Measurement of norepinephrine and 3,4-dihydroxyphenylglycol in urine and plasma for the diagnosis of pheochromocytoma

N Engl J Med. 1988 Jul 21;319(3):136-42. doi: 10.1056/NEJM198807213190303.


We compared the value of plasma samples with that of 24-hour urine samples in identifying patients with pheochromocytoma among those with hypertension. We employed specific gas chromatographic-mass spectrometric analysis of both urine and plasma for simultaneous assay of norepinephrine and its neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG). The study population consisted of 1086 patients with hypertension, among them 25 patients with proved pheochromocytoma. Reference ranges for free norepinephrine and DHPG in plasma and urine were established. Measurement of free norepinephrine in 24-hour urine samples provided the best index of a pheochromocytoma. This technique had 100 percent sensitivity and 98 percent specificity among 1192 urine samples, as compared with 82 percent sensitivity and 95 percent specificity among 358 plasma samples. Simultaneous measurement of norepinephrine and DHPG in urine further improved specificity (to 99 percent), but the use of the ratio of norepinephrine to DHPG reduced sensitivity (to 95 percent), since some patients with pheochromocytoma secrete large amounts of DHPG. We therefore recommend measurement of 24-hour urinary levels of free norepinephrine for the diagnosis of pheochromocytoma and suggest that simultaneous analysis for DHPG may sometimes prove useful in reducing the rate of false positive results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis*
  • Adrenal Gland Neoplasms / metabolism
  • False Positive Reactions
  • Gas Chromatography-Mass Spectrometry
  • Glycols / analysis*
  • Humans
  • Hypertension / complications
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / analysis*
  • Methoxyhydroxyphenylglycol / blood
  • Methoxyhydroxyphenylglycol / urine
  • Norepinephrine / analysis*
  • Norepinephrine / blood
  • Norepinephrine / urine
  • Pheochromocytoma / diagnosis*
  • Pheochromocytoma / metabolism
  • Reference Values


  • Glycols
  • Methoxyhydroxyphenylglycol
  • 3,4-dihydroxyphenylglycol
  • Norepinephrine