Incidence of Adrenal Insufficiency and Cushing's Syndrome After Long-Term Epidural Steroid Injections Over Six Months or Longer: A Preliminary Study

Abstract

Purpose: Endocrinological complications of an epidural steroid injection (ESI) are rare but dangerous. Nevertheless, despite the associated risks, repeated long-term ESIs are indispensable in some clinical situations. However, only a few reports to date have assessed the safety of this procedure. In this study, we evaluate the incidence of adrenal insufficiency (AI) and Cushing's syndrome after long-term ESIs.

Methods: This clinical observational study enrolled herniated nucleus pulposus or spinal stenosis patients who had received ESIs over a period of six months or longer. The adrenocorticotropic hormone (ACTH) stimulation test was performed to confirm AI and the late-night salivary cortisol (LNSC) test was performed to diagnose Cushing's syndrome. To evaluate the hypothalamus pituitary adrenal axis suppression, salivary cortisol (SC) levels were measured on days 0, 1, 7, 21, 28, 35, and 42.

Results: This study included 17 patients. Among these, two patients (11.8%) developed AI, but no cases of Cushing's syndrome were reported. There was no predictor for the development of AI. The SC levels tended to increase with time after an ESI (β = 0.003). The slope of the mixed effect model between the AI and non-AI groups showed a significant difference (p value = 0.015). However, the differences in mean SC levels at each time point between the two groups were not significant (adjusted p value = 0.053).

Conclusion: Long-term ESI use may be associated with AI development. An unexpected adrenal crisis due to AI could be life threatening. Therefore, regular monitoring of adrenal function in patients who have received long-term ESIs may be prudent.

Keywords: adrenal insufficiency; epidural; glucocorticoid; long-term; salivary cortisol.

Figure 1

Flow diagram of the study.

Figure 2

Comparison of the increment rate of SC concentration according to time between the AI group and non-AI groups. (A) Comparison of the mean difference of the slope of the mixed effect model between the AI and non-AI groups expressed as 1/4Q, median, and 3/4Q. (B) Comparison of the mean difference of the slope of linear regression between the AI group and non-AI groups expressed as 1/4Q, median, and 3/4Q. *p value < 0.05. Abbreviations: SC, salivary cortisol; AI, adrenal insufficiency; Q, quartile.

Figure 3

Comparison of the trend of SC for each patient. Black dotted line is linear regression line estimated using population. Red dashed line is the fitted line estimated using a mixed effect model. Blue solid line is linear regression line estimated using subject-specific data. Blue point circle is SC level measured at the corresponding time. X axis shows the time represented as day. Cases 03 and 17 were AI subjects. Abbreviations: SC, salivary cortisol; AI, adrenal insufficiency.

Figure 4

Time trend of mean SC according to complication. The time course and response pattern (mean ± SD) in SC. After the experimental ESI, SC concentrations of all subjects were initially suppressed (D1). In most of the subjects in the non-AI group, SC concentration returned to the normal range of values. However, in the AI group, the SC concentration did not return to the normal range. Abbreviations: ESI, epidural steroid injection; SC, salivary cortisol; AI, adrenal insufficiency; SD, standard deviation.