What is the recommended testing protocol for suspected adrenal insufficiency?

Testing Protocol for Suspected Adrenal Insufficiency

The recommended testing protocol for suspected adrenal insufficiency begins with an early morning serum cortisol measurement followed by a cosyntropin stimulation test for confirmation, with cortisol levels below 18 mcg/dL at 30 or 60 minutes post-stimulation being suggestive of adrenal insufficiency. 1, 2

Initial Screening

1. Morning Cortisol Level:

   • Obtain early morning (approximately 8 am) serum cortisol as initial screening tool 1, 3
   • Interpretation of morning cortisol:
     • <5 μg/dL: Highly suggestive of adrenal insufficiency 3
     • 5-10 μg/dL: Intermediate values require confirmatory testing 3

     • 375 nmol/L (approximately >13.6 μg/dL): May predict adrenal sufficiency with 95% specificity 4

2. Additional Initial Measurements:

   • Serum ACTH level: Helps distinguish between primary and secondary adrenal insufficiency 3
     • Primary: High ACTH, low cortisol
     • Secondary: Low/normal ACTH, low cortisol
   • Dehydroepiandrosterone sulfate (DHEAS): Typically low in adrenal insufficiency 3
   • Electrolytes: Check for hyponatremia and hyperkalemia (common in primary adrenal insufficiency) 1

Confirmatory Testing: Cosyntropin Stimulation Test

1. Preparation:

   • Stop medications that affect test results 2:
     • Glucocorticoids and spironolactone: Stop on day of testing
     • Long-acting glucocorticoids: Stop for longer period before testing
     • Estrogen-containing drugs: Stop 4-6 weeks before testing

2. Dosage:

   • Adults: 0.25 mg cosyntropin IV or IM 2
   • Pediatric patients 2:
     • Birth to <2 years: 0.125 mg
     • 2-17 years: 0.25 mg

3. Test Protocol:

   • Obtain baseline serum cortisol sample
   • Administer cosyntropin IV or IM
   • Collect blood samples at exactly 30 and 60 minutes post-administration 2

4. Interpretation:

   • Stimulated plasma cortisol levels <18 mcg/dL at 30 or 60 minutes suggest adrenal insufficiency 2
   • Note: Cutoff values may vary according to the assay used 2

Characteristics of Primary vs. Secondary Adrenal Insufficiency

Parameter	Primary Adrenal Insufficiency	Secondary Adrenal Insufficiency
ACTH Level	High	Low
Cortisol Level	Low	Low
Electrolytes	↓Na, ↑K	Generally normal
Hyperpigmentation	Present	Absent

1

Pitfalls and Considerations

1. Timing Considerations:

   • Basal cortisol (0900-1300h) may have better diagnostic performance than strictly morning cortisol in some cases 5
   • Consider time of day when interpreting results 6

2. Assay Variability:

   • Different cortisol assays may yield different results 6
   • Be aware of laboratory-specific reference ranges 2

3. Interfering Factors:

   • Medications affecting cortisol or cortisol-binding globulin levels can cause diagnostic inaccuracies 2
   • Acute illness or stress may affect cortisol levels 3

4. Alternative Sampling:

   • Salivary cortisol measurement offers advantages like painless sampling and measurement of free hormone 7
   • May be considered as an alternative to serum cortisol in appropriate settings

5. Clinical Context:

   • Always interpret test results in the context of clinical presentation 6
   • Consider pre-test probability when interpreting borderline results

When to Suspect Adrenal Insufficiency

• Common symptoms include fatigue (50-95%), nausea and vomiting (20-62%), anorexia and weight loss (43-73%) 3
• Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 3
• Hypotension, hyponatremia, and hyperkalemia may suggest adrenal crisis requiring immediate treatment 3