Is a norepinephrine level of 633 picograms per milliliter (pg/ml) considered elevated on a plasma catecholamine test?

From the Guidelines

A norepinephrine level of 633 pg/ml on a plasma catecholamine test is considered elevated and warrants further investigation. Normal plasma norepinephrine levels typically range from 70-750 pg/ml when supine (lying down) and 200-1700 pg/ml when standing, as noted in various clinical contexts 1. However, interpretation depends on several factors including body position during blood collection, medications, stress levels, and fasting status. This elevation could suggest conditions such as pheochromocytoma, paraganglioma, neuroblastoma, or other catecholamine-producing tumors, which are rare but significant causes of secondary hypertension 1.

Given the potential for high morbidity and mortality associated with untreated pheochromocytoma or paraganglioma, it is essential to consider these diagnoses in patients with elevated norepinephrine levels 1. The recent European Society of Cardiology guidelines recommend suspecting phaeochromocytoma/paraganglioma in the presence of signs and symptoms of catecholamine excess, family history, or carriers of a germline mutation in one of the PPGL-causing genes 1.

Key considerations for the next steps include:

• Repeating the test under controlled conditions to confirm the elevation
• Conducting 24-hour urine tests for catecholamines and metanephrines, or plasma metanephrine testing, which are more specific for diagnosing pheochromocytoma or paraganglioma 1
• Discontinuing medications that might affect results under medical supervision
• Consulting with an endocrinologist for proper interpretation and further management, given the complexity and potential risks associated with these conditions.

From the Research

Norepinephrine Levels

• A norepinephrine level of 633 pg/ml is considered high based on the available evidence 2.
• Studies have shown that elevated plasma norepinephrine levels are associated with poor prognosis and shortened life expectancy in patients with left ventricular dysfunction 2.
• Specifically, patients with plasma norepinephrine levels > 900 pg/ml have been found to have a poor prognosis 2.
• However, it is essential to note that the provided value of 633 pg/ml is lower than the threshold of 900 pg/ml mentioned in the study 2.
• Other studies have reported different threshold values for orthostatic plasma norepinephrine levels, such as 3.59 pg/ml, which was found to be an indicator of the effectiveness of metoprolol therapy for postural tachycardia syndrome in children 3.

Comparison with Other Studies

• The study on adrenomedullary response to maximal stress in humans reported plasma norepinephrine levels in normal resting subjects to be around 0.228 +/- 0.01 ng/ml, which is equivalent to approximately 228 pg/ml 4.
• This value is significantly lower than the provided level of 633 pg/ml.
• Another study on the management of pheochromocytoma discussed the importance of biochemical confirmation of the diagnosis but did not provide specific threshold values for plasma norepinephrine levels 5.
• The study on pheochromocytoma and paragangliomas mentioned the secretion of catecholamines, including norepinephrine, but did not provide specific information on plasma norepinephrine levels 6.