Urinary free (unconjugated) metadrenalines in different hereditary forms of catecholamine-secreting phaeochromocytoma/paraganglioma.
BACKGROUND
Catecholamine-producing neuroendocrine tumours are found in chromaffin cells of the adrenal medulla (phaeochromocytoma) or extra-adrenal paraganglia (paraganglioma), known collectively as PPGLs. In approximately a quarter or more of cases of PPGL, these rare tumours arise as a result of germline mutations of several tumour susceptibility genes. At the Crosshouse laboratory, urine tests include free metadrenalines (fMAs) (also known as free metanephrines) which demonstrate superior sensitivity over that obtained by urinary vanillyl mandelic acid, catecholamines or plasma catecholamines in the diagnosis of PPGL. This retrospective audit was to determine if urinary fMAs offered discrimination among the hereditary forms of PPGL.


METHODS
Retrospective biochemical and genetic data were gathered from 1997 to 2011. The identified urine specimens were those obtained at the time of first diagnosis or recurrence of PPGL. Results of catecholamines and metabolites were standardized as multiples of their respective relevant upper reference limits (URLs).


RESULTS
Results were available for 29 affected patients (15 females and 14 males), median age 26 (range 9-63) years, comprising three mutation groups: succinate dehydrogenase subunit B or D ([SDHB/D] 16 patients), multiple endocrine neoplasia type 2 ([MEN 2] 6 patients) and von Hippel-Lindau disease ([VHL] 7 patients). The parent catecholamines exhibited increased values for noradrenaline (NA) and/or adrenaline (AD) for 25/29 (86.2%) patients. Either or both free normetadrenaline (fNMA) and fMA were elevated in 29/29 (100%) patients.


CONCLUSIONS
The ratio of the multiples of URL for fMA/fNMA displayed a clearer separation of MEN 2 patients from those with SDHB/D or VHL than did the equivalent AD/NA ratio.
Biochemistry Department, University Hospital Crosshouse, Kilmarnock KA2 0BE, UK. fraser.davidson@aaaht.scot.nhs.uk
D Fraser
DF
Davidson
Nicola
N
Bradshaw
Colin G
CG
Perry
Robert
R
Lindsay
E Marie
EM
Freel
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000652:urine*; D000328:Adult; D002395:Catecholamines / Q000652:urine*; D002648:Child; D019963:Clinical Chemistry Tests; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000652:urine*; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics / Q000652:urine*; D010673:Pheochromocytoma / Q000235:genetics / Q000652:urine*; D012008:Recurrence; D012189:Retrospective Studies
D002395:Catecholamines; D008676:Metanephrine