TSH and free T4 sit at the two ends of one feedback loop. TSH (thyroid-stimulating hormone) is the order the pituitary gland sends to the thyroid. Free T4 (free thyroxine) is the hormone the thyroid sends back. TSH is the more sensitive first test, and free T4 is the one that tells you how much hormone is reaching your tissues, so most thyroid questions are answered by reading the two as a pair.
What is the difference between TSH and free T4?
The pituitary, a pea-sized gland under the brain, watches the level of thyroid hormone in the blood. When the level dips, it releases more TSH to push the thyroid harder; when the level runs high, it releases less. The thyroid answers mostly with T4, which tissues convert into the active hormone T3. Over 99% of T4 in blood is bound to carrier proteins, and free T4 measures the small unbound part that cells can take up. 1
So TSH is a message about the thyroid, and free T4 is a reading from it. The TSH page and the free T4 page cover each marker's ranges and quirks in full.
A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations.Garber JR, et al. AACE/ATA Clinical Practice Guidelines for Hypothyroidism in Adults, Thyroid 2012 1
Why TSH usually goes first
TSH responds to small changes in free T4 with much larger swings, on a roughly logarithmic scale. A Danish study that tested 16 healthy men every month for a year found each man had his own thyroid set point, and the spread of his own results was about half the width of the group's range. 2 A free T4 can drop from the top of its range to the bottom, a large change for that person, and still be flagged normal, while TSH moves far enough to cross its line.
That sensitivity is the case for TSH as the screen. It is also why a TSH outside its range with a free T4 inside its range counts as a real finding, worth repeating and reading in context.
How to read them as a pair
| TSH | Free T4 | Usual reading |
|---|---|---|
| High | Low | Overt hypothyroidism (underactive thyroid) |
| High | Normal | Subclinical hypothyroidism |
| Low | High | Overt hyperthyroidism (overactive thyroid) |
| Low | Normal | Subclinical hyperthyroidism, or too high a dose of thyroid hormone |
| Low or normal | Low | Possible pituitary or hypothalamic problem (central hypothyroidism) |
| Normal or high | High | Rare: assay interference, a TSH-secreting tumour or thyroid hormone resistance |
What moves TSH without a thyroid problem
Because TSH is a signal from the pituitary, anything that changes the signal moves the number even when the thyroid is fine. Free T4 is a useful cross-check in each of these situations, since it reflects what the gland is producing. 1
- Age: TSH ranges drift upward in older adults, so a mildly raised TSH at 80 means less than the same value at 30.
- Recovery from illness: TSH can dip during a serious illness and overshoot for a while afterwards.
- Medicines: steroids, dopamine and some other drugs can lower TSH; amiodarone and lithium can change thyroid function itself.
- Time of day: TSH is higher at night and in the early morning than in the afternoon, so draw times matter when comparing results.
- Biotin supplements: these can distort both tests, covered below.
When TSH and free T4 disagree
High TSH, normal free T4
This is subclinical hypothyroidism: the pituitary is pushing harder to keep hormone output in range. It is common, especially in older adults, and TSH ranges drift upward with age. 1 A single result is usually repeated before anything is decided, because TSH can rise briefly while recovering from an illness. The hypothyroidism guide covers what different TSH levels mean, and TPO antibodies help show whether an autoimmune process is behind it.
Low or normal TSH with a low free T4
This is the pattern where TSH alone would miss the problem. If the pituitary or hypothalamus is not working, it cannot raise TSH when hormone falls, so TSH reads low, normal or only slightly raised while free T4 sits low. The European Thyroid Association calls this central hypothyroidism, a rare condition where free T4 is the key test and TSH cannot be used to guide treatment. 3 A TSH-only screen will not catch it.
Suppressed TSH, normal free T4 during hyperthyroid treatment
After a long spell of excess thyroid hormone, the pituitary can stay switched off for months even once hormone levels have come down. The American Thyroid Association advises judging early treatment of an overactive thyroid by free T4 and T3, because TSH can remain suppressed well after the gland is under control. 4 See hyperthyroidism.
