Ann. clin. Biochem. 17 (1976) 507-508
Catecbolamine-secreting Tumours and tbeir Clinical Chemistry M.
SANDLER
Bernhard Baron Memorial Research Laboratories, and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, W60XG
Three major tumour groups are associated with as that of the metadrenalines, the output of which is catecholamine overproduction-phaeochromocyto- proportionally much higher. Urinary metadrenaline ma, ganglioneuroma-neuroblastoma-retinoblastoma, assay is the best single test we possess for the and chemodectoma (Sandler, 1967). Phaeochromo- diagnosis of phaeochromocytoma (Sandler, 1964). Although these compounds have traditionally been cytoma is the commonest of these rare tumours and is also clinically the most important, for it is one of measured spectrophotometrically, latterly gas the few causes of hypertension in which cure is chromatography and gas chromatography-mass spectrometry have provided specificity, speed, and possible. Characteristically, phaeochromocytoma arises in versatility to measurements of this type and are the adrenal medulla, though extra-adrenal sites are being used increasingly. well known, including the organ of Zuckerkandl, One important point to remember is that, while and account for about 20 % of the total, and it is the catecholamines are of great importance from the always worth bearing in mind, when the tumour is diagnostic viewpoint, they do not account for all hard to locate, that it may be intrathoracic. In 10% the clinical features associated with the varieties of cases the tumour is multiple, and a similar of tumour making up this disease complex. Other proportion metastasise. The malignant variant may pharmacologically active agents have been identified often be difficult to differentiate from the benign in excess in affected subjects: for example, both the tumour on histological grounds, but it may some- prostaglandins (Sandler et al., 1968) and vasoactive times be helpful to measure homovanillic acid intestinal peptide (Swift et al., 1975) have been put output. There is some evidence to suggest that output forward as possible candidates to account for the of this compound, the major metabolite of dopamine, diarrhoea which accompanies certain forms of is raised in malignant phaeochromocytoma (Robin- ganglioneuroma or neuroblastoma (Smellie and son et al., 1963; Jones et al., 1968). Sandler, 1961; Rosenstein and Engelman, 1963). Tumours belonging to the neuroblastoma group are characteristically dopamine-secreting (Sandler REFERENCES and Ruthven, 1969). Paradoxically, although large amounts of ,B-hydroxylated (noradrenaline and Jones, N. F., Walker, G., Ruthven, C. R. J., Sandler, M. a-Methyl-p-tyrosine in the management of phaeoadrenaline) metabolites are also produced, conchromocytoma. Lancet 2 (1968) 1105. siderably more than in phaeochrornocytoma, the degree of hypertension tends to be relatively small Robinson, R. The clinical chemistry of phaeochromocytornas, In The Clinical Chemistry of Monoamines, (Sandler and Ruthven, 1966), probably because ed. H. Varley and A. H. Gowenlock, p. 63. Amsterdam, pressor amines are metabolised within the tumour Elsevier (1963). tissue before gaining access to the blood stream. Rosenstein, B. J., Engleman, K. Diarrhoea in a child Tumours falling into the chemodectoma group-with a catecholamine-secreting ganglioneuroma. J. carotid body, glomus jugulare, and aortic body Pediat. 63 (1963) 217. tumour-are only occasionally catecholamine-secret- Sandler, M. The laboratory investigation of catecholamine-secreting tumours. J. med. Lab. Technol. 21 ing. They also tend to be characterised by an (1964) 306. increased output of dopamine. A very large number of metabolites derived from Sandler, M. Catecholamine-secreting tumours. Proc. roy. Soc. Med. 60 (1967) 795. the amino acid L-dopa (Sandler, 1972) may be Sandler, M. Catecholamine synthesis and metabolism in found in the urine secreted by patients with these man (with special reference to parkinsonism). In tumours, and the urinary output of many of them Handbook of Experimental Pharmacology Vol. 33, has accordingly been widely employed as a guide to Catecholamines, ed. H. Blaschko and E. Muscholl, diagnosis and prognosis. The major end-product of p. 845. Berlin, Springer (1972). the ,B-hydroxylated catecholamines is 4-hydroxy-3- Sandler, M., Karim, S. M. M., Williams, E. D. Prostamethoxymandelic acid (VMA), while homovanillic glandins in amine-peptide-secreting tumours. Lancet 2 (1968) 1053. acid is the major metabolite of dopamine. Although VMA is widely used in the diagnosis of phaeochro- Sandler, M., Ruthven, C. R. J.4-Hydroxy-3-methoxyphenylglycol and other compounds in neuroblastoma. mocytorna, its "signal to noise" ratio is not as high 507
Downloaded from acb.sagepub.com by guest on June 4, 2016
508
M. Sandler
In Recent Studies in Cancer Research. II. Neuroblastoma, Biochemical Studies, ed. C. Bohuon, p. 55. Berlin, Springer (1966). Sandler, M., Ruthven, C. R. J. The biosynthesis and metabolism of the catecholamines. In Progress in Medicinal Chemistry, 6, ed, G. P. Ellis and G. B. West,
p. 200. London, Butterworth (1969). SmelIie, J. M., Sandler, M. Secreting intrathoracic ganglioneuroma. Proc. roy. Soc. Med. 43 (1961) 327. Swift, P. G. F., Bloom, S. R., Harris, F. Watery diarrhoea and ganglioneuroma with secretion of vasoactive intestinal peptide. Arch. Dis. Childh. 50 (1975) 896.
Downloaded from acb.sagepub.com by guest on June 4, 2016
Catecbolamine-secreting Tumours and tbeir Clinical Chemistry M.
