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Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed – A Review for Primary Care

Open access
Sheehan, Michael T.·2016·Clinical Medicine & Research
DOI 10.3121/cmr.2016.1309PMC PMC5321289
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Abstract

Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers. While management of significant biochemical abnormalities is reasonably straight forward, laboratory tests only slightly outside, or even within, the normal range are becoming more difficult to appropriately manage. A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust. Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry. This review aims to clarify the interpretation of normal and mild abnormalities of thyroid function tests by describing pituitary-thyroid physiology and through an in depth review of, arguably, the three most important biochemical tests of thyroid function: TSH, free T4, and anti-TPO antibodies. It is important for primary care providers to have an understanding of the shortcomings and proper interpretation of these tests to be better able to discuss thyroid function with their patients.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that TSH is the single most useful thyroid function test in primary care, with free T4 and anti-TPO antibodies reserved for specific indications. It reviews thyroid physiology, assay limitations, and natural-history data to support relying on TSH and avoiding unnecessary testing.

Key findings

  • TSH is the most sensitive marker of thyroid function because the free T4/free T3–TSH relationship is log-linear: a 2-fold change in free T4 produces a 100-fold change in TSH (e.g., free T4 1.0 to 0.5 ng/dL corresponds to TSH 0.5 to 50 mIU/mL), while TSH rising from 1.0 to 5.0 mIU/mL reflects free T4 falling only from 1.0 to 0.9 ng/dL. The listed normal TSH range is 0.35–4.50 mIU/mL, but the “most normal” range is suggested as 0.5–2.50 mIU/mL; age-adjusted upper limits were 3.5 mIU/mL for ages 20–29, 4.5 for 50–70, and 7.5 for over 80.
  • Subclinical hypothyroidism (TSH 4.6–8.0 mIU/mL with normal free T4) has a prevalence of 3.9%–8.5%, versus 0.2%–0.4% for overt hypothyroidism. In one study, 52% of patients with initial TSH 5.0–9.9 mIU/mL spontaneously normalized and only 5.6% developed overt hypothyroidism over mean 31.7 months; in the Whickham survey, elevated TSH >6.0 mIU/mL alone progressed to overt hypothyroidism at 2.6% per year (33% over 20 years), rising to 4.3% per year (55%) with anti-TPO antibodies.
  • Subclinical hyperthyroidism has a prevalence of 0.2%–0.9%. In TEARS, among 1,507 patients with baseline TSH 0.1–0.4 mIU/mL, progression to overt hyperthyroidism was 0.5%, 0.7%, and 0% at 2, 5, and 7 years; many remained mildly suppressed (71.8%, 55%, 50.2%) or normalized (16.7%, 31.6%, 37.6%).
  • Free T4 and anti-TPO testing are often unnecessary: approximately 18 million free T4 tests versus 59 million TSH tests were performed in the US in 2008. Free T4 assay accuracy is problematic—4 of 13 methods had >50% of results failing allowable inaccuracy criteria—and correlation with TSH was poor for direct analog immunoassay (Pearson 0.20 when TSH normal, 0.45 when abnormal) versus LC-MS/MS (0.74 and 0.84). Anti-TPO antibodies were present in 14.6% of euthyroid females and 8.0% of euthyroid males in NHANES III; undiagnosed central hypothyroidism was estimated at ~0.05%–0.1% (about 1 per 1,500), with free T4 screening costing $82,500–$162,000 per case identified.

Methods

  • Narrative review for primary care, not a systematic review or meta-analysis; it synthesizes physiology, clinical guidelines, and selected published studies.
  • Focuses on three biochemical tests—TSH, free T4, and anti-thyroid peroxidase antibodies—and discusses their indications, utility, and shortcomings, plus other thyroid tests.
  • Evidence is drawn from cited literature including NHANES III, the Whickham survey, TEARS, assay-comparison studies, and clinical guidelines; no primary data collection is reported.

