From the Guidelines
The initial workup for a 5-year-old with low cortisol should include evaluating morning levels of ACTH and cortisol, along with a basic metabolic panel, renin, and aldosterone levels, as these tests are crucial for determining the cause and severity of adrenal insufficiency. When evaluating a child with suspected adrenal insufficiency, it's essential to consider the potential for primary or secondary adrenal insufficiency. According to the guidelines 1, the workup should include:
- Evaluating AM levels of ACTH (if ≥ 23 ULN) and cortisol level (if ≤ 3 mg/dL)
- Basic metabolic panel (Na, K, CO2, and glucose)
- Renin and aldosterone levels
- Considering a standard dose ACTH stimulation test for indeterminate results (AM cortisol ≥ 3 mg/dL and ≤ 15 mg/dL)
- Evaluating for precipitating causes of crisis, such as infection
- Adrenal CT for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency, although this may not be immediately necessary in a pediatric patient without specific indications. Given the potential for life-threatening complications, it's crucial to monitor the child closely for signs of adrenal crisis, such as hypotension, hypoglycemia, and lethargy, while awaiting test results. The goal of the workup is to determine the underlying cause of the low cortisol levels, which could range from congenital adrenal hyperplasia to central causes affecting pituitary ACTH production, and to initiate appropriate hormone replacement therapy, such as hydrocortisone, to improve morbidity, mortality, and quality of life outcomes.
From the Research
Initial Workup of Low Cortisol in a 5-Year-Old
Overview of Adrenal Insufficiency Diagnosis
The diagnosis of adrenal insufficiency, characterized by cortisol deficiency, can be challenging due to the rarity of the disease and limitations in biochemical assessments 2. The adrenocorticotropic hormone (ACTH) stimulation test is commonly used to diagnose adrenal insufficiency when basal serum cortisol levels are inconclusive.
Role of Basal Cortisol Levels
Basal cortisol levels can be predictive of adrenal insufficiency. A study found that if basal cortisol levels were ≥450 nmol/L, the negative predictive value to rule out adrenal insufficiency was 98.7%, and if cortisol was ≤100 nmol/L, the positive predictive value was 93.2% to rule in adrenal insufficiency 3.
ACTH Stimulation Tests
Both high-dose (250 mcg) and low-dose (1 mcg) ACTH stimulation tests have similar diagnostic accuracy for secondary adrenal insufficiency in adults and children 4. The low-dose ACTH stimulation test can be used to diagnose primary adrenal insufficiency, but data on its sensitivity is limited 4.
Specific Considerations for Children
In children, the response to ACTH stimulation can vary, and the low-dose test may not always accurately diagnose adrenal insufficiency 5. A study found that testing cortisol levels at 15 and 60 minutes, in addition to the standard 30-minute sample, can reduce the risk of false positive low-dose ACTH stimulation test results in children 6.
Key Points for Initial Workup
- Basal cortisol levels can be used to predict adrenal insufficiency, with levels ≥450 nmol/L having a high negative predictive value and levels ≤100 nmol/L having a high positive predictive value 3.
- Both high-dose and low-dose ACTH stimulation tests can be used to diagnose adrenal insufficiency, with similar diagnostic accuracy 4.
- In children, the low-dose ACTH stimulation test may not always accurately diagnose adrenal insufficiency, and testing cortisol levels at multiple time points can reduce the risk of false positive results 6.