What are the key differences in interpreting TSH, Free T4, and Free T3 levels in patients with suspected hypothyroidism?

Interpreting thyroid-stimulating hormone (TSH), free thyroxine (Free T4), and free triiodothyronine (Free T3) levels in patients with suspected hypothyroidism involves a hierarchical approach, with TSH typically serving as the initial screening test ¹.

• Thyroid-Stimulating Hormone (TSH): TSH is the primary screening test for adults when secondary thyroid dysfunction (pituitary disease) is not suspected ¹. A TSH level above the reference range is the key indicator of primary hypothyroidism ¹. Conversely, a TSH level below the reference range, especially when accompanied by a low Free T4, suggests secondary (central) hypothyroidism, which involves pituitary disease ¹ (Trainer and Howard, 1983). In subclinical hypothyroidism, TSH is elevated, but Free T4 levels remain within the reference range ¹.
• Free Thyroxine (Free T4): Free T4 is measured to confirm the diagnosis of primary hypothyroidism when TSH is found to be above the reference range ¹. A low Free T4 in conjunction with an elevated TSH confirms overt primary hypothyroidism ¹ (Perry, 1994). For suspected secondary hypothyroidism, both TSH and Free T4 are measured initially, with a low Free T4 alongside a low or inappropriately normal TSH being indicative ¹ (Trainer and Howard, 1983). In cases of subclinical hypothyroidism, Free T4 levels are typically within the normal reference range despite an elevated TSH ¹.
• Free Triiodothyronine (Free T3): Free T3 generally plays a less significant role in the initial diagnosis of hypothyroidism compared to TSH and Free T4 (Trainer and Howard, 1983). It is often the last thyroid hormone to fall in developing hypothyroidism (Perry, 1994). NICE guidelines recommend measuring Free T3 in the same sample if TSH is below the reference range, which is primarily relevant for suspected hyperthyroidism or when investigating a suppressed TSH ¹. For suspected hypothyroidism, its measurement is not typically a primary diagnostic step unless TSH is low and secondary dysfunction is suspected ¹.

It is important to note that thyroid function tests should generally not be performed during an acute illness unless the illness is suspected to be due to thyroid dysfunction, as acute illness can affect results ¹. Additionally, patients should be asked about biotin intake, as high consumption from dietary supplements can lead to falsely high or low test results ¹. If symptoms worsen or new symptoms develop, tests may be repeated, but no sooner than 6 weeks from the most recent test ¹.