Serum is the sample required for all feline thyroid hormone tests at the MSU VDL. The standard feline thyroid profile (20015) includes total T4 (TT4), total T3 (TT3) and free T4 (fT4). Free T4 is analyzed at the MSU VDL as either a direct serum method or by equilibrium dialysis (fT4D). A free T4 by equilibrium dialysis measurement includes a step which filters out interfering proteins followed by an ultrasensitive radioimmunoassay (RIA) and is included in the premium feline profile (20016). Please see special handling recommendations in the test catalog when preparing and shipping samples for premium profiles.

Feline profiles can also be ordered to include measurement of thyroid stimulating hormone (TSH). The current method of measuring TSH on feline samples at the MSU VDL is by chemiluminescent assay developed for canine samples which has been validated for use on feline serum. The standard feline profile + TSH (20012) includes TT4, TT3, fT4 and TSH. The premium feline profile + TSH (20013) includes TT4, TT3, fT4 by equilibrium dialysis (fT4D) and TSH.

For cats with a high degree of clinical suspicion (appropriate signalment, consistent clinical signs of hyperthyroidism, and a palpable thyroid nodule), documentation of a significantly increased TT4 concentration alone may support a diagnosis of hyperthyroidism (TT4 as a standalone test is not offered through MSU VDL). However, cats with early hyperthyroidism and/or nonthyroidal illness can be challenging to diagnose by clinical signs and TT4 alone. The feline thyroid profile includes multiple measurements of thyroid hormone concentrations which can help develop confidence in (or exclusion of) a differential diagnosis of hyperthyroidism. Significant increases of all thyroid hormone concentrations support a diagnosis of hyperthyroidism.

Low thyroid hormone concentrations may be seen in cats with significant nonthyroidal illness. Hyperthyroid cats with concurrent nonthyroidal illness may have TT4 “suppressed” into the reference interval, but usually TT4 will remain within the upper half of the interval.

Total T3 can be within the reference interval in cats with early or mild hyperthyroidism. Cats with advanced hyperthyroidism would be expected to have an increase in TT3 along with significantly increased TT4 and free T4. A decrease in TT3 as the standalone abnormality on a profile is of equivocal clinical significance.

In hyperthyroid cats with nonthyroidal illness, free T4 can remain increased even when TT4 is suppressed into the reference interval. An increased free T4 or free T4 by equilibrium dialysis with a high-normal TT4 concentration leaves open the possibility of hyperthyroidism in a cat with clinical suspicion. However, a falsely increased free T4 is occasionally detected in euthyroid cats with nonthyroidal illness. Therefore, free T4 is not specific for hyperthyroidism, and false positives have been known to occur when free T4 is used as a standalone test for hyperthyroidism.

Additionally, exposing the serum to warm temperatures and/or prolonged shipment can falsely increase free T4 concentrations due to degradation of binding proteins. Increased plasma concentrations of free fatty acids in some feline hyperlipidemic and negative energy balance states can also displace T4 from binding proteins and result in increased measured free T4. Erroneously high free T4 by equilibrium dialysis results can occur with manufacturing defects affecting the dialysis membrane.

Samples with suspect free T4 by equilibrium dialysis results are reanalyzed before verification of results as one of the many quality control steps of the MSU VDL to avoid releasing spurious results related to faulty assay components.

The majority of cats with hyperthyroidism will have a TSH concentration that suppresses to a value at or below 0.03 ng/mL on the TSH assay utilized at the MSU VDL. However, a low TSH result, while consistent with hyperthyroidism, is not specific for hyperthyroidism as some euthyroid cats will have a TSH result below the level of detection of the assay. A TSH concentration in the upper half of the reference interval would decrease suspicion for hyperthyroidism.

Interpretation of thyroid hormone results should take into consideration the clinical picture and other diagnostic test results. In cats, in which individual thyroid hormone concentrations can result as either high or low in the face of nonthyroidal illness, confidence in clinical signs and elimination of other differential diagnoses is critical. When results are incongruent and clinical signs are vague, other nonthyroidal illness may be present or early hyperthyroidism remains a possibility, a conservative strategy would be to repeat testing in a few weeks to months. In some situations, additional specialized testing such as a thyroid scintigraphy study may be considered depending on availability. Performing a T3 suppression test, which does not require specialized equipment or referral, can also be considered in the primary care practice.

The feline T3 suppression test is a thyroid function test used to determine if the production of thyroid hormones is “suppressible” by the administration of exogenous T3. A baseline serum sample is obtained, centrifuged, separated, labeled, and frozen until shipment. Synthetic T3 (liothyronine, Cytomel®) is administered orally at a dose of 25 ug every 8 hours for 2 days (6 or 7 pills total) with the last dose given 2 to 4 hours prior to obtaining the post sample. Both pre and post samples are submitted. The first step in interpretating the results is to confirm that the TT3 concentration in the post sample is higher than the pre sample, documenting that exogenous T3 was administered and absorbed. The second step in interpreting the results is to compare the pre TT4 and free T4 to the concentrations in the post sample. Cats with hyperthyroidism would be expected to have little to no suppression of TT4 and free T4.

When investigating the possibility of congenital hypothyroidism in kittens, spontaneous hypothyroidism in adult cats, or iatrogenic hypothyroidism as a result of treatment for hyperthyroidism, a profile which includes thyroid stimulating hormone (TSH) should be ordered.

Low thyroid hormone concentrations may be seen as a metabolic response to nonthyroidal illness; however, these cases typically do not have an increased TSH concentration. The presence of generally low circulating thyroid hormone concentrations with concurrent increase in TSH supports a diagnosis of primary hypothyroidism. There is evidence indicating young normal kittens may exhibit transient increases above adult reference ranges for serum T4 and free T4. Therefore, thyroid hormone concentrations near the low end of the adult reference interval with an elevated TSH in a young kitten with clinical signs of hypothyroidism can still support a diagnosis of primary congenital hypothyroidism.

Profiles which include TSH can also be helpful when evaluating the possibility of subclinical hypothyroidism (defined as normal thyroid hormones with an increase in TSH) following radioiodine therapy or when there is concern for the possibility of over suppression with methimazole administration.

The interpretation of thyroid profile results when thyroxine replacement therapy is being administered will depend on the interval post-pill at which the sample was obtained. In most cases, obtaining the sample at 3 to 4 hours post pill (considered to be near-peak absorption) is the most frequently utilized post-pill interval. Therapeutic concentrations at this time period would be expected to be near the upper end of the reference interval.

Thyroid hormone results in an adult cat above the upper end of the reference interval increases concern for excessive supplementation (particularly if TSH is nondetectable), but a high peak result may be acceptable in young kittens. There is evidence indicating young normal kittens may exhibit transient increases above adult reference ranges for TT4 and free T4 concentrations.

In patients receiving once daily administration, a sample obtained near 12 hours post-pill would be expected to provide an “average” daily result. A profile which includes TSH can be helpful in cats receiving replacement therapy as TSH in most patients will be suppressed to within the reference interval if therapy is sufficient.

There is a small subset of cats with iatrogenic hypothyroidism following radioiodine therapy and kittens with congenital hypothyroidism who respond clinically to replacement therapy and exhibit adequate absorption of thyroxine, but the TSH result remains persistently increased. It is unknown if normalization of the TSH result is required for optimal response to thyroxine supplementation in all cases, and it may not be advisable to continue dose increases in pursuit of a “normal” TSH result. It is critical to consider the clinical response in conjunction with thyroid hormone concentration measurements when making therapeutic decisions.