Are Urinary Catecholamines Always Elevated in Neuroblastoma?
No, urinary catecholamines are NOT always elevated in neuroblastoma—approximately 71-97% of patients have elevated levels at diagnosis, meaning 3-29% of cases present with normal catecholamine levels. 1, 2
Diagnostic Sensitivity by Study Quality
The most recent high-quality evidence demonstrates variable sensitivity:
A 2023 multicenter study of 400 neuroblastoma patients found elevated catecholamines in 97% when using an expanded 8-metabolite panel (including HVA, VMA, dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine, and metanephrine). 2
However, a 2010 population-based study showed only 71% had significantly elevated urinary catecholamine metabolites at initial presentation, with VMA elevated in just 57% and HVA in 71% of cases. 1
Traditional two-metabolite testing (HVA and VMA only) misses approximately 20% of neuroblastoma cases at diagnosis. 3
Clinical Implications for Diagnosis
The NCCN 2024 guidelines explicitly acknowledge that catecholamines are not universally elevated, stating that urine catecholamine levels are "no longer included in the revised International Neuroblastoma Response Criteria" and should only be obtained "if levels were elevated at diagnosis" during surveillance. 4
Key diagnostic criteria per NCCN:
Definitive diagnosis requires EITHER: 4
- Unequivocal pathologic diagnosis from tumor tissue, OR
- Bone marrow with unequivocal tumor cells PLUS increased urinary catecholamines
This means tissue diagnosis alone is sufficient even with normal catecholamines. 4
Which Cases Are Most Likely to Have Normal Catecholamines?
Advanced disease paradoxically shows higher rates of normal catecholamines:
In the 2010 study, 75% of cases with normal catecholamines had stage IV disease, suggesting more aggressive or poorly differentiated tumors may not produce catecholamines efficiently. 1
Catecholamine profiles correlate with tumor biology and differentiation status, with less differentiated tumors (profile A) showing different excretion patterns than more differentiated tumors (profile D). 5
Practical Clinical Approach
When neuroblastoma is suspected but catecholamines are normal:
Proceed directly to tissue sampling (core biopsy or surgical resection) without delay, as normal catecholamines do NOT exclude neuroblastoma. 4, 6
Consider expanded catecholamine panel (8 metabolites) rather than just HVA/VMA, as this improves diagnostic sensitivity from 92% to 95%. 2
Use MIBG scan for additional diagnostic support, particularly in cases with opsoclonus-myoclonus-ataxia syndrome (sensitivity 83.3%, specificity 98%). 6
Common Pitfall to Avoid
Never rely solely on catecholamine testing to rule out neuroblastoma. The historical teaching that "90-95% of neuroblastomas secrete catecholamines" has been challenged by more recent population-based studies showing lower sensitivity, particularly when using only traditional two-metabolite testing. 1, 2 A child with concerning clinical features (abdominal mass, periorbital ecchymosis, bone pain) requires imaging and tissue diagnosis regardless of catecholamine results. 6, 7