CLlNlCAL UTILITY OF CORTICOSTEROID-INDUCED ALKALINE

161 Pages·2002·6.96 MB·English

CLlNlCAL UTILITY OF CORTICOSTEROID-INDUCED ALKALINE PHOSPHATASE IN
ADULT DOGS ADMllTED TO A VETERINARY TEACHING HOSPITAL
A Thesis
Presented to
The Faculty of Graduate Studies
of
The University of Guelph
by
PAULA M. KRIMER
In partial fulfillment of requirements
for the degree of
Doctor of Veterinary Science
August, 2001
O Paula M. Krimer, 2001
I * m National Library Bibliothèque nationale
of Canada du Canada
Acquisitions and Acquisitions et
Bibliographie Services services bibliographiques
395 Wellington Street 395. nie Wellington
Ottawa ON KIA ON4 Ottawa ON K 1 A ON4
Canada Canada
Your file Votre rdference
Our file Notre refdrenca
The author has granted a non- L'auteur a accordé une licence non
exclusive licence allowing the exclusive permettant à la
National Library of Canada to Bibliothèque nationale du Canada de
reproduce, loan, distribute or sell reproduire, prêter, dismbuer ou
copies of this thesis in microfom, vendre des copies de cette thèse sous
paper or electronic formats. la forme de microfiche/film, de
reproduction sur papier ou sur format
élecîronique.
The author retains ownership of the L'auteur conserve la propriété du
copyright in this thesis. Neither the droit d'auteur qui protège cette thèse.
thesis nor substantial extracts fiom it Ni fa thèse ni des extraits substantiels
may be printed or othenvise de celle-ci ne doivent être imprimés
reproduced without the author's ou autrement reproduits sans son
permission. autorisation.
ABSTRACT
CLINICAL UTlLlTY OF CORTICOSTEROID-INDUCED ALKALINE PHOSPHATASE IN
ADULT DOGS ADMllTED T0 A VETERINARY TEACHING HOSPITAL
Paula M. Krimer Advisor:
University of Guelph, 2001 Professor R. Jacobs
Objective - To examine the usefulness of corticosteroid-induced alkaline phosphatase
as a diagnostic test.
Design - Retrospective.
Sample Population - Data set A: Dogs over 12 months of age admitted to the Ontario
Veterinary College Veterinary Teaching Hospital (OVC-VIH) between January 1, 1992,
and December 31, 1997, with a total alkaline phosphatase > 2000 IU/L on presentation.
Data set B: The initial biochemical profile of al1 dogs not born in 1997 or 1998, admitted
to the OVC-VTH for the first time between January 1 and December 31, 1998, who had
a biochemical profile performed.
Procedures - Generation of receiver operator characteristic plots to identify activities of
serum absolute corticosteroid-induced alkaline phosphatase (CALP) and relative
activities of CALP (%CALP) useful for diagnosing hyperadrenocorticism (HAC).
Determination of other diseases and medications associated with CALP at these values
using odds ratios with confidence intervals. Diagnostic cornparison between CALP or
%CALP and clinical signs. Modeling a dose-response relationship between cumulative
prednisone dose and CALP or %CALP.
Results - Of medications, only corticosteroids were highly associated with CALP and
%CALP in dogs with elevated alkaline phosphatase. CALP of 50% had a sensitivity of
100% for the diagnosis of HAC in al1 groups. Alimentary diseases were sparing for
CALP. Clinical signs were as useful as measuring CALP or %CALP to diagnose HAC.
No dose-response relationship was evident between steroid exposure and CALP or
%CALP.
Conclusion and Clinical Relevance - Clinicians can request CALP if the dog is not
exposed to corticosteroids, has elevated total alkaline phosphatase, and does not have
clinical signs consistent with Iiver disease. If CALP is <50%, hyperadrenocorticism is
effectively ruled out. Routine rneasurement of CALP on biochemical profiles is not
recornmended.
ACKNOWLEDGEMENTS
Mom, Dad, Jet, Jonathan. Thanks for your unwavering and unconditional support, in
every sense of the word.
Friends. Thanks for ietting me into your lives. You have enriched mine.
Roser and Carolyn - you will always be my sisters.
