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Longevity Library · Lab reference

Written by Daniel Tagge, MD
Updated October 7, 2026
Reviewed October 10, 2026
31 sources · Measured in mIU/L

System: Metabolism & Metabolomics

TSHThyroid-stimulating hormone · Thyrotropin

The clear harm thresholds for TSH are at or above 10 mIU/L (coronary events and coronary deaths rose in pooled cohorts) and below 0.1 (coronary deaths and atrial fibrillation rose). Inside the laboratory range the evidence is contested: 85 percent of antibody-free US adults sit below 2.5, the lowest later thyroid dysfunction and lowest mortality sat near 1 to 2 in two cohorts, but TSH rises with age, higher-normal TSH went with longer life in one Dutch cohort, and randomized trials found no symptom benefit from treating a mildly raised TSH.

TSH is the pituitary's signal to the thyroid, and it moves in the opposite direction to thyroid hormone. Laboratories call about 0.4 or 0.45 to 4.0 or 4.5 mIU/L normal. The harm thresholds at both ends are well established; whether the upper half of the range is healthy or merely common is the most argued question in thyroid testing, and this page gives both sides.

01 · The scale

Where the laboratory range and the evidence sit.

Risk is clear at the edges and contested in the middle. Coronary events and deaths rose at a TSH of 10 or above, coronary deaths and atrial fibrillation rose below 0.1, and the lowest later thyroid dysfunction and lowest mortality sat near 1 to 2 mIU/L in two cohorts; but higher-normal TSH went with longer life in Rotterdam, and treating a TSH of 4.6 to 20 in older adults changed no symptom in a randomized trial.

024681012

  1. Common laboratory reference range

    0.5 to 4.5 mIU/L · Typical US laboratories; Collet 2012; Rodondi 2010

  2. Below 0.1: highest coronary mortality and atrial fibrillation

    0 to 0.1 mIU/L · Collet 2012

  3. Subclinical hyperthyroidism: higher mortality and atrial fibrillation in cohorts

    0.1 to 0.5 mIU/L · Collet 2012

  4. Low-normal: no excess risk reported

    0.5 to 1 mIU/L · Inoue 2020 lowest tertile

  5. Lowest later thyroid dysfunction and lowest mortality in cohorts

    1 to 2 mIU/L · Teng 2006; Inoue 2020

  6. Upper reference range: contested; modest lipid, blood pressure and mortality associations; faster progression with antibodies

    2 to 4.5 mIU/L · Vanderpump 1995; Asvold 2007; Inoue 2020; Surks 2005

  7. Mild subclinical hypothyroidism: no coronary excess, no symptom benefit from treatment

    4.5 to 7 mIU/L · Rodondi 2010; Stott 2017; Feller 2018

  8. Coronary mortality rose at 7 to 9.9

    7 to 10 mIU/L · Rodondi 2010

  9. At or above 10: coronary events and deaths rose; treatment considered

    10 and above mIU/L · Rodondi 2010; Garber 2012

  • Laboratory range
  • Evidence supports
  • Guideline goal or unstudied
  • Higher risk in studies
Scale in mIU/L. mIU/L is the same as µIU/mL. Bands show where studies found something, not a recommendation for any one person.

02 · What it is

What TSH measures.

TSH is made by the pituitary, not the thyroid. It rises when thyroid hormone falls and falls when thyroid hormone rises, and because that response is logarithmically amplified, a small shift in thyroid hormone produces a large shift in TSH. That sensitivity is why guidelines call a serum TSH the single best screening test for primary thyroid dysfunction in outpatients.1,2Grade A

In the NHANES III survey of 17,353 Americans aged 12 and older, hypothyroidism was present in 4.6 percent (0.3 percent overt and 4.3 percent subclinical) and hyperthyroidism in 1.3 percent. Among people without reported thyroid disease the mean TSH was 1.50 mIU/L; 11.3 percent of the population carried thyroid peroxidase antibodies, more often women, and more often with age.3Grade B

TSH is the number used to adjust thyroid hormone replacement, and the American Thyroid Association task force that reaffirmed levothyroxine as the standard treatment also named the development of better biomarkers of thyroid status, to supplement TSH, as a research need. A TSH is a precise instrument with a known blind spot: it reports the pituitary's reading of the hormone supply, not what tissues do with it.4Grade A

03 · The laboratory range

What a laboratory calls normal.

