The Endocrine Response to Acute Illness (Frontiers of Hormone Research)

215 Pages·1999·1.26 MB·English

by  Richard C. Jenkins

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TheEndocrineResponsetoAcuteIllness
..
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Frontiers of Hormone
Research
Vol. 24
Series Editor Ashley B. Grossman, London
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The Endocrine Response to
Acute Illness
Volume Editors Richard C. Jenkins, Sheffield
Richard J.M. Ross, Sheffield
33figuresand10tables,1999
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RichardJ.M.Ross,MD,FRCP
SeniorLecturerinEndocrinology,DepartmentofMedicine,UniversityofSheffield,
NorthernGeneralHospital,Sheffield,UK
RichardC.Jenkins,BMedSci,MRCP
DepartmentofMedicine,UniversityofSheffield,
NorthernGeneralHospital,Sheffield,UK
LibraryofCongressCataloging-in-PublicationData
Theendocrineresponsetoacuteillness/volumeeditors,RichardC.Jenkins,RichardJ.M.Ross
(Frontiersofhormoneresearch;vol.24)Includesbibliographicalreferencesandindex.
(hardcover:alk.paper).
1.Endocrinemanifestationsofgeneraldiseases. 2.Endocrineglands–Pathophysiology.
3.Homeostasis. 4.Hormones–Metabolism.
I.Jenkins,RichardC. II.Ross,RichardJ.M. III.Series.
[DNLM: 1.EndocrineGlands–metabolism. 2.Hormones–metabolism. 3.AcuteDisease.
W1FR946Fv.241999/WK102E5551999]RC649.E52251999616.4–dc21DNLM/DLC
ISSN0301–3073
ISBN3–8055–6822–3
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ÓCopyright1999byS.KargerAG,P.O.Box,CH–4009Basel(Switzerland)
www.karger.com
PrintedinSwitzerlandonacid-freepaperbyReinhardtDruck,Basel
ISBN3–8055–6822–3
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Contents
VII Preface
Grossman,A.B.(London)
The Endocrine Response to Acute Illness
1 Introduction
Jenkins,R.C.;Ross,R.J.M.(Sheffield)
4 Glucose Metabolism
Heller,S.R.;Robinson,R.T.C.(Sheffield)
27 Salt and Water Homeostasis
Arieff,A.I.(SanFrancisco,Calif.)
67 Calcium Metabolism
Lind,L.;Ljunghall,S.(Uppsala)
87 Thyroid Hormones
Hennemann,G.;Krenning,E.P.(Rotterdam)
110 The Pituitary Adrenal Axis
Newell-Price,J.;Trainer,P.J.(London)
131 The Pituitary Gonadal Axis
Fletcher,A.K.(Sheffield)
152 The Regulation of Growth Hormone Secretion
Ghigo,E.;Arvat,E.;Gianotti,L.;Maccario,M.;Camanni,F.(Turin)
176 Growth Hormone and IGF-I as Anabolic Therapy
Botfield,C.;Hinds,C.J.(London)
201 Subject Index
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Preface
I am delighted to introduce this new volume on the endocrine responses
to acute illness. There is now increasing interest in the pathogenesis and
phenomenology of serious critical illness, not least because of the extremely
high morbidity and mortality associated with septic shock in critically ill
patients,anditsimpactontheutilisationofclinicalresources.Thisisparticu-
larly true in patients with multiorgan failure, in whom our apparent under-
standing of its pathophysiology has been associated with the increasing use
ofsupportivetechniquesfortheheart,lungs,liverandkidney.Inspiteofthis,
however,themortalityinsuchpatientsstillremainsextremelyhigh,thereasons
for which remain baffling. Research has suggested that agents such as exoge-
nous endotoxin and the endogenous cytokines produced in response may be
involved in the pathogenesis of disease in such patients, but large-scale trials
basedonspecifictherapieshaverecentlyproventobedisappointinglyineffec-
tive.Inaddition,large-scaletrialsoftheuseofhigh-dosesteroidsandgrowth
hormoneinlargecohortsofsuchpatientshavealsoproventobediscouraging.
Thereasonsforthislackofsuccessareunclear,butalmostcertainlyrelateto
ourlackofunderstatingofthemolecularpathophysiologyofthechangesseen
in critically ill patients. Specifically, unless we can understand in some detail
the endocrine and metabolic changes, then any attempt at intervention is
unlikely to be successful.
Withthisinmind,IamextremelypleasedtowelcomethisvolumebyDrs.
JenkinsandRoss,inwhichadistinguishedpanelofinternationalcontributors
describeandoverviewthecurrentstudiesontheendocrinechangesincritically
illpatients.Iamcertainthatitisonlybyunderstandingsuchchangesindetail,
andcomprehendingtheprecisemolecularpathogenesis,canwebegintomake
anytherapeuticinroadsintothisdifficultsituation.Astheypointoutintheir
Introduction,onceacriticallyillpatienthasmovedintoachronicphase,one
cannotnecessarilyarguethatanyofthemetabolicandendocrinechangesare
adaptive, as there may have been no substrate on which evolution can act in
terms of natural selection. Under such circumstances, it is only by increasing
ourunderstandingthateventualtherapeuticimprovementscanbemaintained.
This volume is a worthy contribution to this important field.
Ashley B. Grossman
London, UK
Preface VIII
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Introduction
Criticalillnessisamodernphenomenonresultingfrommedicaladvances
which allow the survival of patients who would have previously died. The
effects of critical illness are manifold and not least among them are the pro-
found changes seen in metabolic and hormonal systems. Some of these pro-
cesses are disease specific and others are common to many aetiologies of
criticalillness.Thereareanumberofreasonswhyitisimportanttounderstand
thesemetabolicprocesses.Firstly,andpotentiallymostimportantly,thisknow-
ledge may allow the rational use of pharmaceutical interventions aimed at
improving outcome. Secondly, the changes may have prognostic significance
whether or not they have a causal role in outcome or are just markers for
diseaseseverity.Prognosticrelationshipssuggestthatanumberofthemetabolic
changes seen in acute illness may be important in determining outcome.
Ithasbeenproposedthatcriticalillnessfallsintotwometabolicallydistinct
phases–acuteandchronic[1].Itseemslikelythattheacutephasehasevolved
to optimise survival in the face of a temporary non-catastrophic injury or
illness. Before modern medicine the organism would have survived or died
and it seems unlikely therefore that there would have been pressure for the
evolutionofachronicresponse. Thechronicresponseweseetodaymaythus
representhumanphysiologyreactingtocircumstanceswhichithasnotevolved
todealwithanditsresponsesmaythusbeinappropriateandevendeleterious
to survival.
Theobviousimplicationofthisreasoningisthatinterventionsthatmodify
the endocrine/metabolic response may be beneficial. A number of important
studies have attempted to do this and these are discussed in the relevant
chapters.Ingeneral,earlysmallstudieshavebeenpromisingbutlargerbetter
designed studies, often using a sledgehammer approach, have either shown
nobenefitoractualharm.Inthelightofthesefindingsrecentworkhasbegun
to suggest that subtle interventions may be of benefit.