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Cited by 14Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Refractory hypothyroidism: unraveling the complexities of diagnosis and management

Open access
Quiroz-Aldave, Juan Eduardo, Concepción-Zavaleta, Marcio José, Durand-Vásquez, María del Carmen, Concepción-Urteaga, Luis Alberto, Gamarra-Osorio, Elman Rolando, Suárez-Rojas, Jacsel, Rafael-Robles, Luciana del Pilar, Paz-Ibarra, José +1 more·2023·Endocrine Practice
DOI 10.1016/j.eprac.2023.09.003
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Abstract

INTRODUCTION Refractory hypothyroidism (RH) represents a challenge in the diagnosis and treatment within the field of thyroidology. It is defined as the inability to achieve disease control despite using levothyroxine (LT4) doses of 1.9 μg/kg/day or higher. METHODS A comprehensive review, encompassing 103 articles, was conducted using the Scielo, Scopus, and EMBASE databases, providing an approach to evaluation and diagnosis of this condition. RESULTS Levothyroxine disintegrates and dissolves within an acidic gastric environment before being absorbed in the jejunum and ileum. It then extensively binds to serum transporter proteins and undergoes deiodination to yield triiodothyronine, the biologically active hormone. There are various non-pathological causes of RH, such as non-compliance with treatment, changes in the brand of LT4, food and drug interferences, as well as pregnancy. Pathological causes include lactose intolerance, Helicobacter pylori infection, giardiasis, among others. The diagnosis of RH involves conducting a thorough medical history and requesting relevant laboratory tests to rule out causes of treatment resistance. The LT4 absorption test allows for the identification of cases of malabsorption. The treatment of RH involves identifying and addressing the underlying causes of non-compliance or malabsorption. In cases of pseudomalabsorption, supervised and weekly administration of LT4 may be considered. CONCLUSIONS Early recognition of RH and correction of its underlying cause are of utmost importance, as this avoids the use of excessive doses of LT4 and prevents cardiovascular and bone complications associated with this condition.

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Written from the paper’s full text.

TL;DR

Refractory hypothyroidism (RH) is defined as uncontrolled hypothyroidism despite levothyroxine (LT4) doses of 1.9 mg/kg/d or higher, and it affects 15%–20% of LT4-treated patients. This narrative review summarizes causes, diagnostic workup including the LT4 absorption test, and management, emphasizing correction of nonadherence or malabsorption to avoid supratherapeutic LT4 and cardiovascular/bone complications.

Key findings

  • RH is defined as TSH above the upper reference range despite LT4 ≥1.9 mg/kg/d; it occurs in 15%–20% of LT4-treated patients, with nonadherence the most common cause. Nonpathological causes include inadequate intake, brand changes, food/drug interference, pregnancy, and immunoassay interference; pathological causes include gastrointestinal disorders such as lactose intolerance, *Helicobacter pylori* infection, and giardiasis, plus less common causes such as Addison’s disease, nephrotic syndrome, and cystic fibrosis.
  • In cited studies, 28.2% of primary hypothyroidism patients had TSH above range and 85.4% did not take medication properly; in central hypothyroidism, 38.9% had fT4 below range despite prescribed LT4. Adherence studies reported 26% with elevated TSH and 31% low adherence, while over 6 months 40.3% were noncompliant for at least 20% of days and over 12 months 51.9% were nonadherent.
  • The LT4 absorption test distinguishes malabsorption from pseudomalabsorption: a fasting 1000 mg LT4 dose is given (1500 mg if <65 years and BMI ≥40 kg/m²; 600 mg if ≥65 years), with fT4 or tT4 measured hourly for 4 h. Absorption is normal if fT4 peak increases >0.40 ng/dL, tT4 peak exceeds 6 mg/dL, or tT4 absorption is >60%; percentage absorption uses distribution volume = 0.442 × BMI.
  • Management is cause-directed: treat *H. pylori*, eliminate lactose or gluten, treat parasites, use pancreatic enzymes, and consider liquid/soft gel LT4, vitamin C co-administration, or parenteral LT4 if malabsorption persists. For pseudomalabsorption, supervised LT4 ingestion for at least 4 h or weekly/twice-weekly supervised oral LT4 may be considered; idiopathic RH is reported in 10%–20% of RH cases.

Methods

  • Narrative review of 103 articles. The abstract lists Scielo, Scopus, and EMBASE; the Methods section lists PubMed/Medline, EMBASE, and Scielo.
  • Included systematic reviews, narrative reviews, meta-analyses, clinical trials, practice guidelines, case reports, retrospective studies, and cross-sectional studies; excluded correspondence, congress summaries, and conference abstracts. Synthesis is narrative, with figures, tables, and a diagnostic-therapeutic algorithm.

