Download Serum total thyroxine and thyroid stimulating hormone

Journal of Veterinary Behavior (2009) 4, 230-236
RESEARCH
Serum total thyroxine and thyroid stimulating hormone
concentrations in dogs with behavior problems
Gabrielle R. Carter, BVSc, MSc, MACVSc (Behavior)a,
J. Catherine Scott-Moncrieff,
Vet MB, MS, MA Dipl ACVIM, ECVIMb,
Andrew U. Luescher, DVM, PhD Dipl ACVB, ECVBM-CAc,
George Moore, DVM, MS, PhD Dipl ACVIM, Dipl ACVPMb
a
Advanced Vetcare, Kensington, Victoria, Australia;
Small Animal Internal Medicine, Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana; and
c
Animal Behavior Clinic, Purdue University, West Lafayette, Indiana.
b
KEYWORDS:
hypothyroidism;
behavior;
dog;
thyroxine;
thyroid stimulating
hormone
Abstract The aim of this case controlled study was to determine whether dogs with behavioral problems
have evidence of abnormal thyroid function on routine screening tests for hypothyroidism. The hypothesis of
the study was that thyroid function, as assessed by serum total thyroxine (TT4) and serum thyroid stimulating hormone (thyrotropin) (TSH) concentrations, is normal in most dogs with behavioral problems. Concentrations of TT4 and TSH in 39 dogs with behavior problems presenting to a veterinary behavior referral clinic
(abnormal behavior group), were compared with TT4 and TSH concentrations in 39 healthy control dogs
without behavior problems presenting to 5 community veterinary practices (control group). Dogs in the control group were matched for age and breed with the abnormal behavior group. Dogs with behavioral problems had higher TT4 concentrations than dogs without behavioral problems (t-test: t 5 2.77, N 5 39,
P 5 0.009), however none of the TT4 values were outside the reference range. There was no significant difference in TSH concentration between the 2 groups. Two dogs with behavior problems and 1 dog without
behavior problems had results suggestive of hypothyroidism. All other dogs were considered to be euthyroid. There was no evidence to support a diagnosis of hypothyroidism in the majority of dogs with behavior
problems in this study. The higher concentration of TT4 in dogs with behavior problems suggests, however,
that alteration in thyroid hormone production or metabolism may occur in some dogs with behavior
problems. Further studies that include additional indicators of thyroid status such as serum total triiodothyronine, serum, free thyroxine, and anti-thyroid antibody concentrations are necessary to further evaluate the
significance of this finding.
Ó 2009 Elsevier Inc. All rights reserved.
Introduction
Address reprint requests and correspondence: Dr. Gabrielle Carter,
Advanced Vetcare, Level 1, 26 Robertson Street, Kensington, Victoria,
Australia; 3031.
E-mail: [email protected]
1558-7878/$ -see front matter Ó 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.jveb.2009.06.006
A relationship between the status of the thyroid axis and
behavior has been proposed. There are reports of behavioral
change associated with hypothyroidism in humans (Joffe
and Sokolov, 1994; Joffe, 2002), rats (Redei et al., 2001;
Carter et al
Table 1
TT4 and TSH Concentrations in Dogs With Behavioral Problems
231
Questions used to screen for behavior problems in control dogs
Please indicate if your dog shows any of the following behaviors:
1. Growling or biting at visitors in the home (including visiting children)
2. Growling at other dogs
3. House-soiling (urinates or defecates in the house)
4. Destructive behaviors (other than to toys)
5. Excessively repetitive behavior, such as circling, pacing, or licking
6. Aggression when woken
7. Aggression if a person takes away/attempts to take away food or toys
Barykina et al., 2002; Sapronov and Fedotova, 2002;
Tikhonova et al., 2005; Montero-Pedrazuela et al., 2006),
horses (Aronson, 1998), and dogs (Reinhart, 1978; Dodman
et al., 1995; Beaver and Haug, 2003). Alterations in measures of thyroid function have been noted in some human
psychiatric patients (Denicof et al., 1990), and a decrease
in thyroxine concentrations has been correlated with a positive response to antidepressant therapy, regardless of the
modality (Denicof et al., 1990; Joffe et al., 1996; Bauer
and Whybrow, 2002).
