Laboratory Testing for Adrenal Crisis in a 7-Year-Old Female
In a suspected adrenal crisis, immediately obtain serum cortisol and plasma ACTH levels before administering treatment, but never delay emergency hydrocortisone administration while waiting for laboratory results 1.
Critical Initial Laboratory Tests
The diagnostic workup requires the following labs drawn simultaneously:
Primary Diagnostic Tests
- Serum cortisol: A level <250 nmol/L (<9 µg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
- Plasma ACTH: Elevated >2-fold above upper limit of normal confirms primary adrenal insufficiency 2
- Serum cortisol 250-400 nmol/L with elevated ACTH raises strong suspicion and warrants immediate treatment 1
Essential Supporting Laboratory Tests
Beyond the cortisol-ACTH pair, obtain:
- Serum electrolytes: Look for hyponatremia (present in most cases) and hyperkalemia (though hypokalaemia may occur with severe vomiting) 1
- Blood glucose: Hypoglycemia is common in children with adrenal crisis 1, 3
- Plasma renin activity (PRA): Elevated in primary adrenal insufficiency 1
- Serum aldosterone: Low in primary adrenal insufficiency 1
- DHEAS (dehydroepiandrosterone sulfate): Low levels support the diagnosis, though cannot be used in isolation 2, 1
Additional Metabolic Parameters
- Blood gas/pH: Check for metabolic acidosis 1
- Serum calcium: 10-20% of patients have mild-moderate hypercalcemia 1
- Complete blood count: May show anemia, mild eosinophilia, or lymphocytosis 1
- Liver transaminases: May be elevated 1
Critical Diagnostic Thresholds
The evidence provides clear cutoff values:
- Cortisol <140 nmol/L (5 µg/dL) with ACTH >66 pmol/L: Highly diagnostic without need for stimulation testing 2
- In acute illness, cortisol <250 nmol/L with elevated ACTH: Diagnostic of primary adrenal insufficiency 1
- Cortisol <400 nmol/L in acute illness: Raises strong suspicion 1
Confirmatory Testing (When Stable)
If the child is stabilized and initial results are equivocal, perform:
ACTH stimulation test (Synacthen test): Administer 0.25 mg (250 µg) corticotropin IV or IM, measure cortisol at baseline and 30-60 minutes. Peak cortisol <500 nmol/L (<18 µg/dL) confirms primary adrenal insufficiency 2, 1. This test has 92% sensitivity for primary adrenal insufficiency 2.
Important Clinical Caveats
Treatment must never be delayed for diagnostic testing 1. Draw the labs, then immediately administer hydrocortisone 100 mg IV/IM and isotonic saline 1.
Confounding factors to consider:
- Exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) may confound cortisol interpretation 1
- TSH may be mildly elevated (4-10 IU/L) due to lack of cortisol's inhibitory effect 1
- In children <4 months, circadian cortisol rhythm is not established, making only the Synacthen test feasible 3
Etiologic Workup (After Stabilization)
Once the crisis is managed, determine the underlying cause:
- 21-hydroxylase (anti-adrenal) autoantibodies: First-line test for etiology 1
- CT imaging of adrenals: If antibodies negative 1
- Consider APS-1 in children: Especially with hypoparathyroidism or candidiasis; test anti-interferon omega antibodies or AIRE gene mutation 1
The key principle is that laboratory confirmation should support but never delay life-saving treatment in a child with suspected adrenal crisis.