Cortisol Testing in Pancytopenia
Cortisol levels are not routinely checked in the workup of pancytopenia unless there are specific clinical features suggesting adrenal insufficiency, such as unexplained hypotension, hyponatremia, hyperkalemia, or symptoms like nausea, vomiting, and fatigue that cannot be explained by the pancytopenia itself. 1
When to Consider Adrenal Insufficiency Testing in Pancytopenia
The evaluation of pancytopenia follows a systematic approach focused on bone marrow examination, infectious etiologies, nutritional deficiencies, and malignancies—not endocrine disorders. 1 Common causes include megaloblastic anemia (41.9%), acute myeloid leukemia (27.4%), and aplastic anemia (19.4%). 2
However, you should check cortisol if:
- Unexplained hypotension is present, particularly if requiring vasopressors or refractory to fluid resuscitation 3
- Hyponatremia exists (present in 90% of newly diagnosed adrenal insufficiency cases), especially with hypo-osmolality that could mimic SIADH 3
- Hyperkalemia is noted, though this occurs in only ~50% of adrenal insufficiency cases 3
- Constitutional symptoms like severe fatigue, nausea, vomiting, weight loss, or abdominal pain are prominent and disproportionate to the degree of pancytopenia 3
- Patient is on chronic corticosteroids (≥20 mg/day prednisone equivalent for ≥3 weeks) and presents with unexplained clinical deterioration 3
Diagnostic Approach When Adrenal Insufficiency is Suspected
Initial testing should include:
- Morning (8 AM) serum cortisol and plasma ACTH measured simultaneously 4, 3
- Basic metabolic panel to assess for hyponatremia, hyperkalemia, and hypoglycemia 3
- A morning cortisol <275 nmol/L (<10 μg/dL) warrants further evaluation with ACTH stimulation testing 5
- A morning cortisol <250 nmol/L with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 4, 3
For confirmatory testing:
- The cosyntropin stimulation test (0.25 mg IM or IV) with cortisol measurements at 30 and/or 60 minutes is the gold standard 4, 3
- A peak cortisol >550 nmol/L (>18-20 μg/dL) is normal; <500 nmol/L is diagnostic of adrenal insufficiency 4, 3
Critical Pitfalls to Avoid
Never delay treatment if adrenal crisis is suspected. If a patient with pancytopenia develops unexplained hypotension, altered mental status, or severe electrolyte abnormalities, immediately administer IV hydrocortisone 100 mg and 0.9% saline infusion before obtaining diagnostic tests. 4, 3 Blood samples for cortisol and ACTH should be drawn before treatment if possible, but treatment must not be delayed. 4
Do not rely on electrolyte abnormalities alone. Hyperkalemia is absent in ~50% of adrenal insufficiency cases, and hyponatremia can be mild or absent. 3 Between 10-20% of patients may have normal electrolytes at presentation. 3
Distinguish adrenal insufficiency from SIADH. Both conditions present with euvolemic hypo-osmolar hyponatremia and similar laboratory findings. 3 The cosyntropin stimulation test is medically necessary to differentiate these conditions, as treatment approaches differ fundamentally—adrenal insufficiency requires glucocorticoid replacement, while SIADH requires fluid restriction. 3
Practical Algorithm
Evaluate pancytopenia with standard workup: complete blood count, peripheral smear, bone marrow aspiration/biopsy, nutritional studies (B12, folate), viral serologies, and imaging. 1
Screen for adrenal insufficiency only if unexplained hypotension, significant hyponatremia, hyperkalemia, or disproportionate constitutional symptoms are present. 3
If screening is indicated: Obtain morning cortisol and ACTH simultaneously. 3
If cortisol is <275 nmol/L: Proceed with cosyntropin stimulation test unless the patient is unstable (in which case treat empirically). 3, 5
If adrenal insufficiency is confirmed: Determine etiology by measuring 21-hydroxylase autoantibodies (positive in ~85% of autoimmune cases) and consider adrenal CT imaging if antibodies are negative. 4, 3