The 65-year old woman’s stomach started to hurt about a week ago.
She thought nothing much of it at first, but the pain intensified and she started spiking fevers, feeling weak and dizzy. When she couldn’t get out of bed, her husband called for an ambulance.
By the time she arrives at the hospital, her blood pressure is dangerously low. She’s admitted to the intensive care unit in shock. Her team moves quickly to administer antibiotics and place intravenous catheters for better blood pressure monitoring. Her blood pressure remains dangerously low throughout the night.
On rounds the next morning, the medical team discusses her case. After reviewing her medications, a member of her team asks a question anyone who has worked in an ICU in recent years has come to anticipate– “What about glucocorticoids?”
A few years back the answer would have been to perform a cosyntropin stimulation test—a test that aims to determine whether the critically ill patient, whose hypthothalamic-pituitary-adrenal axis should be activated by the stress of illness, is able to produce sufficient glucocorticoids. If our patient hadn’t met the bar of an acceptable response to this challenge, her team would have determined her to have “relative adrenal insufficiency” and would have supplemented her with exogenous glucocorticoids.
But now performing such a stimulation test on the critically ill has fallen out of favor. In 2008, the CORTICUS study published in NEJM showed no mortality benefit in giving glucocorticoids to patients in septic shock, even in those without a response to cosyntropin, suggesting that the concept of ‘relative adrenal insufficiency’ is less useful than previously thought.
Thus, even after decades of study, the role of exogenous glucocorticoids in septic shock remains controversial. Into this hotly debated arena comes a new study published in this week’s issue of NEJM. However, the current study does not seek to change practice regarding the use of glucocorticoids in the ICU, but instead aims to better elucidate the mechanism of elevated cortisol levels in the critically ill.
In this study, Eva Boonen M.D. and colleagues investigate a specific, seemingly paradoxical observation about cortisol in critical illness: High levels of cortisol despite low levels of corticotropin, the hormone that encourages cortisol production. Why might this occur? The investigators postulated that perhaps cortisol might not be metabolized at the same rate in critical illness, which would explain why cortisol levels could be high without producing more cortisol.
To explore this theory, the investigators enrolled 158 intensive care unit patients and tested five aspects of their cortisol metabolism, including daily cortisol levels, the ability to clear exogenously administered glucocorticoids, levels of cortisol metabolites in the urine and levels of cortisol-metabolizing enzymes. They compared these results to those in 64 healthy control patients.
The results suggest that during critical illness, the body metabolizes and inactivates cortisol at a slower rate. These observations offer an explanation for the seemingly counterintuitive observation of high cortisol levels, with lower levels of cortisol-stimulating hormone.
While this study adds to the understanding of cortisol metabolism in critical illness, the treatment implications remain unclear. The authors make a few suggestions as to how their findings could be applied in the clinical setting. First, they write, if cortisol metabolism is decreased then “stress doses” of 200 mg daily of hydrocortisone “are at least three times too high.” Additionally, they note, low cortisol response to corticotropin stimulation does not necessarily translate to adrenal insufficiency. After all, with reduced metabolism, cortisol levels could still remain high.
In the same issue of NEJM, you’ll also find the editorial, “Low Glutamine Levels during Critical Illness — Adaptive or Maladaptive?“