Adrenal insufficiency in post CABG patients: adequacy of ACTH-stimulation tests

Tuhina Raman MD
Fellow MD / MPH Program
Pulmonary and Critical Care Division/School of Graduate Studies
Thomas JeffersonUniversity
1015 Chestnut Street
Suite M100
Philadelphia, PA19107

After cardiac surgery, the adrenal system might be a limiting factor for combating the stress imposed by this procedure. We searched the literature (PubMed, www.pubmed.org) using the words "adrenal insufficiency" AND "coronary artery bypass surgery". After exclusion of adrenal hemorrhage, adrenal neoplasms, adrenal infections and polyglandular disease as cause for adrenal insufficiency in patients undergoing cardiac surgery [1-10], we were left with 2 articles [11, 12]. Both articles addressed the cortisol response to stress caused by coronary artery bypass grafting (CABG).

Henzen et al defined adrenal insufficiency as a plasma cortisol concentration < 20 ug/dL 30 minutes after administration of 1  µg ACTH [11]. They showed that as much as 25% of post-CABG patients had a (partially) deficient adrenal response. These patients were otherwise asymptomatic as regard to endocrine disorders. Remarkably, a blunted adrenal response was already present before surgery, and maximum plasma cortisol concentrations were reached 24 hours later than in patients with normal adrenal function. Among various clinical outcome parameters a correlation was demonstrated between adrenal function and blood loss and volume balance to suggest that adrenal insufficiency is linked to higher blood loss and a negative fluid balance. Although these results are statistically significant, the mechanism and clinical implications are not clear. The reason for the surprisingly high proportion of patients with partial adrenal insufficiency in this study remains unexplained.

Widmer et al did not define adrenal insufficiency [12]. They simply described cortisol responses to ACTH-stimulation in 3 patient groups (controls, hospitalized medical patients, and patients undergoing CABG). ACTH-stimulation was randomly performed with either 1 or 250 ug ACTH. In CABG-patients, cortisol levels peaked shortly after extubation. Peak basal cortisol levels were comparable to those previously described during major surgery and critical illness respectively. During acute maximal stress in the immediate postoperative period, almost all patients had basal cortisol concentrations > 15 ug/dL, whereas over a third had basal cortisol concentrations < 25 ug/dL. ACTH stimulated cortisol to levels > 25 ug/dl in virtually all of the patients in the immediate postoperative period. CABG-patients with a smaller rise in cortisol levels upon ACTH stimulation, an indirect predictor of worse outcome, had higher ACTH/cortisol ratios. No differences were noticed regarding outcomes between the 3 patient groups and between responders and non responders to ACTH. There were no differences in the response to 1 ug versus 250 ug of ACTH in the controls and in the patients undergoing CABG (although in this population there was a higher cortisol response to 250 ug noted on the day of surgery and post extubation). In the group of hospitalized medical patients the 250 ug dose of ACTH generated a higher cortisol response than the 1 ug dose. Intraclass correlations in peak cortisol concentrations after ACTH stimulation were not different between healthy controls and medical patients or between the 1 ug and 250 ug ACTH tests. Marik et al considered peak cortisol levels > 25 ug/dl to be indicative of normal adrenal gland function [13]. An inadequate rise of cortisol levels (< 9 ug/dl) after a 250 ug test is another criterion proposed for the definition of relative adrenal insufficiency in critical illness [14]. Unfortunately, in the two above-cited studies other (or no) criteria were used. Of interest, however, in the study by Widmer et al 38.5% of the clinically euadrenal and maximally stressed surgical patients with an uneventful clinical course showed an inadequate rise of cortisol levels after the 250 ug ACTH-stimulation, when using the 9 ug/dL criterion. Even in healthy, unstressed controls, 12.8% did not meet the 9 ug/dL criterion when using the 250 ug ACTH- stimulation. When the 1 ug ACTH-stimulation was used almost 50% of patients in all three groups did not meet the 9 ug/dL criterion.

Although the 9 ug/dL change was recommended by Annane et al [14] as a criterion for relative adrenal insufficiency his study used the 250 ug ACTH-stimulation and hence it is difficult to interpret the 9 ug/dL change when using the 1 ug ACTH stimulation test as done by Widmer et al which made many more people appear apparently adrenally insufficient. The bottom line is that inability to reach change in plasma cortisol levels of > 9 ug/dL did not translate into worse clinical outcomes regardless of which dose of ACTH was used for the stimulation test. Hence the question of the ideal test for diagnosing relative adrenal insufficiency still remains unanswered.

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