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 (Table 1).
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 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 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 being manifested.
The typical history starts out with a quiet, 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.
Tables 3-4 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 4). 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 dogs.
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.
Table 1. Clinical Signs of Canine Hypothyroidism
Alterations in Cellular Metabolism
neurologic signs: polyneuropathy; seizures
knuckling or dragging feet
ruptured cruciate ligament
dry, scaly skin and dandruff
chronic offensive skin odor
coarse, dull coat
bilaterally symmetrical hair loss
“rat tail”; “puppy coat”
seborrhea with greasy skin
seborrhea with dry skin
pyoderma or skin infections
prolonged interestrus interval
lack of libido
absence of heat cycles
weak, dying or stillborn pups
slow heart rate (bradycardia)
bone marrow failure: low red blood cells (anemia); white blood cells; platelets
corneal lipid deposits
keratoconjunctivitis sicca or “dry eye”
infections of eyelid glands – Meibomian gland
Other Associated Disorders
loss of smell (dysosmia)
loss of taste
chronic active hepatitis
other endocrinopathies: adrenal; pancreatic; parathyroid
Table 2. Diagnosis of Thyroid Disease
• Complete Basic Profile – T4, T3, FT4, FT3, T4AA, T3AA)
• Additional Tests – TSH, TgAA
• Older Tests (T4, T4 + T3)
Serum T4 and/or T3 alone are not reliable for diagnosis because:
– overdiagnose hypothyroidism
– underdiagnose hyperthyroidism
– fail to detect early compensatory disease and thyroiditis
– influenced by nonthyroidal illness and certain drugs
• Newer Tests
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 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
Thyroglobulin autoantibodies are present in serum of cases with lymphocytic thyroiditis.
– positive results confirm diagnosis ; 8% false negative
– 20-40% of cases have circulating T3 and/or T4AA
– allows for early diagnosis and genetic counseling