T4 (thyroxine) is the most abundant thyroid hormone. It serves as a backup for T3 production, a more active form in the tissues. The test measures the small fraction of T4 in the blood (less than 1%) that is not protein-bound. A high level of free T4 can indicate that the thyroid gland is too active (primary hyperthyroidism) as in Graves’ disease or early-stage thyroiditis, or that the doses of T4 (Synthroid©, Levothyroxine) being used to treat hypothyroidism are too high. Since pituitary gland production of TSH is normally suppressed by high levels of T4, high levels of free T4 are most often associated with TSH levels that are below normal. More rarely, high levels of T4 are due to the overproduction of TSH by the pituitary gland (tumour producing TSH or other cause).
A low level of free T4 combined with a high TSH level points to an underactive thyroid gland (primary hypothyroidism). Various conditions could be responsible: destruction of the gland by autoantibodies (Hashimoto thyroiditis), overintensive treatment of hyperthyroidism by medication, radioactive iodine treatment, or thyroid or parathyroid surgery.