About 0.4 or 0.45 to 4.0 or 4.5 mIU/L, depending on the laboratory.

The printed range comes from the central 95 percent of a reference population. In the NHANES III reference group of 14,333 people without known thyroid disease or thyroid antibodies, 85 percent had a TSH below 2.5 mIU/L and a further 9.7 percent sat between 2.5 and 4.5, which the authors estimated at 20.6 million Americans who would be relabeled if the upper limit were lowered.5Grade B

The case for a lower upper limit: the National Academy of Clinical Biochemistry's 2003 laboratory guideline argued that reference populations had been contaminated by people with undiagnosed thyroid disease, that more than 95 percent of rigorously screened normal individuals have a TSH below 2.5 mIU/L, and that Black Americans, who have the lowest rate of autoimmune thyroiditis, have a mean TSH of 1.18, which may be the true normal mean.6,7,3Grade B

The case against: TSH rises with age in people with no thyroid disease and no antibodies. In the same NHANES data, 10.6 percent of 20- to 29-year-olds had a TSH above 2.5, rising to 40 percent of those over 80; the 97.5th percentile was 3.56 mIU/L at 20 to 29 and 7.49 at 80 and over, and 70 percent of older people with a TSH above 4.5 were inside their own age-specific range. The upper limit most laboratories print is too high for a 25-year-old and too low for an 85-year-old.8Grade B

In 465,593 TSH measurements from people without thyroid disease, the lower limit of the range held steady across age and time of day while the upper limit rose from 6.45 to 7.55 mIU/L with age, driven by a larger nocturnal surge in older people; women ran higher than men by no more than 0.1 mIU/L.9Grade C

04 · The evidence

What the studies support.

The clearest high-end threshold comes from individual data on 55,287 adults in 11 prospective cohorts followed for 542,494 person-years. Against a TSH of 0.50 to 4.49, the hazard for coronary events was 1.00 at a TSH of 4.5 to 6.9, 1.17 at 7.0 to 9.9 and 1.89 at 10 to 19.9; for coronary death it was 1.09, 1.42 and 1.58. Total mortality was not raised. The risk did not differ by age or sex, and the authors located the excess in people with a TSH of 10 or greater.10Grade A

At the low end, pooled data on 52,674 adults in 10 cohorts found that a TSH below 0.45 with normal free T4 (4.2 percent of participants) carried a hazard of 1.24 for total mortality, 1.29 for coronary death and 1.68 for atrial fibrillation, with coronary death and atrial fibrillation higher still when TSH was below 0.10 than at 0.10 to 0.44.11Grade A

Inside the reference range, two cohorts point toward the low-to-middle part. In 9,020 US adults followed for a median of 7.3 years, a high-normal TSH of 1.96 to 5.60 carried 1.36 times the all-cause mortality of the middle tertile (1.20 to 1.95), and subclinical hypothyroidism 1.90 times; cardiovascular disease explained only 5.9 and 14.3 percent of those associations. In 3,018 Chinese adults followed for five years, a baseline TSH of 1.0 to 1.9 mIU/L had the lowest subsequent incidence of abnormal thyroid function. Both are associations in cohorts, not trials.12,13Grade B

The strongest evidence running the other way is from Rotterdam. Among 7,785 adults (mean age 64.7) with TSH and free T4 inside the reference range, followed for a median of 8.1 years, men and women in the highest TSH tertile lived 2.0 and 1.4 years longer than those in the lowest, and those in the highest free T4 tertile lived 3.2 and 3.5 years less. The authors read this as low-normal thyroid function favoring longevity and called for the reference ranges to be re-examined, in the direction opposite to the narrow-range argument.14Grade B

