What are the laboratory findings in secondary adrenal insufficiency (Adrenal Insufficiency)?

From the Guidelines

Laboratory evaluation for secondary adrenal insufficiency should include morning cortisol, ACTH levels, and a cosyntropin stimulation test, with a high-dose (250-μg) ACTH stimulation test being the most popular diagnostic test, as suggested by the Society of Critical Care Medicine and European Society of Intensive Care Medicine 1. The cosyntropin test involves measuring baseline cortisol levels, followed by administration of 250 mcg of synthetic ACTH (cosyntropin), with cortisol levels measured at 30 and 60 minutes post-administration.

• In secondary adrenal insufficiency, baseline ACTH levels will be low or inappropriately normal, and morning cortisol will typically be low.
• During the stimulation test, cortisol response is often blunted or delayed, with peak levels below 18-20 mcg/dL indicating insufficiency, as confirmed by the Endocrine Society 2. Additional tests should include:
• Comprehensive metabolic panel to check for hyponatremia, hyperkalemia, and hypoglycemia.
• Thyroid function tests since hypopituitarism often affects multiple hormonal axes. Testing should ideally be performed before starting glucocorticoid therapy, as exogenous steroids can suppress results. If pituitary pathology is suspected, MRI of the pituitary and additional pituitary hormone testing (TSH, free T4, LH, FSH, testosterone/estradiol, prolactin, IGF-1) should be ordered to evaluate the extent of hypopituitarism and identify potential causes such as tumors or infiltrative diseases, as recommended by the Journal of Clinical Oncology 3.

From the FDA Drug Label

Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness The laboratory findings in secondary adrenal insufficiency are not directly stated in the drug label. Key points:

• The label mentions secondary adrenocortical and pituitary unresponsiveness, but does not provide specific laboratory findings. 4

From the Research

Laboratory Findings in Secondary Adrenal Insufficiency

The laboratory findings in secondary adrenal insufficiency can be identified through various tests, including:

• Basal serum cortisol (BSeC) and basal salivary cortisol (BSaC) levels, which can be used as first-line screening methods for the diagnosis of secondary adrenal insufficiency 5
• Insulin tolerance test (ITT), which is considered the gold standard for diagnosing secondary adrenal insufficiency 6, 5, 7
• ACTH stimulation test, which can be used to diagnose secondary adrenal insufficiency, especially when ITT is contraindicated 7
• Plasma ACTH concentration and prolonged ACTH infusion test, which can be useful in differential diagnosis between primary and secondary adrenal insufficiency 7

Diagnostic Thresholds

The diagnostic thresholds for secondary adrenal insufficiency vary depending on the test used, but some studies suggest the following:

• Upper and lower cutoffs for BSeC: 470 and 103 nmol/l, respectively 5
• Upper and lower cutoffs for BSaC: 21.1 and 5.0 nmol/l, respectively 5
• Morning serum cortisol below 3 microg/dl is virtually diagnostic for adrenal insufficiency, while cortisol values between 5-18 microg/dl require additional investigations 7

Blood Chemistry Findings

Patients with secondary adrenal insufficiency may exhibit the following blood chemistry findings:

• Mild hypoglycemia, hyponatremia, and normal-high potassium levels 7
• Mild anemia, lymphocytosis, and eosinophilia 7