Thyroiditis

AUTOIMMUNE THYROIDITIS

W. Jean Dodds, DVM
938 Stanford Street
Santa Monica, CA 90403
310-828-4804; Fax 310-828-8251
Hemopet@hotmail.com

Introduction

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.

Author’s Cases of Autoimmune Thyroiditis

This author has compiled and analyzed 1060 canine cases of autoimmune thyroiditis between
January 1995 and January 1999.  Purebreds made up 96% of this group, and both sexes were equally
represented.  The mean age at diagnosis was 4.4 years (range 2.6-12.0), and mean levels of T3AA and
T4AA were 6.0 (range 1.2-22.2) and 1.6 (range 0.6-8.8), respectively, with normal reference levels being
below 2. The most prevalent circulating thyroid AA was against T3 (996/1060 cases; 94%) and 254/1060
(24%) had combined T3 and T4AA.  In a few instances (51/723;7%), the dogs demonstrated only T4
autoantibodies.   The twelve breeds most affected were the Golden Retriever (209 cases), Shetland
Sheepdog (124), American Cocker Spaniel (68), Boxer (51), Doberman Pinscher (42), Labrador Retriever (40),
German Shepherd (19), Akita (15), Irish Setter (14), English Setter (13), Old English Sheepdog (12), and
Collie (10), although many other breeds and mixed breeds were also represented. All of these dogs also
would be expected to have elevated levels of TgAA. In fact, all 75 dogs selected for testing at random from
this case cohort had high TgAA levels.

Polyglandular Autoimmunity

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; SLE).

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 autoim-
mune 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 psycholo-
gical nature.

An association between behavioral and psychologic changes and thyroid dysfunction has been recog-
nized 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. Further-
more, 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 neurotransmitter levels.

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 ecto-
parasites 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 im-
mune 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 being manifested.

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 situa-
tions 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 col-
leagues at Tufts University School of Veterinary Medicine has shown a favorable response to thyroid replace-
ment 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.

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 be-
havior 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 foun-
d in 62% of the aggressive dogs, 77% of seizuring dogs, 47% of fearful dogs, and 31% of hyperactive dogs.

Outcomes of treatment intervention with standard twice daily doses of thyroid replacement were evalu-
ated 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 appre-
ciable change, and 2 dogs had a worsening of their behavior. When compared to 20 cases of dominance aggres-
sion treated with conventional behavior or other habit modification over the same time period, only 11 dogs im-
proved 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 be-
havior. 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 dys-
function 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.

References

Cameron DL, Crocker Ad. The hypothyroid rat as a model of increased sensitivity to dopa
mine receptor agonists.  Pharm Biochem Behav 37:627-632, 1990.

Denicoff  KD, Joffe  RT, Lakschmanan MC, Robbins J, Rubinow DR. Neuropsychiatric manifestations of altered
thyroid state. Am J  Psych 147:94-99, 1990.

