Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

X. Thyroid Function Tests
629
thyroid-stimulating immunoglobulins or thyroid-stimulating
antibodies (TSAb) do not appear to have a role in normal
thyroid physiology, nor have corresponding stimulators
been found in animals.
X . THYROID FUNCTION TESTS
The diagnosis of thyroid disease is usually obscured by
the nonspecific nature and variety of clinical signs. A thorough
physical examination is essential for the detection
of a potential thyroid disease and as a rationale for laboratory
tests of thyroid function. Initial routine laboratory
tests such as hematology or urinalysis are of limited value
except for a moderate to slight normocytic normochromic
anemia, which may sometimes be observed. The initial
biochemical screen is also limited except for a hypercholesterolemia,
which may be observed. In consequence, the
specific tests of thyroid function are of great importance
in the diagnosis of thyroid disease. Fortunately, improvements
of standard tests and the development of new tests
have made several specific and direct tests of thyroid function
readily available to the veterinary clinician.
A . Indirect Tests of Thyroid Function
1 . Hematology
A moderate normocytic normochromic anemia is sometimes
associated with clinical hypothyroidism in the dog.
This anemia has also been observed in human hypothyroidism
and in experimental animals and is known to be
of a depression type or the anemia of chronic disease.
The stained blood smear characteristically has little or no
evidence of active erythrogenesis such as anisocytosis,
polychromasia, or nucleated red cells. Leptocytosis may
be prominent in some cases. The hemogram, therefore,
is characteristic of the nonresponsive anemia of chronic
diseases such as neoplasia, chronic infection, and so on.
This anemia is not diagnostic for hypothyroidism, but conversely,
in cases of unexplained hypoplastic or nonresponsive
anemia, hypothyroidism is an important differential
diagnosis that should be pursued.
2 . Cholesterol
The serum cholesterol generally varies inversely with thyroid
activity. The net effect of thyroid hormone on cholesterol
metabolism is to increase the rate of its catabolism
by the liver ( Koppers and Palumbo, 1972 ), thereby lowering
the cholesterol. In hypothyroidism, the net effect is
a decrease in cholesterol catabolism and an increase in
cholesterol.
The cholesterol is carried in dog plasma equally by the
low-density lipoproteins (LDL-Chol) and the high-density
lipoproteins (HDL-Chol) (Mahley and Weisgrober, 1974).
In humans, cholesterol is carried mainly by the LDL-Chol
and only about 20% by the HDL-Chol. This partitioning
of cholesterol is important because increased LDL-Chol
is associated with atherosclerosis, whereas increased HDL-
Chol is associated with a reduced risk for heart disease,
hence it is commonly known as “ good ” cholesterol.
Total cholesterol alone is of limited value because
hypercholesterolemia is seen in a variety of conditions
unrelated to thyroid activity. These include the diet,
nephrotic syndrome, hepatic function, biliary obstruction,
and diabetes mellitus. The diagnostic accuracy of serum
cholesterol for hypothyroidism in the dog is about 66%.
However, when the concentrations are very high, 500 mg/
dl ( 12.9 mmol/l), and diabetes mellitus is eliminated, its
diagnostic accuracy increases greatly. Therefore, increased
cholesterol again is simply a signal to further investigate
thyroid disease.
Similarly, hypocholesterolemia has little value as an
index of hyperthyroidism. On the other hand, cholesterol
decreases consistently in response to thyroxine replacement
therapy, so it has value as a guide to therapeutic response.
In thyroidectomized horses with clinical evidence of hypothyroidism,
Lowe et al. (1974) found a 50% decrease in
serum cholesterol shortly after feeding iodinated casein.
Feeding of iodinated casein to these horses also resulted in
a rapid rise of T 4 to above normal. Iodinated casein contains
about 2.5 μ g (3.85 nmol) T 4 and 1.25 μ g (1.61 nmol)
T 3 per gram.
B . Direct Tests of Thyroid Function
Direct approaches to thyroid evaluation are (1) to measure
the amount of the hormones in the blood, (2) to assess
the response of the thyroid to stimulation by the thyroidstimulating
hormone (TSH), or (3) to assess the response
of the pituitary gland to stimulation by the thyrotropinreleasing
hormone (TRH). Because there are thyroid inhibitory
effects among a wide variety of iodine containing
compounds, it is critical that any form of iodine-containing
medication, including thyroid hormones, be ascertained
in the history of the patient. As a general rule, any iodinecontaining
medication or thyroid hormones being given to
the patient should be withdrawn for at least 2 weeks before
any thyroid function tests are undertaken.
1 . Thyroxine by Radioimmunoassay
The principle of competitive protein binding (T 4 -CPB) is
the basis for the now standard radioimmunoassay for all
hormones including T 4 and T 3 . The method is based on
the competitive binding of TBG for patient T 4 and 131 I-
labeled T 4 . The 131 T 4 and patient T 4 bind to the TBG in
proportion to their concentrations so that labeled T 4 binding
is inversely proportional to patient T 4 concentration.