Free T4 (free thyroxine)
Free T4 is the unbound share of the main thyroid hormone, read beside TSH. Published ranges sit near 0.8 to 1.9 ng/dL and depend on the assay, with assays reading up to 42% below the reference method. Higher levels inside the range went with more atrial fibrillation and deaths. Correcting low free T4 in pregnancy did not change child IQ.
- Status
- A blood test ordered by a clinician and also sold direct to consumers by some US laboratories. FDA classifies free thyroxine test systems as class II devices [1]. Most laboratories measure it by immunoassay, and reference intervals are set for each assay [2].
- Measures
- The thyroxine (T4) in blood that is not bound to protein, which FDA describes as thought to reflect the hormone available to cells [1].
- Also called
- free T4, FT4, fT4, free thyroxine, thyroxine free, T4 free, free T4 direct, direct free T4, free T4 by dialysis, free thyroxine by equilibrium dialysis
- Tested for
- thyroid check, underactive thyroid, overactive thyroid, following up an out-of-range TSH, fatigue, checking a thyroid medication dose, thyroid testing in pregnancy
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Linked in research4
- ModerateLinked to more atrial fibrillation at higher free T4 inside the reference range: 45% higher risk in the top quarter than the bottom quarter in pooled cohorts.
- ModerateLinked in a J shape: risk of cardiovascular disease and death was lowest at the 20th to 40th percentiles of free T4, and the top fifth had 34% more deaths.
- LimitedOne cohort found more sudden cardiac death at higher free T4, with a hazard ratio of 2.28 per 1 ng/dL, including in people with normal TSH.
- LimitedOne cohort found less type 2 diabetes at higher free T4, with a hazard ratio of 0.96 per 1 pmol/L, including inside the reference range.
Reported risks0
No risks sourced yet.
Reference ranges
Each range is the one its source published, in ng/dL. Also reported in pmol/L. Where sources differ, each is shown.
US National Library of Medicine, MedlinePlus
Adults · [3]
| Range | What the source calls it |
|---|---|
| below 0.8 ng/dL | No name given |
| 0.8 to 1.9 ng/dL | "normal" |
| above 1.9 ng/dL | No name given |
MedlinePlus calls this a typical normal range and prints it as 0.8 to 1.9 ng/dL, or 10.3 to 24.5 pmol/L. It states that ranges vary slightly among laboratories, that the range is based on a large population and is not necessarily normal for an individual, and that the TSH test may help clarify a result [3]. It names no assay.
American Board of Internal Medicine laboratory reference ranges, 2026
Adults, as a general laboratory reference range · [4]
| Range | What the source calls it |
|---|---|
| below 0.8 ng/dL | No name given |
| 0.8 to 1.8 ng/dL | "reference range" |
| above 1.8 ng/dL | No name given |
The table names no assay, age group or pregnancy status [4].
Rotterdam Study, Netherlands, 2016
Adults aged 45 and older, measured with one electrochemiluminescence immunoassay · [5]
| Range | What the source calls it |
|---|---|
| below 0.86 ng/dL | No name given |
| 0.86 to 1.94 ng/dL | "reference range" |
| above 1.94 ng/dL | No name given |
The cut-off values this cohort used for its free T4 reference range, printed as 11 to 25 pmol/L (0.86 to 1.94 ng/dL) and set according to guidelines and the group's earlier studies. The assay was an electrochemiluminescence immunoassay from Roche. The same cohort took 0.4 to 4.0 mIU/L as its TSH reference range [5].
US trial of thyroid treatment in pregnancy, 2017
Pregnancy before 20 weeks · [6]
| Range | What the source calls it |
|---|---|
| below 0.86 ng/dL | "low" |
| 0.86 to 1.9 ng/dL | "normal" |
| above 1.9 ng/dL | No name given |
The definitions a National Institutes of Health trial used to screen pregnant women, printed as 0.86 to 1.90 ng/dL (11 to 24 pmol/L). The trial called a free T4 below 0.86 ng/dL with a normal TSH hypothyroxinemia. The abstract does not name the assay [6]. The American Thyroid Association states that free T4 immunoassay results in pregnancy vary significantly by manufacturer and calls for ranges specific to the assay and the trimester, without printing numbers [2].