Limitations

  • The paper does not state a formal limitations section.
  • Evident from the text: this is a narrative review without reported systematic search dates, PRISMA-style screening, risk-of-bias assessment, or formal quality appraisal; the evidence base is heterogeneous, including case reports, retrospective studies, and guidelines.
  • Evident from the text: some areas are explicitly uncertain or limited, including ongoing debate about fT3:fT4 ratios and TSH as optimal monitoring, limited evidence for Crohn’s disease and aluminum/chromium effects, and contradictory evidence on LT4 brand switching (2004 recommendations vs. a 2022 study of 15,829 patients finding no clinically significant TSH variations).

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Registry

Crossref · 10.1016/j.eprac.2023.09.003

Cites

96 of 96 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 153 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    In a study of central hypothyroidism patients treated with levothyroxine, 38.9% had free T4 below the reference range despite taking levothyroxine as prescribed.

    “Another study in patients with CeH treated with LT4 revealed that 38.9% of these patients had fT4 levels below the reference range despite taking LT4 as prescribed.31”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Koulouri, 2011, Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine, Clin Endocrinol source

      Not checked in the free run.

  • Premisecitation

    Between 15% and 20% of patients treated with levothyroxine develop refractory hypothyroidism.

    “Between 15% and 20% of patients receiving LT4 treatment develop RH. 10”
    • Also stated in: § Clinical Relevance · plain
      “RH is observed in 15% to 20% of patients undergoing LT4 treatment, with the main causes being non-adherence to treatment and gastrointestinal disorders.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Benvenga, 2017, Refractory hypothyroidism due to improper storage of levothyroxine tablets, Front Endocrinol source

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  • Premisereasoning

    TSH may not be the best marker for monitoring hypothyroidism control because it may not accurately reflect intracellular T3 levels in tissues with different deiodinase 2 and 3 activities.

    “However, TSH may not serve as the optimal indicator for monitoring hypothyroidism control.This potential limitation arises because it can be inadequate in accurately representing intracellular T3 levels within specific tissues, which exhibit distinct activities of deiodinases 2 and 3.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Pituitary TSH release is a highly sensitive indicator of thyroid function, changing markedly with small changes in T4 levels.

    “The release of TSH by the pituitary gland is a highly sensitive indicator of thyroid function, as its levels undergo significant changes in response to minimal variations in T4 levels.27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Pirahanchi, 2023, Physiology, thyroid stimulating hormone

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  • Premisecitation

    Non-adherence is the most common cause of refractory hypothyroidism.

    “with the latter being the most common cause.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Lips, 2004, Diagnosis and treatment of levothyroxine pseudomalabsorption, Neth J Med

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  • Classified as probably not a substantial claim. 25
  • May combine two claims. 50

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

    Premisecitation

    About 80% of circulating T3 comes from deiodination of T4, while the remaining 20% is released directly by the thyroid gland.

    “Eighty percent of circulating T3 is derived from the deiodination of T4, and only the remaining 20% is directly released by the thyroid gland.22,25”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Peeters, 2017, Metabolism of thyroid hormone

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    • cites [25] Gottwald-Hostalek, 2021, Triiodothyronine alongside levothyroxine in the management of hypothyroidism?, Curr Med Res Opin source

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

    Premisecitation

    Levothyroxine is mainly absorbed in the jejunum and ileum, with 70% to 80% absorption when taken fasting, peak concentration at about 3 hours, and 70% to 80% bioavailability.

    “LT4 is predominantly absorbed in the jejunum and ileum, 3 with absorption rates of 70% to 80% when taken on an empty stomach, and reaching its peak concentration in approximately 3 h, with a bioavailability of 70% to 80%.19”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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    • cites [19] Lipp, 2021, Administration and pharmacokinetics of levothyroxine

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

    Premisenone given

    T3 is the biologically active form and is about five times more potent than T4.

    “T3 is the biologically active form, approximately five times more potent than T4, while rT3 has little effect in the body.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Pathological causes of refractory hypothyroidism include obesity and gastrointestinal disorders that cause levothyroxine malabsorption, as well as rarer conditions such as nephrotic syndrome, Addison's disease, and cystic fibrosis.

    “Pathological causes include obesity and gastrointestinal disorders responsible for LT4 malabsorption, as well as other rare conditions such as nephrotic syndrome, Addison's disease, and cystic fibrosis.4,17”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Centanni, 2017, Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report, J Endocrinol Invest source

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    • cites [17] Kalra, 2020, A 6 dimensional approach to diagnosing refractory hypothyroidism, Thyroid Res Pract source

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    Premisecitation

    Levothyroxine tablets first disintegrate and dissolve in the stomach, a step needing an acidic gastric pH of 1.0 to 3.0 to remove the sodium ion and make levothyroxine lipophilic.