Limitations

  • Stated: population-based data on undiagnosed hypothalamic/pituitary disease are limited, prevalence estimates may be under- or overestimates, cost-effectiveness of adding free T4 is uncertain, free T4 assay standardization and accuracy are limited, anti-TPO utility is only predictive, and evidence for low-dose L-T4 in anti-TPO-positive euthyroid infertility/recurrent miscarriage is not fully proven.
  • Evident: as a narrative review, it lacks a systematic search strategy or formal quality appraisal, and several recommendations are explicitly based on author opinion (e.g., discouraging anti-TPO testing, weighting laboratory results over symptoms).
  • Stated: the review focuses on non-hospitalized patients; thyroid function tests are difficult to interpret in acute illness or recent hospitalization.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3121/cmr.2016.1309

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 92 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The effect of age on normal TSH range appears to be more important, especially in advanced age.

    “While there may be slight differences in TSH reference ranges based on race, 6 the effect of age on normal range appears to be more important, especially in advanced age.7”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7]

      Not checked in the free run.

  • Interpretationreasoning

    The goal range for replacement therapy is different than the range at which hypothyroidism is diagnosed.

    “Note that the goal range for replacement therapy is different than the range at which hypothyroidism is diagnosed”
    Quote in the paperSubstantial claim
  • Premisecitation

    In a study assessing TSH values monthly for one year in healthy men, random variation occurred with a mean TSH of 0.75 mIU/mL and a range of 0.2-1.6 mIU/mL.

    “In a study assessing TSH values monthly for one year in healthy men, this apparent random variation occurred with a mean TSH of 0.75 mIU/mL and a range of 0.2-1.6 mIU/mL.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15]

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  • Interpretationreasoning

    Assessment of TSH is the single most useful test of thyroid function in the vast majority of patients.

    “Assessment of TSH is the single most useful test of thyroid function in the vast majority of patients.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    The circadian rhythm may cause a variation in TSH by a mean of between 0.95 mIU/mL to 2.0 mIU/mL.

    “While generally not resulting in TSH values outside the normal range, this circadian rhythm may cause a variation in TSH by a mean of between 0.95 mIU/mL to 2.0 mIU/mL, 13 which could affect treatment decisions.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13]

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  • Classified as probably not a substantial claim. 24
  • May combine two claims. 27

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The inter-assay precision of free T4 assays is generally good, about 4.3% in the authors' laboratory.

    “While the inter-assay precision of free T4 assays is generally good (~4.3% in our laboratory)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Primary care providers should seldom need to order any other biochemical thyroid test.

    “Primary care providers should seldom need to order any other biochemical thyroid test.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Any clinical decision should not be made (in a non-pregnant patient) based on a single TSH value if it is within or close to the normal range.

    “The importance of these issues is mainly that any clinical decision should not be made (in a non-pregnant patient) based on a single TSH value if it is within or close to the normal range.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    In most cases the TSH will be within the normal range, and no further testing is indicated.

    “In most cases the TSH will be within the normal range, and no further testing is indicated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In NHANES III, the upper limit of normal for TSH at the 97.5th percentile was 3.5 mIU/mL for 20-29 year olds, increasing to 4.5 mIU/mL for 50-70 year olds and 7.5 mIU/mL for those over 80 years.

    “In an analysis of the National Health and Nutrition Examination Survey (NHANES) III database, the upper limit of normal for TSH at the 97.5 th percentile was 3.5 mIU/mL for 20-29 year olds increasing to 4.5 mIU/mL for 50-70 year olds and 7.5 mIU/mL for those over the age of 80 years.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Normal ranges are calculated based on the 2.5th to 97.5th percentiles of the distribution of values measured in the population tested.

    “Lastly, it is important to understand that normal ranges are calculated based on the 2.5 th to 97.5 th percentiles of the distribution of values measured in the population tested.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The method used at our institution has a precision of ~3.2%, indicating that variations in the result over time in a single patient are not likely to be related to the assay itself but rather to other factors.

    “The method used at our institution has a precision of ~3.2%, indicating that variations in the result over time in a single patient are not likely to be related to the assay itself but rather to other factors (see below).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    A TSH of 4.2 mIU/mL may warrant an increase in levothyroxine dose but does not warrant initiation of replacement therapy in a non-pregnant patient.

    “(ie, while a TSH of 4.2 mIU/mL may warrant an increase in levothyroxine (L-T4) dose, it does not warrant initiation of replacement therapy in a non-pregnant patient).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Thyroid function tests can be difficult to reliably interpret in patients who are acutely ill, and the severity of the illness plays a role.

    “As mentioned previously, thyroid function tests can be difficult to reliably interpret in patients who are acutely ill, and the severity of the illness plays a role as well.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Farwell. 1

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population.