What has been shown to move it
Shown to lower it2
Lower thyroid hormone on quetiapine
Shown to lower thyroid hormone levels in a dose-related way on quetiapine, with thyroxine about 20% lower at the higher end of the dose range.
Total and free thyroxine fell by about 20% at the higher end of the dose range, reached a maximum in the first six weeks and reversed in nearly all cases after stopping.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The label reports dose-related decreases in thyroid hormone in quetiapine trials. Total and free thyroxine fell by about 20% at the higher end of the dose range, reached a maximum in the first six weeks and reversed in nearly all cases after stopping [3].
- Population
- Adults in quetiapine clinical trials [3].
- Sources
- [3]
- Caveats
- An average change in a blood level. The passage read for this page gives no count of people who became hypothyroid. The evidence is for quetiapine.
Reduced levothyroxine absorption
Limited evidence: in 20 adults on levothyroxine, 1,200 mg of calcium carbonate lowered free T4 and raised TSH, which returned after stopping calcium.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Taking 1,200 mg of calcium as carbonate with levothyroxine for 3 months lowered free T4 from 17 to 15 pmol/L and raised TSH from 1.6 to 2.7 mIU/L. Both returned after calcium stopped. 20% of patients had TSH above the normal range on calcium [15].
- Population
- 20 adults with hypothyroidism on stable levothyroxine [15].
- Sources
- [15]
- Caveats
- A small uncontrolled cohort, with lab data showing T4 binds to calcium carbonate in acid [15].
Tested, and not shown to change it2
Thyroid function
Shown to raise TSH slightly, by 0.25 mIU/L, in pooled trials, with no change in free T3 or free T4.
Free T3 (0.027 pmol/L, 95% CI -0.052 to 0.107) and free T4 (-0.003 pmol/L, 95% CI -0.018 to 0.011) did not change.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Soy raised thyroid stimulating hormone (WMD 0.248 mIU/L, 95% CI 0.001 to 0.494, I² 80.31%). Free T3 (0.027 pmol/L, 95% CI -0.052 to 0.107) and free T4 (-0.003 pmol/L, 95% CI -0.018 to 0.011) did not change. The authors call the clinical significance of the TSH rise unclear [16].
- Population
- Randomized trials in 18 articles [16].
- Sources
- [16]
- Caveats
- High heterogeneity, and the lower bound of the TSH interval is close to zero [16].
Iodine
One trial found urinary iodine fell by half within 6 months in postmenopausal women, while it held steady on a Nordic guideline diet.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Median 24-hour urinary iodine concentration fell from 71.0 to 36.0 μg/L at 6 months (p 0.001), and 24-hour iodine excretion from 134.0 to 77.0 μg/d. Levels did not change on the comparison diet. FT4 and TSH did not differ, and FT3 was lower at 6 months [8]. In a 4-week trial, iodine intake was 47.9 μg a day lower than on the Australian national guide diet (95% CI 16.5 to 79.2) [7].
- Population
- 70 postmenopausal women with overweight or obesity over 2 years [8]; 39 women over 4 weeks [7].
- Sources
- [7], [8]
- Caveats
- The diet excludes table salt and dairy, which the authors call two of the largest iodine sources [8]. Small trials in women.
How it compares with the reference method
Matched the reference method1
Time of day and season
One large study found the free T4 reference interval did not shift with hour of day, time of year, age or sex.
The numbers and sources
- Compared with
- Samples drawn at other hours and seasons
- Effect
- In 112,994 free T4 measurements from people without thyroid disease, age, sex, hour of day and time of year did not affect the free T4 reference interval. Females had higher free T4 than males by no more than 0.1 ng/dL. In the same data the TSH interval did vary by hour of day [16].