Aronson and Dodds (2006) in a study of 1,500 dogs with
behavioral problems reported that .60% of the dogs were
hypothyroid or had sub-optimal thyroid function; however
the diagnostic criteria used to establish a diagnosis of thyroid
dysfunction were not described in detail, and the authors
acknowledge that only some dogs would have been diagnosed as hypothyroid by other laboratories. Whether conventional diagnostic criteria would detect a similar trend remains
unknown. Current clinical opinion supports the use of serum
total thyroxine (TT4) or serum free thyroxine (FT4) and serum thyroid stimulating hormone (thyrotropin) (TSH) for
routine screening of dogs for hypothyroidism. Measurement
of low TT4 or FT4 together with an increased concentration
of TSH has high specificity for diagnosis of hypothyroidism
(Peterson et al., 1997; Ferguson, 2007; Panciera, 2007). On
the other hand, if TT4 or FT4 is well within the normal reference range, hypothyroidism is unlikely. Further testing is appropriate in those dogs with clinical signs of hypothyroidism
in which results of TT4 and TSH are equivocal. The aim of
this case controlled study was to determine whether dogs
with behavioral problems have evidence of abnormal thyroid
function on routine screening tests for hypothyroidism. The
hypothesis of the study was that thyroid function, as assessed
by TT4 and TSH, is normal in most dogs with behavioral
problems.
Materials and methods
Concentrations of serum TT4 and TSH in dogs with
behavioral problems (abnormal behavior group) were compared with concentrations in dogs without behavioral
problems (control group). A TT4 value ,1.3 mg/dl in conjunction with a TSH value .0.65 mg/dl was considered to
be consistent with hypothyroidism (Peterson et al., 1997;
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
No
Scott-Moncrieff et al., 1998; Dixon and Mooney, 1999)
Our reference ranges are very similar to those in the literature, which reports the lower end of the reference range
for TT4 varying from 1–1.5 mg/dl, and the reference range
for TSH being ,0.6–0.7 mg/dl. The study protocol was reviewed and approved by Purdue Animal Care and Use
Committee. Informed consent was obtained from owners
of privately owned dogs in the control group.
Abnormal behavior group
TT4 and TSH concentrations were retrospectively retrieved from the medical records of 39 dogs presented to
the Purdue University Veterinary Teaching Hospital for a
behavioral problem between July 2005 and July 2007. The
blood samples had been drawn either to assess for organic
disease as an underlying cause for the behavioral problem
or for general health screening before starting behavior
modifying drugs. Diagnosis of the problem behavior was an
uncontrolled variable, with diagnoses including generalized
anxiety, global fear, hyperactivity, phobias, and various
forms of aggression.
Control group
Thirty-nine dogs without behavioral problems were identified from 5 community practice clinics within a 16 km
radius of the Purdue University veterinary teaching hospital.
To be eligible for inclusion in the control group, dogs were
required to be free of behavioral problems as assessed by 7
‘‘yes/no’’ questions (Table 1), have no serious health problems that may alter thyroid hormone levels, and were
undergoing blood sampling for routine examinations (e.g.,
heartworm testing, wellness check). The last 2 criteria were
established by the consulting veterinarian. The first criterion
was initially screened by the consulting veterinarian and eligibility confirmed by the principal investigator. Dogs were
assessed as not having behavior problems if the owner answered ‘‘no’’ to all 7 questions, or if no more than one answer
was ‘‘yes,’’ and a qualifying comment added to suggest that
the behavior was not regarded as a problem by the owner,
or by the consulting veterinarian. For example, 1 dog included in the control group chewed on shoes in addition to
toys, but did not chew on other items.
