The University of Southampton
University of Southampton Institutional Repository

Metabolism of catecholamines in some clinical disorders

Metabolism of catecholamines in some clinical disorders
Metabolism of catecholamines in some clinical disorders

This study is concerned with catecholamine metabolism in clinical disease: namely, in the inherited metabolic disorder phenylketonuria and in a group of catecholamine secreting tumours. A reliable and specific method was developed using high pressure liquid chromatography with electrochemical detection for the determination of catecholamine output. This allowed changes in catecholamine metabolism to be defined and these are not always reflected by the production of their urinary metabolites. In classical phenylketonuria the urinary excretion of noradrenaline and adrenaline was shown to be in the lower part of the reference range and only dopamine concentrations were markedly reduced. This finding is contrary to the general thought that all catecholamine levels are reduced in this condition. In classical phenylketonuria there is increased excretion of m-hydroxymandelic acid, which is formed from m-octopamine, an amine which displaces brain catecholamines in animal studies. Oral loading tests with the putative precursor L-m-tyrosine were performed to explore a possible relationship between th production of the meta-phenolamines and catecholamines in this inherited disorder. The results showed an inverse relationship between noradrenaline and adrenaline excretions and that of m-hydroxymandelic acid for up to eight hours after the load. Dopamine output was not appreciably changed by the load, a result which differs from the demonstrated increase in the production of its metabolite, 3,4-dihydroxyphenylalanine, after similar administration of L-m-tyrosine to subjects with this metabolic disorder. The raised urinary dopamine levels in a healthy adult after an oral L-m-tyrosine load are further confirmation that this amino acid is metabolised via ring hydroxylation. In the same study there was decreased excretion of adrenaline and noradrenaline for eight hours after the load, a finding which correlates with the effect of L-m-tyrosine on displacement of brain amines in animals, apparently after decarboxylation to the meta-phenolamines. Dopamines excretion was shown to be a useful prognostic indicator in patients with malignant phaeochromocytoma. Ten of fifteen patients with this tumour had raised dopamine excretion. The survival time for the patients with normal dopamine excretion was better than that for the patients with increased dopamine excretion (p< 0.003). Comparison of the urinary concentrations of dopamine and its metabolite homovanillic acid in patients with malignancy showed that four patients with widespread metastases and raised dopamine excretion had normal homovanillic acid excretion. From this study dopamine excretion appeared to be a more discriminating biochemical index of malignancy and progression of the disease than homovanillic acid.

University of Southampton
Tippett, Patricia Anne Trevella
Tippett, Patricia Anne Trevella

Tippett, Patricia Anne Trevella (1987) Metabolism of catecholamines in some clinical disorders. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This study is concerned with catecholamine metabolism in clinical disease: namely, in the inherited metabolic disorder phenylketonuria and in a group of catecholamine secreting tumours. A reliable and specific method was developed using high pressure liquid chromatography with electrochemical detection for the determination of catecholamine output. This allowed changes in catecholamine metabolism to be defined and these are not always reflected by the production of their urinary metabolites. In classical phenylketonuria the urinary excretion of noradrenaline and adrenaline was shown to be in the lower part of the reference range and only dopamine concentrations were markedly reduced. This finding is contrary to the general thought that all catecholamine levels are reduced in this condition. In classical phenylketonuria there is increased excretion of m-hydroxymandelic acid, which is formed from m-octopamine, an amine which displaces brain catecholamines in animal studies. Oral loading tests with the putative precursor L-m-tyrosine were performed to explore a possible relationship between th production of the meta-phenolamines and catecholamines in this inherited disorder. The results showed an inverse relationship between noradrenaline and adrenaline excretions and that of m-hydroxymandelic acid for up to eight hours after the load. Dopamine output was not appreciably changed by the load, a result which differs from the demonstrated increase in the production of its metabolite, 3,4-dihydroxyphenylalanine, after similar administration of L-m-tyrosine to subjects with this metabolic disorder. The raised urinary dopamine levels in a healthy adult after an oral L-m-tyrosine load are further confirmation that this amino acid is metabolised via ring hydroxylation. In the same study there was decreased excretion of adrenaline and noradrenaline for eight hours after the load, a finding which correlates with the effect of L-m-tyrosine on displacement of brain amines in animals, apparently after decarboxylation to the meta-phenolamines. Dopamines excretion was shown to be a useful prognostic indicator in patients with malignant phaeochromocytoma. Ten of fifteen patients with this tumour had raised dopamine excretion. The survival time for the patients with normal dopamine excretion was better than that for the patients with increased dopamine excretion (p< 0.003). Comparison of the urinary concentrations of dopamine and its metabolite homovanillic acid in patients with malignancy showed that four patients with widespread metastases and raised dopamine excretion had normal homovanillic acid excretion. From this study dopamine excretion appeared to be a more discriminating biochemical index of malignancy and progression of the disease than homovanillic acid.

This record has no associated files available for download.

More information

Published date: 1987

Identifiers

Local EPrints ID: 460790
URI: http://eprints.soton.ac.uk/id/eprint/460790
PURE UUID: c973159a-31e5-4c9c-94f6-9ae34d099f34

Catalogue record

Date deposited: 04 Jul 2022 18:29
Last modified: 04 Jul 2022 18:29

Export record

Contributors

Author: Patricia Anne Trevella Tippett

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×