The thyroid axis: reading TSH and free T4 !

Measurement
Exam priority: high

TSH is the thermostat: it rises when thyroid hormone is short and falls when there is too much. Free T4 tells where the fault is.

Updated 2026-11-01

Also called: Thyroid function tests, Thyroid panel

See it in 3D: Thyroid gland · Pituitary gland

What it is

TSH responds logarithmically to small changes in free T4, so it is the best first test when the axis is intact. Free T4 tells whether there is truly excess or deficit, and the two together locate the lesion: thyroid (primary) or pituitary–hypothalamus (central). Total T4 misleads when binding proteins change.

Hormone axes and feedback

Lesion Hashimoto thyroiditisPattern TRH ↑ · TSH ↑ · T4 ↓ · T3 ↓

Primary hypofunction: Hashimoto thyroiditis

Pattern: TRH ↑ · TSH ↑ · T4 ↓ · T3 ↓

The target gland fails: its hormone falls and, without negative feedback, the pituitary and hypothalamic hormones rise. TSH ↑ with free T4 ↓ (anti-TPO antibodies). Iodine deficiency too. TSH is the best screening test.

Exam rule: if the pituitary hormone moves opposite to the gland hormone, the problem is in the gland (primary); if they move together, it is central (pituitary or hypothalamus).

Stimulates (+)
Inhibits / negative feedback (−)
Level ↑
Level ↓

Illustrative schematic drawn by Durgical: simplified axes and classic lab patterns; not for clinical decisions.

Adult reference values (they vary by laboratory)

Parameter	Value	Note
TSH	≈0.4–4.0 mU/L	lower in the first trimester because of hCG
Free T4	≈0.8–1.8 ng/dL (≈10–23 pmol/L)
Total T3	≈80–180 ng/dL	useful when T3 toxicosis is suspected
T4 half-life	≈6–7 days	a change takes weeks to settle

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

Lab patterns

TSH	Free T4	Interpretation
↑	↓	Primary hypothyroidism
↑	Normal	Subclinical hypothyroidism
↓	↑	Primary hyperthyroidism
↓	Normal (T3 ↑ or normal)	Subclinical hyperthyroidism or T3 toxicosis
↓ or normal	↓	Central hypothyroidism (pituitary or hypothalamus)
↑ or normal	↑	TSH-secreting adenoma or thyroid hormone resistance (rare)

Clinical notes

Non-thyroidal illness in the critically ill: T3 falls (less type 1 deiodinase) with normal or low TSH; it is not read as hypothyroidism.
Biotin supplements interfere with streptavidin immunoassays and can mimic hyperthyroidism.
After hypothyroidism is corrected, TSH is rechecked at 6–8 weeks: that is how long the axis takes to settle.

Test yourself

Think of the answer, then tap the question to see it.

A patient has low TSH and low free T4: where is the lesion and why doesn't TSH rise?

In the pituitary or hypothalamus (central hypothyroidism). The gland is fine but unstimulated; TSH cannot rise because the organ that should raise it is the one damaged.

Why does a woman taking estrogen have high total T4 without being hyperthyroid?

Estrogen raises TBG, which binds more T4: total T4 rises, but free T4 and TSH stay normal because the axis adjusts the active fraction.

Why is TSH a better first test than free T4 in an outpatient?

Its relation to free T4 is log-linear: a small change in free T4 makes a large change in TSH, catching mild dysfunction before free T4 leaves its range.

Why can TSH be low in the first trimester of pregnancy without thyroid disease?

hCG shares the α subunit with TSH and weakly stimulates its receptor; free T4 rises slightly and TSH falls by feedback.

Add to my cards (4)

See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

← All of physiology

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: TSH (Thyroid-stimulating hormone) Test: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2024); 17.4 The Thyroid Gland (OpenStax (Rice University), 2022); Hypothyroidism (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 77). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.