PERSISTENT PROBLEMS WITH THE SPECIFICITY OF IMMUNOMETRIC TSH ASSAYS

Sensitive immunometric TSH assays have led to improved diagnosis of th yroid function abnormalities, and serum TSH is often used as the initi al screening method for evaluation of thyroid function. Shortly after the marketing of the first of these assays, it was discovered that som e sera contained heterophilic antibodies leading to spuriously high TS H values. This problem is considered to be solved by modifications of the assays. We have, however, found that these assays may still give n onspecific results. A panel of sera from 63 patients with untreated hy perthyroidism (51 Graves' disease, 12 Plummer's disease) were used for evaluation of 6 different TSH assays (BeriLux, Spectria, London, Amer lite, Delfia, Delfia Ultra). Several problems were encountered. Most i mportantly, although all 63 sera gave totally suppressed TSH values in at least one of the assays, many sera gave clearly and reproducibly m easurable values in one or more assays. Eleven sera gave values of mor e than 0.10 mU/L (6 more than 0.40 mU/L) in at least one assay. The pa ttern of nonspecific values was different in all 6 assays. TRH stimula tion did not alter the measured values. Addition of 10% mouse serum to the patient sera gave unpredictable alterations with lower TSH measur ements in one assay, but unaffected values in other assays. Hence a me asurable serum TSH alone does not always exclude primary hyperfunction of the thyroid. Nonspecific TSH values are the most common cause of n onsuppressed TSH in hyperthyroidism and should be considered before ot her causes, such as pituitary TSH producing neoplasms or pituitary res istance to thyroid hormone.