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

From the Guidelines

The diagnosis of adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and diagnostic testing should include paired measurement of serum cortisol and plasma ACTH, with a synacthen stimulated peak serum cortisol <500 nmol L-1 being diagnostic of primary adrenal insufficiency. The diagnostic criteria for adrenal insufficiency, also known as Addison's disease, involve a combination of clinical assessment and laboratory testing. According to the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1, the initial evaluation should include a thorough medical history and physical examination, with particular attention to symptoms such as fatigue, weight loss, hyperpigmentation, hypotension, hyponatremia, and hyperkalemia.

Some key points to consider in the diagnosis of adrenal insufficiency include:

• Clinical features that may prompt testing, such as unexplained collapse, hypotension, vomiting, or diarrhea
• Laboratory testing, including paired measurement of serum cortisol and plasma ACTH
• The use of a synacthen stimulation test to confirm the diagnosis, with a peak serum cortisol <500 nmol L-1 being diagnostic of primary adrenal insufficiency
• The importance of differentiating between primary and secondary adrenal insufficiency, with elevated ACTH indicating primary adrenal insufficiency and low or normal ACTH suggesting secondary adrenal insufficiency

It is essential to note that treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 1. Additionally, patients with adrenal insufficiency should be educated on how to manage their condition, including the use of medication and the importance of carrying a steroid/alert card and wearing Medic Alert identification jewelry 1.

In terms of specific diagnostic criteria, the study by 1 recommends the following:

• S-cortisol <250 nmol L-1 and increased ACTH in the presence of acute illness is diagnostic of primary adrenal insufficiency
• S-cortisol <400 nmol L-1 and increased ACTH in the presence of acute illness raises a strong suspicion of primary adrenal insufficiency
• A synacthen stimulated peak serum cortisol <500 nmol L-1 is diagnostic of primary adrenal insufficiency

Overall, the diagnosis of adrenal insufficiency requires a comprehensive approach that takes into account both clinical and laboratory findings. By following the diagnostic criteria outlined in the consensus statement 1, healthcare providers can accurately diagnose and manage patients with adrenal insufficiency, reducing the risk of morbidity and mortality associated with this condition.

From the Research

Diagnostic Criteria for Adrenal Insufficiency

The diagnostic criteria for adrenal insufficiency, also known as Addison's disease, involve a combination of clinical presentation, laboratory tests, and stimulation tests. The following are some key points to consider:

• Adrenal insufficiency is characterized by inadequate secretion of glucocorticoid and/or mineralocorticoid secretion from the adrenal cortex 2.
• Primary adrenal insufficiency is caused by failure of the adrenal gland, while secondary adrenal insufficiency is due to a lack of stimulation via pituitary adrenocorticotropic hormone or hypothalamic corticotropin-releasing hormone 2.
• Symptoms of adrenal insufficiency are often non-specific, making early detection and testing based on clinical suspicion crucial to prevent subsequent presentation with adrenal crisis 2.

Laboratory Tests and Stimulation Tests

Some key laboratory tests and stimulation tests used to diagnose adrenal insufficiency include:

• Baseline cortisol levels: a low baseline cortisol level (often <100 nmol/L) alongside raised adrenocorticotropic hormone (ACTH) can be enough to diagnose primary adrenal insufficiency 2.
• Cosyntropin (Synacthen®) stimulation test: this test is used to confirm the diagnosis of primary adrenal insufficiency 2, 3.
• Insulin tolerance test: this test is the gold standard for secondary adrenal insufficiency 2.
• Adrenocorticotropic hormone (ACTH) stimulation test: this test is commonly used to diagnose adrenal insufficiency, but its interpretation can be challenging due to technical aspects such as time of day, type of assay, and sample source used for cortisol measurement 3.

Clinical Presentation and Diagnosis

The clinical presentation of adrenal insufficiency can vary, but some common features include:

• Hyponatremia, hyperkalemia, and hypotension that are refractory to fluids and vasopressors without any clear causation 4.
• Hemodynamic instability and catecholamine resistance along with the results of the ACTH test 5.
• Non-specific symptoms such as fatigue, weight loss, and skin changes 6, 2. A high index of suspicion and careful interpretation of laboratory tests and stimulation tests are necessary to diagnose adrenal insufficiency accurately 4, 3.