From the Guidelines
Investigations for Addison's disease should include both screening tests and confirmatory tests to establish the diagnosis, with the short Synacthen (ACTH) stimulation test being the definitive diagnostic test, as recommended by the most recent guidelines 1.
Initial Screening
Initial screening should involve measuring morning serum cortisol and plasma ACTH levels, with low cortisol (<140 nmol/L) and elevated ACTH (>80 ng/L) suggesting primary adrenal insufficiency, as noted in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1.
- Electrolyte abnormalities including hyponatremia, hyperkalemia, and metabolic acidosis may be present.
- The high-dose (250-μg) ACTH stimulation test is the most popular diagnostic test for adrenal insufficiency, and its use is suggested due to easier practical modalities and comparable accuracy to the low-dose test 1.
Confirmatory Tests
The short Synacthen (ACTH) stimulation test is the definitive diagnostic test, where 250 μg of synthetic ACTH is administered intravenously or intramuscularly, with cortisol levels measured at baseline, 30 minutes, and 60 minutes, as described in the guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) 1.
- A peak cortisol response below 500-550 nmol/L confirms adrenal insufficiency.
- Once adrenal insufficiency is confirmed, determining the etiology is important, with adrenal antibodies being checked to identify autoimmune adrenalitis, the most common cause, as outlined in the classification and causes of primary adrenal insufficiency 1.
Additional Tests
Additional tests may include:
- Imaging studies, including abdominal CT scan, to detect adrenal calcification, hemorrhage, or infiltrative processes, as recommended in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1.
- Very long-chain fatty acid levels should be measured to rule out adrenoleukodystrophy in younger patients, as suggested in the guidelines for the diagnosis and management of CIRCI 1.
- Tuberculosis screening, fungal serologies, and HIV testing may be necessary depending on clinical suspicion, as noted in the classification and causes of primary adrenal insufficiency 1. These investigations are crucial as early diagnosis allows for appropriate hormone replacement therapy with hydrocortisone and fludrocortisone to prevent life-threatening adrenal crisis, as emphasized in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1.
From the Research
Investigations for Addison's Disease
To investigate Addison's disease, the following steps can be taken:
- A high clinical suspicion is needed to avoid misdiagnosing a life-threatening adrenal crisis 2
- Clinical manifestations before an adrenal crisis can include hyperpigmentation, fatigue, anorexia, orthostasis, nausea, muscle and joint pain, and salt craving 2
- Cortisol levels decrease and adrenocorticotropic hormone levels increase 2
- A cosyntropin stimulation test can be used to confirm the diagnosis when clinically suspected 2
Diagnostic Strategies
Diagnostic strategies for Addison's disease may include:
- Standard care treatments, including the management of patients during pregnancy and adrenal crises 3
- Emerging therapies designed to improve the quality of life and new strategies to modify the natural history of autoimmune AD 3
- Genetic diagnosis, especially in pediatric cases 4
- Awareness of unusual presentations and the importance of pediatric and adult awareness 4
Management and Treatment
Management and treatment of Addison's disease may involve:
- Replacement of mineralocorticoids and glucocorticoids 2
- Stress-dose glucocorticoids during times of stress, such as illness or invasive surgical procedures 2
- Continuous education of patients and health care professionals on the ever-present danger of adrenal crisis 3
- Research on immune checkpoint inhibitors, which can cause a large panel of endocrine side effects, including Addison's disease 4