Yet in the same Rotterdam population, 8,452 adults followed for a mean of 7.9 years, higher TSH predicted more type 2 diabetes (hazard 1.13 per log unit, and 1.24 within the reference range), and people with prediabetes progressed to diabetes more often when their TSH was high-normal (hazard 1.32). The same cohort, two outcomes, two directions: a reminder that TSH is not a single-axis risk factor.15Grade B

In the Norwegian HUNT study of 30,656 people without thyroid disease, total, LDL and non-HDL cholesterol and triglycerides rose linearly, and HDL fell, with increasing TSH across the whole reference range. Eleven years later, in 9,709 women and 4,644 men who started with a TSH of 0.45 to 4.5, a higher baseline TSH predicted modestly higher blood pressure and less favorable lipids, and people whose TSH rose over the decade saw their blood pressure and lipids rise with it. The authors call the associations very modest.16,17Grade B

The best test of whether a mildly raised TSH is worth treating is the TRUST trial: 737 adults aged 65 and over with a persisting TSH of 4.60 to 19.99 (mean 6.40) and normal free T4 were randomized to levothyroxine or placebo. At one year TSH was 3.63 on treatment and 5.48 on placebo, and the hypothyroid symptom score and tiredness score did not differ (between-group differences 0.0 and 0.4 points on 100-point scales, against a minimum important difference of 9). No secondary outcome improved.18Grade A

Pooling 21 randomized trials with 2,192 nonpregnant adults with subclinical hypothyroidism, thyroid hormone brought TSH into the reference range (0.5 to 3.7 versus 4.6 to 14.7 on placebo) but did not improve general quality of life (standardized mean difference -0.11) or thyroid-related symptoms (0.01), with moderate-to-high quality evidence. A BMJ guideline panel then issued a strong recommendation against thyroid hormones for subclinical hypothyroidism, with exceptions for women trying to conceive, a TSH above 20, severe symptoms, and adults of about 30 or younger.19,20Grade A

The 2012 American Association of Clinical Endocrinologists and American Thyroid Association guideline takes a middle position: TSH is the single best screening test, levothyroxine is the standard treatment, and the decision to treat a subclinical hypothyroidism with a TSH below 10 mIU/L should be tailored to the individual rather than made by the number.2Grade A

A TSH in the upper reference range predicts future hypothyroidism, especially with antibodies. In the Whickham cohort of 2,779 British adults followed for 20 years, the odds of developing hypothyroidism were 8 in women and 44 in men with a raised TSH alone, 8 and 25 with thyroid antibodies alone, and 38 and 173 with both; the probability rose with any TSH above 2 mU/L at baseline and rose further in the presence of antibodies. This is the strongest argument that a TSH of 3 or 4 is not always benign, and also the reason an antibody test belongs beside it.21Grade B

05 · What moves it

The levers with evidence behind them.

What is listed here has been tested. The size of each effect, and the size of the study, are in the sentence, so a small effect reads as a small effect.

  • Iodine, too little or too much

    excess raises it, through autoimmune thyroiditis and subclinical hypothyroidism

    In three Chinese regions with mildly deficient, more-than-adequate and excessive iodine intake (median urinary iodine 84, 243 and 651 µg/L), the five-year cumulative incidence of subclinical hypothyroidism was 0.2, 2.6 and 2.9 percent and of autoimmune thyroiditis 0.2, 1.0 and 1.3 percent. More iodine is not better for the thyroid once intake is adequate.13Grade B

  • Selenium

    lowers thyroid antibodies in autoimmune thyroiditis; effect on TSH and symptoms unproven

    The Cochrane review of selenium for Hashimoto's thyroiditis found four trials with 463 participants, at unclear to high risk of bias. Selenomethionine 200 µg lowered thyroid peroxidase antibodies in two trials, but the clinical relevance was unclear, quality of life was not measured, and the reviewers judged the evidence incomplete for or against.22Grade C