- Population
- 112,994 free T4 measurements from people aged 1 to 104, on a single immunoassay method [16].
- Sources
- [16]
- Caveats
- A retrospective analysis of laboratory records from one health system and one assay [16].
Mixed results1
Biotin supplements and the assay
One small study found 10 mg a day of biotin gave falsely high results in 5 of 8 biotin-based competitive immunoassays, across analytes that included free T4.
The numbers and sources
- Compared with
- The same person's result before taking biotin
- Effect
- After 7 days of 10 mg a day of biotin, interference appeared in 9 of 23 assays built on biotin and streptavidin (39%) and in none of 14 assays built without them. Five of 8 biotin-based competitive immunoassays read falsely high and 4 of 15 biotin-based sandwich immunoassays read falsely low. The 11 analytes included free T4, free T3 and TSH, measured on 4 diagnostic systems [17].
- Population
- 6 adults described as healthy, mean age 38 [17].
- Sources
- [17]
- Caveats
- Six people. The abstract does not list which free T4 assays were affected, and many assays showed no interference [17].
Did not match the reference method2
Immunoassays against the reference method
Shown to read low against the reference method: 15 of 17 free T4 procedures tested had negative biases, by as much as 42%.
The numbers and sources
- Compared with
- Equilibrium dialysis with isotope dilution mass spectrometry
- Effect
- An international working group compared 15 immunoassays and 2 dialysis-based laboratory procedures with a candidate reference procedure. Of the 17, 2 had a mean bias within 10% and 15 had negative biases of up to 42%. Correlation with the reference procedure ranged from 0.92 to 0.78, and total imprecision from 1.5% to 14.1% [13]. In a later study, recalibrating 13 manufacturers' assays to the reference procedure cut the spread of assay means from a coefficient of variation of 13% to 5%, and 12 of 13 recalibrated assays met a 10% bias specification. One met the 13% total error specification [14].
- Population
- Panels of single-donor sera measured by 9 manufacturers [13]. Standardization and reference interval panels measured by 13 manufacturers [14].
- Sources
- [13], [14]
- Caveats
- The second study was a proof of concept, and its abstract does not say whether laboratories have adopted the recalibration. Until they do, a result and its reference interval belong to the assay that produced them [14].
Immunoassays in pregnancy
Limited evidence: a guideline review reports that free T4 immunoassays read lower in late pregnancy by an amount that depends on the assay.
The numbers and sources
- Compared with
- Equilibrium dialysis, ultrafiltration or mass spectrometry measurement
- Effect
- The American Thyroid Association reports that automated immunoassays show a significant, assay-dependent fall in measured free T4 in the third trimester, although direct measurement by more precise methods does not show a similar degree of reduction. It attributes this to the rise in thyroxine-binding globulin and fall in albumin during pregnancy [2]. An earlier US guideline states that many pregnant women have values below the nonpregnant range in the third trimester, and that ranges specific to the method and trimester have not been generally established [15].
- Population
- Guideline summaries of earlier studies, whose sizes they do not give [2][15].
- Sources
- [2], [15]
- Caveats
- Secondhand statements from guideline text, not a primary study.
What studies tie it to
Linked in research4
Atrial fibrillation
Linked to more atrial fibrillation at higher free T4 inside the reference range: 45% higher risk in the top quarter than the bottom quarter in pooled cohorts.
The numbers and sources
- Effect
- Among people with a TSH of 0.45 to 4.49 mIU/L in 11 pooled cohorts, the hazard ratio for new atrial fibrillation was 1.45 (95% CI 1.26 to 1.66) for the highest quartile of free T4 against the lowest, with a significant trend across quartiles. TSH itself was not associated [7]. In older US adults whose thyroid tests were all in the reference range, higher free T4 was associated with atrial fibrillation (P below 0.001), and the top quartile had 11.0 more cases per 1,000 person-years than the bottom quartile [8].
