T4 Update and Review with IVS New Methodology

Sonjia Shelly, DVM, DAVCP Clinical Pathologist, IVS Sacramento
May 2000

On May 8, 2000, IDEXX Veterinary Services changed all thyroid testing to a method known as chemiluminesence. This Diagnostic Update provides a general review of interpretation of canine and feline thyroid results.

Before our review, we need to let our clients know that our new methodology does require more serum for T4 testing than the previous method, and consequently more serum from the patient.

When you request a full chemistry panel including T4, please submit a minimum of 0.75 cc of serum. Additional tests (heartworm, FeLV, etc.) require more volume. We recommend that you plan to obtain serum volume above this minimum to allow for add-on tests and/or rechecks.

We are exploring software and instrument changes to reduce this requirement as we understand the limitations you sometimes face in collecting the sample.

General Interpretation of T4 Levels

Your IVS laboratory report includes reference values for normal, healthy, adult patients not on medication. Statistically, 95% of normal dogs and cats will fall into these normal reference ranges. And, statistically, there will be an occasional pet to have a result slightly outside the reference range that still will be "normal." At the same time, on occasion a patient affected by disease (in this case, hyperthyroidism or hypothyroidism) will have a result that falls within the normal range. Because of these statistics, you need to look at all clinical signs and history in order to make a proper diagnosis.

Canines: Goals of Hypothyroidism Therapy

One of the primary goals of post-pill monitoring in canines is to determine that the patient is indeed absorbing the medication. Then, much of monitoring is checking for clinical improvement. Begin your monitoring 2-4 weeks after therapy has begun. Dogs should display increased mental alertness, activity and muscle strength within the first 1-2 weeks of supplementation. Improvement in skin condition and re-growth of hair frequently does not appear until 4-6 weeks or more after therapy has begun.

Notes on Hypothyroidism Administration and Monitoring
Expect to find wide variability in "post-pill" T4 levels due to the wide variability in plasma half-life, and drug preparations, time-to-peak absorption, and absorptive capability of the patient. Remember also that drawing blood 4-6 hours after the medication has been given provides a value at only one time point. The T4 level most likely will decrease from that value over the next several hours.

Specifically, the half-life of thyroid medication ranges from 5.5-11.7 hours for patients on BID dosage, and from 3.1-15 hours for patients on SID supplementation. Therefore, on the correct supplementation dosage for a particular patient, if you check the T4 level just prior to the next dose ("trough time"), the result should be in the normal range. If you check the T4 level 4-6 hours post-pill (approximate "peak absorption"), the result should be in the upper end of, or above, the reference range. If you are not able to achieve these results and see no improvement in the patient, either increase the dosage, frequency of dosing, or consider changing brands of therapy to find better absorption.

In our experience, for most dogs on supplementation T4 levels at "peak absorption" will fall between 2.0 - 7.0 g/dl. Some dogs will have post-pill T4 values up to 8 g/dl and not exhibit signs of hyperthyroidism. Values >8 g/dl are probably too high and warrant decreasing the dose.

Feline Interpretation of T4 Levels

For general screening in cats, the T4 value will usually fall within the reference range (again 95% of the time). In the presence of other disease, some cats will have a T4 result below the reference range. Some older cats with chronic or inflammatory disease may have a T4 in the reference range but still be hyperthyroid. The disease state is suppressing T4 production. In these cases, a T3 suppression test or free T4 by equilibrium dialysis are additional laboratory tests that can be performed to determine hyperthyroidism.

Notes on Administration and Monitoring with Methimazole or Radiation Therapy
The goal of cats treated for hyperthyroidism either with methimazole or radiation is to return the T4 result to the normal reference range. Most cats will have normal to low T4 values after 2-3 weeks of methimazole therapy. The ultimate goal of radioiodine therapy is to restore the pet to euthyroidism.

Methimazole concentrates in the thyroid tissue and blocks synthesis of thyroid hormone. Daily dosage is required to control the hyperthyroid state. T4 values return to high levels in 24-72 hours after medication stops. For long-term therapy, the lowest daily dose that maintains the serum T4 concentration in the low normal range is recommended. We recommend keeping the value in the low normal range to assure controlling the condition. In some cases T4 values below the reference will occur. In these patients, the dose should be lowered (and monitored at 2-4 week intervals) until the T4 value returns to low normal. Signs of hypothyroidism are very uncommon.

In cats treated with radioiodine, T4 values are often subnormal for a few weeks. We recommend testing by free T4 by equilibrium dialysis, which usually show results within the reference range.

Following unilateral thyroidectomy, T4 levels usually fall to subnormal for 2-3 months following surgery, but supplementation is generally not required in these patients. Thyroid supplementation may or may not be necessary in patients who have had bilateral thyroidectomy.

We hope we've provided you with valuable information on thyroid testing at our laboratories. If you have any further questions, please give us a call.

References:

Feldman, E.C. and Nelson, R.W.: Canine and Feline Endocrinology and Reproduction. 2nd ed.1996. Ettinger, S.J. and Feldman, E.C.: Textbook of Veterinary Internal Medicine 5th ed. 2000.