  • Body weight

    higher weight raises it; weight loss lowers it

    In 4,082 Danish adults without overt thyroid disease, body mass index rose across categories of TSH, with a difference of 1.9 kg/m2, about 5.5 kg in women, between the highest and lowest TSH groups, and TSH category predicted weight gain over five years. The direction runs both ways: a meta-analysis of 24 studies found TSH fell after bariatric surgery while free T4 did not change. A modestly raised TSH in a person carrying extra weight is partly a consequence of the weight, not only a cause of it.23,24Grade C

  • Sleep loss

    acute loss raises it; chronic short sleep lowers it slightly

    TSH is highest overnight and in the early morning, and the rise is accentuated by sleep deprivation, strenuous exercise and night-shift work. Acute sleep loss raises TSH; when 11 healthy adults slept 5.5 versus 8.5 hours for 14 days, TSH and free T4 fell modestly, mostly in the women. A TSH drawn after a bad night or a night shift is a different number from one drawn after a normal week.5,25Grade C

  • Medications

    lithium and amiodarone raise it in a substantial minority of people taking them

    In a meta-analysis of 385 studies, lithium raised the odds of clinical hypothyroidism 5.78-fold compared with placebo and raised TSH on average. Pooled across studies of people with heart disease taking amiodarone, 23.4 percent developed hypothyroidism and 11.6 percent hyperthyroidism. Neither drug should be stopped over a TSH; the finding is a conversation with the prescriber.26,27Grade B

06 · Reading it well

Caveats, and what belongs with a physician.

Each person has a narrow set point. In 16 healthy men sampled monthly for a year, the width of each individual's TSH range was about half that of the group, the index of individuality was 0.49, and a single result located a person's set point only to within plus or minus 50 percent. A change of about 0.75 mIU/L (range 0.2 to 1.6) between two draws was needed to be 95 percent confident something had moved. A value inside the laboratory range can therefore be abnormal for the individual, and the best comparison for your TSH is your own prior TSH.1Grade B

TSH follows a daily rhythm, with a nocturnal surge and higher early-morning values that fall through the day; the 97.5th percentile of a very large laboratory dataset moved with the hour of the draw, while time of year made no measurable difference to the reference interval. Repeated measurements in the same person also vary considerably over months. Draw it at the same time of day, and read one result as one result.9,5Grade B

Biotin supplements interfere with the assays many laboratories use. In 10 healthy adults, 5 mg a day for a week produced false results on two of three major analyzer platforms for about 8 hours after the last dose, and 10 mg a day for one to two days. Across more than 150 documented thyroid-assay interferences of all kinds, half or more led to a misdiagnosis or an inappropriate treatment. Stop biotin for at least two days before a thyroid draw, and tell the laboratory if a result does not fit the picture.28,29Grade B

During serious illness TSH stops meaning what it usually means. Critically ill patients typically show low T3, low T4 and a normal or slightly lowered TSH, the nonthyroidal illness syndrome; the depth of the change tracks prognosis without proof that it causes the outcome. A thyroid panel drawn during or soon after an acute illness should be repeated once well.30Grade A

Pregnancy has its own rules: thyroid physiology changes from the first weeks, the reference ranges are trimester-specific, and the American Thyroid Association maintains a separate guideline for preconception, pregnancy and the postpartum period. Nothing on this page applies to a pregnant reader or one planning a pregnancy.31Grade A

A single raised TSH is not a diagnosis. Trials of subclinical hypothyroidism enrolled only people whose TSH stayed raised on repeat testing, and the authors who argue for leaving the reference range alone suggest simply rechecking a TSH in the upper reference range every one to two years.18,5Grade A

See a physician

  • A TSH of 10 mIU/L or higher on any draw, or a TSH that stays above the laboratory range on two draws.
  • A TSH below 0.1 mIU/L, or below the laboratory range with palpitations, tremor, weight loss, heat intolerance or an irregular heartbeat.
  • Any abnormal TSH, or thyroid antibodies, while pregnant, trying to conceive or in the year after a birth.
  • A lump in the neck, a visibly enlarged thyroid, difficulty swallowing, or hoarseness that does not resolve, whatever the TSH.
  • Symptoms of hypothyroidism together with positive thyroid peroxidase antibodies, where the odds of progression are high enough to warrant a plan and a follow-up schedule.
  • A TSH that has risen or fallen by about 0.75 mIU/L or more between two draws, which is beyond one person's usual variation.