- Population
- 30,085 adults in 11 prospective cohorts, 2,574 new cases of atrial fibrillation [7]. 2,843 older adults in the Cardiovascular Health Study not taking thyroid medication [8].
- Sources
- [7], [8]
- Caveats
- Observational. Quartiles were set within each cohort, so the finding is not tied to one ng/dL value [7].
Cardiovascular disease and death
Linked in a J shape: risk of cardiovascular disease and death was lowest at the 20th to 40th percentiles of free T4, and the top fifth had 34% more deaths.
The numbers and sources
- Effect
- In pooled data on 134,346 adults, risk was lowest at the 20th to 40th percentiles of free T4, medians of 13.5 to 14.8 pmol/L. Against that band, the top fifth had hazard ratios of 1.20 (95% CI 1.11 to 1.31) for cardiovascular events or death combined, 1.34 (1.20 to 1.49) for death from any cause, 1.57 (1.31 to 1.89) for cardiovascular death and 1.22 (1.11 to 1.33) for cardiovascular events [9]. In older US adults with thyroid tests in the reference range, the top quartile of free T4 had more coronary heart disease, heart failure and deaths than the bottom quartile, by 8.0, 7.8 and 14.3 per 1,000 person-years [8].
- Population
- 134,346 adults in 26 cohorts, median age 59 [9]. 2,843 older adults [8].
- Sources
- [9], [8]
- Caveats
- Observational, so illness that shifts free T4 before an event cannot be ruled out. The pooled figures are adjusted for age and sex, and the percentile medians are printed in pmol/L [9].
Sudden cardiac death
One cohort found more sudden cardiac death at higher free T4, with a hazard ratio of 2.28 per 1 ng/dL, including in people with normal TSH.
The numbers and sources
- Effect
- In the Rotterdam Study, higher free T4 was associated with sudden cardiac death even in the normal range of thyroid function, with a hazard ratio of 2.28 per 1 ng/dL (95% CI 1.31 to 3.97). The absolute 10-year risk rose from 1% to 4% with increasing free T4 among people with TSH of 0.4 to 4.0 mIU/L [10].
- Population
- 10,318 adults aged 45 and older, 261 sudden cardiac deaths over a median 9.1 years [10].
- Sources
- [10]
- Caveats
- One observational cohort with 261 events [10].
Type 2 diabetes
One cohort found less type 2 diabetes at higher free T4, with a hazard ratio of 0.96 per 1 pmol/L, including inside the reference range.
The numbers and sources
- Effect
- In the Rotterdam Study, each 1 pmol/L higher free T4 had a hazard ratio for diabetes of 0.96 (95% CI 0.93 to 0.99), and the same within the reference range (0.96, 0.92 to 0.99). Higher TSH went with more diabetes (hazard ratio 1.13 per log unit, 1.08 to 1.18). In people with prediabetes, the hazard ratio for progression was 0.63 (0.48 to 0.82) in the highest third of free T4 against the lowest [5].
- Population
- 8,452 adults, mean follow-up 7.9 years, 798 new cases of diabetes [5].
- Sources
- [5]
- Caveats
- One observational cohort [5].
Mixed results1
Pregnancy and child outcomes
Mixed results: low free T4 in pregnancy was linked to lower child IQ and preterm birth, while a trial that treated low free T4 found no change in IQ.
The numbers and sources
- Effect
- In a Dutch birth cohort, maternal free T4 in early pregnancy had an inverted U-shaped association with child IQ, with both low and high concentrations corresponding to a 1.4 to 3.8 point lower mean IQ [11]. In pooled data on 47,045 pregnant women, preterm birth occurred in 7.1% of women with a low free T4 and normal TSH against 5.0% of women with normal results (odds ratio 1.46, 95% CI 1.12 to 1.90) [12]. In a trial of 526 pregnant women with free T4 below 0.86 ng/dL and normal TSH, median child IQ was 94 with levothyroxine and 91 with placebo (P = 0.30), with no significant differences in other pregnancy or neonatal outcomes [6].
