Laboratory Evaluation of Canine Hypothyroidism
Robert Lobingier, DVM, DAVCP • Clinical Pathologist • IVS
Canine Hypothyroidism is the most common endocrinopathy in canine
medicine. Hypothyroidism is also considered the most commonly
over-diagnosed endocrine disorder. It is a disease that can be difficult
to confirm, but relatively easy to treat.
As with most endocrinopathies, a convincing pattern of disease with
both strong clinical signs and consistent laboratory findings is
essential in the diagnosis of Canine Hypothyroidism. The understanding,
selection, and interpretation of laboratory tests can be essential to
both assess thyroid function and confirm the diagnosis of
General Laboratory Tests
General laboratory findings are an important part of the initial
workup for the suspected hypothyroid patient. A Complete Blood Count and
Serum Biochemical Profile will not only aid in ruling out possible
underlying nonthyroidal disease, but should increase the probability of
hypothyroidism. Approximately 75% of hypothyroid dogs will have serum
cholesterol levels in excess of 400 mg/d and 30% will exhibit mild to
moderate nonregenerative anemia.
Total Serum T4
Basal thyroid screening most often involves an initial Total
serum T4 (TT4) measurement. It is an excellent screening test
because it is a sensitive, relatively inexpensive, and readily
available. The TT4 primarily measures the protein bound fraction of
thyroid prohormone that is not directly available for cellular
metabolism. The T4 measurement routinely done in laboratories measures
only the potential reservoir of hormone. The free fraction of T4 (FT4)
makes up less than 1% of the T4 in circulation but it is the biological
available fraction able to enter cells. Relatively large fluctuations of
the Total T4 reservoir can occur with little impact on the free fraction
and cellular metabolism.
The TT4 is broadly influenced by the presence of nonthyroidal disease
and certain drugs which will cause a decrease in serum levels of TT4.
Approximately 75% of dogs ill with nonthyroid related disease will have
TT4 at the low end of or below normal range. A similar result can be
found in dogs with spontaneous Cushing's disease. Drugs that can induce
suppression of serum thyroid hormone levels include glucocorticoids,
anticonvulsants, and nonsteroidal anti-inflammatory drugs. In light of
the above information, TT4 measurement is much more reliable in
reassuring a euthyroid state (with values >1.5 - 2.0 µg/ dl).
Conclusion: TT4 is an excellent
screening test that is very good at reassuring euthyroidism but often
not reliable in confirming hypothyroidism.
Total Serum T3
serum T3 (TT3) measurement has been used in conjunction with TT4 in
an attempt to improve the reliability of thyroid evaluation. TT3 is the
major active hormone at the cellular level formed by deiodinization of
T4; however, TT3 is a minor product of the thyroid gland there is a
broad overlap in serum levels when populations of euthyroid,
hypothyroid, and sick euthyroid dogs. TT3 is considered both relatively
insensitive and often nonspecific in assessment of hypothyroidism.
Conclusion: TT3 is one of the
least reliable indicators of thyroid function and is of minimal value in
assessment of thyroid function in the dog.
Confirmatory testing for hypothyroidism can involve two relatively
new tests that improve the accuracy of laboratory diagnosis. The
measurement of the free fraction of T4
by the equilibrium dialysis method (FT4 ED) has been shown to be a
very sensitive and specific measure of thyroid function. The FT4 ED
analysis is much less influenced by nonthyroidal factors with
sensitivity and specificity greater than 90% over a broad range of
The canine endogenous TSH assay (cTSH) is a test intended to increase
the accuracy in diagnosis of primary hypothyroidism. With a decline in
thyroid function (and negative feedback to the pituitary gland), cTSH
levels should consistently increase; however, current diagnostic
performance of cTSH has been somewhat disappointing with sensitivity and
specificity much less than FT4ED and TT4. The cTSH can be useful when
used in combination with the FT4ED. The combined specificity can exceed
95% making this combination very useful in confirming hypothyroidism in
difficult or unclear cases.
Conclusion: FT4ED is a very
accurate test for evaluating basal thyroid function and is an important
test in confirming hypothyroidism. When a below normal FT4ED level is
combined with an elevated cTSH in a patient, canine hypothyroidism is
Other laboratory tests for hypothyroidism include: antiT4 and antiT3
antibody, and antithyroglobulin antibody (ATA or TgAA). These tests
propose to evaluate patients for immune mediated thyroid disease and
positive results do have an increased statistical correlation with
lymphocytic thyroiditis (particularly ATA). These tests do not relate
directly to thyroid function and the overall diagnostic accuracy and
utility of immune thyroid testing has yet to be shown. Positive results
occur in many patients with no evidence of thyroid related disease.
Interpretation of these tests must be done with some caution. The
overall predictive value and utility of these tests in any broad
screening program for potential thyroid related disease will require
Conclusion: Measuring antibodies
against thyroid hormones or thyroglobulin does not test thyroid function
but does show correlation with the presence of lymphocytic thyroiditis.
Overall clinical significance of these tests in the general canine
population will require further study.
Confirming the Diagnosis
The final, and most important, step in the confirmation of
hypothyroidism is in response to supplementation.
Treatment with sodium levothyroxine (L-thyroxine) is usually
initiated on a divided daily dosage schedule. Dramatic clinical
improvement in related signs should occur within 2-4 weeks of therapy
with more chronic skin and coat changes possibly taking several months
to resolve. 6-8 weeks of therapy should prove to be an adequate time
frame to assess patient response in any therapeutic trial. Therapeutic
drug monitoring for TT4 supplementation should be performed 2-4 weeks
after initiating therapy with peak levels measured 4-6 hours post pill.
Serum TT4 measurement is usually the test of choice to monitor therapy
with peak levels near the high end of normal range . It is interesting
to note that Thyroid supplementation in euthyroid patients can result in
temporary improvement in conditions such as alopecia by stimulating an
androgenic response. Therefore, when assessing a therapeutic trial,
there should be close and objective monitoring for dramatic and lasting
The definitive diagnosis of canine hypothyroidism requires not only a
complete clinical and laboratory assessment, but also a documentation of
response to therapy and remission of clinical signs. Careful
consideration of clinical signs that may mimic thyroid related disease
and confuse the diagnosis should always be part of this diagnostic plan.
The TT4 measurement is a good screening test because of its sensitivity
to disease but can be a poor confirmatory test due to its lower
specificity. More accurate confirmatory tests are now available that
should be considered to aid the diagnosis. A final diagnosis of
hypothyroidism in a patient means the patient will require lifelong
therapy. Inappropriate supplementation in a euthyroid canine will lead
to unnecessary expense, a delay in a more appropriate diagnosis, and the
potential for inducing secondary hypothyroidism.
References and additional reading:
1. Chastain CB and Panciera DL: Hypothyroid Diseases. In Ettinger (ed): Textbook
of Veterinary Internal Medicine. 4th ed. 1995, pp 1487- 1501
2. Scott DW, et. al.: Endocrine and Metabolic Diseases. In Muller and
Kirk?s Small Animal Dermatology. 5th ed. 1995. pp 691 - 703
3. Feldman EC and Nelson RW: Hypothyroidism. In Canine and Feline
Endocrinology and Reproduction. 2nd ed. 1996 pp 68 - 117
4. Nichols, R: Update: Diagnostic Testing for Canine Hypothyroidism. 15th
Annual ACVIM Forum, Lake Buena Vista, FL 1997
5. Melian C. et al.: Evaluation of Free T4 and Endogenous TSH as
Diagnostic Tests for Hypothyroidism in Dogs. 15th Annual ACVIM Forum,
Lake Buena Vista,FL. 1997