From the Guidelines
In adrenal axis insufficiency, diagnosis is primarily based on blood tests showing low morning cortisol levels, often accompanied by high ACTH levels in primary adrenal insufficiency or inappropriately low/normal ACTH in secondary forms, as noted in 1 and 1. When evaluating blood results in adrenal axis insufficiency, it's crucial to consider the relationship between ACTH and cortisol levels.
- Low morning cortisol levels (below 3-5 μg/dL) are a key indicator of adrenal insufficiency.
- High ACTH levels in primary adrenal insufficiency or inappropriately low/normal ACTH in secondary forms can help distinguish between the two types.
- Additional laboratory findings may include hyponatremia, hyperkalemia, hypoglycemia, and mild metabolic acidosis, particularly in primary adrenal insufficiency, as mentioned in 1.
- An ACTH stimulation test can confirm the diagnosis, where cortisol fails to rise above 18-20 μg/dL after synthetic ACTH administration, as discussed in 1 and 1.
- Other relevant tests may include a basic metabolic panel (Na, K, CO, glucose) and evaluation for precipitating causes of crisis, such as infection, as suggested in 1. The diagnostic work-up should prioritize evaluating ACTH and cortisol levels, as well as considering an ACTH stimulation test for indeterminate results, as recommended in 1. In terms of treatment, glucocorticoid replacement, typically with hydrocortisone, and mineralocorticoid replacement with fludrocortisone in primary insufficiency, are essential for managing adrenal axis insufficiency, as generally accepted in clinical practice, and emergency therapy may involve dexamethasone or hydrocortisone, as noted in 1.
From the Research
Blood Results in Adrenal Axis Insufficiency
- Adrenal insufficiency is a condition characterized by an absolute or relative deficiency of adrenal cortisol production 2
- The diagnosis of adrenal insufficiency is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones, and stimulation tests 2
- Basal cortisol levels can be used to predict adrenal insufficiency, with a level of ≥450 nmol/L having a negative predictive value of 98.7% to rule out adrenal insufficiency, and a level of ≤100 nmol/L having a positive predictive value of 93.2% to rule in adrenal insufficiency 3
- Dehydroepiandrosterone sulfate (DHEA-S) measurements can also be valuable in diagnosing adrenal insufficiency, with a normal age- and sex-adjusted serum DHEA-S level practically ruling out the diagnosis 4
Diagnostic Tests
- The ACTH stimulation test is the current standard for assessing primary and secondary adrenal insufficiency 3, 5
- The test involves measuring the level of cortisol in the blood before and after stimulation with adrenocorticotropic hormone (ACTH) 3, 5
- Different assays may have different diagnostic cutoffs for cortisol levels, such as the Abbott Architect immunoassay, which has a recommended threshold of 14.6 μg/dL at 60 minutes after stimulation 6
- The high- and low-dose ACTH stimulation tests have similar diagnostic accuracy, but may have different likelihood ratios for positive and negative tests 5
Interpretation of Results
- A random serum cortisol level of ≥12 μg/dL in the ambulatory setting or a normal age- and sex-adjusted DHEA-S level may make the diagnosis of adrenal insufficiency unlikely 4
- A low basal cortisol level or a low DHEA-S level may indicate adrenal insufficiency, but dynamic testing may be necessary to confirm the diagnosis 3, 4
- The results of the ACTH stimulation test should be interpreted in the context of the patient's clinical presentation and medical history 2, 5