Thyroid testing
1. What is the single best test to screen for abnormal thyroid gland function?
Serum thyroid-stimulating hormone (TSH) measurement is the best test for assessing thyroid function because the vast majority of cases of thyroid dysfunction are due to primary thyroid disease, to which the pituitary gland responds with predictable changes in TSH secretion. TSH levels are misleading, however, when thyroid dysfunction results from pituitary or hypothalamic disease and in patients with non-thyroidal illnesses. Measurement of serum thyroxine (T4) and triiodothyronine (T3) are useful when the TSH level is outside the reference range.
2. How do you interpret the serum TSH level?
When the TSH is elevated, the patient almost always has primary hypothyroidism; when the TSH is low, the patient usually has primary hyperthyroidism. Abnormal serum TSH values reflect mild thyroid dysfunction long before serum T4 and T3 levels are outside their reference ranges. Exceptions to these rules occur in patients who have pituitary-hypothalamic disorders or non-thyroidal illnesses. Measurement of serum free T4 should be performed whenever the TSH level is high; both free T4 and total T3 (or free T3 by equilibrium dialysis) values are often informative when the TSH is low.
3. Explain how the serum TSH is used to manage patients undergoing thyroid hormone therapy.
Thyroid hormone therapy is usually given to patients for one of two purposes, replacement therapy for hypothyroidism or suppression therapy for thyroid cancer. When replacement is the goal, the dosage should be adjusted to maintain the serum TSH level within the reference range. When suppression is the goal, the dosage should be adjusted to keep the serum TSH level low normal or slightly low for most patients and to keep it “undetectable” for those with aggressive or metastatic thyroid cancer.
4. Discuss the advantages of free thyroid hormone assays.
Free T4 and T3 assays determine the amounts of unbound, bioactive thyroid hormones in the circulation. Free thyroid hormone measurements fall into two main categories: equilibrium dialysis and analog assays. Equilibrium dialysis methods are more accurate because they are not affected by serum thyroid hormone–binding protein abnormalities. Analog methods, which are used by most commercial laboratories, are variably affected by protein binding. Currently, free T4 assays are considered reasonably good, but the accuracy of commercially available free T3 assays remains questionable. This is why many experts still prefer total T3 over free T3 measurements.
5. What do total T4 and T3 assays measure?
These assays measure the total T4 and T3 concentrations in the circulation. More than 99% of circulating T4 and approximately 98% of T3 are bound to proteins, such as thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA or transthyretin), and albumin. Serum total T4 and T3 levels can therefore be altered by protein-binding disorders.
6. Name the major disorders of thyroid hormone-binding proteins.
Pregnancy, estrogen use, congenital TBG excess, and familial dysalbuminemic hyperthyroxinemia (FDH) are the most common. FDH is an inherited disorder in which albumin has enhanced affinity for T4, resulting in increased levels of total T4 but not T3. Protein binding of T4 and T3 is reduced by androgens and congenital TBG deficiency.
A T3 resin uptake (T3RU) measurement helps distinguish protein-binding disorders from true thyroid diseases. The T3RU is inversely proportional to the protein-binding capacity; accordingly, T3RU is low when T4 protein binding is increased and high when T4 protein binding is reduced. Table 32-1 indicates how these tests are used to make the correct diagnosis.
TABLE 32-1.