This page is education, not individual medical advice, and reading it creates no physician-patient relationship.

07 · Open questions

What the literature does not settle.

  • No randomized trial has treated people with a TSH inside the laboratory range to a lower target and measured symptoms, cardiovascular events or mortality, so any optimal zone inside the range is an inference from cohorts, not a tested goal.
  • The cohorts disagree on direction inside the range: higher-normal TSH went with higher mortality in NHANES, with more diabetes and worse lipids in Rotterdam and HUNT, and with longer life in Rotterdam. Whether these reflect TSH itself, free T4, age, weight, or undiagnosed autoimmunity is unresolved.
  • Whether an age-adjusted upper limit (about 3.5 at 25, about 7.5 at 85) should replace the single printed limit is argued but not settled; neither laboratories nor guidelines have adopted it.
  • Younger adults with symptoms and a TSH of 4.5 to 10 were under-represented in the treatment trials, which were weighted toward people over 65; the BMJ guideline explicitly excludes them from its recommendation against treatment, and no trial has filled the gap.
  • Whether treating antibody-positive people with a high-normal TSH prevents progression to overt hypothyroidism, or helps symptoms, has not been tested in a trial of adequate size.

08 · In practice

How Dr. Tagge reads it in his own practice.

I like to see TSH between about 0.5 and 2.5, read beside free T4, free T3 and thyroid peroxidase antibodies, and always against the person's own prior values. That window is a judgment on contested ground, and I hold it as one. It is where 85 percent of antibody-free adults sit and where two cohorts found the lowest mortality and the lowest later thyroid trouble; it is also a window the Rotterdam data push back on, and one that an 80-year-old will sit above with no disease at all. So I read the number by age, by antibodies, by symptoms and by trend. A TSH of 3.5 in a 30-year-old with antibodies and symptoms earns a plan; the same number in a 75-year-old with neither earns a recheck in a year. I do not treat a number inside the range on its own, and the trials have convinced me that a mildly raised TSH in an older adult is usually a thing to watch, not to medicate.

A practice judgment, labeled as one (Grade D): it is how one physician reads the number for the people he cares for, not a recommendation for you.

09

Questions

10 · Sources

31 sources, read in full.

Numbered in the order they appear. Each line says what this page relies on from the paper; the link opens the record at PubMed or the publisher.

  1. 1.

    Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. Journal of Clinical Endocrinology and Metabolism. 2002. PMID 11889165. DOI 10.1210/jcem.87.3.8165.

    Laboratory method study · In 16 healthy men sampled monthly for a year, individual TSH ranges were about half the group range, index of individuality 0.49; a change of 0.75 mU/L (range 0.2 to 1.6) was needed for 95 percent confidence of a real change.

  2. 2.

    Garber JR, Cobin RH, Gharib H, et al.; American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine Practice. 2012. PMID 23246686. DOI 10.4158/EP12280.GL.

    Guideline · Serum TSH is the single best screening test for primary thyroid dysfunction; the decision to treat subclinical hypothyroidism with TSH below 10 mIU/L should be tailored to the individual.

  3. 3.

    Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). Journal of Clinical Endocrinology and Metabolism. 2002. PMID 11836274. DOI 10.1210/jcem.87.2.8182.

    Cross-sectional study · In 17,353 Americans, hypothyroidism 4.6 percent and hyperthyroidism 1.3 percent; mean TSH 1.50 mIU/L in people without thyroid disease; TPO antibodies in 11.3 percent; mean TSH 1.18 in Black Americans versus 1.45 in whites in the reference population.

