Thyroid uptake of radioactive isotopes of iodine or technetium may be counted by a special radiation detector that produces a visual overall pattern of gland radioactivity. This permits visual localization of areas that may be hyperactive or hypoactive. Thyroid scan has two major applications:

1. In patients with hyperthyroidism, the scan can differentiate between diffuse hyperplasia and a hyperfunctioning nodule (“toxic nodule”), entities that require different treatment. In addition, occasionally patients with symptoms of hyperthyroidism have chronic lymphocytic thyroiditis. Serum T4 and T3 levels are frequently elevated. Both elevated and low 24-hour RAIU values have been reported. Early (2-6 hours) RAIU values may be elevated more frequently than the 24-hour uptake. Thyroid scan frequently has a rather characteristic nonuniform appearance that can be helpful in suggesting the diagnosis. Factitious (self-medication) hyperthyroidism and subacute thyroiditis usually are associated with a low RAIU value in conjunction with an elevated T4 level (falsely low RAIU due to excess iodine or previous antithyroid therapy must be excluded).

2. In patients with a palpable thyroid nodule, the scan may demonstrate lack of radioactivity in that area (“cold” nodule), suggesting a lack of functional activity that would increase suspicion of carcinoma. Most reports agree that a hyperfunctioning nodule is rarely malignant. Single nonfunctioning nodules have a 10%-20% incidence of malignancy. Truly nonfunctioning nodules are much more likely to be malignant than nodules that retain some function. At times, however, normal thyroid tissue above or below a nodule may contribute some degree of apparent function to a nonfunctioning area. However, there is some controversy over the usefulness of thyroid scanning in the evaluation of thyroid nodules for possible malignancy (see Chapter 33).

Thyroid-stimulating immunoglobulin (TSI) assay

A group of immunoglobulins (antibodies) of the IgG class that could prevent binding of TSH to TSH receptors on the thyroid cell membrane were discovered. The antibody also has the ability to stimulate adenylate cyclase to produce cyclic AMP production, which causes release of T4 and T3. The antibody can exert effect over a relatively prolonged period of time. The antibody was originally named “long-acting thyroid stimulator” (LATS) and was measured with a bioassay system (McKenzie) using mouse thyroid. The LATS was considered to be fairly specific for Graves’ disease, although it was also found in a few patients with Hashimoto’s disease and occasionally in low titer in some other conditions. It could be detected in only 40%-45% (range, 9%-55%) of patients with Graves’ disease. It was present more frequently when the patients had pretibial edema or hyperthyroidism with eye signs (but it was found in only about 15% of patients with so-called isolated Graves’ ophthalmopathy). The titer tended to decrease after 6-12 months of clinically active disease, after treatment was given, or when the disease became inactive. There was not a close relationship between titer and severity of illness.

It was subsequently found that LATS would bind to human thyroid tissue but could not stimulate it, so that the antibody was renamed “mouse thyroid stimulator.” In addition, once serum containing LATS was incubated with human thyroid tissue, that serum no longer showed any LATS activity in the McKenzie mouse bioassay (i.e., the LATS activity was destroyed or neutralized).

More recently, other related IgG antibodies were found that prevented adsorption of LATS onto human thyroid tissue and (as a group) was therefore called “LATS protector.” This abnormal IgG antibody (or antibodies) can be demonstrated by three different assay techniques. One technique used high-titer LATS antibody as the indicator system whose endpoint was to show that antibody in patient serum blocked uptake of the LATS antibody by human thyroid tissue; since the LATS antibody activity in the McKenzie bioassay would be neutralized by human thyroid tissue and the patient antibody prevented such neutralization, the patient antibody was called LATS protector antibody. A second technique measured the ability of patient antibody to inhibit or block the binding of radioactive TSH to human or animal thyroid acinar cell membranes. This has been called the “TSH-binding inhibiting immunoglobulin” (TBII) assay. The third technique measured the ability of the antibody to stimulate human or animal thyroid acinar cell membrane-bound adenylate cyclase, producing increased cyclic adenosine monophosphate (AMP) activity. The original assay method used human thyroid tissue, so the antibody was originally called “human thyroid-stimulating immunoglobulin.” Since animal thyroid tissue can be used, the assay now is simply called “thyroid-stimulating immunoglobulin” (TSI). For example, one modification of the TSI uses special TSH-dependent FRTL-5 rat tissue culture thyroid cells.

The LATS-protector assay is reported to detect about 75%-80% (range, 60%-90%) of patients with Graves’ disease. The LATS-protector assay was very complicated; few laboratories performed the assay and few if any do now. The TBII technique is reported to detect about 70%-80% (range, 39%-100%) of Graves’ disease, and the TBI detects about 75%-80% (range, 18%-100%). Neither the TBII nor the TBI are simple or easy. Most laboratories using either technique use “homemade” reagents, which accounts for much of the great variation in sensitivity reported in the literature. Since many nonresearch laboratories base their test performance claims on data from one or more research laboratories using the same technique but their own reagents, performance claims based on someone else’s results may not be valid. Therefore, it is desirable to send specimens to laboratories that can verify better sensitivity based on adequate numbers of well-diagnosed patients with Graves’ disease that they assayed themselves. Besides sensitivity, it is necessary to question specificity, since different laboratories may find different numbers of false positive results when patients with hyperfunctioning thyroid nodules, nonfunctioning nodules or goiter, thyroiditis, autoimmune disorders, and clinically normal status are tested.

At present, TSI assay is used mainly for patients with borderline or conflicting evidence of Graves’ disease, patients who have some condition that affects the results of other tests, or patients who have “isolated Graves’ ophthalmopathy” (a condition in which all standard thyroid tests are normal). However, a negative test result in most laboratories does not completely exclude the diagnosis, and there is a possibility of false positive results.