232
Table 2
Journal of Veterinary Behavior, Vol 4, No 6, November/December 2009
Concentrations of the matched pairs
Matched pairs
Breed
Sex
Age (years)
TT4(mg/dl)
TSH (mg/dl)
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Boxer
Boxer
Chesapeake bay retriever
Chesapeake bay retriever
Dalmatian
Dalmatian
German shepherd
German shepherd
German short-haired pointer
German short-haired pointer
Golden retriever
Golden retriever
Golden retriever
Golden retriever
Jack russell terrier
Jack russell terrier
Jack russell terrier
Jack russell terrier
Labrador retriever
Labrador retriever
Labrador retriever
Labrador retriever
Labrador retriever
Labrador retriever
Labrador retriever
Labrador retriever
Mixed – 20 kg
Mixed – 20 kg
Miniature rchnauzer
Schnauzer
Mixed – 34 kg
Mixed – 34.5 kg
Mixed – Husky X
Mixed – Husky X
Mixed – Labrador X*
Labrador
Mixed – Foxhound X
Mixed – Labrador X
Mixed – Labrador X
Mixed – Labrador X
Mixed – 41 kg
Mixed – 33.6 kg
Mixed – Chow X
Mixed – Labrador X
Mixed – German Shepherd Xx
Mixed – German Shepherd X
Mixed – Maltese X Poodle, 5 kg
Mixed – Chihuahua X
Mixed – Pit Bull Terrier X
American staffordshire bull terrier
Mixed – Ridgeback X
Mixed – Ridgeback X
Mixed – 28 kg†
Mixed – 33 kg
Mixed – Pointer X
MN
MN
FS
FS
FS
MN
MN
FS
MN
ME
MN
MN
MN
FS
FS
FE
MN
FE
MN
MN
MN
MN
FS
FS
FS
FS
MN
FS
MN
FS
FS
FS
FS
FS
FS
FE
MN
FS
MN
MN
MN
MN
MN
MN
MN
FS
MN
MN
MN
FS
MN
FS
MN
MN
MN
7
5
5
7
6
8
3
2.5
2
1.5
5
3
4
4
3
3
2
1.5
3
1.5
3
4
2
1.5
6
5
3
3
5
6.5
4
6
3
3
1.5
1.5
7
7
7
6
6
6
1
2
1
2
2
5
3
4
3
5
3
5
7
2.4
0.7
2.6
1.1
2.0
1.2
1.7
2.1
1.0
1.3
2.7
2.2
2.9
1.0
0.9
1.3
0.9
1.8
2.1
2.2
1.9
2.0
2.3
2.2
1.7
1.4
1.6
1.2
2.0
1.9
0.9
1.7
1.7
1.8
1.8
1.5
3.2
1.3
1.5
1.0
2.9
2.0
1.2
1.0
1.3
1.4
2.3
2.3
2.3
2.5
2.1
1.7
2.1
1.4
1.4
0.35
0.1
0.13
0.18
0.18
0.22
0.04
0.26
0.06
0.39
0.41
0.08
0.07
0.06
0.12
0.09
0.08
0.07
0.12
0.41
, 0.03
0.14
0.05
0.11
0.32
0.13
0.09
0.08
0.13
0.36
4.3
0.08
0.08
0.07
0.15
0.03
0.16
0.13
0.10
0.41
0.15
0.13
0.03
0.77
, 0.03
0.23
0.06
0.12
0.12
0.23
0.05
0.09
0.04
0.15
0.18
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
(continued on next page)
Carter et al
Table 2
TT4 and TSH Concentrations in Dogs With Behavioral Problems
233
(continued )
Matched pairs
Breed
Sex
Age (years)
TT4(mg/dl)
TSH (mg/dl)
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Abnormal
Control
Mixed – German Shepherd X Husky
Mixed – 37 kg
Mixed – 45 kg
Mixed – Poodle, 20 kg
Mixed –
Mixed – Labrador X‡
Mixed – Labrador X
Scottish terrier
Cairn terrier
Shetland sheepdog
Shetland sheepdog
Mixed – Foxhound X
Mixed – Foxhound X
Mixed – Foxhound X
Mixed – Foxhound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
Mixed – Hound X
FS
MN
MN
FS
FS
FS
MN
FS
MN
FS
FS
FE
FS
FE
MN
ME
FE
ME
FE
FS
MN
FE
FE
8
3
4
5
5
3.5
3.5
3
4
5
3.0
3.5
3.0
1.5
2.5
2
2
2
2
3
3.5
2
2.5
1.1
1.6
1.9
2.2
1.5
1.6
2.3
1.6
1.3
2.1
1.9
2.1
1.9
1.6
1.8
2.5
1.4
2.4
1.9
3.3
1.8
1.8
1.9
0.17
0.07
0.15
0.09
0.13
0.10
0.10
0.09
0.14
0.07
0.09
0.32
0.26
0.73
0.12
0.08
0.07
0.29
0.05
0.08
0.13
0.17
0.06
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
behavior
FE, female entire; FS, female spayed; FT4, serum free thyroxine; ME, male entire; MN, male neutered; TSH, serum thyroid stimulating hormone
(thyrotropin); TT4, serum total thyroxine.