    “The metabolism of LT4 tablets begins with its disintegration and dissolution in the stomach, a process that requires an acidic gastric pH (1.0-3.0) to remove the sodium ion and convert LT4 into a lipophilic molecule.3,18”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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    • cites [18] Seng Yue, 2015, When bioequivalence in healthy volunteers may not translate to bioequivalence in patients: differential effects of increased gastric pH on the pharmacokinetics of levothyroxine capsules and tablets, J Pharm Pharmaceut Sci

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

    Premisecitation

    More than 99% of ingested levothyroxine that reaches systemic circulation, and of its active metabolite T3, binds to T4-binding globulin, albumin, and transthyretin.

    “Over 99% of the ingested LT4 that enters systemic circulation, as well as its biologically active metabolite, T3, bind to T4-binding globulin, albumin, and transthyretin1,19.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers

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    • cites [19] Lipp, 2021, Administration and pharmacokinetics of levothyroxine

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    Premisecitation

    Failure to achieve euthyroidism is linked to higher morbidity and mortality and worse physical and emotional quality of life.

    “Failing to achieve euthyroidism has been associated with increased morbidity and mortality and poorer physical and emotional quality of life, highlighting the need to investigate and address the underlying factors.1,32”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers

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    • cites [32] Vigário, 2013, Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study, Endocrine source

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

    Premisecitation

    The average half-life of T4 is about 7.5 days, and that of T3 is about 1.4 days.

    “The average half-life of T4 is approximately 7.5 days, while that of T3 is approximately 1.4 days.22,25”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Peeters, 2017, Metabolism of thyroid hormone

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    • cites [25] Gottwald-Hostalek, 2021, Triiodothyronine alongside levothyroxine in the management of hypothyroidism?, Curr Med Res Opin source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For primary hypothyroidism, levothyroxine is the standard drug treatment, usually given at an average daily dose of 1.6 to 1.8 mg/kg.

    “The standard pharmacological treatment for patients with primary hypothyroidism is levothyroxine (LT4), 1 typically prescribed at an average daily dose of 1.6 to 1.8 mg/kg in most cases.2,3”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers

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    • cites [2] Jonklaas, 2014, Guidelines for the treatment of hypothyroidism: prepared by the American thyroid association task force on thyroid hormone replacement, Thyroid source

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    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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    Premisecitation

    Not waiting at least 30 minutes before breakfast after levothyroxine, or taking it with a beverage other than water, may reduce levothyroxine absorption.

    “Failing to observe a minimum interval of 30 min before having breakfast after administering the LT4 dose, 33 or consuming it not solely with water, but alongside another beverage, [34][35][36][37] are circumstances that may impede the absorption of LT4.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [33] McMillan, 2016, Comorbidities, concomitant medications, and diet as factors affecting levothyroxine therapy: results of the CONTROL surveillance project, Drugs R source

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    • cites [34] Wiesner, 2021, Levothyroxine interactions with food and dietary supplements-A systematic review, Pharmaceuticals source

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    • cites [35] Liwanpo, 2009, Conditions and drugs interfering with thyroxine absorption, Best Pract Res Clin Endocrinol Metabol source

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  • May combine two claims.

    Premisecitation

    In an observational study of treated primary hypothyroidism, 28.2% had TSH above the reference range, and 85.4% did not take their medication properly.

    “In an observational study conducted in patients with primary hypothyroidism undergoing treatment, 28.2% had TSH levels above the reference range, and 85.4% did not take their medication properly, either due to incorrect timing or concurrent use with other medications.30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Vaisman, 2013, How good is the levothyroxine replacement in primary hypothyroidism patients in Brazil? Data of a multicentre study, J Endocrinol Invest

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

    Premisecitation

    Lactose intolerance results from reduced lactase activity and causes diarrhea, abdominal distension, and flatulence; symptoms relate to the amount consumed and usually occur above 12 g lactose.

    “Lactose intolerance is due to decreased lactase activity, resulting in symptoms such as diarrhea, abdominal distension, and flatulence.The intensity of symptoms is related to the amount of lactose consumed, 57 and gastrointestinal symptoms typically occur when consuming amounts exceeding 12 g of lactose.58”
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    • cites [57] Bayless, 2017, Lactase non-persistence and lactose intolerance, Curr Gastroenterol Rep source

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    • cites [58] Misselwitz, 2019, Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management, Gut source

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  • May combine two claims.

    Premisecitation

    Another study found that over 6 months of levothyroxine treatment, 40.3% did not comply for at least 20% of days, and over 12 months, 51.9% were nonadherent.

    “Another study in patients with hypothyroidism found that, over a 6-month period of LT4 treatment, 40.3% did not comply with the treatment for at least 20% of the days, and over 12 months, 51.9% of them were nonadherent to treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A systematic review found no link between soy isoflavone intake and TSH nonresponse to levothyroxine, but observed a slight TSH increase with higher soy consumption.

    “Regarding soy consumption, a systematic review found no relationship between isoflavone intake and TSH nonresponse to LT4 treatment, but did observe a slight increase in TSH levels in patients exposed to higher soy consumption.49”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Otun, 2019, Systematic review and meta-analysis on the effect of soy on thyroid function, Sci Rep source

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  • May combine two claims.

