From the Guidelines
If you have a random low cortisol result, you should first confirm it with a morning cortisol test (between 7-9 AM) when levels are naturally highest, as recommended by the most recent guidelines 1. This approach is crucial because cortisol levels follow a diurnal rhythm, and a single random measurement may not accurately reflect adrenal function.
- The morning cortisol test helps to establish a baseline and determine if further testing is needed.
- If the morning cortisol is also low (typically below 5 mcg/dL), an ACTH stimulation test should be ordered to evaluate adrenal function, as suggested by 1. While awaiting further testing, it is essential to watch for symptoms like fatigue, dizziness, nausea, weight loss, or salt cravings, which could indicate adrenal insufficiency. In cases of confirmed adrenal insufficiency, treatment typically involves hydrocortisone (usually 15-25 mg daily divided into 2-3 doses) or prednisone (usually 3-5 mg daily), as outlined in 1. Severe cases with symptoms like vomiting, confusion, or low blood pressure require immediate medical attention, as this could indicate adrenal crisis, which needs emergency treatment with IV hydrocortisone (100 mg), fluids, and glucose, as recommended by 1. Random low cortisol values can occur due to various factors, including timing, medications (especially steroid use), lab errors, or medical conditions, so proper evaluation is essential before starting any treatment, as emphasized by 1. It is also important to note that patients with adrenal insufficiency should receive education on stress dosing, emergency injections, and the use of a medical alert bracelet or necklace, as well as guidance on when to seek medical attention for impending adrenal crisis, as recommended by 1 and 1.
From the Research
Diagnosis of Adrenal Insufficiency
To diagnose adrenal insufficiency, several tests can be used, including the adrenocorticotropic hormone (ACTH) stimulation test and the insulin tolerance test (ITT) 2, 3.
Morning Serum Cortisol Level
The morning serum cortisol level can be used as a screening test to predict adrenal insufficiency. A level of <100 nmol/l makes further dynamic testing unnecessary to confirm adrenal insufficiency, while a level of >300 nmol/l excludes the possibility of adrenal insufficiency 4, 5.
- A morning serum cortisol level of >236 nmol/l predicts adrenal sufficiency with sensitivity 84% and specificity 71% 4.
- A basal cortisol value of >375 nmol/l predicts adrenal sufficiency with sensitivity and specificity of 95% 4.
- A mean basal morning serum cortisol of >300 nmol/L excludes the possibility of adrenal insufficiency, and a level of <110 nmol/L suggests adrenal insufficiency 5.
ACTH Stimulation Test
The ACTH stimulation test can be used to diagnose adrenal insufficiency. The high-dose (250 mcg) and low-dose (1 mcg) ACTH stimulation tests have similar diagnostic accuracy in adults and children 3.
- The high-dose ACTH stimulation test has a sensitivity of 92% and a specificity of 95% for primary adrenal insufficiency 3.
- Both high- and low-dose ACTH stimulation tests are adequate to rule in, but not rule out, secondary adrenal insufficiency 3.
Insulin Tolerance Test
The insulin tolerance test (ITT) can be used to diagnose central adrenal insufficiency. A morning serum cortisol level of ≤126.4 nmol/L predicts a deficient response to ITT with a sensitivity of 13.8% and a specificity of 98.7% 6.
- A morning serum cortisol level of >444.7 nmol/L predicts a normal response to ITT with a sensitivity of 96.9% and a specificity of 14.5% 6.
Management of Adrenal Insufficiency
Administration of low-dose corticosteroids for a longer duration decreases both the amount of time that vasopressors are required and mortality at 28 days in critically ill patients 2.
- Hydrocortisone 200-300 mg/day is the preferred corticosteroid in patients with septic shock and should be started as early as possible 2.