Page 807 - Small Animal Internal Medicine, 6th Edition

CHAPTER 48 Disorders of the Thyroid Gland 779

times the baseline serum T 4 concentration. Reconstituted Testing for serum T 4 or Tg autoantibodies is indicated in
rhTSH can be stored at 4° C for 4 weeks and at −20° C for dogs with unusual serum T 4 values. T 4 autoantibodies may
VetBooks.ir 8 weeks without loss of biological activity (De Roover et al., interfere with RIAs used to measure serum T 4 concentrations
and yield spurious and possibly unreliable values. Similar
2006).
Antibody Tests for Lymphocytic Thyroiditis interference does not occur with chemiluminescence immu-
noassay (Piechotta et al., 2010). The type of interference
Circulating thyroglobulin (Tg) and thyroid hormone (T 3 and depends on the separation system used in the RIA. Most T 4
T 4 ) autoantibodies correlate with the presence of lympho- RIAs use a single-step separation system with antibody-
cytic thyroiditis in dogs. Tests for the presence of Tg, T 3 , coated tubes, which results in falsely increased T 4 values.
and T 4 autoantibodies in the serum of dogs can be used to Fortunately, spurious T 4 values resulting from clinically rel-
identify lymphocytic thyroiditis, to explain unusual serum evant concentrations of thyroid hormone antibody account
T 4 test results, and possibly to serve as a genetic screening for less than 1% of such results from commercial endocrine
test for hypothyroidism caused by lymphocytic thyroiditis. laboratories. The effect of T 4 autoantibodies on serum fT 4
Autoantibodies predominantly develop against Tg. T 3 and results is dependent on the fT 4 assay used (see Baseline
T 4 are haptens and are not antigenic by themselves. Tg is Serum fT 4 Concentration, p. 776).
the protein that provides the antigenic stimulus. Because
T 3 and T 4 are attached to the Tg molecule, autoantibodies FACTORS AFFECTING THYROID GLAND
develop against them as well. Dogs with T 3 and T 4 autoan- FUNCTION TESTS
tibodies typically have autoantibodies against Tg, but the Many factors affect baseline thyroid hormone and endog-
converse is not true. As such, the better screening test for enous TSH concentrations (see Table 48.2). Unfortunately,
lymphocytic thyroiditis is the Tg autoantibody test. ELISAs most of these factors decrease baseline thyroid hormone
for detection of Tg autoantibodies are sensitive and specific concentrations and may increase endogenous TSH in
for identification of Tg autoantibodies in dogs and are com- euthyroid dogs, potentially causing misdiagnosis of hypo-
mercially available. Results are reported as negative, positive, thyroidism if the clinician accepts the results out of context.
and inconclusive. The factors that most commonly result in lower baseline
A positive Tg autoantibody test suggests the possibility of thyroid hormone concentrations in euthyroid dogs are
lymphocytic thyroiditis but does not provide information on nonthyroidal illness (i.e., euthyroid sick syndrome), drugs
the severity or progressive nature of the inflammatory (especially glucocorticoids, phenobarbital, and sulfonamide
process. Positive Tg autoantibody test results may remain antibiotics; see Table 48.2), and variation in the reference
positive or may revert to negative on subsequent testing. Tg range between breeds (most notably sighthounds and
autoantibody is not a thyroid function test. Positive results Nordic breeds).
increase the suspicion for hypothyroidism if serum T 4 and
fT 4 concentrations are low but have no bearing on generation Nonthyroidal Illness Syndrome (Euthyroid
of clinical signs if serum T 4 and fT 4 concentrations are Sick Syndrome)
normal. Tg autoantibodies should not be used alone in the Nonthyroidal Illness Syndrome (NTIS), historically referred
diagnosis of hypothyroidism. Dogs with confirmed hypothy- to as euthyroid sick syndrome, refers to suppression of
roidism can be negative, and euthyroid dogs can be positive serum thyroid hormone concentrations in euthyroid dogs in
for Tg autoantibodies. Identification of Tg autoantibodies response to concurrent illness. A decrease in serum thyroid
would support hypothyroidism caused by lymphocytic thy- hormone concentrations may result from a decrease in TSH
roiditis if the dog has clinical signs, physical findings, and secretion secondary to suppression of the hypothalamus
thyroid hormone test results consistent with the disorder. or pituitary gland, from decreased synthesis of T 4 , from
Positive serum T 4 and T 3 autoantibody test results are inter- decreased concentration or binding affinity of circulating
preted in a similar manner. binding proteins (e.g., thyroid binding globulin), from the
The value of serum Tg autoantibodies as a marker for presence of serum protein binding inhibitors, from inhibi-
eventual development of hypothyroidism remains to be clar- tion of the deiodination of T 4 to T 3 , from increased hepatic
ified. A 1-year prospective unpublished study performed by metabolism and excretion of T 4 , or from any combination of
Graham et al at Michigan State University found that these factors. The subsequent decrease in serum total T 4 and,
approximately 20% of 171 dogs with positive Tg autoanti- in many cases, fT 4 concentrations is believed to represent a
body and normal fT 4 and TSH test results developed changes physiologic adaptation by the body, with the purpose being
in fT 4 , TSH, or both test results consistent with hypothyroid- to decrease cellular metabolism during periods of illness. It
ism; 15% reverted to a negative Tg autoantibody test with no is not indicative of hypothyroidism, per se. Generally, the
change in fT 4 and TSH test results; and 65% remained Tg type and magnitude of most alterations in serum thyroid
autoantibody positive or had an inconclusive result with no hormone concentrations are not unique to a specific disorder
change in fT 4 and TSH test results 1 year later. Currently, a but reflect the severity of the illness or the catabolic state and
positive Tg autoantibody test is considered suggestive of appear to represent a continuum of changes. Systemic illness
lymphocytic thyroiditis and supports retesting of thyroid has more of an effect in lowering serum thyroid hormone
gland function in 3 to 6 months. concentrations than do, for example, dermatologic disorders.