TSH is the most sensitive marker, moving before free T4 changes
Mnemonic
“TSH goes the opposite way to the gland”, because it is a feedback hormone:
| TSH | Free T4 | Diagnosis |
|---|---|---|
| High | Low | Primary hypothyroidism |
| High | Normal | Subclinical hypothyroidism |
| Low | High | Primary hyperthyroidism |
| Low | Normal | Subclinical hyperthyroidism |
| Low | Low | Secondary (pituitary), or sick euthyroid |
| High | High | TSH secreting adenoma, resistance, or assay interference |
“Both in the same direction is discordant and means think pituitary or the assay.”
TSH is the most sensitive single test because the relationship is log-linear: a small change in free T4 produces a large change in TSH.
Do not check thyroid function in acutely unwell inpatients unless thyroid disease is genuinely suspected, because non-thyroidal illness depresses TSH and T3 and recovers on its own.
Expansion
| TSH | Free T4 | Interpretation |
|---|---|---|
| High | Low | Primary hypothyroidism |
| High | Normal | Subclinical hypothyroidism |
| Low | High | Primary hyperthyroidism |
| Low | Normal | Subclinical hyperthyroidism |
| Low | Low | Secondary hypothyroidism, or sick euthyroid |
| High | High | TSH-secreting adenoma or resistance |
Subclinical states are common and are defined by an abnormal TSH with normal peripheral hormone, reflecting the sensitivity of the feedback loop.
Sick euthyroid (non-thyroidal illness): in acute illness, T3 falls first (reduced peripheral conversion, with reverse T3 rising), then T4, and TSH is low or normal. Thyroid function should not be tested during acute illness unless thyroid disease is strongly suspected, and abnormal results should be repeated on recovery.
Other pitfalls: biotin supplements interfere with many assays, amiodarone can cause either hypo- or hyperthyroidism, and TSH takes 6 weeks to re-equilibrate after a dose change, so testing earlier is misleading.