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Levothyroxine therapy in elderly patients with hypothyroidism

Open access
Effraimidis, Grigoris, Watt, Torquil, Feldt-Rasmussen, Ulla·2021·Frontiers in Endocrinology
DOI 10.3389/fendo.2021.641560PMC PMC8006441
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Abstract

Levothyroxine (L-T4) treatment of overt hypothyroidism can be more challenging in elderly compared to young patients. The elderly population is growing, and increasing incidence and prevalence of hypothyroidism with age are observed globally. Elderly people have more comorbidities compared to young patients, complicating correct diagnosis and management of hypothyroidism. Most importantly, cardiovascular complications compromise the usual start dosage and upward titration of L-T4 due to higher risk of decompensating cardiac ischemia and -function. It therefore takes more effort and care from the clinician, and the maintenance dose may have to be lower in order to avoid a cardiac incidence. On the other hand, L-T4 has a beneficial effect on cardiac function by increasing performance. The clinical challenge should not prevent treating with L-T4 should the patient develop e.g., cardiac ischemia. The endocrinologist is obliged to collaborate with the cardiologist on prophylactic cardiac measures by invasive cardiac surgery or medical therapy against cardiac ischemic angina. This usually allows subsequent successful treatment. Management of mild (subclinical) hypothyroidism is even more complex. Prevalent comorbidities in the elderly complicate correct diagnosis, since many concomitant morbidities can result in non-thyroidal illness, resembling mild hypothyroidism both clinically and biochemically. The diagnosis is further complicated as methods for measuring thyroid function (thyrotropin and thyroxine) vary immensely according to methodology and background population. It is thus imperative to ensure a correct diagnosis by etiology (e.g., autoimmunity) before deciding to treat. Even then, there is controversy regarding whether or not treatment of such mild forms of hypothyroidism in elderly will improve mortality, morbidity, and quality of life. This should be studied in large cohorts of patients in long-term placebo-controlled trials with clinically relevant outcomes. Other cases of hypothyroidism, e.g., medications, iodine overload or hypothalamus-pituitary-hypothyroidism, each pose specific challenges to management of hypothyroidism; these cases are also more frequent in the elderly. Finally, adherence to treatment is generally challenging. This is also the case in elderly patients, which may necessitate measuring thyroid hormones at individually tailored intervals, which is important to avoid over-treatment with increased risk of cardiac morbidity and mortality, osteoporosis, cognitive dysfunction, and muscle deficiency.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review argues that levothyroxine management in elderly hypothyroid patients is complicated by age-related TSH shifts, comorbidities, polypharmacy, cardiac risk, and high overtreatment risk, requiring cautious diagnosis and individualized titration. It concludes that evidence for treating mild/subclinical hypothyroidism and for specific TSH targets in the elderly remains limited and calls for large randomized trials.

Key findings

  • Prevalence and age-related TSH: overt hypothyroidism is 0.1–2% in the general population, subclinical hypothyroidism 4–10%, and subclinical hypothyroidism affects up to 15% of adults ≥65 years when non-age-specific TSH ranges are used. In NHANES III, the 97.5th percentile TSH was 4.1 mU/L overall, 5.9 mU/L at 70–79 years, and 7.5 mU/L at >80 years; with age-specific ranges, 70% of the >80 group was reclassified as normal.
  • Diagnosis is difficult in the elderly because symptoms are nonspecific and overlap with normal aging, while nonthyroidal illness, medications, and assay interference can falsely elevate TSH. The paper advises measuring fT4 in all cases, not T3 for treatment indication, and confirming diagnosis by repeat sampling after 3–6 months and/or different laboratory methodology.
  • Treatment of overt hypothyroidism is indicated similarly to younger patients, but most clinicians start at lower doses and up-titrate more slowly; cardiac assessment and possible cardiology collaboration are advised before starting. The usual target is a higher TSH than in younger patients and fT4 in the lower half of the reference range, though no trials substantiate this approach.
  • Overtreatment risk is high: 5–24% of all patients taking L-T4 develop iatrogenic thyrotoxicosis, rising to up to 41% in the elderly; about half of prevalent and incident low TSH events relate to L-T4 overtreatment, with highest rates in older women. Suppressed TSH is associated with higher mortality, atrial fibrillation (>5-fold higher likelihood in subclinical and overt hyperthyroidism), bone loss/fractures, cognitive disturbance, and muscle loss.