TSH lagging after a levothyroxine dose change
TSH takes weeks to settle after a change in thyroid hormone dose, so a test drawn too soon reflects the old dose. Guidelines advise rechecking TSH about 4 to 8 weeks after a change. 1 5 Free T4 also rises for a few hours after a levothyroxine dose, so the timing of the tablet relative to the blood draw can move it. The levothyroxine guide covers reading TSH on treatment.
Results that fit no pattern
Biotin, sold in hair, skin and nail supplements, interferes with many lab tests that use a biotin-streptavidin method. In a JAMA study, six healthy adults took 10 mg of biotin a day for a week; 9 of 23 such assays gave wrong results, including falsely high free T4 and falsely low TSH, a pattern that can look like an overactive thyroid. 6 If your results do not add up, tell whoever ordered the test about any biotin you take.
Which one to ask about
For a first check in someone without known thyroid disease, TSH alone is the standard starting point, and many labs add free T4 automatically when TSH is out of range. Ask about free T4 as well when you have pituitary disease or a history of head injury or brain surgery, when you are being treated for an overactive thyroid, when you are pregnant or planning pregnancy, or when your symptoms and a normal TSH do not fit together.
- Was free T4 measured, or only TSH?
- Is my TSH outside the range by a little or a lot, and should it be repeated?
- Could a recent illness, a medicine or biotin have affected the result?
- If I am on levothyroxine, how long after my last dose change was this drawn?
- Would TPO antibodies or free T3 add anything for me?
The thyroid panel guide puts TSH and free T4 in reading order with free T3 and the antibodies. If your numbers are in range but you do not feel right, this piece on normal thyroid labs goes through the next questions to ask.
Link · American Thyroid Association (patient resources)Thyroid function testsA plain-language reference from the ATA on what TSH, free T4 and the other thyroid tests measure.thyroid.orgThe working rule: TSH tells you whether the thyroid system is under strain, and free T4 tells you how much hormone is getting through. When the pituitary itself is in question, or the system is still adjusting to treatment, free T4 is the number to read.
Questions
Which is more important, TSH or free T4?
TSH is the better first test because it changes earlier. Free T4 is more important when TSH is abnormal, when pituitary disease is possible, and early in treatment for an overactive thyroid. Most thyroid questions are answered by reading the two together.
Can I have a normal TSH and a low free T4?
Yes. It can point to a pituitary or hypothalamic problem (central hypothyroidism), where the pituitary cannot raise TSH in response to low hormone. It can also follow a serious illness or reflect an assay issue. It is a result to discuss with a clinician rather than dismiss because the TSH looks fine.
What does high TSH with normal free T4 mean?
Usually subclinical hypothyroidism: the pituitary is working harder to keep thyroid hormone in range. It is common, and a single result is usually repeated, because TSH can rise briefly after an illness and drifts upward with age.
Why test TSH instead of free T4 alone?
Each person's own range of free T4 is about half as wide as the lab range, so free T4 can change a lot for you while still reading normal. TSH amplifies those changes and crosses its cutoff earlier.
Does biotin affect TSH and free T4 results?
It can. In a JAMA study, 10 mg of biotin a day for a week caused falsely high or falsely low results in several biotin-based assays, including thyroid tests. Tell the person ordering your test about any biotin you take.
Citations
- Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-1235.
- Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87(3):1068-1072.
- Persani L, Brabant G, Dattani M, et al. 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism. Eur Thyroid J. 2018;7(5):225-237.
- Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343-1421.
- Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751.
- Li D, Radulescu A, Shrestha RT, et al. Association of biotin ingestion with performance of hormone and nonhormone assays in healthy adults. JAMA. 2017;318(12):1150-1160.
- Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017;27(3):315-389.
Educational context only, not medical advice or a diagnosis. Always discuss your results with a clinician.