TSH vs free T4: how they work together

This is the hypothalamic-pituitary-thyroid axis. Most thyroid hormone in blood is bound to carrier proteins; the free fraction is what tissues can use, which is why labs measure free T4 rather than total T4 in most cases.

• TSH comes from the pituitary and is measured in mIU/L.
• Free T4 is the main thyroid hormone, reported in ng/dL or pmol/L (1 ng/dL is about 12.9 pmol/L) [5]. In one large outpatient study, mean free T4 was 17.5 to 18.3 pmol/L, about 1.4 ng/dL [6].
• T3 is the active hormone, mostly made from T4 in tissues.

When the axis is intact, TSH is a sensitive mirror of free T4. When the pituitary or hypothalamus is unwell, or someone is critically ill, the mirror breaks and TSH can mislead [7][8].

Spencer and colleagues described the relationship in 1990 as log TSH = 2.56 minus 0.022 times the free T4 index, with a correlation of 0.84 [1]. After T4 was given to healthy volunteers, TSH fell in parallel with that slope and then plateaued, which suggests each person has a pituitary set point [1].

Andersen and colleagues found that TSH responds with logarithmically amplified variation to minor changes in T4 and T3 [9]. A person whose normal free T4 sits high in the lab range can have a raised TSH after a drop that still leaves free T4 in range, which is why subclinical hypothyroidism exists as a category [9].

NICE recommends TSH alone for adults when pituitary disease is not suspected, adding free T4 in the same sample if TSH is high and free T4 plus free T3 if TSH is low [2]. It recommends both TSH and free T4 from the start when pituitary disease is suspected and for children [2], and free T4 as well as TSH for adults on levothyroxine with ongoing symptoms [2].

In pregnancy, both TSH and free T4 have trimester-specific ranges [10][5]. Many labs offer "TSH with reflex to free T4", which automates the cascade. More on the practical side is in the TSH test.

• Low TSH, low free T4: central hypothyroidism or non-thyroidal illness, where low T3, low T4 and normal or slightly low TSH are typical [7].
• Normal TSH, high free T4: biotin can push competitive assays such as free T4 falsely high [11].
• Low TSH, normal free T4, high T3: T3 toxicosis, which the NICE cascade detects by adding free T3 when TSH is low [2].
• High TSH, normal free T4: subclinical hypothyroidism or recovery from illness [12][13].
• High TSH, high free T4: uncommon; repeat testing on another assay and a specialist review are usual.

The full grid is on the TSH hub.

Overt hyperthyroidism is defined by a suppressed TSH with high T3 and/or free T4 [14], so T3 is part of the workup of a low TSH [2]. In hypothyroidism, TSH and free T4 drive the diagnosis [4].

Some thyroid experts argue that TSH and T4 alone miss tissue-level effects of thyroid hormone, especially in people who feel unwell on levothyroxine despite normal TSH. That debate, including combination T4 and T3 treatment, is ongoing; any change to thyroid medication belongs to a clinician.