Methods

  • Design: narrative review/synthesis, not a systematic review or primary study; the authors state all contributed to the idea, collection of information and references, writing, and approval.
  • Data: published literature, guidelines, and population studies (e.g., NHANES III, Whickham Survey, Colorado Thyroid Disease Prevalence Study, Leiden 85-Plus and Leiden Longevity studies); no primary cohort or trial data were collected.
  • Analysis: thematic discussion of diagnosis, treatment indication, titration and monitoring, adherence, overtreatment risks, and future clinical trials; no formal meta-analysis or quality appraisal is described.

Limitations

  • Stated: no blinded randomized placebo-controlled trials of L-T4 treatment in elderly patients with hypothyroidism comparing different TSH targets have been published; no counterpart to the Stott et al. trial exists in overt disease, and even well-designed descriptive longitudinal studies on quality of life in elderly patients are lacking.
  • Stated: controversy remains over whether treating mild/subclinical hypothyroidism in the elderly improves mortality, morbidity, and quality of life; the paper says this should be studied in large cohorts in long-term placebo-controlled trials with clinically relevant outcomes. It also notes no clinical evidence on how cautious L-T4 replacement in primary hypothyroidism should translate to secondary hypothyroidism, and no studies evaluating systematic patient-reported outcome monitoring.
  • Evident: as a narrative review, it lacks a systematic search strategy and formal quality appraisal; many cited risks of overtreatment come from endogenous hyperthyroidism or from younger/non-elderly populations used as surrogates, limiting direct applicability to elderly patients receiving L-T4.

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

Integrity signals

Registry

Crossref · 10.3389/fendo.2021.641560

Cites

121 of 121 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 111 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Although hypothyroidism-associated symptoms may indicate hypothyroidism in most young patients, this is rarely the case in the elderly.

    “Although hypothyroidism-associated symptoms may indicate and identify hypothyroidism in most young patients, this is rarely the case in the elderly (16).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Carlé, 2016, Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study, Am J Med source

      Not checked in the free run.

  • Premisecitation

    Men and women aged 85 years with abnormally high TSH concentrations according to the general reference range for younger people and abnormally low concentrations of fT4 had the lowest mortality rate during the 3.7-year follow-up.

    “Men and women aged 85 years with abnormally high TSH concentrations according to the general reference range for younger people and abnormally low concentrations of fT4 had the lowest mortality rate during the 3.7-yr follow-up (33).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Gussekloo, 2004, Thyroid Status, Disability and Cognitive Function, and Survival in Old Age, JAMA source

      Not checked in the free run.

  • Premisecitation

    There is an age-dependent shift in TSH distribution towards higher concentrations with increasing age.

    “Convincing evidence during the last decades has shown an age-dependent shift in TSH distribution towards higher concentrations with increasing age.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Hollowell, 2002, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J Clin Endocrinol Metab source

      Not checked in the free run.

  • Premisecitation

    When age-adjusted TSH reference ranges were used, no association was found between thyroid function and quality of life, mood, and cognition at baseline nor over 5-8 years of follow-up in community-dwelling older men.

    “In addition, when the age-adjusted TSH reference ranges were used, no association between thyroid function and quality of life, mood, and cognition at baseline nor over the 5–8 years of follow-up in community-dwelling older men was found (32).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Samuels, 2016, Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men, Thyroid source

      Not checked in the free run.

  • Interpretationreasoning

    The higher prevalence of thyroid autoimmunity in the older population can only partially explain the higher TSH concentrations with increasing age.

    “Nevertheless, the higher prevalence of thyroid autoimmunity in the older population can only partially explain the higher TSH concentrations with increasing age.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 16

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

    Premisecitation

    Autoimmune hypothyroidism is the most common cause of hypothyroidism at all ages, and the prevalence of thyroid autoimmunity increases with aging.

    “Autoimmune hypothyroidism is the most common cause of hypothyroidism at all ages and the prevalence of thyroid autoimmunity increases with aging (23, 26, 27).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [23] Dayan, 1996, Chronic Autoimmune Thyroiditis, N Engl J Med source

      Not checked in the free run.

