No role for tri-iodothyronine (T3) testing in the assessment of levothyroxine (T4) over-replacement in hypothyroid patients

Abstract

ABSTRACTTri-iodothyronine (T3) is a sensitive marker of endogenous hyperthyroidism. In levothyroxine (T4)-induced hyperthyroidism, there is no reason for T3 to be elevated, but this test is often requested in over-treated hypothyroid patients. This study investigated how informative T3 levels are in these patients. Our hypothesis is that T3 measurement would not add anything to the assessmentof T4 over-replacement in primary hypothyroidism. Over a 15-week period, consecutive thyroid functiontest requests in patients on levothyroxine had T3 levels measured if thyroidstimulating hormone (TSH) was below th reference range (RR; <0.27 miu/L) and free T4 was within or above the RR (12–22 pmol/L). Those with fully suppressed TSH (<0.02 mu/L) and high free T4 (>27 pmol/L) were defined as being over-replaced, while those with low, but measurable TSH and a normal free T4 were defined as unlikely to be overreplaced (control group). Receiver operating characteristic (ROC) curve analysis was used to assess the discriminant power of T3 to detect over-replacement. Of the 542 patientsexamined, 33 were included in the over-replaced group and236 patients in the control group. A total of 273 patients wereexcluded for not fulfilling the criteria for either of thesegroups. In the over-replaced group, none had a raised T3.The most discriminant T3 level, using ROC curve analysis, was 1.6 nmol/L (RR=1.3–2.6 nmol/L), with a corresponding sensitivity and specificity of 58% and 71%, respectively (P=0.16). T3 levels bear ittle relation to thyroid status in patients on levothyroxine replacement, and normal levels can be seen in over-replaced patients. Measurement of T3 in this situation is of doubtful clinical value.What’s already known about this topic?: Thyroid function tests are the way that adequacy of levothyroxine replacement is determined. Where the test is available, T3 is often requested together with T4 and TSH by clinicians. The question is whether T3 measurement adds any further information.What does this article add?: The presented data supports the position that T3 measurement does not add anything tothe interpretation of thyroid hormone levels in subjects with hypothyroidism on levothyroxine replacement therapy. Unnecessary testing could be avoided if this were more widely appreciated. In addition,over-replacement, with its attendant risks, would be more readily recognised and not wrongly excludedon the basis of a falsely reassuring normal T3 result.