Thyroid Disease and Autoimmune Thyroiditis
by W. Jean Dodds, DVM
938 Stanford Street
Santa Monica, CA 90403
(310) 828-4804;FAX (310)-828-8251
Copyright 2004, W. Jean Dodds, DVM
Hypothyroidism is the most common endocrine disorder of canines, and up
to 80% of cases result from autoimmune (lymphocytic) thyroiditis. The heritable
nature of this disorder poses significant genetic implications for breeding
stock. Thus, accurate diagnosis of the early compensatory stages of canine
autoimmune thyroiditis leading up to hypothyroidism affords important genetic
and clinical options for prompt intervention and case management.
Although thyroid dysfunction is the most frequently recognized endocrine
disorder of pet animals, it is often difficult to make a definitive diagnosis.
As the thyroid gland regulates metabolism of all body cellular functions,
reduced thyroid function can produce a wide range of clinical manifestations.
Many of these clinical signs mimic those resulting from other causes and
so recognition of the condition and interpretation of thyroid function tests
can be problematic.
Baseline Thyroid Profiles
A complete baseline thyroid profile is measured and typically includes
total T4, total T3, free T4, free T3, T3AA and T4AA, and can include cTSH
and/or TgAA. The TgAA assay is especially important in screening breeding
stock for heritable autoimmune thyroid disease.
The normal reference ranges for thyroid analytes of healthy adult animals
tend to be similar for most breeds of companion animals. Exceptions are
the sighthound and giant breeds of dogs which have lower basal levels. Typical
thyroid levels for healthy sighthounds, such as retired racing greyhounds,
are at or just below the established laboratory reference ranges, whereas
healthy giant breeds have optimal levels around the midpoint of these ranges.
Similarly, because young animals are still growing and adolescents are
maturing, optimal thyroid levels are expected to be in the upper half of
the references ranges. For geriatric animals, basal metabolism is usually
slowing down, and so optimal thyroid levels are likely to be closer to midrange
or even slightly lower.
Genetic Screening for Thyroid Disease
Most cases of thyroiditis have elevated serum TgAA levels, whereas only
about 20-40% of cases have elevated circulating T3 and/or T4 AA. Thus, the
presence of elevated T3 and/or T4 AA confirms a diagnosis of autoimmune
thyroiditis but underestimates its prevalence, as negative (non-elevated)
autoantibody levels do not rule out thyroiditis. Measuring TgAA levels also
permits early recognition of the disorder, and facilitates genetic counselling.
Affected dogs should not be used for breeding.
The commercial TgAA test can give false negative results if the dog has
received thyroid supplement within the previous 90 days, thereby allowing
unscrupulous owners to test dogs while on treatment to assert there normalcy,
or to obtain certification with health registries such as the OFA Thyroid
Registry. False negative TgAA results also can occur in about 5% of dogs
verified to have high T3AA and/or T4AA. Furthermore, false positive TgAA
results may be obtained if the dog has been vaccinated within the previous
30-45 days, or in some cases of non-thyroidal illness. Vaccination of pet
and research dogs with polyvalent vaccines containing rabies virus or rabies
vaccine alone was recently shown to induce production of antithyroglobulin
autoantibodies, a provocative and important finding with implications for
the subsequent development of hypothyroidism
A population study of 287,948 dogs was recently published by the MSU Animal
Health Diagnostic Laboratory. Circulating thyroid hormone autoantibodies
(T3AA and/or T4AA) were found in 18,135 of these dogs (6.3%). The 10 breeds
with the highest prevalence of thyroid AA from their study were: Pointer,
English Setter, English Pointer, Skye Terrier, German Wirehaired Pointer,
Old English Sheepdog, Boxer, Maltese, Kuvasz, and Petit Basset Griffon Vendeen.
Prevalence was associated with body weight and was highest in dogs 2-4 years
old. Females were significantly more likely to have thyroid AA than males.
A bitch with circulating thyroid AA has the potential to pass these along
to the puppies transplacentally as well as via the colostrum. Furthermore,
any dog having thyroid AA may eventually develop clinical symptoms of thyroid
disease and/or be susceptible to other autoimmune diseases. Thyroid screening
is thus very important for selecting potential breeding stock as well as
for clinical diagnosis.
Thyroid testing for genetic screening purposes is less likely to be meaningful
before puberty. Screening is initiated, therefore, once healthy dogs and
bitches have reached sexual maturity (between 10-14 months in males and
during the first anestrous period for females following their maiden heat).
