When to consider workup for adrenal insufficiency (Addison's disease)?

From the Guidelines

Consider workup for adrenal insufficiency in patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, as these symptoms increase clinical suspicion of primary adrenal insufficiency (PAI) 1. When evaluating patients for adrenal insufficiency, it is essential to consider the clinical presentation and risk factors.

• Suggestive symptoms include unexplained collapse, hypotension, vomiting, or diarrhea, as well as hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia 1.
• The diagnostic workup should include paired measurement of serum cortisol and plasma ACTH, with a synacthen-stimulated peak serum cortisol <500 nmol/L being diagnostic of PAI in equivocal cases 1.
• In cases of suspected acute adrenal insufficiency, treatment should not be delayed by diagnostic procedures, and hydrocortisone 100 mg IV should be administered immediately after blood sampling without waiting for results 1.
• Additional testing, such as an adrenal CT, may be necessary to evaluate for precipitating causes of crisis, such as infection or metastasis 1.
• It is crucial to differentiate between primary and secondary adrenal insufficiency by measuring ACTH levels, as this will guide further management and treatment 1.
• The initial screening test is a morning cortisol level, but the most recent and highest quality study 1 recommends paired measurement of serum cortisol and plasma ACTH for diagnosis.
• For patients with confirmed PAI, management should include education on daily medications, situations of minor to moderate concurrent illnesses, and provision of supplies for self-injection of parenteral hydrocortisone 1.

From the FDA Drug Label

In the event transient hypertension develops as a consequence of therapy, the dose should be reduced to 0.05 mg daily. Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted

Consider workup for adrenal insufficiency (Addison's disease) in situations of stress such as:

• Surgery
• Infection
• Trauma When drug-induced secondary adrenocortical insufficiency is suspected, especially after discontinuation of corticosteroid therapy 2, 3.

From the Research

Considerations for Workup of Adrenal Insufficiency

When considering a workup for adrenal insufficiency (Addison's disease), several factors should be taken into account:

• Non-specific symptoms such as fatigue, anorexia, weight loss, hypotension, hyponatremia, and hyperkalemia may indicate adrenal insufficiency 4, 5, 6, 7
• A diagnosis of adrenal insufficiency should be suspected in patients with pituitary disease or a state of shock 7
• The presence of symptoms such as hypoglycemia, dehydration, and convulsions in children younger than 2 years, or virilization in young girls, may also suggest adrenal insufficiency 7
• Patients who have undergone chronic glucocorticoid therapy are at risk of adrenal insufficiency and should be evaluated accordingly 5

Diagnostic Evaluation

The diagnostic workup for adrenal insufficiency typically involves:

• Laboratory analysis, including measurement of basal serum cortisol levels 8, 7
• Assessment of adrenocorticotropic hormone (ACTH) levels to determine the underlying etiology of adrenal insufficiency 8, 7
• The cosyntropin stimulation test (Synacthen test) to confirm the diagnosis of adrenal insufficiency 4, 8, 7
• Imaging studies, when clinically indicated, to evaluate the adrenal glands and pituitary gland 4

Special Considerations

In certain situations, additional considerations should be taken into account:

• In patients with primary adrenal insufficiency, mineralocorticoid replacement therapy may be necessary in addition to glucocorticoid replacement therapy 5
• In children, the diagnostic approach may vary depending on age, with the Synacthen test being the only feasible option in children younger than 2 years 7
• After cessation of corticosteroid treatment, patient education and monitoring for signs of adrenal insufficiency are essential, with the possibility of prescribing hydrocortisone in case of stress or evaluating the ACTH axis over time until normal function is recovered 7