    “Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population.”
    • Also stated in: § Subclinical Hypothyroidism · plain
      “The difficultly in determining which, if any, symptoms are truly related is the non-specific nature of the symptoms of hypothyroidism and the high prevalence of many of these same complaints in the general population.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [17]

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    • cites [18]

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    • cites [19]

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  • May combine two claims.

    Premisecitation

    TSH may be mildly suppressed in acute illness and mildly elevated during recovery from acute illness.

    “Most important to this discussion is that the TSH may be mildly suppressed in acute illness and mildly elevated during recovery from acute illness.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Farwell. 1

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There may be slight differences in TSH reference ranges based on race.

    “While there may be slight differences in TSH reference ranges based on race, 6 the effect of age on normal range appears to be more important, especially in advanced age.7”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Even though the normal range for TSH is generally listed at between 0.35 mIU/mL and 4.50 mIU/mL, it is likely that the 'most normal' range is between 0.5 mIU/mL and 2.50 mIU/mL.

    “Indeed, even though the normal range for TSH is generally listed at between 0.35 mIU/mL and 4.50 mIU/mL, it is likely that the “most normal” range is between 0.5 mIU/mL and 2.50 mIU/ mL.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [2]

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    • cites [3]

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    • cites [4]

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  • May combine two claims.

    Interpretationreasoning

    Therefore, 2.5% of people with completely normal thyroid function will have a TSH slightly below the listed normal range (and 2.5% slightly above the normal range).

    “Therefore, 2.5% of people with completely normal thyroid function will have a TSH slightly below the listed normal range (and 2.5% slightly above the normal range).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    The age-related increase in TSH may be an adaptive mechanism, as there is evidence showing increased mortality in advanced age as TSH declines within the normal range.

    “This agerelated increase in TSH may be an adaptive mechanism, as there is evidence showing increased mortality in advanced age as TSH declines within the normal range.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Disruption of the hypothalamic-pituitary-thyroid axis is uncommon to rare and, when present, is usually already diagnosed.

    “Thankfully, disruption of this hormonal axis is uncommon to rare and, when present is usually already diagnosed (ie, a patient with a history of a pituitary macroadenoma).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    This prevalence is likely an underestimate based on flaws in case identification inherent in population-based studies.

    “This prevalence is likely an underestimate based on flaws in case identification inherent in population-based studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Several other fleetingly rare genetic disorders of thyroid hormone transport, metabolism, or action can result in a falsely normal TSH, but only a handful of cases have thus far been described in the literature.

    “There are several other fleetingly rare genetic disorders of thyroid hormone transport, metabolism, or action that can result in a falsely normal TSH, but only a handful of cases have thus far been described in the literature.42”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42]

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The reliable interpretation of thyroid function tests requires an intact hypothalamic-pituitary-thyroid axis.

    “As already described, the reliable interpretation of thyroid function tests requires an intact hypothalamic-pituitarythyroid axis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In one study, spontaneous normalization occurred in 52% of patients with an initial TSH of 5.0-9.9 mIU/mL, while only 5.6% developed overt hypothyroidism over a mean follow-up of 31.7 months.

    “Indeed, in one study, spontaneous normalization occurred in 52% of patients with an initial TSH of 5.0-9.9mIU/mL, while only 5.6% developed overt hypothyroidism over a mean follow-up of 31.7 months.23”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Regal et al. reported a prevalence of hypothyroidism due to hypopituitarism of 19-29/100,000 (perhaps 1 case per 4355 patients) in an adult Caucasian population in northwestern Spain.

    “Population-based data on this subject is limited, but Regal et al 27 reported a prevalence of hypothyroidism due to hypopituitarism of just 19-29/100,000 (perhaps 1 case per 4355 patients) in an adult Caucasian population in northwestern Spain.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27]

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  • May combine two claims.

    Interpretationcitation

    The studies with the highest prevalence of central hypothyroidism (14.3% and 22.2%) were either a retrospective analysis or analyzed patients admitted to the hospital and may overestimate the prevalence.

    “However, it should be noted that the studies with the highest prevalence of central hypothyroidism (14.3% and 22.2%, respectively) were either a retrospective analysis 34 or analyzed patients admitted to the hospital 38 and, thus, may overestimate the prevalence.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34]

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    • cites [38]

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  • May combine two claims.