Dewey CW, Shelton GD, Bailey, CS. Neuromuscular dysfunction in five dogs with acquired myasthenia gravis
and presumptive hypothyroidism. Prog Vet Neurol 6: 117-123, 1995.
Dixon RM, Graham PA, Mooney CT. Serum thyrotropin concentrations: a new diagnostic test for canine hypo-
thyroidism.  Vet Rec  138: 594-595, 1996.
Dodds, WJ.  Thyroid can alter behavior.  Dog World 1992, 77(10); 40-42.
Dodds WJ. Estimating disease prevalence with health surveys and genetic screening. Adv Vet Sci Comp Med,
39: 29-96, 1995.
Dodds WJ. Autoimmune thyroiditis and  polyglandular autoimmunity of purebred dogs.  Can  Pract 22 (1):
18-19, 1997.
Dodds WJ. What’s new in thyroid disease ?  Proc Am Hol Vet Med Assoc 1997; pp 82-95.
Dodds WJ.  Beha-
vioral changes associated with thyroid dysfunction in dogs.  Proc Am Hol Vet Med Assoc, 80-82, 1999.
Dodman NH, Mertens PA, Aronson, LP. Aggression in two hypothyroid dogs, behavior case of the month.
J  Am Vet Med Assoc 207:1168-1171, 1995.
Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. Second Edition. Philadelphia:
WB Saunders Co, 1996.
Frank LA.  Comparison of  thyrotropin-releasing hormone (TRH) to thyrotropin (TSH) stimulation for evaluating
thyroid function in dogs.  J Am An Hosp Assoc  32: 481- 487, 1996.
Hall IA, Campbell KC, Chambers MD, et al. Effect of trimethoprim-sulfamethoxazole on thyroid function in dogs
with pyoderma.  J Am Vet Med Assoc 202:1959-1962, 1993.
Happ GM.   Thyroiditis – A model canine autoimmune disease.  Adv Vet Sci Comp Med  39: 97-139, 1995.
Hauser P, Zametkin AJ, Martinez, P et al. Attention deficit-hyperactivity disorder in people with generalized
resistence to thyroid hormone.  N Eng J  Med 328:997-1001, 1993.
Henley WN, Chen X, Klettner C. Bellush LL, Notestine MA. Hypothyroidism increases serotonin turnover and
sympathetic activity in the adult rat.  Can J  Physiol Pharmacol 69:205-210, 1991.
International Symposium on Canine Hypothyroidism, University of California, Davis. Can  Pract 22 (1) :  4-62,
1997.
Iverson L, Jensen AL, Høier R, et al. Biological variation of canine serum thyrotropin (TSH) concentration. Vet
Clin Pathol 28:16-19, 1999.
Jensen AL, Iversen L, Høier R, et al. Evaluation of an immunoradiometric assay for thyrotropin in serum and
plasma samples of dogs with primary hypothyroidism.  J Comp Pathol 114: 339-346, 1996.
Kaptein EM. Thyroid hormone metabolism and thyroid diseases in chronic renal failure. End Rev 17:45-63,
1996.
McGregor AM. Autoimmunity in the thyroid – Can the molecular revolution contribute to our understanding?
Quart J  Med  82 (297): 1-13, 1992.
Nachreiner RF, Refsal KR. Radioimmunoassay monitoring of thyroid hormone concentrations in dogs on thyroid
replacement therapy: 2,674 cases (1985-1987). J Am Vet Med Assoc  201: 623-629, 1992.
Nachreiner RF, Refsal KR, Davis WR, et al.  Pharmacokinetics of L-thyroxine after its oral administration in dogs.  Am J Vet Res  54: 2091-2098, 1993.
Nachreiner RF, Refsal KR, Graham PA, et al.  Prevalence of autoantibodies to thyroglobulin in dogs with
nonthyroidal illness. Am J Vet Res 59:951-955, 1998.
Overall KL. Clinical Behavioral Medicine for the Small Animal. St. Louis, Mosby, 1998
Panciera DL, Johnson GS.  Hypothyroidism and von Willebrand factor. J Am Vet Med Assoc  206: 595-596,
1995.
Panciera DL.  Clinical manifestations of canine hypothyroidism.  Vet Med  92: 44-49, 1997.
Panciera DL. Thyroid-function testing: Is the future here?  Vet Med  92: 50-57, 1997.
Panciera DL. Treating hypothyroidism.  Vet Med  92: 58-68, 1997.
Panciera DL. Hypothyroidism in dogs: 66 cases (1987-1992).  J Am Vet Med Assoc  204: 761-767, 1994.
Paradis M, Pagé N, Larivière N, et al. Serum-free thyroxine concentrations, measured by chemiluminescence
assay before and after thyrotropin administration in healthy dogs, hypothyroid dogs, and euthyroid dogs with
dermatopathies.  Can Vet  J  37: 289-294, 1996.
Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and
thyrotropin concentrations for diagnosis of hypothyroidism in dogs. J Am Vet Med Assoc 211:1396-1402, 1997.
Schmidt MA, Bland JS.  Thyroid gland as sentinel: Interface between internal and external environment.  Altern
Ther 3: 78-81, 1997.
Scott-Moncrieff JCR, Nelson RW. Change in serum thyroid stimulating hormone concentration in response to
administration of  thyrotropin-releasing  hormone to healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease.  J Am Vet Med Assoc 213:1435-1438, 1998.
Scott-Moncrieff JCR, Nelson RW, Bruner JM, et al. Comparison of thyroid-stimulating hormone in healthy dogs,
hypothyroid dogs, and euthyroid dogs with concurrent disease. J Am Vet Med Assoc 212:387-391, 1998.
Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, Glickman LT, HogenEsch H. Evalu ation of antithyroglobulin
antibodies after routine vaccination in pet and research dogs. J Am Vet Med Asspc 221: 515-521,2002.
Surks MI, Sievert R. Drugs and thyroid function. N Eng J Med 333: 1688-1694, 1995.
Thacker EL, Refsal KR, Bull RW. Prevalence of autoantibodies to thyroglobulin, thyroxine, or triiodothronine and
relationship of autoantibodies and serum concentration of iodothyronines in dogs.  Am J Vet Res 53: 449-453,
1992.
Thacker EL, Davis JM, Refsal KR, et al. Isolation of thyroid peroxidase and lack of antibodies to the enzyme in
dogs with autoimmune thyroid disease.  Am J Vet Res  56: 34-38, 1995.
Tomer Y, Davies TF.  Infection, thyroid disease, and autoimmunity.  End Rev 14: 107-120, 1993.
Uchida Y, Dodman NH, DeNapoli J, Aronson LP. Characterization and treatment of 20 canine dominance ag-
gression cases.  J  Vet Med Sci 59:397-399. 1997.
Vajner L. Lymphocytic thyroiditis in bon. 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 neurotransmitter levels.