  4. 4.

    Jonklaas J, Bianco AC, Bauer AJ, et al.; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014. PMID 25266247. DOI 10.1089/thy.2014.0028.

    Guideline · Levothyroxine remains the standard of care; the task force names superior biomarkers of euthyroidism to supplement TSH as a research need.

  5. 5.

    Surks MI, Goswami G, Daniels GH. The thyrotropin reference range should remain unchanged. Journal of Clinical Endocrinology and Metabolism. 2005. PMID 16148346. DOI 10.1210/jc.2005-0170.

    Review · In the NHANES III reference group of 14,333, 85 percent had TSH below 2.5 and 9.7 percent sat at 2.5 to 4.5 (20.6 million Americans); TSH varies with time of day, sleep deprivation, exercise and shift work; suggests rechecking an upper-range TSH every 1 to 2 years.

  6. 6.

    Baloch Z, Carayon P, Conte-Devolx B, et al.; Guidelines Committee, National Academy of Clinical Biochemistry. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003. PMID 12625976. DOI 10.1089/105072503321086962.

    Guideline · The NACB laboratory guideline whose reading of screened reference populations underlies the proposal for a TSH upper limit near 2.5 mIU/L.

  7. 7.

    Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. Journal of Clinical Endocrinology and Metabolism. 2005. PMID 16148345. DOI 10.1210/jc.2005-0455.

    Review · Argues from the NACB guideline that more than 95 percent of normal individuals have TSH below 2.5 mIU/L, and that the mean of 1.18 in African Americans may be the true normal mean.

  8. 8.

    Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. Journal of Clinical Endocrinology and Metabolism. 2007. PMID 17911171. DOI 10.1210/jc.2007-1499.

    Cross-sectional study · Without thyroid disease, 10.6 percent of 20- to 29-year-olds and 40 percent of those over 80 had TSH above 2.5; 97.5th percentiles 3.56 and 7.49 mIU/L; 70 percent of older people with TSH above 4.5 were within their age-specific range.

  9. 9.

    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. PMID 26061389. DOI 10.1089/thy.2014.0589.

    Cross-sectional study · In 465,593 TSH measurements, the upper limit rose from 6.45 to 7.55 mIU/L with age through a larger nocturnal surge; hour of day mattered, time of year did not; sex difference at most 0.1 mIU/L.

  10. 10.

    Rodondi N, den Elzen WP, Bauer DC, et al.; Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010. PMID 20858880. DOI 10.1001/jama.2010.1361.

    Systematic review and meta-analysis · In 55,287 adults from 11 cohorts, coronary event hazard was 1.00 at TSH 4.5 to 6.9, 1.17 at 7.0 to 9.9 and 1.89 at 10 to 19.9; coronary death 1.09, 1.42 and 1.58; total mortality not raised.

  11. 11.

    Collet TH, Gussekloo J, Bauer DC, et al.; Thyroid Studies Collaboration. Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Archives of Internal Medicine. 2012. PMID 22529182. DOI 10.1001/archinternmed.2012.402.

    Systematic review and meta-analysis · In 52,674 adults from 10 cohorts, TSH below 0.45 carried hazards of 1.24 for mortality, 1.29 for coronary death and 1.68 for atrial fibrillation, highest below 0.10.

  12. 12.

    Inoue K, Ritz B, Brent GA, Ebrahimi R, Rhee CM, Leung AM. Association of Subclinical Hypothyroidism and Cardiovascular Disease With Mortality. JAMA Network Open. 2020. PMID 32031647. DOI 10.1001/jamanetworkopen.2019.20745.

    Prospective cohort · In 9,020 US adults, high-normal TSH (1.96 to 5.60) carried hazard 1.36 and subclinical hypothyroidism 1.90 for all-cause mortality versus the middle tertile (1.20 to 1.95); cardiovascular disease mediated 5.9 and 14.3 percent.

  13. 13.

