From the Guidelines
A cortisol baseline level of less than 250 nmol/L, in the presence of acute illness, is diagnostic of primary adrenal insufficiency, while a level of less than 400 nmol/L raises a strong suspicion of the condition. This is based on the recommendations from the Journal of Internal Medicine, 1, which provides guidelines for the diagnosis and treatment of primary adrenal insufficiency. The guidelines emphasize the importance of considering the diagnosis of primary adrenal insufficiency in patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and highlight the role of paired measurement of serum cortisol and plasma ACTH in making the diagnosis.
Key points to consider in the diagnosis of adrenal insufficiency include:
- A morning cortisol level below 250 nmol/L is diagnostic of primary adrenal insufficiency in the presence of acute illness, while a level below 400 nmol/L raises a strong suspicion of the condition, 1.
- The ACTH stimulation test is a useful diagnostic tool, with a peak cortisol response below 500 nmol/L confirming adrenal insufficiency, 1.
- The timing of cortisol measurement is crucial, with levels typically highest in the early morning and lowest at midnight, 1.
- Certain medications, such as oral contraceptives and estrogen, can affect cortisol measurements by increasing cortisol-binding globulin, 1.
In terms of treatment, hydrocortisone replacement therapy is typically recommended, with a daily dose of 15-25 mg in divided doses, 1. It is also important to note that patients with adrenal insufficiency should wear Medic Alert identification jewelry and carry a steroid/alert card, and should receive education on how to manage their condition, including how to adjust their medication doses during times of stress or illness, 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Cortisol Baseline Indicating Adrenal Insufficiency
- Adrenal insufficiency is a rare disease characterized by cortisol deficiency, and its evaluation can be challenging due to the rarity of the disease and limitations in biochemical assessment of cortisol status 2.
- The diagnosis of adrenal insufficiency is made by demonstrating low basal and/or stimulated serum cortisol, and should be followed by appropriate investigations to establish the underlying aetiology 3.
- A morning serum cortisol of <100 nmol/l makes further dynamic testing such as the Synacthen stimulation test (SST) unnecessary to confirm adrenal insufficiency, while a basal cortisol value of >236 nmol/l can predict adrenal sufficiency with sensitivity 84% and specificity 71% 4.
- Home waking salivary cortisone level can be used to screen for adrenal insufficiency, with a negative predictive value of 96% and a positive predictive value of 95% to exclude and confirm adrenal insufficiency, respectively 5.
- The accurate interpretation of the cosyntropin stimulation test requires method- and assay-specific cutoffs of the level of cortisol, with a recommended threshold of 14.6 μg/dL for the Abbott Architect immunoassay 6.
Diagnostic Cutoffs for Adrenal Insufficiency
- The use of assay-specific cutoffs is essential for reducing misclassification and overtreatment in patients with suspected adrenal insufficiency 6.
- A basal cortisol cut-off of >375 nmol/l can predict adrenal sufficiency with a specificity of 95%, while a cut-off of >214 nmol/l may obviate the need for SST in patients with known pituitary disease 4.
- The area under the receiver-operating characteristic curve for waking salivary cortisone as a predictor of adrenal insufficiency was 0.95, indicating high accuracy for the diagnosis of adrenal insufficiency 5.
Clinical Presentation and Diagnosis
- Clinicians evaluating patients with suspected adrenal insufficiency should take into consideration the clinical presentation and be aware of clinical and technical factors that can affect cortisol values and diagnostic accuracy of the ACTH stimulation test 2.
- Patients with primary adrenal insufficiency also require mineralocorticoid replacement, and regular monitoring for features of under- and over-replacement is essential during follow-up 3.