Thyroid function tests and the effects of drugs

The assessment of thyroid function by laboratory testing began in about 1934 with the measurement of oxygen consumption or basal metabolic rate. Twenty years later measurement of protein-bound iodine became the standard technique and after a further 20 years this assay was superseded by radioimmunoassays of thyroxine (T₄) and triiodothyronine (T₃). Radioimmunoassays for thyroid-stimulating hormone (TSH) were reported from 1965, but early techniques could not distinguish normal values from the suppressed levels found in thyrotoxicosis. Until about 1990 this distinction was made by the administration of intravenous thyrotropin-releasing hormone (TRH), which fails to increase TSH to measurable levels in thyrotoxicosis, while producing a clear 5- to 15-fold increase in serum TSH in euthyroid subjects with normal pituitary function. Immunometric TSH assays now allow the suppressed serum TSH levels of thyrotoxicosis to be clearly distinguished from normal. This fundamental advance has coincided with the development of ingenious techniques to estimate the minute fraction of total serum T₄ that circulates in the unbound state, but even the best free T₄ methods offer only a marginal diagnostic advantage over the measurement of total T₄, e.g. when the concentration of thyroxine-binding globulin (TBG) is abnormal. Current enthusiasm for free T₄ and T₃ estimation needs to be tempered by an understanding of the method-dependent limitations of these techniques, particularly in situations where assessment of thyroid function is most difficult (see below).