As the female sexual cycle is quiescent during anestrus, any influence of
sex hormones on baseline thyroid function will be minimized. This period
generally begins 12 weeks from the onset of the previous heat and lasts
one month or longer. The interpretation of results from baseline thyroid
profiles in intact females will be more reliable when they are tested in
anestrus. In fact, genetic screening of intact females for other disorders
such as von Willebrand disease (vWD), hip dysplasia, and wellness or reproductive
checkups (vaginal cultures, hormone testing) is best scheduled during anestrus.
Once the initial thyroid profile is obtained, dogs and bitches should be
rechecked on an annual basis to assess their thyroid function and overall
health. Generation of annual test results provides comparisons that permit
early recognition of developing thyroid dysfunction. This allows for early
treatment, where indicated, to avoid the appearance or advancement of clinical
signs associated with hypothyroidism.
Individuals genetically susceptible to autoimmune thyroid disease may also
become more susceptible to immune-mediated diseases affecting other target
tissues and organs, especially the bone marrow, liver, adrenal gland, pancreas,
skin, kidney, joints, bowel, and central nervous system. The resulting “polyglandular
autoimmune syndrome” of humans is becoming more commonly recognized
in the dog, and probably occurs in other species as well. The syndrome tends
to run in families and is believed to have an inherited basis. Multiple
endocrine glands and nonendocrine systems become involved in a systemic
immune-mediated process. This multiple endocrinopathy often occurs in patients
with underlying autoimmune thyroid disease (hypo- or hyperthyroidism) and
concurrent Addison’s disease, diabetes, reproductive gonadal failure,
skin disease and alopecia, and malabsorption syndrome. The most common nonendocrinologic
autoimmune disorders associated with this syndrome are autoimmune hemolytic
anemia (AIHA), idiopathic thrombocytopenic purpura (ITP), chronic active
hepatitis, and immune-complex glomerulonephritis (systemic lupus erythematosus;
The most commonly recognized polyglandular endocrinopathy of dogs is Schmidt’s
syndrome (thyroiditis and Addison’s disease). Examples of breeds genetically
predisposed to this disorder include the Standard Poodle, Old English Sheepdog,
Bearded Collie, Portuguese Water Dog, Nova Scotia Duck Tolling Retriever,
and Leonberger, although any breed or mixed breed can be affected. Our study
cohort of 162 cases of autoimmune blood and endocrine disorders in Old English
Sheepdogs (1980-1989) included 115 AIHA and/or ITP, 99 thyroid disease,
23 Addison’s disease, 7 vaccine reactions, 3 SLE, 2 diabetes, 1 rheumatoid
arthritis and 1 hypoparathyroidism. The group comprised 110 females (15
spayed) and 52 males (3 neutered). Seven of the most recent 103 cases had
two or more endocrine disorders, and 101 of the 108 cases where pedigrees
were available showed a familial relationship going back several generations.
Data from surveying the Bearded Collie breed reported 55 hypothyroid, 17
Addison’s disease, and 31 polyglandular autoimmunity (5 were hypothyroid).
Aberrant Behavior and Thyroid Dysfunction
The principal reason for pet euthanasia stems not from disease, but undesirable
behavior. While this abnormal behavior can have a variety of medical causes,
it also can reflect underlying problems of a psychological nature.
An association between behavioral and psychologic changes and thyroid dysfunction
has been recognized in humans since the 19th century. In a recent study,
66% of people with attention deficit-hyperactivity disorder were found to
be hypothyroid, and supplementing their thyroid levels was largely curative.
Furthermore, an association has recently been established between aberrant
behavior and thyroid dysfunction in the dog, and has been noticed in cats
with hyperthyroidism. Typical clinical signs include unprovoked aggression
towards other animals and/or people, sudden onset of seizure disorder in
adulthood, disorientation, moodiness, erratic temperament, periods of hyperactivity,
hypoattentiveness, depression, fearfulness and phobias, anxiety, submissiveness,
passivity, compulsiveness, and irritability. After episodes, most of the
animals appeared to come out of a trance like state, and were unaware of
their bizarre behavior.
The mechanism whereby diminished thyroid function affects behavior is unclear.