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 ecto-
parasites 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 im-
mune 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 being manifested.

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 situa-
tions 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 col-
leagues at Tufts University School of Veterinary Medicine has shown a favorable response to thyroid replace-
ment 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.

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 be-
havior 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 foun-
d in 62% of the aggressive dogs, 77% of seizuring dogs, 47% of fearful dogs, and 31% of hyperactive dogs.

Outcomes of treatment intervention with standard twice daily doses of thyroid replacement were evalu-
ated 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 appre-
ciable change, and 2 dogs had a worsening of their behavior. When compared to 20 cases of dominance aggres-
sion treated with conventional behavior or other habit modification over the same time period, only 11 dogs im-
proved 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 be-
havior. 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 dys-
function 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.

References

Cameron DL, Crocker Ad. The hypothyroid rat as a model of increased sensitivity to dopa
mine receptor agonists.  Pharm Biochem Behav 37:627-632, 1990.

Denicoff  KD, Joffe  RT, Lakschmanan MC, Robbins J, Rubinow DR. Neuropsychiatric manifestations of altered
thyroid state. Am J  Psych 147:94-99, 1990.

Dewey CW, Shelton GD, Bailey, CS. Neuromuscular dysfunction in five dogs with acquired myasthenia gravis
and presumptive hypothyroidism. Prog Vet Neurol 6: 117-123, 1995.
Dixon RM, Graham PA, Mooney CT. Serum thyrotropin concentrations: a new diagnostic test for canine hypo-
thyroidism.  Vet Rec  138: 594-595, 1996.
Dodds, WJ.  Thyroid can alter behavior.  Dog World 1992, 77(10); 40-42.
Dodds WJ. Estimating disease prevalence with health surveys and genetic screening. Adv Vet Sci Comp Med,
39: 29-96, 1995.
Dodds WJ. Autoimmune thyroiditis and  polyglandular autoimmunity of purebred dogs.  Can  Pract 22 (1):
18-19, 1997.
Dodds WJ. What’s new in thyroid disease ?  Proc Am Hol Vet Med Assoc 1997; pp 82-95.
Dodds WJ.  Beha-
vioral changes associated with thyroid dysfunction in dogs.  Proc Am Hol Vet Med Assoc, 80-82, 1999.
Dodman NH, Mertens PA, Aronson, LP. Aggression in two hypothyroid dogs, behavior case of the month.
J  Am Vet Med Assoc 207:1168-1171, 1995.
Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction. Second Edition. Philadelphia:
WB Saunders Co, 1996.
Frank LA.  Comparison of  thyrotropin-releasing hormone (TRH) to thyrotropin (TSH) stimulation for evaluating
thyroid function in dogs.  J Am An Hosp Assoc  32: 481- 487, 1996.
Hall IA, Campbell KC, Chambers MD, et al. Effect of trimethoprim-sulfamethoxazole on thyroid function in dogs
with pyoderma.  J Am Vet Med Assoc 202:1959-1962, 1993.
Happ GM.   Thyroiditis – A model canine autoimmune disease.  Adv Vet Sci Comp Med  39: 97-139, 1995.
Hauser P, Zametkin AJ, Martinez, P et al. Attention deficit-hyperactivity disorder in people with generalized
resistence to thyroid hormone.  N Eng J  Med 328:997-1001, 1993.
Henley WN, Chen X, Klettner C. Bellush LL, Notestine MA. Hypothyroidism increases serotonin turnover and
sympathetic activity in the adult rat.  Can J  Physiol Pharmacol 69:205-210, 1991.
International Symposium on Canine Hypothyroidism, University of California, Davis. Can  Pract 22 (1) :  4-62,
1997.
Iverson L, Jensen AL, Høier R, et al. Biological variation of canine serum thyrotropin (TSH) concentration. Vet
Clin Pathol 28:16-19, 1999.
Jensen AL, Iversen L, Høier R, et al. Evaluation of an immunoradiometric assay for thyrotropin in serum and
