In the absence of characteristic clinical stigmata and family history, plasma metanephrine, normetanephrine, and methoxytyramine may be useful in guiding genetic testing. Germline mutations account for roughly 30% of phaeochromocytomas/paragangliomas. Nine tumour-susceptibility genes have been identified so far; von Hippel-Lindau tumour suppressor (VHL); succinate dehydrogenase complex, subunit B, iron sulfur (SDHB); and succinate dehydrogenase complex, subunit D, integral membrane protein (SDHD).

About a quarter of phaeochromocytomas/paragangliomas patients are likely to carry a germline mutation and hence routine genetic testing is recommended, particularly in young patients, even in the absence of family history. A full genetic screen testing for all known mutations is expensive. This study assessed whether measurements of plasma metanephrine, normetanephrine, and methoxytyramine, might aid rationalisation of genetic testing.

Plasma metanephrine, normetanephrine, and methoxytyramine were measured in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD. While patients with MEN and NF1 mutations secreted increased metanephrines (suggestive of increased epinephrine production), patients with VHL showed a solitary increase in normetanephrines and 70% of patients with SDH mutations presented with raised methoxytyramine in addition to normetanephrine. The authors were able to discriminate between patients with NF1 and MEN 2 from those with VHL, SDHB, and SDHD gene mutations in 99% of cases by using a combination of normetanephrine and metanephrine. Methoxytyramine was useful in differentiating between SDH mutations andVHL mutations in 78% of cases.

Imperial Centre for Endocrinology felt:

1. Units should analyse their own internal data of urine catecholamines, methoxytyramine and metanephrines
2. Urine metanephrines, which the paper suggest have comparable efficacy, may be as useful in clinical practice.

3. Since metanephrines are released at a steady rate, it may be possible to discriminate using single void spot urines.