    • cites [26] Mariotti, 1998, Thyroid autoimmunity and aging, Exp Gerontol source

      Not checked in the free run.

    • cites [27] Cooper, 2012, Subclinical thyroid disease, Lancet source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In NHANES III, median TSH concentrations progressively increased with age and the 97.5th percentiles were higher in the >70 years old reference population without thyroid antibodies.

    “In the NHANES III study, median TSH concentrations progressively increased with age and the 97.5th percentiles were considerably higher in the >70 years old reference population without thyroid antibodies (97.5th percentile TSH in the reference population: total 4.1 mU/l; 70–79 yo 5.9 mIU/l; >80 yo 7.5 mU/l) (11).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Hollowell, 2002, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J Clin Endocrinol Metab source

      Not checked in the free run.

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

    Premisecitation

    The proportion of the population aged 65 years or over rose from 6% in 1990 to 9% in 2019 and is expected to rise to 16% by 2050.

    “According to World Population Prospects 2019 (United Nations, 2019), the proportion of the population aged 65 years or over has risen from 6% in 1990 to 9% in 2019 and it is expected to rise further to 16% by 2050 (1).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites United Nations, 2019

      Not checked in the free run.

    • cites [1]

      Not checked in the free run.

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

    Premisecitation

    The prevalence of hypothyroidism increases with age, and subclinical hypothyroidism affects up to 15% of adults aged 65 years or older when non-age-specific TSH reference ranges are used.

    “The prevalence of hypothyroidism increases with age and subclinical hypothyroidism affects up to 15% of adults 65 years of age or older, when non-age-specific TSH reference ranges are used (9, 12–14).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [9] Canaris, 2000, The Colorado Thyroid Disease Prevalence Study, Arch Internal Med source

      Not checked in the free run.

    • cites [12] Bensenor, 2012, Hypothyroidism in the elderly: diagnosis and management, Clin Interv Aging source

      Not checked in the free run.

    • cites [13] Boelaert, 2013, Thyroid dysfunction in the elderly, Nat Rev Endocrinol source

      Not checked in the free run.

    • cites [14] Leng, 2019, Hypothyroidism in the older population, Thyroid Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Longevity was associated with higher TSH concentrations in the Ashkenazi population and confirmed by two Dutch studies.

    “Longevity was associated with higher TSH concentrations in the Ashkenazi population (19) and confirmed by two Dutch studies (the Leiden 85-Plus Study and the Leiden Longevity Study) (33–35).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [19] Atzmon, 2009, Extreme Longevity Is Associated with Increased Serum Thyrotropin, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [33] Gussekloo, 2004, Thyroid Status, Disability and Cognitive Function, and Survival in Old Age, JAMA source

      Not checked in the free run.

    • cites [34] Rozing, 2010, Familial Longevity Is Associated with Decreased Thyroid Function, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [35] Van den Beld, 2005, Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men, J Clin Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypothyroid symptoms are non-specific and vary among patients, especially in subclinical hypothyroidism, and overlap with symptoms common in euthyroid individuals.

    “Hypothyroid symptoms are non-specific and vary among patients, especially in the setting of subclinical hypothyroidism. The same symptoms are also quite common in euthyroid individuals and thus often overlap with the symptoms developed in patients with hypothyroidism (9).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] Canaris, 2000, The Colorado Thyroid Disease Prevalence Study, Arch Internal Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A number of medications can affect thyroid function tests by interfering with the synthesis, transport, and metabolism of TSH and thyroid hormones and by interfering with thyroid function immunoassays.

    “A number of medications can affect the thyroid function tests not only by interfering with the synthesis, transport, and metabolism of TSH and thyroid hormones but also by interfering with thyroid function immunoassays (30, 37–40) ( Table 1 ).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [30] Feldt-Rasmussen, 2021

      Not checked in the free run.

    • cites [37] Burch, 2019, Drug Effects on the Thyroid, N Engl J Med source

      Not checked in the free run.

    • cites [38] Favresse, 2018, Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm, Endocrine Rev source

      Not checked in the free run.

    • cites [39] Feldt- Rasmussen, 2018, Drug effects and thyroid function source

      Not checked in the free run.