    Interpretationreasoning

    Based on these data (5.5-35% prevalence of empty sella and an estimated prevalence of resultant hypothyroidism of 3.4%), central hypothyroidism due to empty sella would appear to be more common than that due to pituitary macroadenoma: between 1 per 83 and 1 per 526 patients.

    “Based on these data (5.5-35%prevalence of empty sella and an estimated prevalence of resultant hypothyroidism of 3.4%), central hypothyroidism due to empty sella would appear to be more common than that due to pituitary macroadenoma: between 1 per 83 and 1 per 526 patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The hallmarks of RTH are goiter, sinus tachycardia, and attention deficit hyperactivity disorder.

    “The hallmarks of this condition are goiter, sinus tachycardia, and attention deficit hyperactivity disorder.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The presence of a TSH-secreting pituitary adenoma can have laboratory results indistinguishable from RTH and may present with a normal TSH in the setting of hyperthyroidism.

    “The presence of a TSH-secreting pituitary adenoma can have laboratory results indistinguishable from RTH and may present with a normal TSH in the setting of hyperthyroidism.41”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41]

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The prevalence of subclinical hypothyroidism is between 3.9% and 8.5%, versus 0.2%-0.4% for overt hypothyroidism.

    “That being said, the prevalence of subclinical hypothyroidism is quite high at between 3.9% and 8.5% (versus the 0.2%-0.4% prevalence of overt hypothyroidism).6,22”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6]

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    • cites [22]

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  • May combine two claims.

    Premisecitation

    In a study of 500 consecutive subjects undergoing MRI of the brain, Foresti et al. found 12.4% to have a total empty sella, and an additional 15.6% had a partially empty sella.

    “In a study of 500 consecutive subjects undergoing MRI of the brain, Foresti et al 33 found 12.4% to have a total empty sella, and an additional 15.6% had a partially empty sella.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33]

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Resistance to thyroid hormone (RTH) is a rare condition generally caused by a mutation in the thyroid hormone receptor β gene resulting in elevated levels of free T3 and free T4, but a normal (or slightly elevated) TSH.

    “Resistance to thyroid hormone (RTH) is a rare condition generally caused by a mutation in the thyroid hormone receptor β gene resulting in elevated levels of free T3 and free T4, but a normal (or slightly elevated) TSH.40”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40]

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  • Classified as probably not a substantial claim.

    Interpretationnone given

    Elderly patients are likely a group best to follow without treatment for subclinical hypothyroidism.

    “Lastly, as mentioned earlier, it is likely that elderly patients are a group best to follow without treatment for subclinical hypothyroidism.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the TEARS study, the majority of patients continued with a mildly suppressed TSH during follow-up (71.8%, 55%, and 50.2%), while a significant number spontaneously resolved to normal (16.7%, 31.6%, and 37.6%).

    “The majority of patients continued with a mildly suppressed TSH during the same follow-up time periods (71.8%, 55%, and 50.2%), while a significant number spontaneously resolved to normal (16.7%, 31.6%, and 37.6%).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of subclinical hyperthyroidism is between 0.2% and 0.9%.

    “The primary care provider will see fewer of these patients owing to the lower prevalence of between 0.2-0.9%.6,22,26”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [6]

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    • cites [22]

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    • cites [26]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The prevalence of pituitary macroadenoma, based on MRI incidental lesions, is estimated at between 0.16-0.2%.

    “The prevalence of pituitary macroadenoma, based on data from magnetic resonance imaging (MRI) studies showing incidentally discovered lesions, has been estimated at between 0.16-0.2%.28,29”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28]

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    It is plausible that a truly elevated TSH could be falsely lowered into the normal range by the presence of heterophile antibodies.

    “Therefore, it is plausible that a truly elevated TSH could be falsely lowered into the normal range by the presence of heterophile antibodies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Assessment of free T4 is required in the diagnosis of subclinical hypothyroidism in the setting of a mildly elevated TSH.

    “the assessment of free T4 is required in the diagnosis of subclinical hypothyroidism in the setting of a mildly elevated TSH.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Because maintaining euthyroidism in pregnancy is important, pre-conception identification of women at risk for hypothyroidism is essential.

    “Because of the importance of maintaining euthyroidism in pregnancy, the pre-conception identification of women at risk for hypothyroidism is essential.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Maintaining euthyroidism in pregnancy is important.