*Dog was medicated with clomipramine 1.7 mg/kg once daily for 5 months before blood sampling.
†
Dog was medicated with amitriptyline 3.6 mg/kg twice daily for 10 days before blood sampling.
‡
Dog was medicated with Deracoxib (DeramaxxÒ) 3 mg/kg once daily for 2 days, then 1.5 mg/kg once daily for 4 days, starting 2/20/06.
x
Dog was medicated with Deracoxib (DeramaxxÒ) 1.8 mg/kg once daily for 2 weeks. Blood sample was taken 2 weeks after Deramaxx was discontinued.
Because factors such as breed and age may affect concentrations of TT4 (Musser and Graham, 1968; Fritz et al., 1970;
Haines et al., 1984; Conaway et al., 1985a, b; Reimers et al.
1990; Panciera, 1994; Benjamin et al., 1996; Graham et al.,
2001; Nachreiner et al., 2002; Scott-Moncrieff, 2007), it was
deemed important to match the control group with the abnormal behavior group for these variables. Participating clinics
were given a list detailing the breed, age, sex, neuter status,
and weight of dogs in the abnormal behavior group, and asked
to select control dogs that matched these criteria as closely as
possible. Priority was given to matching breed and age, because
reference ranges for thyroid hormone concentrations vary between breeds, and dogs show a progressive decline in concentrations of TT4 with increasing age (Reimers et al., 1990;
Ferguson, 1994, 2007; Nachreiner et al., 2002; Graham et al.,
2007; Sheil et al., 2007). To match a pure bred abnormal behavior dog, the control dog had to be from the same or a related
breed. To match a cross-bred abnormal behavior dog, the control dog had to be of a similar weight, and was ideally a crossbred dog with its assumed breeding related to one of the breeds
in the abnormal behavior dog. To match for age, the control dog
was required to be within 2 years either side of the behavior
problem dog age, but had to be .1 year of age (Table 2).
Because some medications may lower TT4 values (Ferguson, 2007), the histories of all dogs in the study were
scrutinized for use of glucocorticoids, sulfonamides, iodine
containing agents, radio contrast dyes, phenobarbital, propanolol, potassium bromide, furosemide, tricyclic anti-depressants, general anesthetic agents, and nonsteroidal analgesics
within 2 months before blood sampling.
Testing procedure
Blood was drawn from all dogs in the study and TT4 and
TSH levels were measured, using the Immulite Immunoassay System (Siemens Healthcare Diagnostics, Deerfield,
IL) (Bruner et al., 1998).
Data analysis
Statistical analyses were carried out with a commercial
statistical software package (SAS version 9.1.3, SAS
Institute, Cary, NC). Signed rank tests were used to test
for difference in concentrations of TT4 and TSH between
the abnormal behavior and control samples. Additionally, a
paired Student’s t-test was used to compare TT4 values between the 2 groups. Comparisons were assessed at the 0.05
level of significance. The effects of diagnosis, breed, age,
234
Journal of Veterinary Behavior, Vol 4, No 6, November/December 2009
and sex on the difference between the abnormal behavior
and control groups for TT4 was assessed using ANOVA.
The effects of these variables on the difference between
the abnormal behavior and control groups for TSH was assessed using Friedman’s non-parametric ANOVA.