    • cites [40] Feldt-Rasmussen, 2020, Laboratory measurement of thyroid-related hormones, proteins, and autoantibodies in serum

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Subclinical hyperthyroidism is associated with greater annual bone loss at the femoral neck but not at the lumbar spine in prospective cohorts.

    “Subclinical hyperthyroidism was also associated with greater annual bone loss at the femoral neck but not at the lumbar spine in prospective cohorts (101)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Segna, 2017, Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts, J Internal Med source

      Not checked in the free run.

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

    Premisecitation

    High dose biotin ingestion by the patient has been shown to result in serious distortion of analyte- and platform-specific assay results, and is now a frequent cause of false results due to the current popularity of biotin ingestion for skin and hair beauty products.

    “High dose biotin ingestion by the patient has also been shown to result in serious distortion of analyte- and platformspecific assay results, and is now a frequent cause of false results due to the current popularity of biotin ingestion for skin and hair beauty products (47).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] SpencerCA South Dartmouth, MAEndocrine Education IncAssay of thyroid hormones and related substances

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The limited symptomatology of hypothyroidism in the elderly implies smaller patient-experienced treatment effects, which may decrease motivation for treatment initiation and adherence.

    “The limited symptomatology implies smaller patient-experienced treatment effects, which may also decrease motivation for treatment initiation and adherence in individual patients.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    In euthyroid women with a history of Graves' hyperthyroidism, lumbar spine bone density is negatively associated with TSH receptor antibodies in postmenopausal but not premenopausal women.

    “in euthyroid women with a history of Graves’ hyperthyroidism lumbar spine bone density was negatively associated with TSH receptor antibodies in post- but not premenopausal women (102).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Ercolano, 2013, Negative correlation between bone mineral density and TSH receptor antibodies in long-term euthyroid postmenopausal women with treated Graves’ disease, Thyroid Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Increased bone loss and risk of fracture are found in euthyroid postmenopausal women with fT4 and/or fT3 levels within the upper normal range and in older adults with low TSH.

    “Increased bone loss and risk of fracture was also found in euthyroid postmenopausal women with fT4 and/or fT3 levels within the upper normal range and in older adults with low TSH (104–106).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [104] Murphy, 2010, Thyroid Function within the Upper Normal Range Is Associated with Reduced Bone Mineral Density and an Increased Risk of Nonvertebral Fractures in Healthy Euthyroid Postmenopausal Women, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [105] Bauer, 2001, Risk for Fracture in Women with Low Serum Levels of Thyroid-Stimulating Hormone, Ann Internal Med source

      Not checked in the free run.

    • cites [106] Lee, 2010, Subclinical Thyroid Dysfunction and Incident Hip Fracture in Older Adults, Arch Internal Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effect of current use of L-T4 treatment in elderly on the risk of fractures seems dose-related, particularly in women aged ≥65 years with osteoporosis.

    “The effect of current use of L-T4 treatment in elderly on the risk of fractures seems dose-related (107)”
    • Also stated in: § Adherence and Risk of Overtreatment in Elderly Patients With Hypothyroidism · plain
      “particularly in women aged ≥65 years with osteoporosis (108).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [107] Turner, 2011, Levothyroxine dose and risk of fractures in older adults: nested case-control study, BMJ source

      Not checked in the free run.

    • cites [108] Ko, 2014, Levothyroxine Dose and Fracture Risk According to the Osteoporosis Status in Elderly Women, J Prev Med Public Health source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypothyroidism has a profoundly negative effect on cardiac performance, resulting in low exercise performance, and more prominently so in elderly patients.

    “Hypothyroidism has a profoundly negative effect on cardiac performance ( Table 3 ) which results in low exercise performance, and more prominently so in elderly patients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Table 3

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Apart from higher mortality in patients with suppressed TSH, the most important risks of overtreatment affect the heart, bones, brain, and muscle function.

    “Apart from the higher mortality in patients with suppressed TSH the most important risks of overtreatment are those affecting the heart (50), the bones (91), the brain (92) and muscle function (93).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [50] Biondi, 2019, Kahaly Heart in Hypothyroidism

      Not checked in the free run.

    • cites [91] Uzzan, 1996, Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [92] Aubert, 2017, The association between subclinical thyroid dysfunction and dementia: The Health, Aging and Body Composition (Health ABC) Study, Clin Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Five to 24 percent of all patients taking L-T4 develop iatrogenic thyrotoxicosis, a proportion that is even higher in the elderly (up to 41%).

