Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic–pituitary–adrenal axis: a randomized controlled study

Abstract

The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic-pituitary-adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80 mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6 ml (60 mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1 μg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7 μg/dl increase in the serum cortisol level and absolute levels of <18 μg/dl 30 min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25 % of patients had SAI vs. none in group 2 (p = 0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80 mg MPA at the knee joint induced a transient SAI in 25 % of the patients, an effect that was observed between week 2 and week 4 following the IACI.

Simultaneous Bilateral Knee Injection of Methylprednisolone Acetate and the Hypothalamic-Pituitary Adrenal Axis: A Single-Blind Case-Control Study

“…Such a phenomenon was also observed in a previous study. 15 We think it reflects, at least in patient 12, variation in systemic absorption of the methylprednisolone from the knee cavity over a period, rather than intrinsic variability in ACTH stimulation test. This conclusion is supported by the fact that both basal and poststimulation serum cortisol levels in this patient at each time point, including at the time of SAI, were in the same trend.…”

“…15 Thus, it seems that simultaneous IAIs of MPA at the bilateral knees have an additive or even synergistic effect for the development of SAI with a much more prolonged effect.…”

Joint Corticosteroid Injection Associated With Increased Influenza Risk

“…In immunosuppressed individuals, the humoral immune response may be compromised, resulting in less effective immune response to vaccination. Intraarticular corticosteroid injection is known to cause transient suppression of endogenous cortisol production, 1 and corticosteroids (CSs) are known to cause immunosuppression by multiple mechanisms 2 . Despite well over a half century of use to treat inflammatory, crystalline, and degenerative arthritis, 3 no data exist regarding the risk of intraarticular or bursa CS injections and susceptibility to influenza infection.…”

Methylprednisolone Pulse Treatment of Graves' Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency

“…Suppression of the HPA axis has been reported as a side effect of many different glucocorticoid treatment schedules for various inflammatory diseases [5,6]. …”