What is the utility of Triiodothyronine (T3) testing and what other thyroid function tests are recommended for a patient presenting with symptoms of fatigue?

From the Guidelines

T3 testing is not recommended as a first-line test for evaluating fatigue symptoms, and instead, TSH (thyroid stimulating hormone) should be the initial test, followed by free T4 if TSH is abnormal. This approach is supported by the American Society of Clinical Oncology clinical practice guideline adaptation, which suggests considering laboratory evaluation based on the presence of other symptoms, onset, and severity of fatigue, including endocrinologic evaluation with TSH 1. The US Preventive Services Task Force also recommends screening for thyroid dysfunction with TSH, followed by free T4 if TSH is abnormal, as the most effective approach for detecting thyroid dysfunction 1.

When evaluating fatigue, it's essential to consider non-thyroid causes such as anemia, sleep disorders, depression, vitamin deficiencies, and other endocrine disorders, which may require additional testing beyond thyroid function. A complete thyroid panel would include TSH, free T4, and then potentially free T3 if the initial tests suggest thyroid dysfunction but don't fully explain symptoms. Additional helpful tests include thyroid antibodies (anti-TPO and anti-thyroglobulin) to check for autoimmune thyroid conditions like Hashimoto's thyroiditis, which commonly causes fatigue.

The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for cancer-related fatigue also emphasize the importance of assessing for non-cancer comorbidities, such as cardiac, pulmonary, renal, hepatic, neurologic, and endocrine dysfunction, including hypothyroidism, which can contribute to fatigue symptoms 1.

Key points to consider when evaluating fatigue include:

• Initial testing with TSH, followed by free T4 if TSH is abnormal
• Consideration of non-thyroid causes of fatigue, such as anemia, sleep disorders, and depression
• Assessment for non-cancer comorbidities, including endocrine dysfunction
• Potential use of thyroid antibodies and free T3 testing if initial tests suggest thyroid dysfunction but don't fully explain symptoms.

From the FDA Drug Label

Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation, bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones Serum T4 levels can be used to test the effectiveness of all thyroid medications except products containing liothyronine sodium. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted Specific measurements of T4 and T3 by competitive protein binding or radioimmunoassay are not influenced by blood levels of organic or inorganic iodine and have essentially replaced older tests of thyroid hormone measurements, i.e., PBI, BEI and T4 by column.

The utility of T3 testing is to assess the effectiveness of thyroid medications, particularly those containing liothyronine sodium. If a patient has symptoms of fatigue, the following thyroid tests are recommended:

• TSH suppression test to test the effectiveness of any thyroid preparation
• Serum T4 levels to test the effectiveness of all thyroid medications except products containing liothyronine sodium
• Free T4 levels when the total serum T4 is low but TSH is normal
• T3 measurements by competitive protein binding or radioimmunoassay to assess the level of triiodothyronine in the blood 2.

From the Research

Utility of T3 Testing

• There is no direct evidence in the provided studies to support the utility of T3 testing for patients with symptoms of fatigue.
• However, it is essential to note that thyroid function tests, including T3 and T4, may be ordered as part of a comprehensive workup for fatigue, especially if the patient has symptoms suggestive of thyroid dysfunction 3, 4.

Recommended Thyroid Tests

• If a patient has symptoms of fatigue, the following thyroid tests may be recommended:
  • Thyroid-stimulating hormone (TSH) test to evaluate thyroid function 3, 4.
  • Free thyroxine (FT4) test to assess thyroid hormone levels 3, 4.
  • Free triiodothyronine (FT3) test to evaluate T3 levels, although this is not always necessary 3, 4.
• It is crucial to interpret thyroid test results in the context of the patient's clinical presentation and medical history 5.

Approach to Investigation

• A comprehensive history and examination are essential in evaluating patients with fatigue 3, 4, 5.
• A period of watchful waiting may be considered in the absence of red flags, and tests should be ordered judiciously once the decision to investigate is made 3.
• A structured approach to diagnosis and management, including consideration of medical, psychiatric, and lifestyle factors, is necessary to address chronic fatigue 5.