Thyroid Dysfunction as a Cause of Aggression in Dogs and Cats
In human medicine,
behavioral and psychological changes associated with thyroid dysfunction were
noted in the nineteenth century. The behavioral abnormalities seen in the
hyperthyroid cat have been well described in the literature, and mimic closely
the restlessness, insomnia and irritability or aggression described in humans
with thyrotoxicosis. Approximately 80% of hyperthyroid cats are hyperactive,
while 10-25% are reported to be aggressive, Cats, as well as people, may
experience the rarer manifestation of apathetic thyrotoxicosis, characterized
by lethargy and depression. This is seen in approximately 10% of feline cases.
Hyperthyroid cats are rarely presented to the veterinarian for behavioral
signs, Perhaps because aggression is primarily wen when the cat is restrained,
we as a profession are more likely to experience this aspect of the disease
than the cats' owners, Treating the underlying thyroid problem generally
resolves the behavioral problems however, and because onset is often insidious,
it is only after the endocrine imbalance has been addressed that the owners
appreciate the deterioration in their animal's behavior.
While much has been
written about the behavioral signs of hyperthyroidism in cats, the hypothyroid
dog has been depicted, from a behavioral standpoint, as being lethargic and
mentally dull. The hypothyroid human patient has been reported to show a wider
range of behavioral symptoms. Particularly in the early stages of the disease
reduced cognitive function and concentration together with impaired short-term
memory may be confused with attention deficit-hyperactivity disorder, and in
one study 66% of patients diagnosed with ADBD were found to be hypothyroid.
Supplementing their thyroid levels was largely curative. Visual and auditory
hallucinations may result from altered perception and have been misdiagnosed as
schizophrenia or psychosis. Other behavioral symptoms have included fear -
ranging from mild anxiety to frank paranoia, mood swings and
aggression.
Scattered reports of
aggression and hyperactivity in hypothyroid dogs suggested that dogs also might
exhibit a wider repertoire of behaviors in response to low thyroid levels.
Hypothyroidism is the most prevalent endocrine disease in dogs. In a 1994
survey conducted by the American Kennel Club of its parent breed clubs,
hypothyroidism was found to be the health issue of greatest concern overall, as
well as for each of the seven groups except for the toy dog group, where it was
rated fourth in importance. Despite the debate concerning diagnosis the
condition is widespread throughout the canine, and probably the equine,
population.
In dogs, as in humans,
behavioral signs often precede the more traditional skin, coat and metabolic
changes characteristic of the condition. To diagnose hypothyroidism we rely
upon the six analyte panel offered by Antech Diagnostics, Irvine CA (as well as
Michigan State University). These panels are interpreted for us by W. Jean
Dodds DVM of Hemopet. Following her lead, we believe that truly euthyroid dogs
in most breeds should have hormonal levels falling in the upper half of
previously accepted normal ranges, This is particularly true of dogs under 18
months of age. We feel that the panel gives a clearer picture of overall
thyroid function. Indeed of the cases treated so far only about 40% would have
been considered hypothyroid on a standard T4 test, the rest would mostly fall
in the borderline category. Some cases in which elevated autoantibody levels
indicate autoimmune disease would otherwise have been considered thyroid normal
at the time of presentation.
Numerator = Thyroid
dysfunction; Denominator = Aberrant behavior Some dogs had more than one
aberrant behavior Data taken from 319 cases representing 63 breeds W.J. Dodds
DVM unpublished data As of January this year, 319 cases of dogs with a variety
of behavior problems had been presented to Dr. Dodds for thyroid evaluation. Of
these almost two thirds were diagnosed as being hypothyroid.
{The following data
are provided by Dr. Jean Dodds (1/4/98) and were not included in the
presentation by Dr. Aronson.}
{Out of 13 Bearded
Collies (11 in Dr. Dodd's group, 2 in Dr. Aronson's), 10 were hypothyroid and
exhibiting significant aggression. Two cases had hyperactivity with major
attention deficit-type behavior and were hypothyroid. One case with bizarre
erratic behavior had very normal levels of thyroid and I advised retesting in
6-12 months. The owners couldn't cope with the dog as an unruly pet, and I fear
gave it away or put it to sleep.