    “Five to 24 percent of all patients taking L-T4 develop iatrogenic thyrotoxicosis (9, 11, 78, 81–83), a proportion that is even higher in the elderly [up to 41% (79)].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [9] Canaris, 2000, The Colorado Thyroid Disease Prevalence Study, Arch Internal Med source

      Not checked in the free run.

    • cites [11] Hollowell, 2002, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III), J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [78] Parle, 1993, Thyroxine prescription in the community: serum thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment, Br J Gen Pract

      Not checked in the free run.

    • cites [81] Diez, 2002, Hypothyroidism in Patients Older Than 55 Years: An Analysis of the Etiology and Assessment of the Effectiveness of Therapy, J Gerontol Ser A: Biol Sci Med Sci source

      Not checked in the free run.

    • cites [82] Ross, 1990, The Use and Limitations of a Chemiluminescent Thyrotropin Assay as a Single Thyroid Function Test in an Out-Patient Endocrine Clinic*, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [83] Vaisman, 2013, How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study, J Endocrinol Invest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The frail elderly are vulnerable to drug side effects, overtreatment and poor compliance.

    “The frail elderly are vulnerable to drugs side effects, overtreatment and poor compliance (54).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Calsolaro, 2019, Overt and Subclinical Hypothyroidism in the Elderly: When to Treat, Front Endocrinol source

      Not checked in the free run.

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

    Premisecitation

    Other studies found positive associations between T3/fT3 and muscle mass.

    “Nevertheless, data on the association between T3/fT3 and muscle mass are conflicting and some studies found negative (35, 123), while others positive associations (124–126), with some differences between men and women.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [124] Park, 2020, The prospective relationship between low muscle mass and thyroid hormones among 198 069 euthyroid men and women; comparing different definitions of low muscle mass, Int J Clin Pract source

      Not checked in the free run.

    • cites [125] Kong, 2020, Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population, Osteoporosis Int source

      Not checked in the free run.

    • cites [126] Sheng, 2019, Association of thyroid function with sarcopenia in elderly Chinese euthyroid subjects, Aging Clin Exp Res source

      Not checked in the free run.

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

    Premisecitation

    Some studies found negative associations between T3/fT3 and muscle mass.

    “Nevertheless, data on the association between T3/fT3 and muscle mass are conflicting and some studies found negative (35, 123), while others positive associations (124–126), with some differences between men and women.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [35] Van den Beld, 2005, Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [123] Szlejf, 2020, Thyroid Function and Sarcopenia: Results from the ELSA-Brasil Study, J Am Geriatr Soc source

      Not checked in the free run.

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

    Premisecitation

    There are some differences between men and women in the association between T3/fT3 and muscle mass.

    “Nevertheless, data on the association between T3/fT3 and muscle mass are conflicting and some studies found negative (35, 123), while others positive associations (124–126), with some differences between men and women.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [35] Van den Beld, 2005, Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [123] Szlejf, 2020, Thyroid Function and Sarcopenia: Results from the ELSA-Brasil Study, J Am Geriatr Soc source

      Not checked in the free run.

    • cites [124] Park, 2020, The prospective relationship between low muscle mass and thyroid hormones among 198 069 euthyroid men and women; comparing different definitions of low muscle mass, Int J Clin Pract source

      Not checked in the free run.

    • cites [125] Kong, 2020, Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population, Osteoporosis Int source

      Not checked in the free run.

    • cites [126] Sheng, 2019, Association of thyroid function with sarcopenia in elderly Chinese euthyroid subjects, Aging Clin Exp Res source

      Not checked in the free run.

20 of 20

  • The paper relies on this without support.

    The indication for L-T4 treatment of overt hypothyroidism is similar in young and elderly hypothyroid patients.

    “The indication for L-T4 treatment of overt hypothyroidism is similar in young and elderly hypothyroid patients.”

  • The paper relies on this without support.

    Elderly people have more comorbidities compared to young patients, complicating correct diagnosis and management of hypothyroidism.

    “Elderly people have more comorbidities compared to young patients, complicating correct diagnosis and management of hypothyroidism.”

  • The paper relies on this without support.