    Teng W, Shan Z, Teng X, et al.. Effect of iodine intake on thyroid diseases in China. New England Journal of Medicine. 2006. PMID 16807415. DOI 10.1056/NEJMoa054022.

    Prospective cohort · Across regions with median urinary iodine 84, 243 and 651 µg/L, five-year incidence of subclinical hypothyroidism was 0.2, 2.6 and 2.9 percent; a baseline TSH of 1.0 to 1.9 mIU/L had the lowest subsequent incidence of abnormal thyroid function.

  14. 14.

    Bano A, Dhana K, Chaker L, et al.. Association of Thyroid Function With Life Expectancy With and Without Cardiovascular Disease: The Rotterdam Study. JAMA Internal Medicine. 2017. PMID 28975207. DOI 10.1001/jamainternmed.2017.4836.

    Prospective cohort · In 7,785 euthyroid adults, the highest TSH tertile lived 2.0 (men) and 1.4 (women) years longer than the lowest; the highest free T4 tertile lived 3.2 and 3.5 years less.

  15. 15.

    Chaker L, Ligthart S, Korevaar TI, et al.. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Medicine. 2016. PMID 27686165. DOI 10.1186/s12916-016-0693-4.

    Prospective cohort · In 8,452 Rotterdam adults, higher TSH carried hazard 1.13 per log unit for type 2 diabetes, 1.24 within the reference range, and 1.32 for progression from prediabetes.

  16. 16.

    Asvold BO, Vatten LJ, Nilsen TI, Bjøro T. The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. European Journal of Endocrinology. 2007. PMID 17287407. DOI 10.1530/eje.1.02333.

    Cross-sectional study · In 30,656 people, total, LDL and non-HDL cholesterol and triglycerides rose linearly and HDL fell with increasing TSH across the reference range.

  17. 17.

    Asvold BO, Bjøro T, Vatten LJ. Associations of TSH levels within the reference range with future blood pressure and lipid concentrations: 11-year follow-up of the HUNT study. European Journal of Endocrinology. 2013. PMID 23641017. DOI 10.1530/EJE-13-0087.

    Prospective cohort · In 9,709 women and 4,644 men with baseline TSH 0.45 to 4.5, higher TSH predicted modestly higher blood pressure and adverse lipids 11 years later; changes in TSH tracked changes in blood pressure and lipids.

  18. 18.

    Stott DJ, Rodondi N, Kearney PM, et al.; TRUST Study Group. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. New England Journal of Medicine. 2017. PMID 28402245. DOI 10.1056/NEJMoa1603825.

    Randomized trial · In 737 adults aged 65 and over with TSH 4.60 to 19.99, levothyroxine lowered TSH to 3.63 versus 5.48 on placebo and produced no difference in hypothyroid symptom or tiredness scores at one year.

  19. 19.

    Feller M, Snel M, Moutzouri E, et al.. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018. PMID 30285179. DOI 10.1001/jama.2018.13770.

    Systematic review and meta-analysis · Across 21 trials and 2,192 adults, thyroid hormone normalized TSH but did not improve quality of life (SMD -0.11) or thyroid symptoms (SMD 0.01).

  20. 20.

    Bekkering GE, Agoritsas T, Lytvyn L, et al.. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019. PMID 31088853. DOI 10.1136/bmj.l2006.

    Guideline · Strong recommendation against thyroid hormones for subclinical hypothyroidism, not applying to women trying to conceive or TSH above 20, and possibly not to severe symptoms or adults of 30 or younger.

  21. 21.

    Vanderpump MP, Tunbridge WM, French JM, et al.. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clinical Endocrinology. 1995. PMID 7641412. DOI 10.1111/j.1365-2265.1995.tb01894.x.

    Prospective cohort · Over 20 years in 2,779 adults, odds of hypothyroidism were 8 (women) and 44 (men) with raised TSH alone, 8 and 25 with antibodies alone, 38 and 173 with both; probability rose with TSH above 2 mU/L.