plasma samples of dogs with primary hypothyroidism.  J Comp Pathol 114: 339-346, 1996.
Kaptein EM. Thyroid hormone metabolism and thyroid diseases in chronic renal failure. End Rev 17:45-63,
1996.
McGregor AM. Autoimmunity in the thyroid – Can the molecular revolution contribute to our understanding?
Quart J  Med  82 (297): 1-13, 1992.
Nachreiner RF, Refsal KR. Radioimmunoassay monitoring of thyroid hormone concentrations in dogs on thyroid
replacement therapy: 2,674 cases (1985-1987). J Am Vet Med Assoc  201: 623-629, 1992.
Nachreiner RF, Refsal KR, Davis WR, et al.  Pharmacokinetics of L-thyroxine after its oral administration in dogs.  Am J Vet Res  54: 2091-2098, 1993.
Nachreiner RF, Refsal KR, Graham PA, et al.  Prevalence of autoantibodies to thyroglobulin in dogs with
nonthyroidal illness. Am J Vet Res 59:951-955, 1998.
Overall KL. Clinical Behavioral Medicine for the Small Animal. St. Louis, Mosby, 1998
Panciera DL, Johnson GS.  Hypothyroidism and von Willebrand factor. J Am Vet Med Assoc  206: 595-596,
1995.
Panciera DL.  Clinical manifestations of canine hypothyroidism.  Vet Med  92: 44-49, 1997.
Panciera DL. Thyroid-function testing: Is the future here?  Vet Med  92: 50-57, 1997.
Panciera DL. Treating hypothyroidism.  Vet Med  92: 58-68, 1997.
Panciera DL. Hypothyroidism in dogs: 66 cases (1987-1992).  J Am Vet Med Assoc  204: 761-767, 1994.
Paradis M, Pagé N, Larivière N, et al. Serum-free thyroxine concentrations, measured by chemiluminescence
assay before and after thyrotropin administration in healthy dogs, hypothyroid dogs, and euthyroid dogs with
dermatopathies.  Can Vet  J  37: 289-294, 1996.
Peterson ME, Melian C, Nichols R. Measurement of serum total thyroxine, triiodothyronine, free thyroxine, and
thyrotropin concentrations for diagnosis of hypothyroidism in dogs. J Am Vet Med Assoc 211:1396-1402, 1997.
Schmidt MA, Bland JS.  Thyroid gland as sentinel: Interface between internal and external environment.  Altern
Ther 3: 78-81, 1997.
Scott-Moncrieff JCR, Nelson RW. Change in serum thyroid stimulating hormone concentration in response to
administration of  thyrotropin-releasing  hormone to healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease.  J Am Vet Med Assoc 213:1435-1438, 1998.
Scott-Moncrieff JCR, Nelson RW, Bruner JM, et al. Comparison of thyroid-stimulating hormone in healthy dogs,
hypothyroid dogs, and euthyroid dogs with concurrent disease. J Am Vet Med Assoc 212:387-391, 1998.
Scott-Moncrieff JC, Azcona-Olivera J, Glickman NW, Glickman LT, HogenEsch H. Evalu ation of antithyroglobulin
antibodies after routine vaccination in pet and research dogs. J Am Vet Med Asspc 221: 515-521,2002.
Surks MI, Sievert R. Drugs and thyroid function. N Eng J Med 333: 1688-1694, 1995.
Thacker EL, Refsal KR, Bull RW. Prevalence of autoantibodies to thyroglobulin, thyroxine, or triiodothronine and
relationship of autoantibodies and serum concentration of iodothyronines in dogs.  Am J Vet Res 53: 449-453,
1992.
Thacker EL, Davis JM, Refsal KR, et al. Isolation of thyroid peroxidase and lack of antibodies to the enzyme in
dogs with autoimmune thyroid disease.  Am J Vet Res  56: 34-38, 1995.
Tomer Y, Davies TF.  Infection, thyroid disease, and autoimmunity.  End Rev 14: 107-120, 1993.
Uchida Y, Dodman NH, DeNapoli J, Aronson LP. Characterization and treatment of 20 canine dominance ag-
gression cases.  J  Vet Med Sci 59:397-399. 1997.
Vajner L. Lymphocytic thyroiditis in beagle dogs in a breeding colony: findings of serum autoantibodies.  Vet
Med Czech 11:333-338, 1997.
Williams DA, Scott-Moncrieff C, Bruner J, et al.  Validation of an  immunoassay for canine thyroid-stimulating
hormone and changes in serum concentration following induction of hypothyroidism in dogs.  J Am Vet Med
Assoc  209: 1730-1732, 1996.