Of my 10 cases with
hypothyroidism there was considerable or nearly total improvement in their
behavior once thyroid supplementation was given and dosage stabilized. This
usually took about 6 weeks, but clear benefit was noted by the owners in 2-14
days. One case has since slipped back a little, but became better again once
thyroid dosage was increased slightly. I am very encouraged by these cases. Its
particularly remarkable in cases of working obedience dogs, as their owners are
very aware of performance nuances - such as changes in power of concentration
which wanes with thyroid imbalance and is restored on supplement. This latter
comment applies in general and not to the beardie cohort per
se.}
Our figures have been
similar, but we have only submitted blood on dogs which we suspect might be
hypothyroid based on other signs of disease, breed or combination of behavioral
signs. Interestingly, although hypothyroidism has classically been thought to
primarily affect bitches, the breakdown by sex shows more male hypothyroid
behavioral cases. However, more male dogs are presented for behavioral
problems. Sixty three pure breeds as well as mixed breeds were represented in
these cases, Table I represents data for the seven most commonly represented
breeds as well as mixed breeds, and the four most commonly reported behavioral
problems. The numerator represents the number of animals which were hypothyroid
and the denominator the number showing aberrant behavior.
There were 177 cases
reported to exhibit aggression (type unspecified), 43 with seizures; 34
fearful; and 33 hyperactive. While some breeds are clearly more prone to
thyroid disease than others, our data include two Bichon Frises which both
proved to be hypothyroid and responded behaviorally quite well to thyroid
replacement therapy, although this is not a breed which has shown much evidence
of hypothyroidism in the past. Breed alone should not rule out hypothyroidism
as a possible cause of a behavioral problem, although clearly if a dog is of a
breed with a higher incidence of the disease one's level of suspicion will be
higher.
Initially at Tufts we
were looking for a hypothyroid - aggression/hyperactivity connection.
Aggression is the most common behavior problem among dogs presented to our
clinic for treatment. While some of the cases showed more characteristic skin
and coat problem or obesity in many cases the dog appeared healthy apart from
its behavioral problems. Many of these cases fell into two
categories.
1. Young dogs which
were aggressive and whose owners often complained their dog could or would not
listen/concentrate and/or repeatedly failed obedience classes.
2. Older dogs for
whom aggression was a new and totally unexpected behavior.
Treating the latter
category brought reports of a return to youthful energy levels which the owners
thought had gradually diminished purely because of the dog's age, while the
former suddenly were able to concentrate and learn commands. Dogs were
evaluated over at least eight weeks following diagnosis of a thyroid problem.
Most of these dogs were placed on behavior modification programs, and it was
recommended that exercise should be increased, and dietary protein reduced.
Some were fitted with Promise collars. Two dogs had previously received
psychopharmacological treatment. In one case, the dog's dominance was no longer
controlled by 20mg q l2h fluoxetine and 40mg q 8h propranolol, thyroxine
supplementation did not improve the dog's behavior and it was euthanatized. In
the other case a dog with fear and intraspecies aggression had not been helped
with amitryptiline, and the dog was completely weaned from the drug after
complete remission of its aggression on thyroxine.
Dogs were evaluated on
a 6 point subjective scale by their owners (Table 2. Only the scoring system is
shown below). Aggression was classified as dominance, fear, territorial,
intraspecies, or predatory. Of the 57 cases of aggression treated with
thyroxine replacement (levothyroxine sodium (Soloxine) at a dose of 0.1
mg/12-15# body weight q 12h, only one showed a worsening of aggression, 6
failed to respond and one showed less than 25% improvement. The remainder
showed more than 25% improvement to complete resolution.
Data collected over
the same period for 20 dogs with dominance aggression treated with behavior
modification, exercise, diet and Promise Collars alone, showed that one dog was
euthanatized for worsening behavior, two were placed after failure to improve
or worsening of behavior, 3 failed to improve and 3 showed less than 25%
improvement. Although the sample size is not large, the successful outcome of
cases treated with thyroid replacement was significantly better than that of
those treated with behavioral modification alone. We have also successfully
treated one case where a hypothyroid horse exhibited intraspecies aggression
with thyroid replacement. This horse had failed to respond to behavior
modification or cyproheptidine.