    Cardiovascular complications compromise the usual start dosage and upward titration of L-T4 due to higher risk of decompensating cardiac ischemia and function.

    “Most importantly, cardiovascular complications compromise the usual start dosage and upward titration of L-T4 due to higher risk of decompensating cardiac ischemia and -function.”

  • The paper relies on this without support.

    Other cases of hypothyroidism, such as medications, iodine overload or hypothalamus-pituitary-hypothyroidism, are more frequent in the elderly.

    “Other cases of hypothyroidism, e.g., medications, iodine overload or hypothalamus-pituitary-hypothyroidism, each pose specific challenges to management of hypothyroidism; these cases are also more frequent in the elderly.”

  • The paper relies on this without support.

    Adherence to treatment is generally challenging.

    “Finally, adherence to treatment is generally challenging.”

  • The paper relies on this without support.

    The upper reference limit of serum TSH concentrations in healthy normal elderly people is highly variable with age and not studied in populations at large, nor by different laboratory platforms.

    “The upper reference limit of serum TSH concentrations in healthy normal elderly people is highly variable with age and not studied in populations at large, nor by different laboratory platforms.”
6 of 6

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?

  • The detrimental effects of both over- and under-replacement have been reported.

    “The detrimental effects of both over- and under-replacement have been reported (94, 95).”

    From ETA guidelines for the use of levothyroxine sodium preparations in monotherapy to optimize the treatment of hypothyroidism (2025) · cites this paper as [95]

    The ‘Adherence and Risk of Overtreatment’ section explicitly reports adverse effects of levothyroxine over-replacement. The ‘Indication for Levothyroxine Treatment’ section describes harmful cardiac effects of overt hypothyroidism and benefits of treatment, but does not specifically report detrimental effects of under-replacement in treated patients. No page numbers are available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The higher TSH in the elderly is not explained only by higher prevalence of thyroid autoimmunity.

    “The 97.5th percentiles of the reference population are considerably higher in the elderly (older than 70 years old) than in younger adults [32–35], which is not explained only by higher prevalence of thyroid autoimmunity [36, 37].”

    From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [36]

Cites

Flagged first, then by citations

4 of the 125 references couldn’t be matched to a known paper.

Research works printed but not linked: 6

  1. Feldt-Rasmussen, 2021, Thyroid Function Tests and the Effects of Drugs. In Oxford Textbook of Endocrinology and Diabetes
  2. Feldt-Rasmussen, 2020, Laboratory measurement of thyroid-related hormones, proteins, and autoantibodies in serum, 868
  3. Peeters, 2021, Non-Thyroidal Illness (NTI). In Oxford Textbook of Endocrinology and Diabetes
  4. Feldt-Rasmussen, 2020, Clinical Strategies In The Testing Of Thyroid Function
  5. Biondi, 2019, Kahaly Heart in Hypothyroidism
  6. Weiss, 2006, Diagnostic tests of the thyroid: tests that assess the effects of thyroid hormone on body tissues

Cited by

Sorted by citations

Related

Authors
Effraimidis, G., Watt, T., & Feldt-Rasmussen, U.
Affiliations
  • Copenhagen University Hospital (DK)
  • University of Copenhagen (DK)
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2021-03-12
Volume
12
Pages
641560-641560
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2021.641560
PMC
PMC8006441
OpenAlex
W3138361278
Semantic Scholar
51cf1ae5cc40695f6bf7374b7944553968bd7d59
Cited by
60
References
125
Citations by year
2026: 13 · 2025: 11 · 2024: 11 · 2023: 17 · 2022: 6 · 2021: 1
FWCI
1.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Kirsten og Freddy Johansens Fond
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
levothyroxine, hypothyroidism, elderly patients, overt hypothyroidism, subclinical hypothyroidism, comorbidities, cardiovascular complications, myocardial ischemia, thyroid function tests, low T3 syndrome, autoimmunity, iodine excess, medication adherence, overtreatment
MeSH terms
Overtreatment, Aged, Aged, 80 and over, Female, Hemodynamics, Humans, Hypothyroidism, Male, Quality of Life, Risk, Thyroid Function Tests, Thyroid Hormones, Thyrotropin, Thyroxine, Comorbidity, Treatment Outcome, Patient-Centered Care

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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