From the Guidelines
The workup for adrenal insufficiency should begin with evaluating morning cortisol and ACTH levels, specifically checking AM levels of ACTH (if ≥ 23 ULN) and cortisol level (if ≤ 3 mg/dL), as recommended by the most recent guideline update 1. The initial evaluation should also include a basic metabolic panel (Na, K, CO2, and glucose) and measurement of renin and aldosterone levels.
- If the initial results are inconclusive, a standard dose ACTH stimulation test should be considered to confirm the diagnosis.
- The workup should also include an evaluation for precipitating causes of crisis, such as infection.
- Adrenal CT imaging is recommended to check for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency. Key points to consider in the workup include:
- Differentiating between primary and secondary adrenal insufficiency based on ACTH levels, with elevated ACTH indicating primary adrenal insufficiency and low or normal ACTH suggesting secondary adrenal insufficiency 1.
- Monitoring patients closely for signs of adrenal crisis and initiating treatment with hydrocortisone promptly if symptomatic, without waiting for test results.
- Considering additional testing, such as measuring adrenal antibodies and performing adrenal imaging with CT or MRI, in cases of primary adrenal insufficiency. The most recent guideline update 1 provides a comprehensive approach to the workup and evaluation of adrenal insufficiency, emphasizing the importance of prompt diagnosis and treatment to prevent adrenal crisis and improve patient outcomes.
From the Research
Adrenal Insufficiency Workup
The workup for adrenal insufficiency involves several steps and tests to determine the presence and type of adrenal insufficiency.
- The diagnosis of primary adrenal insufficiency (PAI) can be made by measuring morning cortisol concentrations, with values above 350 nmol/l considered to safely rule out Addison's disease 2.
- Elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 μg/dl) 2.
- However, normal cortisol concentrations do not rule out primary adrenal insufficiency, as approximately 10% of patients with PAI may present with normal cortisol levels 2.
- The diagnosis of secondary adrenal insufficiency (SAI) can be made by measuring unstimulated early morning cortisol in saliva and serum, with upper and lower thresholds calculated by ROC analysis 3.
- The insulin tolerance test (ITT) is considered the gold standard for diagnosing SAI, but basal cortisol measurements can be used as a first-line screening method 3.
- The rapid adrenocorticotropin (ACTH) test is an indirect screening test for adrenocortical insufficiency, and single measurements of plasma cortisol, ACTH, aldosterone, and PRA can be used as a definitive diagnostic test of primary adrenocortical insufficiency (PAI) 4.
- Plasma renin activity (PRA) measurements during treatment with hydro- and fludrocortisone can be used as a guide for correct mineralocorticoid substitution 4.
- Early recognition and appropriate treatment of primary adrenal insufficiency can greatly improve patient outcomes and quality of life 5.
Diagnostic Tests
The following diagnostic tests can be used to diagnose adrenal insufficiency:
- Morning cortisol concentrations
- Corticotropin concentrations
- Unstimulated early morning cortisol in saliva and serum
- Insulin tolerance test (ITT)
- Rapid adrenocorticotropin (ACTH) test
- Single measurements of plasma cortisol, ACTH, aldosterone, and PRA
- Plasma renin activity (PRA) measurements during treatment with hydro- and fludrocortisone 2, 3, 4.
Treatment
The treatment of adrenal insufficiency involves hormone replacement therapy, with the goal of establishing a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs 6.