    Premisecitation

    Iron supplements hinder reaching optimal TSH; in thyroidectomy patients, iron use increased the need for levothyroxine dose adjustment (OR 2.4, 95% CI 1.3-4.13, P=.004).

    “The use of iron supplements also hampers achieving optimal TSH levels, as demonstrated in a study of patients that underwent thyroidectomy, where iron supplement use increased the need for LT4 dose adjustment (OR: 2.4, 95% CI: 1.3-4.13,P ¼ .004).53”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Atruktsang, 2019, Identifying predictors of prolonged levothyroxine dose adjustment after thyroidectomy, J Surg Res source

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  • May combine two claims.

    Premisecitation

    Chronic gastritis and gastric atrophy reduce gastric acid production, which can be blocked by PPIs; in H. pylori infection, ammonia partially counters acid, increasing levothyroxine requirements.

    “Patients with chronic gastritis and gastric atrophy show a decrease in gastric acid production, which can be blocked by PPIs.In other cases, gastric acid production is partially blocked and countered by ammonia in patients infected with Helicobacter pylori, leading to increased LT4 requirements.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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  • May combine two claims.

    Premisecitation

    In hypothyroid women, levothyroxine dose may need to increase by up to 50% during the first trimester and remain at that level until delivery.

    “In women with hypothyroidism, an up to 50% increase in LT4 dose is required during the first trimester, and this dose is maintained until delivery.55”
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    • cites [55] Soldin, 2010, Longitudinal comparison of thyroxine pharmacokinetics between pregnant and nonpregnant women: a stable isotope study, Ther Drug Monit source

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    Premisecitation

    Aluminum and chromium may reduce levothyroxine bioavailability, but evidence is limited.

    “Aluminum and chromium may also decrease LT4 bioavailability, although evidence on this is limited.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Wiesner, 2021, Levothyroxine interactions with food and dietary supplements-A systematic review, Pharmaceuticals source

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    Premisecitation

    Milk and coffee interfere with levothyroxine absorption when taken together with the medication, though the exact necessary time interval is unknown.

    “Milk and coffee interfere with LT4 absorption when consumed together with the medication, although the exact time interval for adequate absorption remains unknown.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Wiesner, 2021, Levothyroxine interactions with food and dietary supplements-A systematic review, Pharmaceuticals source

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    Premisecitation

    A study found that only 54.1% of pregnant women achieved adequate treatment adherence, possibly because of concurrent nutritional supplements.

    “A study showed that only 54.1% of pregnant women achieved adequate treatment adherence, possibly due to concurrent use of nutritional supplements.56”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [56] Siscart, 2022, Adherence to treatment for hypothyroidism in pregnancy and relationship with thyrotropin control: a retrospective observational cohort study, BMC Pregnancy Childbirth source

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    Premisecitation

    Ciprofloxacin and rifampin alter transmembrane transport, while proton pump inhibitors and histamine H2 receptor agonists can change gastric pH.

    “Other medications alter transmembrane transport, such as ciprofloxacin and rifampin.Proton pump inhibitors (PPIs) and histamine H2 receptor agonists can modify gastric pH.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [38] Skelin, 2017, Factors affecting gastrointestinal absorption of levothyroxine: a review, Clin Ther source

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    • cites [54] Liu, 2023, Medications and food interfering with the bioavailability of levothyroxine: a systematic review, Therapeut Clin Risk Manag source

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  • May combine two claims.

    Premisecitation

    Regular intake of 600 to 1000 mg calcium carbonate near levothyroxine can raise TSH, with the effect lessening as the interval between them increases.

    “Regular consumption of 600 to 1000 mg of calcium carbonate near the time of taking LT4 can elevate TSH levels, although this situation diminishes as the time interval between them increases.34,52”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [34] Wiesner, 2021, Levothyroxine interactions with food and dietary supplements-A systematic review, Pharmaceuticals source

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    • cites [52] Morini, 2019, L-thyroxine malabsorption due to calcium carbonate impairs blood pressure, total cholesterolemia, and fasting glycemia, Endocrine source

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  • May combine two claims.

    Premisecitation

    A study found that 26% of hypothyroid patients had elevated TSH, and patients with low adherence (31%) had higher TSH than adherent patients.

    “A study demonstrated that 26% of patients with hypothyroidism had elevated TSH levels, and patients with low treatment adherence (31%) had even higher levels compared to adherent patients, highlighting treatment nonadherence as a major obstacle to achieving optimal TSH levels.42”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Yavuz, 2017, Out-of-Reference range thyroid-stimulating hormone levels in levothyroxine-treated primary hypothyroid patients: a multicenter observational study, Front Endocrinol source

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  • May combine two claims.

    Premisecitation

    Short bowel syndrome is a clear cause of levothyroxine malabsorption because surgical resection reduces absorptive surface area and alters intestinal motility.

