Diagnosing hypothyroidism and hyperthyroidism
  Serum TSH and free T4 estimates are altered more frequently by non-thyroidal illnesses than by thyroid diseases in sick patients (9). Serum TSH values may be transiently increased or reduced without reciprocal changes in free T4 values, and free T4 values by direct equilibrium dialysis are frequently elevated without reductions in TSH, and may be artifactually reduced in critically ill patients and those with end-stage renal failure without elevations of serum TSH levels (8,10). Thus, in sick patients, serum TSH levels may not reflect thyroid hormone status or bioactive TSH. Elevated free T4 levels may be secondary to reduced transfer of T4 from serum to tissue sites and relatively reduced T4 clearance rates, and not to increased T4 production rates. Conversely, reduced free T4 values may reflect in vitro artifacts in methods which employ serum dilution or dialysis. In vitro reductions of free T4 values may result in misdiagnosis of central hypothyroidism. Thus, a working knowledge of the performance of free T4 methods in sera from patients with nonthyroidal illnesses is essential to accurately interpret these test values. Serum reverse T3 levels do not reliably differentiate sick hypothyroid patients from euthyroid sick patients (11), and are not clinically useful. Currently, measurement of serum TSH and a free T4 estimate, and careful clinical evaluation, are used to assess thyroid hormone status in patients with nonthyroidal illnesses (Figures 1 and 2) (12). The primary clinical goal is to accurately diagnose hypothyroidism or hyperthyroidism in patients with concurrent nonthyroidal illnesses, and to initiate specific treatment to minimize morbidity and potentially mortality related to concurrent hypothalamic, pituitary, or thyroid disease.

Figure 1:



* Probably hypothyroid - remove precipitating factor or initiate L-thyroxine therapy

**Free T4 values by direct equilibrium dialysis may be reduced in euthyroid patients with the low T4 state of nonthyroidal illness and in end-stage renal failure. Further evaluations to rule out the causes of hypothyroidism listed should be undertaken. In acute nonthyroidal illnesses, thyroid function should be re-assessed after recovery.



Figure 2:



* Probably hyperthyroid, initiate therapy. A second-generation TSH assay has a 20% inter-assay coefficient of variation between a TSH level of 0.1 and 0.2 mU/l.

A third-generation TSH assay has a 20% inter-assay coefficient of variation between a TSH level of 0.01 and 0.02 mU/l.

Free T4 and free T3 estimates are confirmatory tests. Values may be reduced by some methods in severely ill patients despite hyperthyroidism, and free T4 values may be increased by many methods in sick patients without hyperthyroidism.