Scoring Behavior
Problems Medicated with Thyroid
-1 Problem became
worse
0 No appreciable
change
1 <25% improvement
2 >25, but <50%
improvement
3 >50 but <75%
improvement
4 >75% improved to
completely resolved
After our initial
success with aggressive dogs, we have looked at the role of hypothyroidism in
other behavioral conditions. Although the sample size is too small to be
conclusive, it would certainly seem worthwhile to look for an underlying
thyroid deficiency in these cases. Similarly, other behavioral conditions have
shown variable response to thyroid supplementation. We have not seen much
improvement in those dogs we have treated with seizure-related disorders,
although Dodds has found seizure activity to be responsive to thyroid
replacement, however, our sample size is extremely small.
The mechanism whereby
diminished thyroid function affects behavior is unclear. Hypothyroid patients
have reduced cortisol clearance, and the constantly elevated levels of
circulating cortisol mimic the condition of an animal in a constant state of
stress, as well as suppressing TSH production and thereby further reducing T4
and T3 levels. In humans, and seemingly in dogs, mental function is impaired
and the animal is likely to respond to stress in a stereotypical rather than a
reasoned fashion. We have noted that the type of aberrant behavior exhibited by
hypothyroid dogs tends to be typical of the behavioral problems seen for its
breed, or predominant breed, rather than hypothyroidism producing a specific
behavioral problem. Chronic stress in humans has been implicated in the
pathogenesis of affective disorders such as depression. Major depression has,
in turn, been shown in imaging studies to cause changes in neural activity or
volume in the amygdala, prefrontal cortex and hippocampus - areas of the brain
which regulate aggressive and other behaviors. The role of the
neurotransmitters dopamine and serotonin has been clearly demonstrated in
aggressive pathways in the CNS. Hypothyroid rats have been shown to have both
an increased turnover of serotonin; and dopamine receptors with an increased
sensitivity to ambient neurotransmitter levels. Interestingly, several of the
dogs which failed to respond to thyroid replacement or in which response was
suboptimal have subsequently been treated with selective serotonin reuptake
inhibitors or tricyclic antidepressants either without or with limited success.
Given the far reaching effects of thyroid hormones throughout the body it is
likely that these as well as other mechanisms are involved in its behavioral
role.
Psychiatrists at
Harvard Medical School have recently used low level thyroxine replacement for
euthyroid and suboptimal thyroid normal patients with some success. They feel
that the thyroid damps down the background noise in the brain, thereby enabling
the patients to function better. In a limited number of cases where we have
tried to boost dogs with suboptimal but normal thyroid levels into the optimal
range, we have failed to achieve behavioral improvement. However, we have tried
this in only a half dozen or so cases to date. Dodds reports some success using
this strategy in a larger number of cases.
Case Study
I.
Signalment: Seven-year
old, 28kg, spayed female German Shepherd Dog
Problem: Fear
aggression and intraspecies aggression. Previous treatment had included
clorniprantine 25mg q 12h. (Note: this dose is too low to produce significant
behavioral effect). No change was reported in problem behaviors, although the
dog had behaved more affectionately with its owners. Owner is an obedience
trainer, and extensive obedience training and following a behavior modification
(desensitization and counterconditioning) program had not helped, The dog had
to be muzzled when strangers came to the house or for walks off the owners'
property.
Physical Examination:
Evidence of arthritis and hip dysplasia, otherwise the dog appeared
healthy
Thyroid panel
abnormalities: Total T3 86 ng/dl (normal 100-250, optimal 125-225); Total T4
1.39 pg/dl (normal1.5-4.5; optimal 3-5); Free T4 0.92ng/dl (normal1.0-4.0;
optimal2-4).
Treatment: Soloxine
(levothyroxine sodium) 0.4mg q 12h. Clomiprarnine dose dropped to 25mg q 24h
before dog started thyroid replacement
Follow-up: Five days
after dog started on thyroid replacement therapy the owner took it to a
neighborhood park and let it play off leash with a number of dogs. She reported
that the dog showed no aggression and it played like a puppy, including a game
of tug-of-war over a stick played with a puppy. The dog showed no aggression.
The dog also accepted and greeted appropriately strangers coming onto its
property or encountered on walks. Several weeks later, the dog was no longer
behaving like a puppy, but like a mature German Shepherd with arthritis. It
showed appropriate aggression when other dogs acted aggressively towards it, or
if they were too exuberant in their greeting. Inappropriate aggression has not
returned over the succeeding twelve months. The dog has remained fit and
active. Clomipramine has been completely withdrawn,
Case Study
2.