    “Short bowel syndrome is an evident cause of LT4 malabsorption, occurring as a result of issues requiring surgical resection of a significant portion of the small intestine.3,64 This reduces the available surface area for absorption and leads to alterations in intestinal motility.3”
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    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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    • cites [64] Vorre, 2022, Drug use in patients with short bowel syndrome and intestinal failure, Dan Med J

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  • May combine two claims.

    Premisecitation

    Biotin at doses above 1.5 mg/day can cause falsely low TSH and elevated free T4 and free T3, with the effect depending on the assay platform and avoidable by a washout period.

    “Biotin (in doses higher than 1.5 mg/d) can cause falsely low TSH levels and elevated fT4 and fT3, with its impact depending on the platform used, and being avoided with a washout period.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [81] Favresse, 2018, Interferences with thyroid function immunoassays: clinical implications and detection algorithm, Endocr Rev source

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    • cites [82] Verdickt, 2012, TSH-assay interference: still with us, Clin Lab

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  • May combine two claims.

    Premisecitation

    Crohn's disease might increase levothyroxine requirements, but evidence is limited.

    “Crohn's disease might potentially elevate LT4 requirements; however, there is limited evidence regarding this.66”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Caron, 2022, Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults, Rev Endocr Metab Disord source

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  • May combine two claims.

    Premisecitation

    Anti-T4 and anti-T3 autoantibodies, present in 40% of autoimmune thyroid disease cases, can cause falsely elevated hormone levels.

    “Anti-T4 and anti-T3 autoantibodies, found in 40% of autoimmune thyroid disease cases, can lead to false hormone elevations”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [81] Favresse, 2018, Interferences with thyroid function immunoassays: clinical implications and detection algorithm, Endocr Rev source

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    • cites [82] Verdickt, 2012, TSH-assay interference: still with us, Clin Lab

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  • May combine two claims.

    Premisecitation

    Pseudomalabsorption occurs when the patient does not adhere to treatment; in some cases it is a factitious disorder linked to psychiatric issues in which the patient denies nonadherence.

    “Pseudomalabsorption occurs when there is nonadherence to treatment.In some cases, it refers to a factitious disorder associated with psychiatric issues, in which the patient denies their lack of adherence to LT4 therapy.40,41”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Elbasan, 2020, Refractory hypothyroidism to levothyroxine treatment: five cases of pseudomalabsorption, Acta Endocrinol

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    • cites [41] Van Wilder, 2017, Pseudomalabsorption of levothyroxine: a challenge for the endocrinologist in the treatment of hypothyroidism, Eur Thyroid J source

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  • May combine two claims.

    Premisecitation

    Pancreatic insufficiency in cystic fibrosis lowers lipase secretion to about 10% of normal, causing steatorrhea and increased fecal T4 excretion.

    “Pancreatic insufficiency, occurring in cystic fibrosis, 53 reduces lipase secretion to approximately 10% of normal, resulting in steatorrhea and an increase in fecal excretion of T4. 3”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [53] Atruktsang, 2019, Identifying predictors of prolonged levothyroxine dose adjustment after thyroidectomy, J Surg Res source

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    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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  • May combine two claims.

    Premisecitation

    Celiac disease is more common in Hashimoto's thyroiditis and causes lymphocytic infiltration and enterocyte atrophy, reducing intestinal surface area for levothyroxine absorption and increasing dose needs; it can present without gastrointestinal symptoms.

    “Celiac disease is more prevalent in patients with Hashimoto's thyroiditis 62 and causes lymphocytic infiltration and enterocyte atrophy, leading to a progressive reduction in the available intestinal surface area for LT4 absorption, thereby increasing LT4 dosage requirements.3 It can also present atypically without gastrointestinal symptoms, further complicating its recognition.63”
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    • cites [62] Ashok, 2022, Celiac disease and autoimmune thyroid disease: the two peas in a pod, Cureus

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    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

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    • cites [63] Admou, 2012, Atypical celiac disease: from recognizing to managing, Gastroenterol Res Pract source

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

    Premisecitation

    Levothyroxine absorption is considered normal if the free T4 peak rises by more than 0.40 ng/dL, if total T4 peak exceeds 6 mg/dL, or if total T4 absorption exceeds 60%.

    “LT4 absorption is considered normal in any of these 3 scenarios: if there is an increase greater than 0.40 ng/dL in the peak concentration of fT4, if the peak concentration of tT4 exceeds 6 mg/dL, or if the percentage absorption of tT4 is greater than 60% 76”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] Caron, 2023, The use of levothyroxine absorption tests in clinical practice, J Clin Endocrinol Metab source

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    Premisecitation

    Type B thyroid hormone resistance syndrome features goiter, mental retardation, short stature, and cardiac disorders, usually with elevated T4 and T3 and normal or elevated TSH, often due to a thyroid hormone receptor beta mutation that impairs TSH negative feedback.

