What are the initial laboratory evaluations and treatment options for a child suspected of having adrenal insufficiency?

Laboratory Evaluations and Treatment for Suspected Adrenal Insufficiency in Children

The initial laboratory evaluation for a child with suspected adrenal insufficiency should include morning serum cortisol and plasma ACTH measurements, followed by immediate treatment with intravenous hydrocortisone and physiologic saline if adrenal crisis is suspected, without delaying treatment for diagnostic procedures. 1, 2

Initial Laboratory Evaluation

First-line Testing

• Morning cortisol and ACTH levels (8 AM paired samples) 2
  • Primary adrenal insufficiency: Low cortisol with high ACTH
  • Secondary adrenal insufficiency: Low cortisol with low/normal ACTH
• Serum electrolytes
  • Look for hyponatremia and hyperkalemia (more common in primary adrenal insufficiency) 2, 3
• Blood glucose (hypoglycemia is more common in children) 2

Confirmatory Testing

• ACTH stimulation test (Synacthen/cosyntropin test) 2, 4
  • Gold standard for diagnosis
  • Administration of cosyntropin 250 μg IV/IM
  • Measure cortisol at baseline and 60 minutes post-administration
  • Peak cortisol <500 nmol/L (18 μg/dL) confirms adrenal insufficiency
  • Note: Some centers may use a 30-minute sample, but this can be analyzed only if the 60-minute result is abnormal 4

Etiologic Evaluation

• 21-hydroxylase (21OH) autoantibodies - first test to determine etiology 1
  • Positive: Autoimmune adrenalitis (most common acquired cause in children) 3
  • Negative: Consider other etiologies
• Additional testing based on clinical suspicion:
  • CT imaging of adrenal glands if antibodies are negative 1
  • Very long-chain fatty acids in males to rule out adrenoleukodystrophy 1, 2
  • Consider testing for autoimmune polyglandular syndromes (check thyroid function) 1, 3

Treatment Approach

Acute Management (Suspected Adrenal Crisis)

• Immediate administration of hydrocortisone 1, 2
  • 100 mg IV/IM immediately, followed by 100 mg every 6-8 hours until recovered
  • Blood samples for cortisol and ACTH should be secured prior to treatment if possible, but never delay treatment
• Rapid infusion of isotonic (0.9%) saline 1, 2
  • Initial rate of 1 L/hour until hemodynamic improvement
• Identify and treat the underlying precipitant (e.g., infection) 1

Maintenance Therapy

• Glucocorticoid replacement 1, 2
  • Hydrocortisone: 6-10 mg/m² of body surface area daily in divided doses
  • First dose immediately after waking, last dose not less than 6 hours before bedtime
  • Use lowest dose compatible with health and well-being
• Mineralocorticoid replacement (for primary adrenal insufficiency) 1, 2
  • Fludrocortisone: 50-200 μg as a single daily dose
  • Children may require higher doses
  • Advise salt and salty foods ad libitum

Patient Education and Follow-up

• All patients should receive: 1, 2
  • Medical alert identification (bracelet/card)
  • Education on daily medication management
  • Instructions for managing minor to moderate illnesses ("sick day rules")
  • Supplies for self-injection of parenteral hydrocortisone
• Annual follow-up 1
  • Assessment of health and well-being
  • Measurement of weight, blood pressure, and serum electrolytes
  • Monitoring for development of other autoimmune disorders, particularly hypothyroidism

Special Considerations for Children

• Dosing adjustments 1, 2
  • Hydrocortisone doses must be calculated based on body surface area (6-10 mg/m²)
  • More frequent dose adjustments may be needed during growth periods
• Growth monitoring 5
  • Carefully observe growth and development in children on prolonged corticosteroid therapy
• Higher vigilance for hypoglycemia 2, 6
  • More common presentation in pediatric patients

Common Pitfalls and Caveats

• Never delay treatment if adrenal crisis is suspected - give hydrocortisone immediately 1, 2
• Diagnosis can always be established later, even after treatment has commenced 1
• 21OH antibodies are often absent in children despite autoimmune etiology - further investigation may be needed 1
• Consider adrenal insufficiency in children with non-specific symptoms like fatigue, weight loss, nausea, and vomiting, as diagnosis is often delayed (median 4.5 months in one study) 3
• Monitor for other autoimmune conditions as part of autoimmune polyglandular syndromes 1, 3

By following this systematic approach to laboratory evaluation and treatment, clinicians can effectively diagnose and manage adrenal insufficiency in children, potentially preventing life-threatening adrenal crises.