Cosyntropin testing does not predict response to glucocorticoids in community‐acquired pneumonia in a randomized controlled trial

Abstract

Summary Objective Glucocorticoids have been shown to improve outcome in community‐acquired pneumonia (CAP). However, glucocorticoids have potential side‐effects, and treatment response may vary. It is thus crucial to select patients with high likelihood to respond favourably. In critical illness, cosyntropin testing is recommended to identify patients in need for glucocorticoids. We investigated whether cosyntropin testing predicts treatment response to glucocorticoids in CAP. Design Predefined secondary analysis of a randomized controlled trial. Patients Hospitalized patients with CAP. Measurements We performed 1 µg cosyntropin tests in a randomized trial comparing prednisone 50 mg for 7 days to placebo. We investigated whether subgroups based on baseline and stimulated cortisol levels responded differently to glucocorticoids with regard to time to clinical stability (TTCS) and other outcomes by inclusion of interaction terms into statistical models. Results A total of 326 patients in the prednisone and 309 patients in the placebo group were evaluated. Neither basal cortisol nor a Δcortisol <250 nmol/L after stimulation nor the combination of basal cortisol and Δcortisol predicted treatment response as measured by TTCS (all P for interaction >0.05). Similarly, we found no effect modification with respect to mortality, rehospitalization, antibiotic treatment duration or CAP‐related complications (all P for interaction >0.05). However, glucocorticoids had a stronger effect on shortening length of hospital stay in patients with a baseline cortisol of ≥938 nmol/L (P for interaction = 0.015). Conclusions Neither baseline nor stimulated cortisol after low‐dose cosyntropin testing at a dose of 1 µg predicted glucocorticoid responsiveness in mild to moderate CAP. A treatment decision for or against adjunct glucocorticoids in CAP should not be made depending on cortisol values or cosyntropin testing results.

Secondary adrenal insufficiency induced by long-term use of opioid analgesics

“…However, even a cortisol value above this should not preclude treatment with glucocorticoids if the clinical presentation is consistent with cortisol deficiency. 3 Moreover, even low-dose cosyntropin testing may not predict response to glucocorticoids 4 and thus initial cosyntropin testing may miss secondary cortisol deficiency. 5 We agree with Burgos et al 6 that the patient's clinical presentation should be considered when interpreting cosyntropin tests.…”

Critical illness-related corticosteroid insufficiency: What we know and what we don’t know

“…23,24 Steroid benefit does not seem to correlate to the response to a cosyntropin stimulation test in this setting. 25 The benefits of the use of hydrocortisone and fludrocortisone in patients with major trauma are not well established at this time. 5 Relative adrenal insufficiency has also been described in patients with ischemic stroke 26 and has been found to be highly prevalent in patients with liver disease, 27 and burn patients.…”

Cytokines and Cortisol – predictors of treatment response to corticosteroids in community‐acquired pneumonia?

“…In contrast, the CORTICUS trial found no treatment prediction by adrenal function testing with 250 μg synthetic adrenocorticotropin (ACTH) . Similarly, we recently showed that adrenal function testing using the low‐dose 1 μg ACTH test does not predict response to corticosteroid therapy in patients with CAP . Consequently, the current guidelines for the diagnosis and management of CIRCI did not reach consensus in this point and therefore make no recommendation in terms of adrenal function testing in the context of critical illness .…”