    “Type B THR syndrome is characterized by goiter, mental retardation, short stature, and cardiac disorders.This syndrome typically presents with elevated levels of T4 and T3, along with normal or elevated TSH levels.This syndrome usually occurs due to a mutation in the thyroid hormone receptor beta, impairing the negative feedback loop on TSH secretion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Rivas, 2016, Thyroid hormone resistance and its management, SAVE Proc

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The diagnostic workup for refractory hypothyroidism starts with a full medical history to assess adherence and how levothyroxine is taken, because treatment errors are the most common cause.

    “The diagnostic approach for a patient with RH begins with a comprehensive medical history to assess compliance and the method of LT4 consumption, as treatment errors are the most common cause of this issue.11”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Lips, 2004, Diagnosis and treatment of levothyroxine pseudomalabsorption, Neth J Med

      Not checked in the free run.

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

    Premisecitation

    Thyroid hormones are essential in nearly all organs, and their deficiency raises the risk of neurological, cardiovascular, myxedema, and osteoporosis-related problems.

    “Thyroid hormones play a fundamental role in nearly all organs of the body, and their deficiency increases the risk of neurological, cardiovascular, myxedema, and osteoporosis-related problems.1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers

      Not checked in the free run.

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

    Premisecitation

    The doctor-patient relationship is important for medication adherence.

    “The doctor-patient relationship plays a key role in achieving adherence to the medication regimen.88”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [88] Biondi, 2014, Treatment with thyroid hormone, Endocr Rev source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The TSH-T4 relationship is not inverse log-linear but consists of two overlapping negative sigmoid curves and varies with age and sex.

    “This is not an inverse log-linear relationship but is composed of two overlapping negative sigmoid curves, and it varies with age and sex.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Hadlow, 2013, The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex, J Clin Endocrinol Metab source

      Not checked in the free run.

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

    Premisecitation

    The normal thyroid gland releases T4 and T3 in a ratio of about 14:1.

    “The normal release ratio of T4:T3 by the thyroid gland is approximately 14:1.24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Wartofsky, 2013, Combination L-T3 and L-T4 therapy for hypothyroidism, Curr Opin Endocrinol Diabetes Obes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Elevated serum thyroglobulin and increased thyroid radioactive iodine uptake support normal thyroid stimulation.

    “Elevated serum thyroglobulin levels and augmented thyroid radioactive iodine uptake corroborate the normal thyroid stimulation.72”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [72] Maynard, 2014, Thyroid hormone inactivation in gastrointestinal stromal tumors, N Engl J Med source

      Not checked in the free run.

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

    Premisecitation

    T3 binds nuclear receptors, affects gene transcription, and raises overall body metabolism by enhancing gluconeogenesis, protein synthesis, glycogen mobilization, and other processes.

    “T3 binds to its nuclear receptors, influencing the transcription of genetic material and resulting in an increase in overall body metabolism by enhancing processes such as gluconeogenesis, protein synthesis, mobilization of glycogen stores, and other functions.1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Early recognition of refractory hypothyroidism and correction of its cause are very important because they avoid excessive levothyroxine doses and prevent cardiovascular and bone complications.

    “Early recognition of RH and correction of its underlying cause are of utmost importance, as this avoids the use of excessive doses of LT4 and prevents cardiovascular and bone complications associated with this condition.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    A paracellular pathway may also contribute to levothyroxine absorption.

    “There may also be a paracellular pathway that contributes to the absorption of LT4.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Liu, 2022, Levothyroxine: conventional and novel drug delivery formulations, Endocr Rev source

      Not checked in the free run.

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

    Interpretationnone given

    Refractory hypothyroidism can also occur in central hypothyroidism, which should be monitored by measuring free T4 with the aim of keeping it in the upper half of the reference range.

    “However, it is also possible to occur in central hypothyroidism (CeH), which should be monitored by measuring free thyroxine (fT4), with the goal of maintaining it in the upper half of the reference range.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Levothyroxine metabolism includes conjugation and deiodination; in the liver some levothyroxine is glucuronidated and sulfated, becoming more water-soluble, then secreted with bile into the intestine, where microbiota break it down and it is partly reabsorbed.

    “The metabolism of LT4 involves conjugation and deiodination processes.22 In the liver, a portion of LT4 is conjugated by glucuronidation and sulfation, increasing its water solubility.Conjugated LT4 is secreted with bile into the intestine, 22 where it is broken down by intestinal microbiota and partially reabsorbed.23”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Peeters, 2017, Metabolism of thyroid hormone

      Not checked in the free run.

    • cites [23] Virili, 2017, “With a little help from my friends” - the role of microbiota in thyroid hormone metabolism and enterohepatic recycling, Mol Cell Endocrinol source

      Not checked in the free run.