Advisory Cornmittee. Thanks for helping me complete this thesis.
Richard, it would not have existed without you.
Educators. Thanks to those who challenged me, opened my mind, and
helped me grow. I hope it was reciprocal. Dorothee, I'm grateful for your
arrivai.
Support Staff in Medical Records, the Clinical Pathology Laboratory, and
Histology Laboratory. You are al1 wonderful, helpful, and tremendously
patient people.
Trudy, Edith, Joan, and Jean. This department is nothing without you.
Squirrel and ChIoe. You're the best.
TABLE OF CONTENTS
.................................................................................................................
List of Tables v
..............................................................................................................
List of Figures xi
..
......................................................................................................
List of Appendices XII
. ...............................................................................................
CHAPTER 1 OVERVIEW 1
. ...........................
Section A Introduction: Eighty Years of Alkaline Phosphatase 3
Section B . Literature Review: What We Think We Know ........................................ 1
. .................................................................
Part 7 Structure. Function and Genetics 7
Part 2. Tissue Alkaline Phosphafase ........................................................................ 5
Part 3. Serum Alkaline Phosphatase ...i n Health ............................................... 70
Part 4 . Serum Alkaline Phosphafase. .. and in Disease ........................................... 72
Part 5. Corticosteroid-induced Alkaline Phosphafase ................ ......................... 76
,.
Part 6. Corticosteroid-induced Alkaline Phosphatase and Hyperadrenocorficism ... 18
. ........................................
Section C Study Objectives: What We Want To Know 22
. ...................................................................
Chapter 2 MATERIALS AND METHODS 26
. ...................
Section A Data Collection and Organization of 1992-1997 Data set 26
. .........................
Section B Data Collection and Organization of 1998 Data Base 33
. ........................................................................................
Section C Data Analysis 35
Part 1. General Sfatistics ........................................................................................ 35
Parf 2. Receiver Operator Characteristic Plots ....................................................... 35
Part 3. Associations ............................................................................................... 36
Part4. Comparison with Clinical Signs .................................................................. 36
Part 5. Linear Regression ...................................................................................... 38
. ..................................................................................................
C hapter 3 RESULTS 39
. ......................................................................*.............
Section A Descriptive Data 39
Part 7 . Descriptive Data for 7992- 7997 Data Set. .............................................. -39
Part 2. Descriptive Data for 7 998 Data Sef ......................................................... 42
. ................................
Section B Receiver Operator Characteristic (ROC) Plots 44
Part 1. ROC plots for 1992- 1997 Data .................................................................. -44
Part 2. ROCplofs for 7998 Data Set. ..................................................................... 54
. ...................................................................................
Section C Associations 59
Corticosferoid Exposure: ........................................................................................ -53
Diseasesr ..................... ... ....................................................................................... 59
Medications: .......................................................................................................... 6 0
. .......................................................
Section D Cornparison with Clinical Signs 94
. .............................................................................
Section E Linear Regression 98
. ... .........................................................
Chapter 4 DISCUSSION What We Learned 100
. .........................................
Section A Receiver Operator Characteristic Plots 400
. ....................................................................................
Section B Associations 103
. .....................................................
Section C Comparison with Clinical Signs 109
. ...........................................................................
Section D Linear Regression IIO
. ... ............................................................
Chapter 5 CONCLUSION What We Know iA2
... .............................................................................
What We Still Need Ta Learn 115
.............................................................................................................
References 121
.................................................................................................................
Appendix i 129
.................................................................................................................
Appendix 2 130
.................................................................................................................
Appendix 3 132
.........................................................................=.......................................
Appendix 4 134
.................................................................................................................
Appendix 5 136
.................................................................................................................
Appendix 6 138
.................................................................................................................
Appendix 7 139
iii
.................................................................................................................
Appendix 8 140
.................................................................................................................
Appendix 9 141
...............................................................................................................
Appendix 10 142
...............................................................................................................
Appendix 11 143
List of Tables
Title Page
Methods of detection of canine alkaline phosphatase isoenzyrnes 9
Diagnostic criteria for disease categories in adult dogs admitted to a 30
veterinary teaching hospital, with total serum alkaline phosphatase
>ZOO0 IUIL on initial presentation, frorn 1992-19 97.
