13.

CANINE HYPOTHYREOIDISM

Hypothyroidism is a disorder that results from inadequate production of T4 and T3.

It is relatively common in dogs but is rarely seen in cats. Primary hypothyroidism
accounts for mor than 95% of cases and develops as a result of progressive
destruction of the thyroid gland. Frequently, this occurs either from an immune-
mediated process called lymphocytic thyroiditis in which thyroid tissue is destroyed
and replaced by fibrous connective tissue or by idiopathic atrophy in which the
thyroid tissue atrophies and is replaced by adipose tissue.
Less common causes of primary hypothyroidism include follicular cell hyperplasia
and infiltrative neoplasia. Secondary hypothyroidism is rare but may be caused by
pituitary malformation or neoplasia.
Hypothyroidism can arise at any age and in any breed. Most commonly affected
breeds include Golden retrievers, Doberman pinschers, Irish setters, Great Danes,
Airedale terriers, Old English sheepdogs, dachshunds, miniature schnauzers,
cocker spaniels, poodles, and boxers. There is no apparent gender predisposition;
however, spayed females and neutered males are at increased risk for developing
hypothyroidism compared with sexually intact animals.
Clinical signs
Thyroid hormones influence the function of almost all organ systems within the
body, and, when deficient, a wide range of clinical signs is possible. At a cellular
level, thyroid hormones influence multiple metabolic processes, from the regulation
of mitochondrial oxygen demand to the control of protein synthesis. As a
consequence, the onset of the disease is insidiously progressive and, although the
clinical signs can be varied and extensive, most are non-specific.
The most common clinical signs (approximately 70% of cases) relate to a decline in
metabolic rate, together with a variety of dermatological changes. However, in
some dogs only one abnormality is present, while in others clinical signs involving
the neuromuscular, cardiovascular, reproductive, ophthalmological and
gastrointestinal systems develop, and may even predominate.
Hypothyroidism is associated with a decline in metabolic rate. Related clinical
signs, including weight gain, lethargy, exercise intolerance and weakness, occur in
the majority of hypothyroid dogs. In hypothyroid humans, basal metabolic rate
reduces by up to 40%; a decline in resting energy expenditure has also been
demonstrated in hypothyroid dogs.
The
onset of metabolic signs in dogs is typically insidious and, consequently, often
missed or dismissed by owners. However, the clinical response following
appropriate therapy can be dramatic, retrospectively confirming the extent of the
problem. At least one 'metabolic' sign is recognized in approximately 85% of
hypothyroid dogs.
Lethargy is the most common metabolic change, affecting up to 80% of cases. The
duration of the underlying illness appears to correspond with the severity of
lethargy. In some cases lethargy is profound. Unusually, some affected dogs
appear unperturbed by veterinary examination and may fall asleep during a
consultation.
Exercise intolerance affects just over 25% of all cases, although many owners
confuse lethargy with exercise intolerance. Frequently, dogs appear to have a
normal capacity for short-term exercise, or when excited will behave appropriately.
However, this is relatively short-lived, and recovery is prolonged, as shown by a
need for excessive rest or sleep thereafter.
Weight gain and obesity is a common finding in hypothyroidism, occurring in
approximately 40% of cases during the few months prior to initial presentation.
Weight gain occurs despite a normal or slightly reduced appetite, and may be
exacerbated by a concurrent unwillingness to exercise. In some affected dogs,
weight gain can be marked with recorded weights >75% above the expected breed
average. Despite this, a large proportion of hypothyroid dogs do not gain significant
weight, and hypothyroidism cannot be ruled out based on a lack of this finding
alone. In addition, whilst obesity is extremely common in dogs, most cases relate to
simple overfeeding, with hypothyroidism only accounting for a small proportion of
cases. Thus the presence or absence of obesity is of little diagnostic
consequence for hypothyroidism.
Cold intolerance or heat seeking is reported in approximately 10% of hypothyroid
dogs, and affected dogs may be noted as shivering excessively. However, the
presence of heat seeking is non-specific as it is also a common feature of euthyroid
dogs.
Thyroid hormones play an important role in the maintenance of dermal health.
Dermatological abnormalities can be extensive and more worrying to owners than
the more subtle metabolic signs. They are reported in approximately 80% of
affected dogs. The particular dermatological signs vary and reflect the severity and
duration of the disease.
Hyperkeratosis causing scaling and scurfing of the skin, and poor quality hair coat,
is common. Excessive dandruff or a dry dull coat is often noted in the early stages
of the disorder. Otitis externa is reported in a number of hypothyroid dogs, and
dryness and scaling of the external ear canal may be noted. Thyroid hormones are
necessary for the initiation of the anagen phase of hair growth. Absence of thyroid
hormones results in persistence of the telogen phase; hairs become easily epilated,
with resultant alopecia, and there is a failure of regrowth after clipping. Hair loss
commonly begins in areas undergoing friction, such as on the neck in dogs that
wear collars and on the tail, resulting in the typical 'rat-tail' appearance of
hypothyroidism. Affected animals commonly develop a bilaterally symmetrical
nonpruritic 'endocrine' alopecia, with progressive hair loss along the flanks and on