- Population
- 3,839 mother and child pairs, with IQ tested at a median age of 6 [11]. 47,045 pregnant women in 19 cohorts [12]. 526 women randomized at a mean of 17.8 weeks of pregnancy [6].
- Sources
- [11], [12], [6]
- Caveats
- A marker that tracks an outcome is not always one whose correction changes it. The cohort findings are observational, and the trial began treatment between 8 and 20 weeks of pregnancy [6].
Sources
- US Food and Drug Administration. 21 CFR 862.1695, Free thyroxine test system. Electronic Code of Federal Regulations. https://www.ecfr.gov/current/title-21/section-862.1695
- 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. https://doi.org/10.1089/thy.2016.0457
- US National Library of Medicine. Free T4 test. MedlinePlus Medical Encyclopedia. Reviewed January 25, 2026. https://medlineplus.gov/ency/article/003517.htm
- American Board of Internal Medicine. ABIM Laboratory Test Reference Ranges. January 2026. https://www.abim.org/Media/bfijryql/laboratory-reference-ranges.pdf
- Chaker L, Ligthart S, Korevaar TIM, et al. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Medicine. 2016. https://doi.org/10.1186/s12916-016-0693-4
- Casey BM, Thom EA, Peaceman AM, et al. Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy. New England Journal of Medicine. 2017. https://doi.org/10.1056/nejmoa1606205
- Baumgartner C, da Costa BR, Collet TH, et al. Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation. Circulation. 2017. https://doi.org/10.1161/circulationaha.117.028753
- Cappola AR, Arnold AM, Wulczyn K, et al. Thyroid Function in the Euthyroid Range and Adverse Outcomes in Older Adults. The Journal of Clinical Endocrinology and Metabolism. 2015. https://doi.org/10.1210/jc.2014-3586
- Xu Y, Derakhshan A, Hysaj O, et al. The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis. The Lancet Diabetes and Endocrinology. 2023. https://doi.org/10.1016/s2213-8587(23)00227-9
- Chaker L, van den Berg ME, Niemeijer MN, et al. Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study. Circulation. 2016. https://doi.org/10.1161/circulationaha.115.020789
- Korevaar TIM, Muetzel R, Medici M, et al. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. The Lancet Diabetes and Endocrinology. 2016. https://doi.org/10.1016/s2213-8587(15)00327-7
- Consortium on Thyroid and Pregnancy Study Group on Preterm Birth, Korevaar TIM, Derakhshan A, et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA. 2019. https://doi.org/10.1001/jama.2019.10931
- Thienpont LM, Van Uytfanghe K, Beastall G, et al. Report of the IFCC Working Group for Standardization of Thyroid Function Tests; Part 2: Free Thyroxine and Free Triiodothyronine. Clinical Chemistry. 2010. https://doi.org/10.1373/clinchem.2009.140194
- De Grande LAC, Van Uytfanghe K, Reynders D, et al. Standardization of Free Thyroxine Measurements Allows the Adoption of a More Uniform Reference Interval. Clinical Chemistry. 2017. https://doi.org/10.1373/clinchem.2017.274407
- 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. Endocrine Practice. 2012. https://doi.org/10.4158/ep12280.gl
- Ehrenkranz J, Bach PR, Snow GL, et al. Circadian and Circannual Rhythms in Thyroid Hormones: Determining the TSH and Free T4 Reference Intervals Based Upon Time of Day, Age, and Sex. Thyroid. 2015. https://doi.org/10.1089/thy.2014.0589
- Li D, Radulescu A, Shrestha RT, et al. Association of Biotin Ingestion With Performance of Hormone and Nonhormone Assays in Healthy Adults. JAMA. 2017. https://doi.org/10.1001/jama.2017.13705