Disease categories used to classify clinical diagnoses in adult dogs 34
adrnitted to a veterinary teaching hospital, with clinical chemistry
profiles perforrned, in 1998.
Number of adult dogs, by breed, adrnitted to a veterinary teaching 40
hospital, with >ZOO0 IUIL total serum alkaline phosphatase on initial
presentation, frorn 1992-19 97.
Number of adult dogs, by disease category, admitted to a veterinary 40
teaching hospital, with >2000 IU/L total serum alkaline phosphatase
on initial presentation, from 1992-19 97.
Number of adult dogs, by medication exposure, admitted to a 41
veterinary teaching hospital, with >2000 IU/L total serurn alkaline
phosphatase on initial presentation, frorn i9 92-1 997.
Nurnber of adult dogs, by breed, admitted to a veterinary teaching 42
hospital, with clinical chemistry profiles performed, in 1998.
Number of adult dogs, by disease category, adrnitted to a veterinary 43
teaching hospital, with clinical chemistry profiles perforrned, in 1998.
Parameters for absolute corticosteroid-induced alkaline phosphatase 47
(CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
admitted to a veterinary teaching hospital, with total serum alkaline
phosphatase >2000 IU!L on initial presentation, from i99S-'l997.
Parameters for relative corticosteroid-induced alkaline phosphatase 49
(%CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
admitted to a veterinary teaching hospital, with total serurn alkaline
phosphatase >2000 IU/L on initial presentation, frorn 19924997.
Parameters for absolute corticosteroid-induced alkaline phosphatase 51
(CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
admitted to a veterinary teaching hospital, not exposed to
corticosteroids or phenobarbital, with total serum alkaline phosphatase
>2000 I UIL on initial presentation, from l992-l997.
Parameters for relative corticosteroid-induced alkaline phosphatase
(%CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
adrnitted to a veterinary teaching hospital, not exposed to
corticosteroids or phenobarbital, with total serum alkaline phosphatase
>2000 IUIL on initial presentation, from 1992-19 97.
Parameters for absolute corticosteroid-induced alkaline phosphatase
(CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
admitted to a veterinary teaching hospital, with clinical chemistry
profiles performed, in 1998.
Parameters for relative corticosteroid-induced alkaline phosphatase
(%CALP) as a diagnostic test for hyperadrenocorticism in adult dogs
adrnitted to a veterinary teaching hospital, with clinical chemistry
profiles performed, in 1998.
Association of corticosteroids with absolute corticosteroid-induced
alkaline phosphatase (CALP) and relative CALP (%CALP) in adult
dogs admitted to a veterinary teaching hospital, with total serum
alkaline phosphatase >ZOO0 IUIL on initial presentation, from 1992-
1997.
Association of central nervous system diseases with absolute
corticosteroid-induced alkaline phosphatase (CALP) and relative
CALP (%CALP) in adult dogs admitted to a veterinary teaching
hospital from 1992-19 97, with >2000 IUIL total serum alkaline
phosphatase on initial presentation, or admitted in 19 98, with clinical
chemistry profiles performed.
Association of cardiovascular diseases with absolute corticosteroid-
induced alkaline phosphatase (CALP) and relative CALP (%CALP) in
adult dogs admitted to a veterinary teaching hospital from 1992-19 97,
with >2000 IU/L total serum alkaiine phosphatase on initial
presentation, or admitted in 1998, with clinical chemistry profiles
performed.
Association of dermatological diseases with absolute corticosteroid-
induced alkaline phosphatase (CALP) and relative CALP (%CALP) in
adult dogs admitted to a veterinary teaching hospital from 1992-19 97,
with >2000 IUIL total senirn alkaline phosphatase on initial
presentation, or admitted in 1998, with clinical chernistry profiles
perforrned.
Association of diabetes mellitus with absolute corticosteroid-induced
alkaline phosphatase (CALP) and relative CALP (%CALP) in adult
dogs admitted to a veterinary teaching hospital from 1992-19 97, with
>2000 IUIL total serum alkaline phosphatase on initial presentation, or
admitted in 1998. with clinical chemistrv ~rofiIes~ erforrned-