  22. 22.

    van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H. Selenium supplementation for Hashimoto's thyroiditis. Cochrane Database of Systematic Reviews. 2013. PMID 23744563. DOI 10.1002/14651858.CD010223.pub2.

    Systematic review and meta-analysis · Four trials, 463 participants, unclear to high risk of bias; selenomethionine 200 µg lowered TPO antibodies with unclear clinical relevance; evidence incomplete for or against.

  23. 23.

    Knudsen N, Laurberg P, Rasmussen LB, Bülow I, Perrild H, Ovesen L, Jørgensen T. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. Journal of Clinical Endocrinology and Metabolism. 2005. PMID 15870128. DOI 10.1210/jc.2004-2225.

    Cross-sectional study · In 4,082 Danish adults, BMI differed by 1.9 kg/m2 (5.5 kg in women) between highest and lowest TSH categories, and TSH category predicted weight gain over 5 years.

  24. 24.

    Guan B, Chen Y, Yang J, Yang W, Wang C. Effect of Bariatric Surgery on Thyroid Function in Obese Patients: a Systematic Review and Meta-Analysis. Obesity Surgery. 2017. PMID 29039052. DOI 10.1007/s11695-017-2965-2.

    Systematic review and meta-analysis · Across 24 studies, bariatric surgery was followed by a significant fall in TSH, free T3 and T3, with no change in free T4.

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    Randomized trial · In 11 healthy adults, 14 days of 5.5 versus 8.5 hours in bed produced a modest fall in TSH and free T4, mainly in women, in contrast to the known rise in TSH during acute sleep loss.

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    Systematic review and meta-analysis · Across 385 studies, lithium raised the odds of clinical hypothyroidism 5.78-fold versus placebo and raised TSH on average.

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    Rahimi-Bashar F, Vahedian-Azimi A, Dalvand S, et al.. Prevalence of Amiodarone Induced Hypothyroidism and Hyperthyroidism in Patients with Heart Diseases: A Systematic Review and Meta-Analysis. Current Medicinal Chemistry. 2023. PMID 36045523. DOI 10.2174/0929867329666220831145651.

    Systematic review and meta-analysis · Pooled prevalence of hypothyroidism 23.43 percent and hyperthyroidism 11.61 percent in people with heart disease taking amiodarone.

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    Zhang Y, Wang R, Dong Y, Huang G, Ji B, Wang Q. Assessment of biotin interference in thyroid function tests. Medicine (Baltimore). 2020. PMID 32118725. DOI 10.1097/MD.0000000000019232.

    Laboratory method study · In 10 healthy adults, biotin 5 mg a day for 7 days interfered with thyroid tests on Roche and Beckman platforms for 8 hours after the last dose, and 10 mg a day for 1 to 2 days; no interference on Abbott.

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    Favresse J, Burlacu MC, Maiter D, Gruson D. Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocrine Reviews. 2018. PMID 29982406. DOI 10.1210/er.2018-00119.

    Review · Six main assay interferences including biotin and macro-TSH; prevalence of some approaches 1 percent; half or more of more than 150 documented cases led to misdiagnosis or inappropriate management.

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    Fliers E, Bianco AC, Langouche L, Boelen A. Thyroid function in critically ill patients. Lancet Diabetes and Endocrinology. 2015. PMID 26071885. DOI 10.1016/S2213-8587(15)00225-9.

    Review · Critical illness produces low T3, low T4 and normal or slightly lowered TSH (nonthyroidal illness syndrome); its extent tracks prognosis without proof of causality.

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    Korevaar TIM, Leung AM, Alexander EK, et al.. American Thyroid Association 2026 Guidelines for Thyroid Disease in Preconception, Pregnancy, and Postpartum. Thyroid. 2026. PMID 42219800. DOI 10.1177/10507256261445624.

    Guideline · The current ATA guideline for thyroid testing and treatment before, during and after pregnancy, including thyroid function testing, iodine, autoimmunity and hypothyroidism.

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