Results suggestive of hypothyroid status
TT4
TSH
concentration
concentration
(1.3–4.0 mg/dl)* (0.0–0.65 mg/dl)*
Abnormal behavior dog 0.9
Abnormal behavior dog 1.6
Control dog
1.0
Results
Signed rank tests on matched pairs found a significant
difference between the abnormal behavior and control
groups for TT4 (S 5 164, N 5 39, P 5 0.015), but no
significant difference for TSH (S 5 263.5, N 5 39,
P 5 0.364). A non-parametric signed ranks test was chosen
as the test statistic because the data for TSH were not normally distributed and their distribution met the assumptions
of the test (Table 3). The data for TT4 however, was close
to normally distributed (Table 3) and a t-test was applied to
this data for a more robust analysis. The t-test produced
similar results, showing a significant difference between
the abnormal behavior problem and control groups for
TT4 (t 5 2.77, N 5 39, P 5 0.009). The direction of difference was towards higher, not lower, concentrations of TT4
in the group with abnormal behavior (Table 3), This is in
contrast to the claim that many dogs with behavior problems are hypothyroid or have suboptimal thyroid function.
Eighty percent of the dogs with behavioral problems had a
TT4 well within the reference range (.1.5 mg/dl), including 3 dogs treated with medications known to lower TT4
concentrations. ANOVA did not find any significant effects
of diagnosis, breed, sex or age on the differences between
the control and abnormal behavior groups for TT4. Similarly, Friedman’s non-parametric ANOVA analysis did not
find any effects of these variables on the difference between
the two groups for TSH. Table 2 shows the breed, age, sex,
neuter status, T4, and TSH values for the matched pairs.
One dog in the abnormal behavior group and 1 dog in the
control group had results consistent with hypothyroidism,
and another dog in the abnormal behavior group had results
suspicious of hypothyroidism (Table 4). Four dogs in the
abnormal behavior group had received medications in the
2 months before testing that may lower concentrations of
TT4. None of the control dogs had received medications
that are known to affect TT4 concentrations (Table 2).
None of the dogs with results suggestive of hypothyroidism
had received medications known to affect thyroid hormone
concentrations.
Table 3
Table 4
Sample means and standard errors
T4 – abnormal behavior
T4 – control
TSH – abnormal behavior
Mean
Standard error
1.9553846
1.6432500
0.2487179
0.0966803
0.0703566
0.1087682
TSH, serum thyroid stimulating hormone (thyrotropin); T4, thyroxine.
4.3
0.73
0.77
TSH, serum thyroid stimulating hormone (thyrotropin); TT4, serum
total thyroxine.
*Reference range.
Discussion
In this study, dogs with behavior problems had higher
concentrations of TT4 compared to dogs without behavior
problems. An unpublished study comparing Bearded Collies with and without behavior problems identified lower
concentrations of TT4 in Bearded Collies with behavior
problems (S. Hamilton Andrews, MSc, CCAB, unpublished
data). These differing results are consistent with the human
literature, with some studies reporting increased and others
decreased TT4 and FT4 in depressed patients (Joffe and
Sokolov, 1994; Bauer and Whybrow, 2002; Joffe, 2002). It
is possible that there are individuals in the canine population,
analogous to those in the human population, who show
changes in the thyroid axis in association with behavioral disorders. Although the difference in concentrations of TT4
between the abnormal behavior and control groups is statistically significant, the difference is small (Table 3) and may
not be clinically significant or repeatable if a larger sample
size was used. If these alterations are repeatable, it is unclear
whether they are linked in a causal manner to the pathophysiology of behavioral disorders or whether behavioral disorders nonspecifically disrupt thyroid homeostasis. That is,
thyroid hormone concentrations may have a primary causal
link, be compensatory, or simply be an epiphenomenon, to
the development of behavioral problems.
Various mechanisms have been proposed to explain a
relationship between abnormalities of the thyroid axis and
behavior. Changes in the activity of the monoamine neurotransmitters, serotonin and norepinephrine, are proposed
to play a significant role in the pathogenesis of behavioral
disorders (Bear et al., 2001), and are also known to modulate TSH response to TRH (Joffe, 2002). Conversely, thyroid hormone deficiencies have been shown to result in
disturbances of noradrenergic, serotonergic, and g amino
butyric acid neurotransmission, and impair functioning of
intracellular signaling pathways (Bauer and Whybrow,
2002), which all have the potential to alter behavioral responses. These neurotransmitter abnormalities are reversible with thyroid hormone supplementation. Decreases in
thyroid hormone, and corresponding decreases in serotonergic activity have been correlated with memory and
learning deficits in rats (Sapronov and Fedotova, 2002).
