From the Guidelines
The short Synacthen test is a crucial diagnostic tool for assessing adrenal function, particularly in critically ill patients, and its significance lies in identifying relative adrenal insufficiency (RAI) with a delta total serum cortisol <250 nmol/L after adrenocorticotrophic hormone administration. The test is utilized to evaluate the response of the adrenal glands to adrenocorticotrophic hormone (ACTH) stimulation, which is essential in patients with cirrhosis, as they are at risk of developing RAI 1. The diagnosis of RAI is critical, as it can impact patient outcomes, including morbidity, mortality, and quality of life.
Key Findings
- The short Synacthen test can be used to diagnose RAI in patients with cirrhosis, with a delta total serum cortisol <250 nmol/L after ACTH administration 1.
- However, the diagnosis of RAI based on serum total cortisol concentration may be flawed due to reduced serum levels of cortisol binding globulin (CBG) and albumin in patients with cirrhosis 1.
- Serum-free cortisol levels <50 nmol/L at baseline, or <86 nmol/L after ACTH, suggest the presence of RAI in critically ill patients 1.
- Salivary cortisol has been proposed as an alternative to serum cortisol, with baseline salivary cortisol <1.8 ng/ml or an increment <3 ng/ml following a standard-dose short Synacthen test suggestive of RAI 1.
Clinical Implications
- The short Synacthen test should be used in conjunction with clinical judgment to diagnose RAI in patients with cirrhosis 1.
- Patients with suspected RAI should be managed with organ support and treatment of precipitating factors, and referral to liver transplant centers should be considered 1.
- The use of surrogate methods for calculating plasma free cortisol is not fully reliable in patients with cirrhosis, and salivary cortisol may be a useful alternative 1.
From the Research
Significance of the Short Synacthen Test
The short Synacthen test is a widely used assessment for adrenal reserve, with its significance lying in its ability to diagnose adrenal insufficiency. The test involves administering synthetic adrenocorticotropic hormone (ACTH) and measuring the resulting cortisol levels in the blood at various time points, typically 0, 30, and 60 minutes.
Optimum Sampling Times
- The optimum sampling times for the short Synacthen test have been a subject of debate, with some studies suggesting that a 60-minute sample may not be necessary for all patients 2, 3.
- A study found that using the 30-minute cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases, with only a small subset of patients having a suboptimal response at 30 minutes but a 60-minute cortisol concentration above the threshold for a pass 2.
- Another study suggested that the 30-minute sample does not add any additional diagnostic utility and can be omitted, proposing that a single measurement after 60 minutes of administration of synthetic ACTH is a sufficient screening test for adrenal insufficiency 3.
Diagnostic Accuracy
- The diagnostic accuracy of the short Synacthen test has been compared to other tests, such as the insulin tolerance test (ITT), with some studies finding that the low-dose short Synacthen test (1 μg) is a more reliable and safer alternative to ITT 4.
- A study found that the sensitivity of the low-dose short Synacthen test was 100% (cortisol response of >600 nmol/L indicates intact HPA axis), with no falsely reassuring results 4.
- The conventional dose short Synacthen test (250 μg) was found to be less sensitive than the low-dose test, producing 2 of 64 (3%) falsely reassuring results 4.
Cut-Off Values
- The cut-off values for the short Synacthen test have been debated, with some studies suggesting that a cortisol level of ≥500 nmol/L is sufficient to rule out adrenal insufficiency 5.
- However, other studies have suggested that a higher cut-off value, such as ≥600 nmol/L, may be more helpful for clinical decision-making 4.
- A study found that a morning basal serum cortisol level of ≥354 nmol/L was able to predict normal adrenal function with 100% sensitivity, suggesting that basal morning serum cortisol can be safely used as a first step in the evaluation of patients with suspected adrenal insufficiency 6.