Variations in major
thyroid hormone transport proteins may be inherited or acquired and may be associated with changes in serum concentration of the
proteins or their affinity for
thyroid hormones. These variations most frequently involve
thyroxine-binding globulin (TBG), but changes in
transthyretin and
albumin are also observed. The consequent alteration of
thyroid hormone-binding capacity in serum is associated with variations in total
thyroid hormone concentration. Increased serum total
thyroid hormone levels are found in subjects with TBG excess,
familial dysalbuminemic hyperthyroxinemia, and
transthyretin-associated
hyperthyroxinemia. Conversely, diminished serum
thyroid hormone values are observed in subjects with
TBG deficiency, and decreased concentration or affinity of
transthyretin and
albumin is not associated with variations in serum concentrations of
thyroid hormones. The
transport protein-associated variations in serum total
thyroid hormone concentrations do not reflect a change in thyroid status. Euthyroidism can be easily established in subjects with
transport protein abnormalities by the normal free
thyroid hormone and TSH concentrations. It is, however, crucial to select methods for free
thyroid hormone measurement that are not affected by abnormalities of
transport proteins. Some assays, such as the analog method, often provide artifactual and misleading results, which may lead to inappropriate and even detrimental treatments. The evolutionary advantage of TBG (and
albumin) in terms of thyroid homeostasis still remains to be elucidated.