Carter et al
TT4 and TSH Concentrations in Dogs With Behavioral Problems
Hypothyroidism also induces a depressive disorder in rats,
which correlates with impaired hippocampal neurogenesis;
a condition reversible with thyroid supplementation (Montero-Pedrazuela et al., 2006).
Despite the proposed relationships between hypothyroidism, altered neurological function, and behavior, in this
study only 1 dog with behavioral problems and 1 control
dog had TT4 and TSH concentrations diagnostic of hypothyroidism. One other dog with behavioral problems had
results that could be consistent with hypothyroidism, but
further analysis of the thyroid axis would be required to
confirm the thyroid status of this dog. In this study, 80% of
the dogs with behavioral problems had a TT4 well within
the reference range (.1.5 mg/dl). In most cases a diagnosis
of hypothyroidism can be excluded if the TT4 is well
within the reference range. The only exception to this is patients in which there is interference due to the presence of
anti-T4 antibodies. Anti-T4 antibodies are found in 1.7% of
samples from dogs with clinical signs consistent with hypothyroidism and in 15% of confirmed hypothyroid dogs
(Graham et al., 2001; Nachreiner et al., 2002). In general,
these antibodies increase the TT4 above the reference range,
but theoretically they could increase the TT4 into the normal
reference range. Therefore, in those dogs with a low normal
TT4 (1.3 mg/dl , TT4 , 1.5 mg/dl: 20% of abnormal behavior dogs, 46% of control dogs) a diagnosis of hypothyroidism
can not be completely excluded. Measurement of FT4 (by dialysis), direct measurement of anti-T4 antibodies, or a TSH
stimulation test would have been ideal to allow us to exclude
hypothyroidism in these dogs (Petersen et al., 1997; Nachreiner et al., 2002; Diaz-Espineira et al., 2007). FT4 has
higher specificity and sensitivity than TT4 (Peterson et al.,
1997; Ferguson, 2007), and the inclusion of FT4 may have
improved the ability to detect abnormalities in thyroid function. However, as this study was in part retrospective, inclusion of FT4 was not possible.
Limitations of this study include the small sample size
that limits the ability to generalize the results. Additionally,
it is possible that the abnormal behavior group may have
been biased toward particular types of behavioral problems.
First, the population of dogs presenting to a behavior
referral clinic may differ from the general population of
dogs with behavioral problems. Second, blood samples
were taken from dogs with behavioral problems that the
consulting clinician had determined to require anti-anxiety
medication, or in which the clinician suspected that organic
disease may be contributing to the problem. These criteria
may have defined a specific category of problems or
etiology. Further, some medications are known to alter
TT4 concentrations. Although 4 dogs with behavior problems had received medication at the time of sampling, all
these medications would tend to lower TT4 concentrations,
and such changes would not have altered the finding that
dogs with behavior problems had higher levels of TT4 than
the control dogs. Finally, it is also important to recognize
that the synthesis and actions of thyroid hormone in the
235
brain, may not parallel that in the periphery. That is, the
function tests used commonly may not give an accurate
representation of thyroid activity in the brain.
In this study, we confirmed our hypothesis that routine
thyroid screening tests yield normal results in most dogs
with behavioral problems. Further studies are necessary to
determine if thyroid dysfunction would be identified in a
larger proportion of dogs with behavioral problems, if
larger sample sizes and a full panel of thyroid tests were
used. In addition, monitoring of TT4 concentrations and
correlating the TT4 concentration with clinical progression
or improvement might shed light on the clinical relevance
of change. The significance of the increased concentration
of TT4 in the dogs with behavior problems is unclear.
Acknowledgments
This work was supported by the General Fund, School of
Veterinary Medicine, Purdue University.
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