infected patients receiving protease inhibitors. Pharmacokinetic drug interactions caused by inhibition of the metabolism by ritonavir of various corticosteroids have been demonstrated with oral, inhaled (including intranasal), and intra-articular administration [11][12][13][14][15][16].…”

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

“…There is abundant evidence highlighting this issue. 1,[6][7][8][9][10][11] However, a structured approach to identify and manage potentially affected individuals has not been established. We aim to summarise the current management of ICS/SAI in three large HIV patient cohorts, review the available literature and develop practice recommendations.…”

“…24,25 In HIV, there are at least 30 published cases of ICS/SAI following intra-articular/epidural steroid in patients on antiretrovirals; [8][9][10][11]26 26 were on ritonavir and 4 on other ARVs. All of these patients were injected with triamcinolone, except one who was injected with methylprednisolone.…”

“…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).…”