A serum thyroid panel reveals an increase in total T4, normal TSH, and normal free T4. What is the most likely cause of these results?

The presence of an increased total T4 level, coupled with normal levels of TSH and free T4, strongly indicates an increase in thyroxine-binding proteins rather than an intrinsic issue with thyroid hormone production. In this scenario, the total T4 reflects both the free hormone and the hormone that is bound to transport proteins.

When there is a rise in thyroxine-binding proteins—such as during pregnancy or due to the use of certain medications—it can lead to an increased total T4 measurement, while the actual amount of free T4 available for metabolic activity remains unchanged. This maintains the normal levels of TSH and free T4 because the feedback mechanisms regulating thyroid function are unaffected by changes in binding proteins.

In contrast, primary or secondary hyperthyroidism would typically show elevated TSH levels, or abnormalities in free T4 measurements because they represent an actual increase in hormone production rather than a change in binding capacity. Similarly, subclinical hypothyroidism would not account for the increased total T4 without impacting TSH and free T4 levels. Thus, the explanation aligns perfectly with the notion of a euthyroid state paired with increased thyroxine-binding proteins, making this the most plausible cause of the observed results.