From the Guidelines
FT4 is preferred over T4 for diagnosing hypothyroidism because it more accurately reflects the amount of thyroid hormone available to tissues, as evidenced by the 2021 ASCO guideline update 1. When evaluating thyroid function, measuring FT4 alongside TSH is crucial, as TSH is the most sensitive initial test for primary hypothyroidism. The distinction between FT4 and total T4 is significant because various conditions can alter protein binding without affecting thyroid function. Some key points to consider include:
- FT4 measures only the unbound, biologically active portion of T4 that can enter cells and exert hormonal effects.
- Total T4 includes both free hormone and T4 bound to carrier proteins like thyroxine-binding globulin (TBG), which cannot enter cells or produce biological effects.
- Conditions such as pregnancy, oral contraceptive use, liver disease, and certain medications can change total T4 levels while free T4 remains normal, potentially leading to misdiagnosis if total T4 is used alone. According to the 2021 ASCO guideline update 1, TSH and FT4 should be used for case detection in symptomatic patients, and FT4 can be used to help interpret ongoing abnormal TSH levels on therapy. In clinical practice, using FT4 instead of total T4 can help avoid misdiagnosis and ensure accurate assessment of thyroid function, particularly in patients with conditions that affect protein binding.
From the Research
Diagnosis of Hypothyroidism
- Free thyroxine (FT4) is preferred over thyroxine (T4) to diagnose hypothyroidism because it represents a more useful index of thyroid status than total thyroid hormones 2.
- FT4 is not influenced by variations of thyroid hormone-binding proteins, especially T4-binding globulin (TBG), which can affect total T4 measurements 2.
- Measuring serum FT4 levels, along with TSH, is essential for the diagnosis of thyroid dysfunction, particularly in cases of suspected hypothyroidism 2, 3.
Advantages of FT4 over T4
- FT4 levels are a more reliable indicator of thyroid function than total T4 levels, as they are not affected by changes in thyroid hormone-binding proteins 2.
- In cases of suspected hypothyroidism, FT4 levels (together with TSH) are the most reliable tests, as FT3 may still be normal in patients with subclinical or mild thyroid failure 2.
- FT4 levels are used to monitor the adequacy of replacement therapy in central hypothyroidism, as TSH levels cannot be used in this context 3.
Clinical Utility of FT4 and TSH
- First-line combined TSH and FT4 testing is preferred by many laboratories as it detects individuals with undiagnosed central hypothyroidism who may be missed with a first-line TSH-only strategy 4.
- The clinical utility of first-line TSH and FT4 in the detection of central hypothyroidism has been evaluated, and it is found to be a useful approach in current day practice 4.
- A combination of clinical symptoms and FT4 levels are typically used to make a diagnosis and monitor replacement in patients with TSH deficiency 5.