Table 1.  Clinical  Signs of Canine Hypothyroidism

Alterations in Cellular Metabolism

lethargy                                        weight gain

mental dullness                            cold intolerance

exercise intolerance                     mood swings
neurologic signs                           hyperexcitability
polyneuropathy                            stunted growth
seizures                                        chronic infections

Neuromuscular Problems

weakness                                     knuckling or dragging feet
stiffness                                        muscle wasting
laryngeal paralysis                        megaesophagus
facial paralysis                              head tilt
“tragic” expression                       drooping eyelids
incontinence                                  ruptured cruciate ligament

Dermatologic Diseases
dry, scaly skin and dandruff             chronic offensive skin odor
coarse, dull coat                               bilaterally symmetrical hair loss
“rat tail”; “puppy coat”                     seborrhea with greasy skin
hyperpigmentation                           seborrhea with dry skin

pyoderma or skin infections              myxedema

Reproductive Disorders
infertility                                     prolonged interestrus interval
lack of libido                               absence of heat cycles
testicular atrophy                       silent heats
hypospermia                               pseudopregnancy
aspermia                                     weak, dying or stillborn pups

Cardiac Abnormalities
slow heart rate (bradycardia)
cardiac arrhythmias
cardiomyopathy

Gastrointestinal Disorders
constipation
diarrhea
vomiting

Hematologic Disorders
bleeding
bone marrow failure

Table 1 (continued)

│  red blood cells (anemia)

low    ┤ white blood cells

│ platelets

Ocular Diseases
corneal lipid deposits                   corneal ulceration
uveitis                                          keratoconjunctivitis sicca or “dry eye”
infections of eyelid glands            Vogt-Koyanagi-Harada syndrome
(Meibomian gland)

Other Associated Disorders
IgA deficiency                             loss of smell (dysosmia)
loss of taste                                 glycosuria
other endocrinopathies                     chronic active hepatitis
adrenal
pancreatic
parathyroid

Table 2. Diagnosis of Thyroid Disease

X Complete Basic Profile
— (T4, T3, FT4, FT3, T4AA, T3AA)

X  Additional Tests
—  (TSH, TgAA)

X  Older Tests (T4, T4 + T3)
Serum T4 and/or T3 alone are not reliable
for diagnosis because:

— overdiagnose hypothyroidism
— underdiagnose hyperthyroidism
— fail to dectect early compensatory

disease and thyroiditis
— influenced by nonthyroidal illness

and certain drugs

Table 2 (continued)

X   Newer Tests

Free (Unbound) T4
Less likely to be influenced by nonthyroidal

illness or drugs                                      

Valid
— equilibrium dialysis
— solid-phase analog RIA
— chemiluminescence solid-phase

Less reliable  — liquid-phase analog RIA

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