A Study on the Place of Low Dose Etomidate as the First Line Drug in Treating Severe Cushing Syndrome

Objective : Etomidate is a preferred drug option in treating Severe Cushing Syndrome (SCS) especially when there is failed response to other drugs like ketoconazole.


Methods:

A descriptive retrospective analytic study of 9 patients with SCS treated with Etomidate in Sri Lanka between the years 2016 – 2020.

Results:

3 out of 9 patients with SCS were treated with etomidate as the 1st line therapy, of which all recovered successfully, and neither developed adrenal insufficiency (AI). These 3 cases comprised 2 ACTH secreting pituitary microadenomas and 1 bilateral macronodular adrenal hyperplasia. 4 cases, including 2 which were treated with etomidate as 3rd line were switched to etomidate from ketoconazole due to failed response, but all 4 succumbed to sepsis.

The mean percentage drop of cortisol from baseline in etomidate being used as 1st, 2nd, and 3rd line were 71%, 62%, and 40% respectively, indicating better efficacy when etomidate was being given as 1st line. The mean rate of reduction of cortisol was highest, being 104.3 nmol/l/hour, when etomidate was used as 1st line, followed by 2nd and 3rd line respectively, with the rates being 30 nmol/l/hour and 11 nmol/l/hour. All patients took a mean of 48 hours to reach target cortisol levels since starting etomidate infusion, and those who recovered successfully took a mean of 38 hours. The mean time taken for cortisol to normalize was 15 hours when etomidate was used as 1st line, followed by 80 and 48 hours when etomidate was used as 2nd line and 3rd line respectively. There was a statistically significant difference of mean times taken for cortisol to normalize based on the place of etomidate in treatment according to the one way ANOVA test (p=0.001)

One patient was treated with block and replacement regime with etomidate and hydrocortisone without developing AI. None others, of those which targeted partial reduction of cortisol to normal levels with etomidate developed AI, except for one patient who was started on a high dose etomidate infusion rate of 0.3mg/kg/hour, compared to the standard low dose rate of 0.02 – 0.05 mg/kg/hour, resulting in AI on day 5. Only one patient was given an etomidate bolus prior to infusion, and had no significant difference in outcome, and recovered successfully, without AI.

Discussion/Conclusion:

Etomidate used as 1^st line in treating SCS has better efficacy in normalizing cortisol levels and overall survival outcome than using Etomidate as 2^nd or 3^rd line therapy. Etomidate use in treating SCS is unlikely to cause AI unless initiated as a high dose rate of infusion of 0.3 mg/kg/hour. Thus, low dose Etomidate infusion with or without prior bolus is considered safe.