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

    Premisecitation

    The full mechanism by which levothyroxine crosses the intestinal mucosa is not known, but it appears to involve transmembrane proteins such as organic anion transporters, Na-taurocholate cotransporter, L-type amino acid transporters 1 and 2, and monocarboxylate transporters 8 and 10.

    “The complete mechanism of LT4 transport across the intestinal mucosa is not fully understood, but it appears to involve the participation of transmembrane proteins, such as the organic anion transporters family, Na-taurocholate cotransporter, amino acid transporters type L 1 and 2, and monocarboxylate transporters 8 and 10, which are responsible for the entry and exit of thyroxine (T4).20”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Chung, 2021, Decreased expression of ileal thyroid hormone transporters in a hypothyroid patient: a case report, Front Endocrinol source

      Not checked in the free run.

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

    Premisecitation

    Deiodination uses type 1 and type 2 deiodinases to convert T4 to T3 and degrade T3 to reverse T3 and 3,3'-T2, and type 3 enzyme to degrade T4 to reverse T3 and then 3,3'-T2.

    “Deiodination involves type 1 and type 2 (D2) iodothyronine deiodinases, which convert T4 to triiodothyronine (T3) and degrade T3 to reverse T3 (rT3) and 3,3'-diiodothyronine (3,3'-T2), and type 3 (D3) enzyme, which degrades T4 to rT3 and then to 3,3'-T2.22”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Peeters, 2017, Metabolism of thyroid hormone

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    In 2017, it was proposed to classify the main causes of refractory hypothyroidism as pathological or nonpathological.

    “In 2017, it was suggested to classify the main causes of RH as either pathological or nonpathological.4”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Centanni, 2017, Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report, J Endocrinol Invest source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    The body does not distinguish endogenous T4 from levothyroxine, and both, along with T3, exert negative feedback on the hypothalamic-pituitary-thyroid axis.

    “Our body does not distinguish between endogenous T4 and LT4, and both, along with T3, have a negative feedback effect on the hypothalamic-pituitary-thyroid axis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Heterophilic antibody interference can produce both low and high measurements, with elevated values being more common.

    “interference from heterophilic antibodies can result in both low and high measures, with elevated values being more common.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [81] Favresse, 2018, Interferences with thyroid function immunoassays: clinical implications and detection algorithm, Endocr Rev source

      Not checked in the free run.

    • cites [82] Verdickt, 2012, TSH-assay interference: still with us, Clin Lab

      Not checked in the free run.

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

    Premisecitation

    In rare cases, refractory hypothyroidism may be associated with myxedema coma.

    “In rare cases, RH may be associated with myxedema coma.15”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Nakano, 2019, A case of refractory hypothyroidism due to poor compliance treated with the weekly intravenous and oral levothyroxine administration, Case Rep Endocrinol

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Supratherapeutic levothyroxine doses can cause cardiac and bone toxicity and are associated with increased mortality risk.

    “as the use of supratherapeutic doses of LT4, can result in cardiac and bone toxicity, as well as being associated with an increased risk of mortality.[12][13][14]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] Ko, 2014, Levothyroxine dose and fracture risk according to the osteoporosis status in elderly women, J Prev Med Public Health

      Not checked in the free run.

    • cites [13] Lillevang-Johansen, 2019, Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk, Eur J Endocrinol source

      Not checked in the free run.

    • cites [14] Lillevang-Johansen, 2018, Over- and under-treatment of hypothyroidism is associated with excess mortality: a register-based cohort study, Thyroid source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    In central hypothyroidism, inadequate levothyroxine treatment is defined by free T4 at or below the lower limit of normal, especially when hypothyroid symptoms are present.

    “In these cases, inadequate LT4 treatment is determined when fT4 is at or below the lower limit of the normal range, especially if hypothyroidism symptoms are present.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    After absorption, levothyroxine travels through the mesenteric and portal veins to the liver.

    “After absorption, LT4 molecules are transported through the mesenteric and portal veins to the liver.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Liu, 2022, Levothyroxine: conventional and novel drug delivery formulations, Endocr Rev source

      Not checked in the free run.

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

    Premisecitation

    Thyroid hormones are mainly eliminated by the kidneys, with only 20% excreted in feces.

    “Thyroid hormones are primarily eliminated through the kidneys, with only 20% excreted in the feces.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Eghtedari, 2023, Levothyroxine

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the short term, weekly oral LT4 treatment produces higher total T4 and free T4 levels, echocardiographic changes, tachycardia, and palpitations, but these do not persist long term.

    “In the short term, higher total T4 and free T4 levels are observed, as well as echocardiographic changes, tachycardia, and palpitations, but these symptoms do not persist in the long term.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [93] Chiu, 2021, Weekly versus daily levothyroxine tablet replacement in adults with hypothyroidism: a meta-analysis, JASEAN Fed Endocr Soc

      Not checked in the free run.