  • May combine two claims.

    Interpretationreasoning

    The increasingly maligned TSH is still the best, and often only, thyroid function test needed in the assessment of most patients.

    “The increasingly maligned TSH is still the best, and often only, thyroid function test that is needed in the assessment of most patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The validity of free T4 results by direct analog immunoassay is debated and poorly standardized.

    “again the validity of the results are debated and poorly standardized.43,44,47”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [43]

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    • cites [44]

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    • cites [47]

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  • May combine two claims.

    Premisecitation

    Recent guidelines give the practice of assessing anti-TPO antibodies a grade B, as it is only predictive in nature.

    “As such, recent guidelines give this practice a grade “B,” as it is only predictive in nature.4”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4]

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  • May combine two claims.

    Premisecitation

    The Whickham survey demonstrated a rate of progression to overt hypothyroidism of 2.1% per year based on just the presence of anti-TPO antibodies with a normal TSH, increasing to 4.3% per year with a combination of TSH > 6.0 and positive anti-TPO antibodies.

    “Indeed, the Whickham survey demonstrated a rate of progression to overt hypothyroidism of 2.1% per year based on just the presence of anti-TPO ABs (with a normal TSH) with an increase in that risk to 4.3% per year with a combination of a TSH > 6.0 and positive anti-TPO ABs.24”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24]

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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    There is really nothing to be done about the presence of anti-TPO antibodies.

    “Thus, there is really nothing to be done about the presence of these antibodies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Many endocrinologists and gynecologists recommend treatment with low-dose L-T4 therapy in anti-TPO antibody positive, euthyroid patients with a history of infertility and/or recurrent miscarriage.

    “Many endocrinologists and gynecologists will recommend treatment with low-dose L-T4 therapy in anti-TPO ABs positive, euthyroid patients with a history of infertility and/or recurrent miscarriage.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A working group for the international standardization of the free T4 assay has been formed.

    “a working group for the international standardization of the free T4 assay has been formed.[45][46][47]”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [45]

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    • cites [46]

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    • cites [47]

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The remaining thyroid function tests beyond TSH, free T4, and anti-TPO antibodies are seldom needed, even by endocrinologists outside of very well-defined clinical scenarios.

    “However, it should be noted that these remaining tests are seldom needed, even by endocrinologists outside of very well-defined clinical scenarios.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a comparison of the IA and LC-MS/MS methods in 109 patients, the correlation between free T4 and TSH was quite poor for the IA method and substantially better for LC-MS/MS.

    “In a comparison of the IA and LC-MS/MS method in 109 patients, the correlation between free T4 and TSH was quite poor for the IA method and substantially better for LC-MS/MS.49”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49]

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  • May combine two claims.

    Premisecitation

    The presence of anti-TPO antibodies is a hallmark of autoimmune thyroid disease, especially Hashimoto's thyroiditis, and is also highly prevalent in postpartum thyroiditis and Graves' disease.

    “The presence of anti-TPO ABs is a hallmark of autoimmune thyroid disease, especially Hashimoto's thyroiditis, but also being highly prevalent in postpartum thyroiditis and Graves' disease.50”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50]

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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    One instance where assessment of anti-TPO antibodies is recommended, even when TSH is normal, is in some women in relation to pregnancy or planned pregnancy.

    “One instance where assessment of anti-TPO AB is recommended (even when the TSH is normal) is in some women in relation to pregnancy or planned pregnancy.”
    Quote in the paperSubstantial claim
46 of 46

  • The paper relies on this without support.

    Disorders of thyroid function are common.

    “Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers.”

  • The paper relies on this without support.

    Many patients request and even demand certain biochemical tests or treatments that may not be indicated.

    “A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated.”
    “This has become a more complex process, with many patients requesting and even demanding certain biochemical tests that may not be indicated.”

  • The paper relies on this without support.

    A growing body of lay press and internet information suggests that traditional thyroid function testing is not reliable, fostering patient mistrust.

    “This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust.”

  • The paper relies on this without support.

    When a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry.

    “Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry.”

  • The paper relies on this without support.

    Each individual has a set point for their own free T3 and free T4 level that is quite stable in the absence of disease.

