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J Clin Pathol. 2007 May; 60(5): 583–584.
PMCID: PMC1994550

Catecholamine and metanephrine excess in intracerebral haemorrhage: revisiting an obscure yet common “pseudophaeochromocytoma”

We prospectively recruited five patients with CT evidence of intracerebral haemorrhage (ICH), having excluded trauma, a history of phaeochromocytoma (PHEO) and sympathomimetics/antihypertensives capable of increasing catecholamines (CATS)/metanephrines (METS). Informed consent was obtained from the next of kin. Plasma METS are superior to plasma CATS, although both are unavailable locally. Urinary CATS/METS, which integrate CATS/METS secretion and has greater sensitivity than plasma CATS in the absence of PHEO spells, was used.1 24 h urinary CATS/METS were sampled on days 1 and 7 and before discharge. Catheterised urine was transferred into bottles containing 10 ml 6 N HCl, and analysed by high‐performance liquid chromatography (HPLC)–electrochemical detection. Patients with increases in CATS/METS underwent abdominal CT. ICH volume was estimated from CT. This research was ethically approved by our hospital's institutional review board.

Four of five cases had urinary METS and/or CATS exceeding twice the upper normal limit. On day 1, CATS were not measured for patients 2–4, and METS were not measured for patients 1 and 2 before discharge owing to logistic difficulties. Generally, CATS/METS peaked on day 7, and then declined ((figsfigs 1 and 22).). On day 7, the average CATS/METS (reference intervals within parentheses) values were as follows: epinephrine 328.8 (9.3–122) nmol/day, norepinephrine 1079.3 (72–505) nmol/day, metanephrine 2075 (264–1729) nmol/day and normetanephrine 7029.8 (480–2424) nmol/day.

figure cp36640.f1
Figure 1 24 h urinary total catecholamines (CATS; ie, sum of epinephrine and norepinephrine) of five patients with intracerebral haemorrhage. Using a catecholamine cut‐off of >1300 nmol/day, patients who exceeded ...
figure cp36640.f2
Figure 2 24 h urinary metanephrines (METS; ie, sum of metanephrine and normetanephrine) of five patients with intracerebral haemorrhage. Using a metanephrine cut‐off of >8300 nmol/day, patients who exceeded these ...

Patients 4 and 5 with massive “day 7” total CATS (1070 and 2505 nmol/day, respectively) and METS (10 365 and 12 392 nmol/day, respectively) had normal total CATS (44 and 165 nmol/day, respectively) and METS (2154 and 1189 nmol/day, respectively) when re‐evaluated 2 years later.

The PHEO suspects revealed no adrenal/extra‐adrenal lesions on abdominal CT and were unlikely to harbour PHEO. All four false positives (patients 2–5) had larger ICH (cerebral haematoma >25 ml with or without intraventricular extension) requiring extra‐ventricular drainage/craniotomy, whereas patient 1 with normal CATS/METS had a basal ganglia haematoma of 11.8 ml treated conservatively.

Syed et al2 recently reported (n = 5) that urinary CATS/METS were insignificantly increased perioperatively, a state of profound stress. However, their results cannot be extrapolated to catastrophic stresses of ICH. Currently, there is a dearth of literature on the latter.3,4 We confirmed that CATS/METS excess occurs temporarily after ICH, probably from an autonomic storm analogous to sympathetic dysautonomia in traumatic brain injury.5 As patient 1 with minimal ICH had normal CATS/METS, the degree of dysautonomia seemed to be proportional to ICH size. The temporal trajectory of increases in CATS/METS provided an evidence‐based optimal PHEO screening rationale, unconfounded by ICH and allowed differentiation from PHEO. Among those with increased METS, CATS were below the PHEO diagnostic threshold in patients 2 and 4. As METS are CATS derivatives, we believe the true “CATS peak” occurred before day 7, and could be higher between days 3 and 6.

In conclusion, screening patients with ICH for PHEO is best avoided in the first week and deferred for at least a month, although a PHEO should be excluded when CATS/METS are persistently raised. This has pragmatic implications to the medical community including chemical pathologists, neurosurgeons and endocrinologists.

Acknowledgements

We thank Mrs Sim Joo Tan for her secretarial assistance. This study was supported by a research grant (TTSH R100/20C) from Tan Tock Seng Hospital.

Footnotes

Competing interests: None.

References

1. Lenders J W, Pacak K, Walther M M. et al Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002. 2871427–1434.1434 [PubMed]
2. Syed A A, Wheatley H A, Badminton M N. et al Urinary catecholamines and metabolites in the immediate postoperative period following major surgery. J Clin Pathol 2004. 57548–550.550 [PMC free article] [PubMed]
3. Hamann G F, Strittmatter M, Hoffmann K H. et al Pattern of elevation of urinary catecholamines in intracerebral hemorrhage. Acta Neurochir (Wien) 1995. 13242–47.47 [PubMed]
4. Naredi S, Lambert G, Eden E. et al Increased sympathetic nervous activity in patients with non‐traumatic subarachnoid hemorrhage. Stroke 2000. 31901–906.906 [PubMed]
5. Baguley I J, Nicholls J L, Felmingham K L. et al Dysautonomia after traumatic brain injury: a forgotten syndrome? J Neurol Neurosurg Psychiatry 1999. 6739–43.43 [PMC free article] [PubMed]

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