Hypothyroid patients have reduced cortisol clearance, as well as suppressed
TSH output and lowered production of thyroid hormones. Constantly elevated
levels of circulating cortisol mimic the condition of an animal in a constant
state of stress. In people and seemingly in dogs, mental function is impaired
and the animal is likely to respond to stress in a stereotypical rather
than reasoned fashion. Chronic stress in humans has been implicated in the
pathogenesis of affective disorders such as depression. Major depression
has been shown in imaging studies to produce changes in neural activity
or volume in areas of the brain which regulate aggressive and other behaviors.
Dopamine and serotonin receptors have been clearly demonstrated to be involved
in aggressive pathways in the CNS. Hypothyroid rats have increased turnover
of serotonin and dopamine receptors, and an increased sensitivity to ambient
Investigators in recent years have noted the sudden onset of behavioral
changes in dogs around the time of puberty or as young adults. Most of the
dogs have been purebreds or crossbreeds, with an apparent predilection for
certain breeds. For a significant proportion of these animals, neutering
does not alter the symptoms and in some cases the behaviors intensify. The
seasonal effects of allergies to inhalants and ectoparasites such as fleas
and ticks, followed by the onset of skin and coat disorders including pyoderma,
allergic dermatitis, alopecia, and intense itching, have also been linked
to changes in behavior.
Many of these dogs belong to a certain group of breeds or dog families
susceptible to a variety of immune problems and allergies (e.g. Golden Retriever,
Akita, Rottweiler, Doberman Pinscher, English Springer Spaniel, Shetland
Sheepdog, and German Shepherd Dog). The clinical signs in these animals,
before they show the sudden onset of behavioral aggression, can include
minor problems such as inattentiveness, fearfulness, seasonal allergies,
skin and coat disorders, and intense itching. These may be early subtle
signs of thyroid dysfunction, with no other typical signs of thyroid disease
The typical history starts out with a quite, well-mannered and sweet-natured
puppy or young adult dog. The animal was outgoing, attended training classes
for obedience, working, or dog show events, and came from a reputable breeder
whose kennel has had no prior history of producing animals with behavioral
problems. At the onset of puberty or thereafter, however, sudden changes
in personality are observed. Typical signs can be incessant whining, nervousness,
schizoid behavior, fear in the presence of strangers, hyperventilating and
undue sweating, disorientation, and failure to be attentive. These changes
can progress to sudden unprovoked aggressiveness in unfamiliar situations
with other animals, people and especially with children.
Another group of dogs show seizure or seizure-like disorders of sudden
onset that can occur at any time from puberty to mid-life. These dogs appear
perfectly healthy outwardly, have normal hair coats and energy, but suddenly
seizure for no apparent reason. The seizures are often spaced several weeks
to months apart, may coincide with the full moon, and can appear in brief
clusters. In some cases the animals become aggressive and attack those around
them shortly before or after having one of the seizures. Two recent cases
involved young dogs referred for sudden onset seizure disorder shortly after
puberty. Both dogs were found to have early onset autoimmune thyroiditis,
which was clinically responsive to thyroid supplementation, to the extent
that anticonvulsant medications could be gradually withdrawn. The numbers
of animals showing these various types of aberrant behavior appear to be
increasing in frequency over the last decade.
In dogs with aberrant aggression, a large collaborative study between our
group and Dr. Dodman and colleagues at Tufts University School of Veterinary
Medicine has shown a favorable response to thyroid replacement therapy within
the first week of treatment, whereas it took about three weeks to correct
their metabolic deficit. Dramatic reversal of behavior with resumption of
previous problems has occurred in some cases if only a single dose is missed.
A similar pattern of aggression responsive to thyroid replacement has been
reported in a horse.
