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不同糖皮质激素经囊内注射致下丘脑-垂体-肾上腺轴抑制的对比评估:一项初步研究。

Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study.

机构信息

Pituitary Unit, IRCCS Institute of Neurological Sciences of Bologna, Bologna-Department of Biomedical and Neuromotor Sciences, University of Bologna, via Altura 3, 40139, Bologna, Italy.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

出版信息

J Endocrinol Invest. 2019 Sep;42(9):1117-1124. doi: 10.1007/s40618-019-01033-6. Epub 2019 Mar 15.

Abstract

BACKGROUND

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.

OBJECTIVE

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

下丘脑-垂体-肾上腺轴(HPAA)抑制是糖皮质激素治疗中最常见且最危险的,尽管通常未被识别和未得到治疗的副作用。风险和持续时间既取决于患者又取决于治疗特点。高效液相色谱-串联质谱法(HPLC-MS/MS)目前是评估内源性和外源性类固醇代谢的金标准方法。

目的

评估两种具有等效效力但药代动力学不同的类固醇注射后 HPAA 抑制的发生率、严重程度和持续时间。

受试者和方法

单盲随机对照初步研究。40 例(22 例女性;年龄 48.7±7.2 岁)肩钙化性肌腱炎患者接受 40mg 6α-甲基泼尼松龙醋酸酯(MA)或曲安奈德(TA)的关节内注射。在基线(T0)和注射后 1 天(T1)、7 天(T2)、15 天(T3)、30 天(T4)和 45 天(T5),我们通过 RIA 评估了早晨的皮质醇和 ACTH,通过 HPLC-MS/MS 评估了 24 小时 MA、TA 和游离皮质醇的尿水平。

结果

HPAA 功能在基线时正常。在 T1 时,所有患者均出现 HPAA 抑制,皮质醇、ACTH 和 UFC 水平达到最低,两组间无差异。在 TA 组中,T2 时平均皮质醇仍低于基线(p<0.0001)。在两组中,皮质醇和 ACTH 水平逐渐恢复正常,提示 HPA 恢复,MA 组有 3 例和 TA 组有 2 例除外。尽管外源性 GC 消失,但 UFC 水平仍低于正常(p<0.0001)直至 T5。无患者出现皮质功能减退的表现。

结论

单次关节内注射 40mg MA 或 TA 足以抑制 HPAA 45 天。尽管通常无症状,但应告知患者识别和报告提示皮质功能减退的症状,以便及时诊断和治疗,从而避免严重并发症。

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