Thyroid-Stimulating Hormone (TSH)

TSH is a heterodimeric glycoprotein released by pituitary thyrotrophs. Its alpha subunit is shared with LH, FSH and hCG while the beta subunit confers specificity, and that shared alpha chain is why very high hCG in early pregnancy or trophoblastic disease stimulates the thyroid receptor directly. TSH binds a Gs-coupled receptor on the thyroid follicular cell, raising cyclic AMP and driving iodide uptake, thyroglobulin synthesis and hormone release.

The relationship between TSH and free T4 is approximately log-linear: a change in free T4 too small to leave the reference interval can move TSH several-fold. That amplification is why one TSH screens thyroid status better than measuring the hormones it regulates. Secretion is also pulsatile with a nocturnal peak around midnight, so an afternoon sample can read meaningfully lower than a morning one from the same person, enough to matter near a decision threshold.

Because TSH is a feedback signal, it is interpretable only when the pituitary is intact. In central hypothyroidism the free T4 is low while TSH sits low or unremarkable, so a normal TSH is falsely reassuring; the same trap follows recent treatment for thyrotoxicosis, where TSH can stay suppressed for months after the hormones have normalised. Subclinical disease is defined by TSH alone against a normal free T4 - a statement about the loop, not about symptoms.

The frequent practical error is rechecking too early. TSH needs about six weeks to re-equilibrate after a levothyroxine change, and a level drawn at two or three weeks invites a dose adjustment chasing a number still in transit. A second error is treating the upper reference limit as biologically fixed. It varies with assay, iodine intake and reference population, and it drifts upward with age, so an older patient flagged against a young-adult cut-off may not be abnormal at all.