Clinical Signs of Canine Hypothyroidism
Alterations in Cellular Metabolism
- mental dullness
- exercise intolerance
- neurologic signs
- weight gain
- cold intolerance
- mood swings
- stunted growth
- chronic infections
- laryngeal paralysis
- facial paralysis
- "tragic" expression
- knuckling or dragging feet
- muscle wasting
- head tilt
- drooping eyelids
- ruptured cruciate ligament
- dry, scaly skin and dandruff
- coarse, dull coat
- "rat tail"; "puppy coat"
- pyoderma or skin infections
- chronic offensive skin odor
- bilaterally symmetrical hair loss
- seborrhea with greasy skin
- seborrhea with dry skin
- lack of libido
- testicular atrophy
- prolonged interestrus interval
- absence of heat cycles
- silent heats
- weak, dying or stillborn pups
- slow heart rate (bradycardia)
- cardiac arrhythmias
- bone marrow failure
- low red blood cells (anemia)
- white blood cells
- corneal lipid deposits
- infections of eyelid glands
- corneal ulceration
- keratoconjunctivitis sicca or "dry eye"
- Vogt-Koyanagi-Harada syndrome
Other Associated Disorders
- IgA deficiency
- loss of taste
- other endocrinopathies
- loss of smell (dysosmia)
- chronic active hepatitis
Diagnosis of Thyroid Disease
Complete Basic Profile
(T4, T3, FT4, FT3, T4AA, T3AA)
Older Tests (T4, T4 + T3)
- Serum T4 and/or T3 alone are not reliable for diagnosis
- overdiagnose hypothyroidism
- underdiagnose hyperthyroidism
- fail to dectect early compensatory disease and thyroiditis
- influenced by nonthyroidal illness and certain drug
- Free (Unbound) T4
Less likely to be influenced by nonthyroidal illness or drugs
-- equilibrium dialysis
-- solid-phase analog RIA
-- chemiluminescence solid-phase
- Less reliable -- liquid-phase analog RIA
- Endogenous Canine TSH
In primary hypothyroidism, as serum free T4 levels fall, pituitary
output of TSH rises.
-- elevated TSH usually indicates primary thyroid disease
-- 20-40% discordancy observed between expected and actual findings
-- published normal ranges may need revising upwards
-- affected by concomitant chronic renal disease
- Canine TgAA
Thyroglobulin autoantibodies are present in serum of cases with
-- positive results confirm diagnosis
-- 20-40% of cases have circulating T3 and/or T4AA
-- allows for early diagnosis and genetic counselling
Tables 1-2 summarize results of complete thyroid diagnostic
profiling on 634 canine cases of aberrant behavior, compiled by this author
in collaboration with Drs. Nicholas Dodman, Linda Aronson, and Jean DeNapoli
of Tufts University School of Veterinary Medicine, North Grafton, MA.
Ninety percent (568 dogs) were purebreds and 10% were mixed breeds. There
was no sex predilection found in this case cohort, whether or not the
animals were intact or neutered. Sixty-three percent of the dogs had thyroid
dysfunction as judged by finding 3 or more abnormal results on the comprehensive
thyroid profile. The major categories of aberrant behavior were aggression
(40% of cases), seizures (30%), fearfulness (9%), and hyperactivity (7%);
some dogs exhibited more than one of these behaviors (Table 2). Within
these 4 categories, thyroid dysfunction was found in 62% of the aggressive
dogs, 77% of seizuring dogs, 47% of fearful dogs, and 31% of hyperactive
Outcomes of treatment intervention with standard twice daily doses of thyroid
replacement were evaluated in 95 cases, and showed a significant behavioral
improvement in 61% of the dogs. Of these, 58 dogs had greater than 50% improvement
in their behavior as judged by a predefined 6-point subjective scale (34
were improved > 75%), and another 23 dogs had >25 but <50% improvement.
Only 10 dogs experienced no appreciable change, and 2 dogs had a worsening
of their behavior. When compared to 20 cases of dominance aggression treated
with conventional behavior or other habit modification over the same time
period, only 11 dogs improved more than 25%, and of the remaining 9 cases,
3 failed to improve and 3 were euthanized or placed in another home. These
initial results are so promising that complete thyroid diagnostic profiling
and treatment with thyroid supplement, where indicated, is warranted for
all cases presenting with aberrant behavior.
Our ongoing study now includes over 1500 cases of dogs presented to veterinary
clinics for aberrant behavior. The first 499 cases have been analyzed independently
by a neural network correlative statistical program. Results showed
a significant relationship between thyroid dysfunction and seizure disorder,
and thyroid dysfunction and dog-to-human aggression.
Collectively, these findings confirm the importance of including a complete
thyroid antibody profile as part of the laboratory and clinical work up
of any behavioral case.
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Canine Aberrant Behavior *
Total No. of Cases
* Mean Age, 3.7 years ( Range 0.5-12 years ). Median Age, 2.5 years.
Most Commonly Represented Breeds with Thyroid
Dysfunction and Aberrant Behavior *
* Some dogs had more than 1 abnormal behavior.
Numerator = Thyroid dysfunction Denominator = Aberrant behavior
† Total 634 cases; 72 dogs breeds represented.