Thyrotropin stimulation test. In some patients with myxedema, the question arises as to whether the etiology is primary thyroid disease or a malfunction secondary to pituitary deficiency. Normally, administration of TSH more than doubles a baseline RAIU or T4 value. Failure of the thyroid to respond to TSH stimulation strongly suggests primary thyroid failure, whereas normal gland response implies either a pituitary or hypothalamic problem or else some artifactual abnormality in the original screening tests. The same procedure can be used to confirm the diagnosis of primary hypothyroidism, since the thyroid should not be able to respond to TSH. The test may be helpful in patients who have been on long-term thyroid hormone treatment and who must be reevaluated as to whether the original diagnosis of hypothyroidism was correct. The TSH stimulation test can be done while thyroid hormone is still being administered, whereas it would take several weeks after cessation of long-term therapy for the pituitary-thyroid relationship to reach pretherapy equilibrium. An occasional use for TSH stimulation is to see whether parts of the thyroid that are not functioning on a thyroid scan are capable of function (versus being not capable of function or being suppressed by hypersecretion from other thyroid areas).

Drawbacks. The TSH stimulation test is performed using bovine TSH. Some persons form antibodies against this material that may interfere with future TSH assay or produce allergic reaction if TSH is used again. Therefore, the test is infrequently used today. To avoid this potential problem, some investigators use a T3 withdrawal test rather than TSH stimulation. A potential problem using RAIU in TSH stimulation tests is some correlation of patient iodine status to degree of RAIU response to TSH. In general, as iodine deprivation increases, RAIU response also increases; iodine overload decreases the RAIU response.

Triiodothyronine withdrawal test. The patient is placed on T3 therapy for 1 month (instead of other therapy). The T3 is then discontinued for 10 days, after which a serum TSH assay is performed. With medication containing T4 it is necessary to wait at least 4 weeks after withdrawal before routine thyroid function tests (T4, T3, TSH), are performed to allow the thyroid-pituitary-hypothalamic feedback system to regain normal equilibrium. After T3 withdrawal, it takes only 10 days to achieve the same effect. If the patient has primary hypothyroidism, the serum TSH level will be elevated after 10 days without T3. In euthyroid persons or those with secondary and tertiary hypothyroidism, the TSH level will be normal or decreased. The major drawbacks to this procedure are the long time intervals necessary and the fact that not enough experience with this test has been reported to ascertain how many exceptions or false results may be expected. This test also is rarely used today.

Thyroid suppression test. This is frequently called “T3 suppression,” although T4 could be used instead of T3, and the pituitary rather than the thyroid is the actual organ directly suppressed by T3 administration (the thyroid is affected secondarily). A standard dose of T3 is given daily for 1 week. In normal persons, exogenous T3 (added to the patient’s own T4) suppresses pituitary secretion of TSH, leading to a decrease in patient thyroid hormone manufacture. Values of RAIU or T4 after T3 administration drop to less than 50% of baseline. In hyperthyroidism, the thyroid is autonomous and continues to manufacture hormone (with little change in RAIU or T4 level), although the pituitary is no longer stimulating the thyroid. The suppression test is thought to be very reliable in confirming borderline hyperthyroidism, although there are reports that 25% or more of patients with nontoxic nodular goiter may fail to show suppression. The same basic technique may be used in conjunction with the thyroid scan to demonstrate that a nodule seen on original scan is autonomous. This may be helpful, since reports indicate that 50%-80% of toxic nodular goiter patients have normal RAIU values and many have normal T4 test results. The procedure must be used with caution in elderly persons or patients with cardiac disease. The T3 suppression test has been largely replaced by the TRH test.