    “It is also important to note that each individual has a set point for their own free T3 and free T4 level that is quite stable in the absence of disease.”

  • The paper relies on this without support.

    The prevalence of pituitary microadenoma is about 10% of the population.

    “While pituitary microadenoma is quite common (~10% of the population), the vast majority of these small tumors are not large enough to adversely affect normal pituitary function.”

  • The paper relies on this without support.

    Not all pituitary macroadenomas adversely affect normal pituitary function, and when they do, limitation of growth hormone secretion and gonadal function are more common than an effect on thyroid function.

    “Importantly, however, not all pituitary macroadenomas adversely affect normal pituitary function, and when they do, limitation of growth hormone secretion and gonadal function are more common than an effect on thyroid function.”

  • The paper relies on this without support.

    Not all patients with empty sella will have central hypothyroidism.

    “Just as with pituitary macroadenoma, not all patients with empty sella will have central hypothyroidism, and the data is limited.”

  • The paper relies on this without support.

    The prevalence of subclinical or overt hyperthyroidism is 0.2-0.9%.

    “the prevalence of subclinical or overt hyperthyroidism is perhaps just 0.2-0.9%”

  • The paper relies on this without support.

    Virtually all hypothyroid patients in iodine-sufficient areas of the world without a prior history of thyroid surgery or radioactive iodine therapy have Hashimoto's thyroiditis.

    “virtually all hypothyroid patients in iodine-sufficient areas of the world without a prior history of thyroid surgery or radioactive iodine therapy will have Hashimoto's thyroiditis”

  • The paper relies on this without support.

    Maintaining euthyroidism in pregnancy is important.

    “Because of the importance of maintaining euthyroidism in pregnancy”

  • The paper relies on this without support.

    Primary hypothyroidism is one of the most common endocrine disorders encountered and managed by primary care providers.

    “Primary hypothyroidism is one of the most common endocrine disorders encountered and managed by primary care providers.”

  • The paper relies on this without support.

    The symptoms of hypothyroidism are extremely non-specific and otherwise highly prevalent in the population.

    “the symptoms of hypothyroidism are extremely non-specific and otherwise highly prevalent in the population.”
13 of 13

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TSH release is highly sensitive to the prevailing level of T4: reducing FT4 by half would typically increase the TSH level by up to 100-fold; conversely, a five-fold increase in the TSH level might be seen when FT4 is reduced by only about 10%.

    “reducing FT4 by half would typically increase the TSH level by up to 100-fold; conversely, a five-fold increase in the TSH level might be seen when FT4 is reduced by only about 10%”

    From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [21]

The citation lists haven’t been fetched yet

References 63 · Cited by 179

Research works printed but not linked: 1

  1. Steel BW, Wang, E, Klee GC, Thienpont LM, Soldin SJ, Sokoll LJ, Winter W, Fuhrman SA and Elin RJ. Analytic bias of thyroid function tests. Arch Pathol Lab Med 2005;129:310317.

Authors
Sheehan, M. T.
Affiliations
Marshfield Clinic Weston Center (US)
Corresponding author
Sheehan, Michael T.
ORCID
Sheehan, Michael T.
Venue
Clinical Medicine & Research
Publisher
Marshfield Clinic Research Institute
Published
2016-05-26
Volume
14
Issue
2
Pages
83-92
ISSN
  • 1539-4182 (ISSN-L)
  • 1554-6179
DOI
10.3121/cmr.2016.1309
PMC
PMC5321289
OpenAlex
W2396671315
Semantic Scholar
c087e43d9387af695a0a76a3a19e73ad6c621225
Cited by
179
References
63
Citations by year
2026: 7 · 2025: 21 · 2024: 20 · 2023: 35 · 2022: 27 · 2021: 19 · 2020: 14 · 2019: 19 · 2018: 9 · 2017: 7 · 2016: 1
FWCI
1.76
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Clinical Medicine & Research (publishedVersion, public-domain)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
thyroid function tests, thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies, thyroid dysfunction, patient trust, primary care, test interpretation
MeSH terms
Adult, Aged, Antibodies, Autoantigens, Circadian Rhythm, Cost-Benefit Analysis, Female, Humans, Hyperthyroidism, Hypothyroidism, Iodide Peroxidase, Male, Middle Aged, Pituitary Gland, Primary Health Care, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Iron-Binding Proteins, Young Adult

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