When to consider workup for adrenal insufficiency (Adrenal Insufficiency) or adrenal gland dysfunction?

From the Guidelines

A workup for adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, as well as those with hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia. According to the most recent and highest quality study 1, evaluation of adrenal insufficiency should include morning cortisol and adrenocorticotropic hormone (ACTH) levels, basic metabolic panel, renin and aldosterone levels, and consideration of a standard dose ACTH stimulation test for indeterminate results. The study also recommends evaluating for precipitating causes of crisis, such as infection, and considering adrenal CT for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency.

Key Considerations

• Unexplained collapse, hypotension, vomiting, or diarrhea
• Hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia
• Morning cortisol and ACTH levels
• Basic metabolic panel
• Renin and aldosterone levels
• Standard dose ACTH stimulation test for indeterminate results
• Evaluation for precipitating causes of crisis, such as infection
• Adrenal CT for metastasis or hemorrhage As stated in the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1, treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures, and the diagnostic test for primary adrenal insufficiency should be paired measurement of serum cortisol and plasma ACTH.

Diagnostic Criteria

• 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
• Synacthen (tetracosactide) stimulated peak serum cortisol <500 nmol L-1 is diagnostic of primary adrenal insufficiency Early detection and treatment of adrenal insufficiency are crucial to prevent significant morbidity and mortality, as highlighted in the study 1.

From the FDA Drug Label

Assess ability of patient's adrenals to respond to exogenous ACTH before Metopirone is employed as a test [see Warnings and Precautions (5.1)] Patients with suspected adrenocortical insufficiency based on the test results previously performed should be hospitalized overnight as a precautionary measure ( see Warnings and Precaution (5. 1)) Adrenal Insufficiency: May induce acute adrenal insufficiency. Ability of adrenals to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test ( 5.1)

Consider workup for adrenal insufficiency or adrenal gland dysfunction:

• Before administering Metopirone as a test, especially if the patient has suspected adrenocortical insufficiency.
• If the patient has a high risk for acute adrenal insufficiency, a prophylactic dose of glucocorticoid may be considered after the blood sample is collected.
• If the patient's ACTH and 11-desoxycortisol levels do not indicate an intact HPA axis function after Metopirone administration 2. It is crucial to assess the patient's adrenal function before employing Metopirone as a test to avoid inducing acute adrenal insufficiency 2.

From the Research

Adrenal Insufficiency Diagnosis

Consider workup for adrenal insufficiency in patients presenting with non-specific symptoms such as:

• Fatigue
• Anorexia
• Weight loss
• Hypotension
• Hyponatremia
• Hyperkalemia 3, 4, 5, 6 These symptoms can be indicative of primary or secondary adrenal insufficiency, and a thorough evaluation is necessary to determine the underlying cause.

Clinical Presentation

Adrenal insufficiency can manifest in different ways, including:

• Primary adrenal insufficiency: characterized by skin hyperpigmentation, salt cravings, and low plasma cortisol and high ACTH levels 4, 6
• Secondary adrenal insufficiency: characterized by low plasma cortisol and normal to low plasma ACTH levels, often due to pituitary disease 4, 5
• Adrenal crisis: a life-threatening condition that requires immediate treatment with hydrocortisone, intravenous fluid, and glucose repletion 3, 6

Diagnostic Testing

The diagnosis of adrenal insufficiency is confirmed by specific testing, including:

• Cosyntropin stimulation test: a dynamic test that evaluates the adrenal gland's response to ACTH stimulation 3, 7
• Basal serum cortisol levels: can be inconclusive, and the ACTH stimulation test is often necessary to confirm the diagnosis 7
• Imaging studies: may be necessary to evaluate the underlying cause of adrenal insufficiency, such as pituitary disease or adrenal gland abnormalities 3

Special Considerations

In certain populations, such as children, the diagnosis and management of adrenal insufficiency may differ:

• Children under 2 years: hypoglycemia, dehydration, and convulsions are common presentations, and the Synacthen test is the only feasible diagnostic test 4
• Children over 2 years: the signs and diagnostic methods are similar to those in adults 4
• Patients with a history of corticosteroid treatment: cessation of treatment requires careful evaluation and management to prevent adrenal crisis 4, 6