Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study
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Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids.
To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics.
Subjects and methods
Single-blind randomized case–control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC–MS/MS.
HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism.
A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.
KeywordsAdrenal insufficiency Glucocorticoids Methylprednisolone acetate Triamcinolone acetonide Liquid chromatography-tandem mass spectrometry
The study was supported by a IRCCS Rizzoli Orthopaedic Institute research grant to M.B.
Compliance with ethical standards
The Authors declare they have nothing to disclose.
Conflict of interest
The Authors declare that they have no conflict of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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