the trunk, usually sparing the head and extremities.
Accumulation of mucopolysaccharides and hyaluronic acid in the skin occurs due to
an imbalance in their normal thyroid-controlled production and degradation. lt
results in myxoedematous non-pitting thickening of the skin. This thickening is most
pronounced over the head where it can give rise to a tragic facial expression with
thickening of the lips, thickened skin over the forehead and drooping of the eyelids.
Diagnosis
Prior to any diagnostic testing, it is important to take into consideration any
concurrent medical therapies the patient may be receiving. Common drugs
including (but not limited to) glucocorticoids, phenobarbital, sulfa antibiotics,
furosemide, some nonsteroidal antiinflammatory drugs (NSAIDs), clomipramine,
and radiocontrast agents have been reported to alter thyroid concentrations,2,6
thereby making diagnostic interpretation that much more difficult. Another factor that
should be considered is that of concurrent illness causing a reduction in thyroid
hormone levels. This phenomenon, known as nonthyroidal illness or euthyroid sick
syndrome, can be brought on by conditions such as HAC, renal disease, hepatic
disease, heart failure, severe infections, and diabetic ketoacidosis (DKA). It is
thought to be a physiological adaptation of the body in an attempt to decrease
cellular metabolism1 and to conserve energy. In general, the relative reduction in
basal T4 levels correlates with the severity of clinical illness. For dogs
demonstrating signs typical of hypothyroidism, a minimum database including a
CBC, a chemistry profile with electrolytes, urinalysis, and total T4 (TT4) is
recommended for the initial diagnostic workup. Abnormal findings in the CBC that
may be consistent with hypothyroidism are a mild, normocytic, normochromic,
nonregenerative anemia, as well as leukocytosis, which could be a result of any
skin infections that are present.
Common abnormalities found in the serum chemistry profile are
hypercholesterolemia and/or hypertriglyceridemia despite the collection of fasted
samples. This may be due to the body’s diminished capability to degrade lipids in its
hypothyroid state.
Urinalysis is often normal in dogs with primary hypothyroidism; however, in dogs
with lymphocytic thyroiditis, immune complex glomerulonephritis may result in
proteinuria. PU, hyposthenuria, and urinary tract infections are not typical of
hypothyroidism.
Endocrine testing
Total T4 values will fall below normal reference range in most hypothyroid dogs;
however, because this test is highly sensitive but not as specific, it is recommended
that a free T4 by equilibrium dialysis (fT4 [ED]) and a TSH level be evaluated. A
decreased fT4 (ED) and an increased TSH in a dog with typical hypothyroid signs is
highly suggestive of a true hypothyroid condition. It should be emphasized that
measuring fT4 (ED) is considered more accurate than radioimmunoassay (RIA) and
should be specifically requested when submitting samples for testing. Certain dog
breeds such as greyhounds, whippets, basenjis, and conditioned sled dogs have
been shown to have T4 concentrations lower than established reference ranges of
most other dogs. A diagnosis of hypothyroidism can therefore be difficult in these
breeds and further diagnostic testing is recommended. Due to highly variable T3
concentrations in both hypothyroid and euthyroid dogs, this test is of little value in
the diagnosis of canine hypothyroidism.
The TSH stimulation test has been reported as highly accurate in diagnosing
hypothyroidism in dogs; however, cost and availability of TSH has limited its use in
veterinary medicine.
Dogs demonstrating abnormalities in other parameters of testing should be further
evaluated for other conditions that may have overlapping diagnostic findings and
clinical signs such as HAC or other nonthyroidal illnesses.
Treatments
The treatment of choice for hypothyroid dogs with clinical signs is supplementation
of a name brand synthetic levothyroxine sodium product that is approved for use in
dogs. Initial standard doses are 0.02 mg/kg (0.1 mg/10 lb) twice daily, up to a
maximum of 0.8 mg twice daily. Animal origin and generic synthetic thyroid
supplements have historically been criticized for either having variable
bioavailability or the potential of having variable, and sometimes considerably less,
hormone than what is stated on the label.
It is recommended that a T4 level be reevaluated 4–8 weeks after starting
replacement therapy or after any changes in dose or supplement brand. Dosage
should then be adjusted according to test results as well as clinical response. If the
patient responds well to therapy, once-daily therapy can be tried; however, some
patients will require continued twice-daily therapy. In dogs, peak plasma
concentrations after oral dosing reportedly occur 4–12 h after administration, and
the serum half-life is approximately 12–16 h. Ideally, blood samples should be
drawn immediately before the next dose is due (trough level) and then 4–6 h post
pill (peak level). Once a consistent therapeutic dose has been achieved, routine
monitoringmay only require testing of peak T4 levels every 6–12 months.
Clinical improvement should be observed within 4–6 weeks of initiation of therapy,
although improvement in mental alertness and activity level may be seen in as little
as 1–2 weeks. Dermatologic and reproductive abnormalities may take several
months to completely resolve. If resolution of symptoms is not noted within this time
frame, the diagnosis of hypothyroidism should be reevaluated.
Prognosis and survival times
With proper diagnosis, therapy, and monitoring, the prognosis for canine
hypothyroidism is excellent and life expectancy is normal.