From the Guidelines
Free T4 is the preferred initial measurement for assessing thyroid function, as it provides a more accurate reflection of the patient's true thyroid status. When evaluating thyroid function, it is essential to consider the most effective and informative tests. Both free T4 and free T3 measurements are generally better than total T4 and T3 for assessing thyroid function, as they measure the unbound, biologically active portion of thyroid hormones that can enter tissues and exert effects 1.
Key Points to Consider
- Free hormone tests are preferred because they aren't affected by changes in binding protein levels that can occur with various conditions, such as pregnancy, oral contraceptives, certain medications, or liver disease.
- Free T4 is the primary test ordered along with TSH, as it provides a comprehensive assessment of thyroid function.
- Free T3 testing is typically reserved for specific situations like suspected T3 thyrotoxicosis or monitoring patients on T3 replacement therapy.
- Total hormone tests may still be useful in certain specialized situations, but for routine thyroid assessment, free hormone measurements provide a more accurate reflection of the patient's true thyroid status. According to the American Diabetes Association, thyroid function should be monitored after metabolic control has been established for several weeks, and this should be done with a TSH measurement, followed by free T4 and, if indicated, total T3 measurements if TSH is abnormal 1.
Clinical Application
In clinical practice, the choice between free and total T4 and T3 measurements depends on the specific patient scenario and the suspected underlying thyroid condition. However, as a general rule, free T4 is the preferred initial measurement for assessing thyroid function, as it provides a more accurate reflection of the patient's true thyroid status.
From the FDA Drug Label
Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active
- Free hormone is the metabolically active form of thyroid hormones, including T4 and T3.
- Since only unbound hormone is metabolically active, measuring free T4 and free T3 may be more relevant than measuring total T4 and T3.
- However, the FDA drug label does not provide a direct comparison of the benefits of measuring free versus total T4 and T3, so no conclusion can be drawn about which is better to measure 2, 2.
From the Research
Measurement of Thyroid Hormones
- Free thyroid hormones (free thyroxine, FT4, and free triiodothyronine, FT3) are considered a more useful index of thyroid status than total thyroid hormones, as they are not influenced by variations of thyroid hormone-binding proteins 3.
- Total thyroid hormones (total T4, TT4, and total T3, TT3) can be affected by conditions such as TBG excess, familial dysalbuminemic hyperthyroxinemia, and transthyretin-associated hyperthyroxinemia, leading to incorrect diagnoses 3.
Diagnosis of Thyroid Dysfunction
- Measurement of serum FT4 and FT3 levels can correctly establish the diagnosis of euthyroidism in cases where total thyroid hormone levels are misleading 3.
- In cases of suspected hyperthyroidism, serum FT3 (and TSH) measurement is recommended, as FT4 may be elevated in euthyroid subjects, such as those under chronic amiodarone or L-T4 treatment 3.
- When hypothyroidism is suspected, FT4 (together with TSH) is considered the most reliable test, as FT3 may still be normal in patients with subclinical or mild thyroid failure 3.
Treatment of Hypothyroidism
- Current guidelines recommend treatment with levothyroxine, which normalizes serum FT4, T3, and TSH levels in most cases, but some patients may remain symptomatic despite normal serum FT4 and TSH levels 4.
- The use of combination therapy with levothyroxine and liothyronine is not consistently supported by clinical trials, but may be beneficial for some patients, such as those with polymorphisms in the DIO2 gene 4, 5, 6.
- A trial of combination therapy may be indicated in patients who remain symptomatic despite adequate levothyroxine monotherapy, but should be undertaken by experienced clinicians with appropriate monitoring for adverse outcomes 7.