Total T4: why most UK laboratories now measure free T4 instead

Thyroxine (T4) is the main hormone made by the thyroid gland. Lab Tests Online UK explains that T4 makes up nearly all of the thyroid hormone, with triiodothyronine (T3) making up less than 10 per cent, and that most T4 in blood is attached to a protein and cannot act directly on the body, with less than 1 per cent unattached as free T4. Total T4 adds both together.

This matters because the free fraction is what the body can use. A total T4 result is therefore a mix of hormone activity and the amount of carrier protein in the blood.

Because binding protein levels vary, total T4 can be abnormal in someone with a healthy thyroid. Lab Tests Online UK says total T4 levels rise during pregnancy because of changes in protein levels in the blood, while free T4 does not usually change significantly, and that a rise in total T4 does not mean you have thyroid disease and usually resolves after delivery. The same source states that the FT4 test is preferred to a total T4 test, and its thyroid function tests page notes that currently the majority of UK laboratories measure the free form of the hormones.

Serious illness can also affect thyroid hormone levels even when there is no thyroid condition, sometimes called non-thyroidal illness, and some medicines change the binding proteins or the hormones themselves.

You may meet total T4 in older results, results from other countries, or in some laboratories as a follow-up when TSH is abnormal. Lab Tests Online UK says that in some laboratories the initial test is TSH, and if TSH is abnormal it is followed by measuring FT4, or occasionally total T4, and sometimes FT3 or total T3. In practice most UK reports today show TSH and free T4, and the clinician interprets them as a pair.

If you have a total T4 result, look at whether the report also gives TSH. TSH is the pituitary signal that rises when the thyroid is underactive and falls when it is overactive, and it is the most sensitive indicator of thyroid status.

Lab Tests Online UK provides a pattern guide that applies to T4 results in general: a high TSH with normal T4 suggests mild (subclinical) hypothyroidism; high TSH with low T4 suggests hypothyroidism; low TSH with normal T4 suggests mild (subclinical) hyperthyroidism; low TSH with high or normal T4 suggests hyperthyroidism; and low TSH with low or normal T4 suggests non-thyroidal illness or, rarely, hypothyroidism due to pituitary disease. For people on thyroxine replacement, a low TSH with high T4 may indicate over-replacement.

Symptoms of an underactive thyroid may include weight gain, dry skin, constipation, feeling cold, puffy skin, hair loss, fatigue and menstrual irregularity; overactive thyroid may cause a faster heart rate, anxiety, weight loss, difficulty sleeping, tremor, weakness, diarrhoea and sometimes eye puffiness or bulging. The NHS says an underactive thyroid is common, usually treated with levothyroxine taken for life, with regular blood tests to check the dose.

If your result is abnormal your doctor will usually check TSH and free T4, and possibly thyroid antibodies, before deciding on treatment. If you are pregnant or on hormonal contraception, tell the clinician, because total T4 will be affected and pregnancy-specific reference ranges may apply. Seek urgent advice for chest pain, a very fast heartbeat, severe agitation or drowsiness with confusion; call 999 or NHS 111.