What are the diagnostic criteria for adrenal insufficiency (Addison's disease)?

From the Guidelines

Diagnosis of adrenal insufficiency (Addison's disease) is typically made through a combination of clinical evaluation, laboratory tests, and imaging studies, with a focus on assessing adrenal cortex function and establishing the underlying aetiology 1.

Diagnostic Criteria

The diagnostic criteria for primary adrenal insufficiency (PAI) include:

• Low serum cortisol levels: usually below the normal range, with plasma adrenocorticotropic hormone (ACTH) levels clearly increased 1
• Inappropriately low cortisol levels: in some patients presenting with serum cortisol levels within the normal range, but inappropriately low for the disease state, such as patients with sepsis 1
• Increased plasma renin activity (PRA): whilst serum aldosterone and dehydroepiandrosterone sulphate (DHEAS) levels are low 1
• Electrolyte imbalance: hyponatraemia and hyperkalaemia, although not reliable markers, are present in many cases 1

Laboratory Tests

Laboratory tests used to diagnose adrenal insufficiency include:

• Morning cortisol level: if below 3 mcg/dL, adrenal insufficiency is likely 1
• Cosyntropin stimulation test: 250 mcg of cosyntropin is administered intravenously, and cortisol levels are measured at 30 and 60 minutes after administration, with an increase in cortisol level of less than 18 mcg/dL at 30 or 60 minutes indicating adrenal insufficiency 1
• ACTH level: to assess adrenal cortex function and establish the underlying aetiology 1
• Electrolyte panel and renal function tests: to evaluate for electrolyte imbalance and renal function abnormalities 1

Imaging Studies

Imaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI) of the adrenal glands, may be necessary to evaluate for adrenal gland abnormalities 1. It is essential to note that the diagnosis of adrenal insufficiency should be made by a qualified healthcare professional, and treatment should be initiated promptly if the diagnosis is confirmed, with hydrocortisone being the preferred medication for treatment, and the typical dose being 15-25 mg per day, divided into two or three doses 1.

From the Research

Diagnostic Criteria for Adrenal Insufficiency

The diagnosis of adrenal insufficiency (AI) requires a combination of clinical assessment, laboratory evaluation, and imaging studies. The diagnostic criteria for AI include:

• Clinical characteristics such as insidious onset, fatigue, weight loss, and hypotension 2, 3, 4
• Laboratory tests including:
  • Basal serum cortisol levels (<140 nmol/L or 5 mcg/dL) 2
  • Adrenocorticotrophin (ACTH) levels 2
  • Cosyntropin stimulation (short synacthen) test for confirmation of diagnosis 2, 5, 6
  • Salivary cortisol test, especially in conditions with abnormal cortisol binding globulin (CBG) levels 2
• Evaluation of the hypothalamic-pituitary-adrenal (HPA) axis 2, 3, 4
• Imaging studies to rule out systemic causes and identify any adrenal gland abnormalities 2, 3, 4
• Testing for 21-hydroxylase antibodies to rule out autoimmunity 2

Diagnostic Thresholds

The diagnostic thresholds for adrenal insufficiency have been revised with the use of highly specific cortisol immunoassays. A study found that the optimized diagnostic threshold for adrenal insufficiency using the Roche Cortisol II assay is 350nmol/L, with a sensitivity of 91% and specificity of 97% 5. This is lower than the traditional threshold of 500nmol/L.

Special Considerations

Special considerations are needed for certain populations, such as:

• Children and infants, who require lower doses of cosyntropin for testing 2
• Patients with abnormal cortisol binding globulin (CBG) levels, who may require salivary cortisol testing 2
• Patients with cancer treated with immune checkpoint inhibitors (ICI), who are at risk of developing adrenal insufficiency and require close follow-up 2