SANDLER
Bernhard Baron Memorial Research Laboratories, and Institute of Obstetrics and Gynaecology, Queen Charlotte's Maternity Hospital, London, W60XG
Three major tumour groups are associated with as that of the metadrenalines, the output of which is catecholamine overproduction-phaeochromocyto- proportionally much higher. Urinary metadrenaline ma, ganglioneuroma-neuroblastoma-retinoblastoma, assay is the best single test we possess for the and chemodectoma (Sandler, 1967). Phaeochromo- diagnosis of phaeochromocytoma (Sandler, 1964). Although these compounds have traditionally been cytoma is the commonest of these rare tumours and is also clinically the most important, for it is one of measured spectrophotometrically, latterly gas the few causes of hypertension in which cure is chromatography and gas chromatography-mass spectrometry have provided specificity, speed, and possible. Characteristically, phaeochromocytoma arises in versatility to measurements of this type and are the adrenal medulla, though extra-adrenal sites are being used increasingly. well known, including the organ of Zuckerkandl, One important point to remember is that, while and account for about 20 % of the total, and it is the catecholamines are of great importance from the always worth bearing in mind, when the tumour is diagnostic viewpoint, they do not account for all hard to locate, that it may be intrathoracic. In 10% the clinical features associated with the varieties of cases the tumour is multiple, and a similar of tumour making up this disease complex. Other proportion metastasise. The malignant variant may pharmacologically active agents have been identified often be difficult to differentiate from the benign in excess in affected subjects: for example, both the tumour on histological grounds, but it may some- prostaglandins (Sandler et al., 1968) and vasoactive times be helpful to measure homovanillic acid intestinal peptide (Swift et al., 1975) have been put output. There is some evidence to suggest that output forward as possible candidates to account for the of this compound, the major metabolite of dopamine, diarrhoea which accompanies certain forms of is raised in malignant phaeochromocytoma (Robin- ganglioneuroma or neuroblastoma (Smellie and son et al., 1963; Jones et al., 1968). Sandler, 1961; Rosenstein and Engelman, 1963). Tumours belonging to the neuroblastoma group are characteristically dopamine-secreting (Sandler REFERENCES and Ruthven, 1969). Paradoxically, although large amounts of ,B-hydroxylated (noradrenaline and Jones, N. F., Walker, G., Ruthven, C. R. J., Sandler, M. a-Methyl-p-tyrosine in the management of phaeoadrenaline) metabolites are also produced, conchromocytoma. Lancet 2 (1968) 1105. siderably more than in phaeochrornocytoma, the degree of hypertension tends to be relatively small Robinson, R. The clinical chemistry of phaeochromocytornas, In The Clinical Chemistry of Monoamines, (Sandler and Ruthven, 1966), probably because ed. H. Varley and A. H. Gowenlock, p. 63. Amsterdam, pressor amines are metabolised within the tumour Elsevier (1963). tissue before gaining access to the blood stream. Rosenstein, B. J., Engleman, K. Diarrhoea in a child Tumours falling into the chemodectoma group-with a catecholamine-secreting ganglioneuroma. J. carotid body, glomus jugulare, and aortic body Pediat. 63 (1963) 217. tumour-are only occasionally catecholamine-secret- Sandler, M. The laboratory investigation of catecholamine-secreting tumours. J. med. Lab. Technol. 21 ing. They also tend to be characterised by an (1964) 306. increased output of dopamine. A very large number of metabolites derived from Sandler, M. Catecholamine-secreting tumours. Proc. roy. Soc. Med. 60 (1967) 795. the amino acid L-dopa (Sandler, 1972) may be Sandler, M. Catecholamine synthesis and metabolism in found in the urine secreted by patients with these man (with special reference to parkinsonism). In tumours, and the urinary output of many of them Handbook of Experimental Pharmacology Vol. 33, has accordingly been widely employed as a guide to Catecholamines, ed. H. Blaschko and E. Muscholl, diagnosis and prognosis. The major end-product of p. 845. Berlin, Springer (1972). the ,B-hydroxylated catecholamines is 4-hydroxy-3- Sandler, M., Karim, S. M. M., Williams, E. D. Prostamethoxymandelic acid (VMA), while homovanillic glandins in amine-peptide-secreting tumours. Lancet 2 (1968) 1053. acid is the major metabolite of dopamine. Although VMA is widely used in the diagnosis of phaeochro- Sandler, M., Ruthven, C. R. J.4-Hydroxy-3-methoxyphenylglycol and other compounds in neuroblastoma. mocytorna, its "signal to noise" ratio is not as high 507
Downloaded from acb.sagepub.com by guest on June 4, 2016
508
M. Sandler
In Recent Studies in Cancer Research. II. Neuroblastoma, Biochemical Studies, ed. C. Bohuon, p. 55. Berlin, Springer (1966). Sandler, M., Ruthven, C. R. J. The biosynthesis and metabolism of the catecholamines. In Progress in Medicinal Chemistry, 6, ed, G. P. Ellis and G. B. West,
p. 200. London, Butterworth (1969). SmelIie, J. M., Sandler, M. Secreting intrathoracic ganglioneuroma. Proc. roy. Soc. Med. 43 (1961) 327. Swift, P. G. F., Bloom, S. R., Harris, F. Watery diarrhoea and ganglioneuroma with secretion of vasoactive intestinal peptide. Arch. Dis. Childh. 50 (1975) 896.
Downloaded from acb.sagepub.com by guest on June 4, 2016
