ENDOCRINOLOGY
ENDOCRINOLOGY
Thyroid Hormone
Interpretation of Assay Results in Dogs
By: Dr Liesel L van der Merwe,
BVSc Hons. MMedVet(Med).
Reviewed: Prof F. Reyers
BVSc Hons. MMedVet(K.Pat).
With the increased availability of in-house hormone assays there is a real risk of incorrect
interpretation of test results. Before we go into any details - I would just like to emphasize
the title. The definition of the word “interpretation” in the Oxford dictionary is “the action of
explaining the meaning of something”. I emphasize this, as just looking at the value and using it as a given is not interpretation - it is “reading a result”.
Interpretation implies that there are factors which may
affect the meaning of a result, and there are many factors which affect thyroid hormone levels in the dog. It
is also vital that we realise that use of the thyroid tests
may not lead to a definitive diagnosis. Early stages of
dysfunction often present with discordant, confusing
results.1
Most of the time a careful history, physical examination and screening tests and common sense allow the
vet to differentiate between non-thyroidal illness/euthyroid sick syndrome (ESS) and true hypothyroidism.
Hypothyroidism is common in certain breeds: Dobermans, Schnauzers, Spaniel , Daschunds and Irish setters. It is a disease of middle aged to older dogs, but
individuals in predisposed breeds may present as early
as 2 years of age.3 All circulating T4 and only 20% of
circulating T3 is from the thyroid gland. The majority of T3 formation occurs outside the thyroid by deiodination (5’-deiodinase). Tissues having the highest
concentration of de-iodinating enzymes are the liver
and kidney but muscle tissue produces the most T3
due to its volume.1,3
lin (TBG), albumin, transthyretin and apolipoproteins.
TBG has a high affinity for T4 (and T3) but low capacity
due to low concentrations in the plasma. Albumin has
a low affinity for T3 and T4, but a high capacity due to
high concentrations in the plasma.1,3 Tests currently
available at veterinary laboratories in south Africa include Total T4 (TT4), canine thyroid stimulating hormone (cTSH) and freeT4 ( fT4)
Total T4
TT4 is diagnostic only if the value is normal or elevated. TT4 is about 90% sensitive in diagnosing hypothyroidism in dogs. What this means is that if the
animal is hypothyroid - 90% of cases will be correctly
identified. However the test is not very specific (75%)
– this means that a low TT4 can also occur with nonthyroidal illness. This makes its use, as a single test
for the diagnosis of canine hypothyroidism not all that
reliable.1,3 BaselineTT4 can be lowered with non-thyroidal illness and certain medications. The mechanism
is thought to be an alteration in the serum proteins
which decreases the total binding capacity as the proteins are utilised in the disease process and drug metabolism as well.1,3
Lipid soluble hormones are transported in the plasma
by binding to specific proteins, in which there is considerable species variation. Thyroid hormone is highly
protein bound in blood (> 99%), T4 greater so than T3.
The thyroid hormone binding protein has less affinity
for T4 in the dog than in humans - thus the fraction
of circulating T4 is higher at 0.1% than in humans at
0.03%.1,3 The equilibrium is easily shifted by anything
impacting the binding proteins. 1,3
Sulphonamide drugs can induce true clinical hypothyroidism in a patient as well as laboratory signs of
decreased function.1 Other medications causing a
decrease in TT4 are glucocorticoids, phenobarbitone, potassium bromide, propranolol, clomipramine
(Clomicalm®) , aspirin, ketoprofen and carprofen (Rimadyl®).1
Additionally the dog has only 15% the concentration
of thyroxine binding globulin (TBG) of humans thus
T4 binds to other protein as well.1 Thyroid binding proteins in the dog are: thyroid hormone binding globu-
It is thus clear that interpretation of TT4 results should
be made with care in patients on chronic phenobarbitone therapy for seizures as well as those on carprofen
for arthritis. The effect of other NSAIDS has not been
published. A 3 week withdrawal period is required after use of Purbac ® or other sulphonamides as well as
glucocorticoids. 1,3
Certain breeds have also been shown to have TT4
reference ranges which are below the “normal” reference ranges for all dogs - these include sight-hounds
(Greyhounds , Salukis , Irish Wolfhounds as well as
sled dogs (Huskies , Malamutes).3 Obesity causes a
slight increase in TT4 and TT4 was decreased immediately (24hrs) after a seizure event in patients with
seizure disorders.
Canine TSH
TSH is generally elevated only in true hypothyroidism.
However elevations above normal also occur with
sulphonamides and elevations into the top normal
range may occur during recovery from non-thyroidal
illness. In humans TSH is an excellent screening test
for hypothyroidism - being elevated in almost 100%
of cases. Several studies have shown however that
about 25% - 40% of dogs with hypothyroidism had
normal TSH levels .1,3 Thus the sensitivity is not great.
However the specificity is very good as, apart from
recovering non- thyroidal illness patients, TSH is not
elevated in euthyroid dogs. A positive cTSH will therefore add specificity to a low TT4 value.
fT4
In the literature you will read about the use of fT4ED
- free T4 measured by equilibrium dialysis. This is the
most sensitive way of measuring thyroid hormone
and is considered the gold standard. In South Africa
the laboratories do not use this methodology as it is
expensive, time-consuming and require radio-immunoassay. The fT4 you get from your South African laboratory has been done using an immunofluorescence
test - and is susceptible to the same interference as
TT4. There is thus no benefit in requesting a TT4 as
well a