Problem: Aggression
directed at owner, her husband and his teenage daughters from a previous
marriage. The dog would growl and threaten if confronted over food, stolen
objects, when woken, asked to move, or otherwise disturbed, particularly while
it was sleeping in the owner's bed. This behavior had been increasing over the
previous year since the owner's marriage, and at the time of presentation was
occurring on at least a daily basis. Prior to that time there had been three
isolated incidents of aggression when the dog was confronted over food or
stolen objects either by the owner or children the dog knew well. The dog had
never bitten. It was friendly with strangers, but did growl and threaten
strange dogs occasionally.
Physical examination:
The owner reported a 4kg weight gain in the dog over the previous 2 months. The
dog also had a history of urinary incontinence, for which it had been receiving
diethylstilbestrol (DES), and vaginitis. The dog was lethargic, with a poor,
dull hair coat. Multiple open sores were apparent on the forepaws resulting
from the dog licking and chewing - this was later attributed to atopy.
Otherwise the dog appeared normal on physical examination.
CBC and Biochemical
Profile: The only abnormality was severe hypercholesterolemia: 601 mg/dl;
reference range. 110-314mg/dl.
Thyroid panel: Total
T4, 14 nmol/L (reference range 5-50; optimal range 30-50); Total T3 0.0 nmol/L
(normal 1.0 2.5; optimal 1.25-2.25); Free T4 15 pmol/L (normal 12-33; optimal
20-40); Free T3 5.1 pmol/L (normal 2.8-6.5; optimal 3.5-6.5); T4 Autoantibody10
(<20); T3 autoantibody 84 (< 10).
Follow-up.- The dog
was placed on 0. 7mg levothyroxine sodium PO q 12h, and within a week
aggressive behavior had decreased by 60-70%, Its aggression continued to
decrease over subsequent weeks. Lethargy disappeared after about 6 weeks of
thyroid replacement therapy. The dog had also lost all the weight it had
gained, and skin and coat condition improved. There was a single incident in
which the dog growled during these 5 weeks. The dog continued to receive DES.
There were no further incidents of vaginitis. On two subsequent occasions the
efficacy of the thyroxine in controlling the dog's aggression was demonstrated.
One time the dog did not swallow its morning pill. it spent the day sleeping,
but growled when a family member approached its food bowl to feed it. On the
second occasion the owner ran out of medication and the dog was not medicated
for 48h, Within 24h aggression had returned to the same level it had been at
prior to medication, After thyroxine supplementation was resumed aggression was
extinguished over the subsequent 2-5days. Although the dog slept more during
this period, it was not lethargic as it had been prior to
treatment.
Discussion: While
these are two of the more dramatic cases of hypothyroid aggression we have
treated, they are illustrative of the response we have experienced.
Metabolically, thyroid replacement takes about three weeks to be effective.
Frequently, behavioral response is reported within the first week of treatment.
Several owners also report dramatic resumption of previous aberrant behaviors
if even a single pill is missed or not swallowed by the dog. Similarly, the
horse mentioned earlier showed a rapid resumption of aggression when its dose
was halved while its owner awaited the arrival of more medication.
Hypothyroidism may be linked to a number of different behavioral conditions.
Aberrant behavior may be one of the earliest signs of thyroid deficiency. The
condition is clearly more prevalent in some breeds than in others, and a
genetic predisposition is probably involved in the expression of the disease.
However, environmental factors are probably also involved, and there have been
numerous reports of owners and animals in the same household having thyroid
dysfunction and/or other autoimmune diseases.
At Tufts we have
seriously considered obtaining a thyroid panel on all dogs presented for
evaluation, and we feel that it is a very good screen for a condition which may
underlie a wide variety of behavioral problems, and one which is relatively
easily and cheaply treated. It is our recommendation that hypothyroidism be
considered as a rule out for dogs and horses showing inappropriate aggression.
It should also be a rule out for dogs which show an inability to learn or
concentrate on the owner, or for older dogs which have developed a personality
change either rapidly or more gradually. It is probably a good rule out for
dogs which exhibit fears or anxieties and possibly for some dogs with
compulsive disorders.
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L.P. Aronson DVM
& N.H. Dodman RVMS
Presented at the 43.
Jahrestagung der Deutschen Veterinarmedizinischen Gesellschaft Fachgruppe
Kleintierkrankheiten 29-31 August 1997 in HCC Hannover
