CANINE HYPOTHYROIDISM
(310) 828-4804;FAX (310)-828-8251
www.hemopet.org; hemopet@hotmail.com
Hypothyroidism is the most common
endocrine disorder of dogs, and up to 80% of cases result from an autoimmune
disease that progressively destroys the thyroid gland (autoimmune thyroiditis).
Once more than 75% of the gland is destroyed by this process, classical
clinical signs of hypothyroidism appear. Because the condition is heritable, it
has significant genetic implications for breeding stock. Accurate diagnosis of the early stages of
autoimmune thyroiditis offers important genetic and clinical options for prompt
intervention and case management. However, 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 signs (see Table 1). Many of these clinical symptoms mimic those resulting from other causes and so recognition of the condition and interpretation of results of thyroid function tests can be problematic.
A complete baseline thyroid profile
is measured and typically includes total T4, total T3, free T4, free T3, T3
autoantibody (T3AA) and T4 autoantibody (T4AA), and can include canine
endogenous thyroid stimulating hormone (cTSH) and/or thyroglobulin autoantibody
(TgAA) (see Table 2) . The TgAA assay is especially important in screening
breeding stock for heritable autoimmune thyroid disease. Affected dogs should not be used for
breeding.
The normal reference ranges for thyroid parameters of healthy adult animals tend to be similar for most dog breeds, with exception of the sight hounds and giant breeds of dogs which have lower basal levels. 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
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. 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.
Most confirmed cases of
thyroiditis have elevated serum TgAA
levels, whereas only about 20-40% of cases have elevated circulating T3 and/or
T4 AA. False negative TgAA
results also can occur in about 8% of dogs verified to have high T3AA and/or
T4AA. Furthermore, false
positive TgAA results may be obtained if the dog has been vaccinated,
especially with rabies vaccine, within
the previous 30-45 days, or in some cases of non-thyroidal illness.
Canine autoimuune thyroid disease is very similar to Hashimoto’s thyroiditis of humans, which has been shown to be associated with the tissue major histocompatibility complex (MHC) genes. A similar association with MHC genes in hypothyroid dogs has recently been reported in Doberman Pinschers, English Setters and Rhodesian Ridgebacks. The presence of this unique genetic determinant doubles the risk of a dog developing hypothyroidism. This exciting finding hopefully will lead to development of a genetic marker test to identify affected breeding stock so that the disease incidence in pure-bred dogs can be reduced.
Individuals genetically susceptible to autoimmune thyroid disease may also become more susceptible to immune-mediated diseases affecting other tissues and organs, especially the bone marrow, liver, adrenal gland, pancreas, skin, kidney, joints, bowel, and central nervous system. The resulting “polyglandular autoimmune syndrome” tends to run in families and is believed to have an inherited basis.
The principal reason for pet euthanasia stems
not from disease, but undesirable behavior.
While this abnormal behavior can have a variety of medical and
psychological causes in animals, it recently has been associated with
thyroiditis and hypothyroidism in dogs, and hyperthyroidism in cats. 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 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.
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.
Of the initial 634 canine cases of aberrant behavior, 90%
(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. 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.
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Alterations in Cellular Metabolism
lethargy weight gain
mental dullness cold intolerance
exercise intolerance mood swings
neurologic signs hyperexcitability
polyneuropathy stunted growth
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
low red blood cells (anemia), 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 parathyroid
pancreatic
C Complete Basic Profile
-- (T4, T3, FT4, FT3, T4AA, T3AA)
C Additional Tests
-- (TSH, TgAA)
C 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
C
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
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
Canine TgAA
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