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Intra-articular injection (IAI) of corticosteroids is a common procedure. It is a proven modality for pain relief in patients with symptomatic knee osteoarthritis (KO). 1 It can be given into 1 or more affected joints at the same visit to the clinic. 2 The major advantage of IAI is maximal local effect of the corticosteroid compound with less systemic spread. Yet, a significant proportion of the injected steroids had reached the circulation. 3 Most of the "exogenous" circulating steroids in the blood were cleared quite rapidly within few days, with very low levels (below physiologic levels) of these exogenous steroid still observed in the blood for at least 2 weeks after the IAI. 3
A wide spectrum of systemic effects, including the effect on the hypothalamic-pituitary-adrenal (HPA) axis, had been reported. 4-9 Suppression of this axis with secondary adrenal insufficiency (SAI) is a real consideration whenever an individual is subjected to depot steroid compounds including IAI of corticosteroids. Secondary adrenal insufficiency following IAI of corticosteroids depends on the type of the injected steroids, dose, type of the injected joint, number of the injected joints, and others. 3
Traditionally, the insulin tolerance test is considered the criterion standard for the evaluation of the HPA. 10 However, this test could be associated with serious adverse effects. 11 Currently, the adrenocorticotropin hormone (ACTH) stimulation test, mainly the 1-[micro]g (low dose) test, is becoming more and more popular in evaluating the HPA axis, especially SAI. 12 It is quicker, cheaper, and safer than the insulin tolerance test. 13 It has a sensitivity of ~97% and a specificity of ~78%. 14
To the best of our knowledge, there were no published studies assessing the effect of simultaneous bilateral knee injection of corticosteroids on the HPA axis. There were 2 studies assessing only the adrenal function using ACTH stimulation test following IAI of methylprednisolone acetate (MPA) at a single knee. 4,15 In the first study, there was a blunted adrenal response to ACTH stimulation in 4%, 12%, and in 4% of the patients, 2, 7, and 14 days after the IAI. In the other study, 25% of the patients with KO who had IAI of 80 mg of MPA at a single knee joint had SAI at least at one...