    • cites [94] Dutta, 2021, Efficacy and safety of once weekly thyroxine as compared to daily thyroxine in managing primary hypothyroidism: a systematic review and meta-analysis, Indian J Endocrinol Metab source

      Not checked in the free run.

    • cites [95] Rajput, 2017, The effect of daily versus weekly levothyroxine replacement on thyroid function test in hypothyroid patients at a tertiary care centre in Haryana, Eur Thyroid J source

      Not checked in the free run.

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

    Premisecitation

    Consumptive hypothyroidism usually requires aggressive thyroid replacement with gradual LT4 dose increases until TSH normalizes, and TSH should be measured more frequently than usual.

    “Consumptive hypothyroidism usually requires aggressive thyroid replacement treatment, involving gradual LT4 dose increases until TSH normalizes, which should be measured more frequently than usual.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [73] Luongo, 2013, Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease, Front Endocrinol source

      Not checked in the free run.

    • cites [92] Jassam, 2011, Consumptive hypothyroidism: a case report and review of the literature, Ann Clin Biochem source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Systematic reviews indicate that bariatric surgery is associated with lower TSH and lower daily LT4 needs.

    “Bariatric surgery can impact LT4 pharmacokinetics, and systematic reviews show that it is correlated with a reduction in TSH levels and daily LT4 requirements, 101,102 possibly due to changes in lean body mass.103”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [101] Azran, 2021, Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review, meta-analysis, network meta-analysis, and meta-regression, Surg Obes Relat Dis source

      Not checked in the free run.

    • cites [102] Guan, 2017, Effect of bariatric surgery on thyroid function in obese patients: a systematic review and meta-analysis, Obes Surg source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Weekly oral LT4 treatment gives slightly less effective control of hypothyroidism, with higher TSH and lower total T3 levels.

    “Weekly oral treatment shows slightly less effective control of hypothyroidism, with higher TSH levels and lower total T3 levels.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [93] Chiu, 2021, Weekly versus daily levothyroxine tablet replacement in adults with hypothyroidism: a meta-analysis, JASEAN Fed Endocr Soc

      Not checked in the free run.

    • cites [94] Dutta, 2021, Efficacy and safety of once weekly thyroxine as compared to daily thyroxine in managing primary hypothyroidism: a systematic review and meta-analysis, Indian J Endocrinol Metab source

      Not checked in the free run.

    • cites [95] Rajput, 2017, The effect of daily versus weekly levothyroxine replacement on thyroid function test in hypothyroid patients at a tertiary care centre in Haryana, Eur Thyroid J source

      Not checked in the free run.

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

    Premisecitation

    Management of obstructive liver disease or cirrhosis is supportive and focuses on controlling protein and sodium intake.

    “Management is supportive and focuses on controlling protein and sodium intake.3,69”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] Virili, 2019, Gastrointestinal malabsorption of thyroxine, Endocr Rev source

      Not checked in the free run.

    • cites [69] Benvenga, 2013, When thyroid hormone replacement is ineffective?, Curr Opin Endocrinol Diabetes Obes source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies suggest lean body mass is a better predictor of LT4 requirements, with around 2.3 mg/kg per day.

    “While there are no specific guidelines for hypothyroidism and obesity, studies suggest lean body mass is a better predictor, with around 2.3 mg/kg per day.97,99,100”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [97] Santini, 2005, Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases, J Clin Endocrinol Metab source

      Not checked in the free run.

    • cites [99] Ratanapornsompong, 2021, Appropriate dose of levothyroxine replacement therapy for hypothyroid obese patients, J Clin Transl Endocrinol

      Not checked in the free run.

    • cites [100] Cunningham, 1984, Lean body mass is a predictor of the daily requirement for thyroid hormone in older men and women, J Am Geriatr Soc source

      Not checked in the free run.

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

    Premisecitation

    Addison's disease is treated with corticosteroids.

    “Treatment for TSH-omas involves neurosurgical intervention, and corticosteroid therapy is used to treat Addison's disease.69,71,85”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [69] Benvenga, 2013, When thyroid hormone replacement is ineffective?, Curr Opin Endocrinol Diabetes Obes source

      Not checked in the free run.

    • cites [71] Beck-Peccoz, 2019, 2019 update on TSH-secreting pituitary adenomas, J Endocrinol Invest source

      Not checked in the free run.

    • cites [85] Sahoo, 2016, Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison’s disease with primary hypothyroidism, Indian J Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Early recognition of refractory hypothyroidism and correction of identifiable causes helps prevent supratherapeutic LT4 doses and reduces cardiovascular and skeletal complications.

    “Early recognition of RH, along with the identification and correction of any identifiable underlying cause, is crucial.This approach helps prevent the use of supratherapeutic doses of LT4, thereby reducing the risk of cardiovascular and skeletal complications associated with this condition.”
    Quote in the paperSubstantial claim
61 of 61

  • The paper relies on this without support.

    Patients with refractory hypothyroidism may experience thyroid emergencies such as myxedema coma and may require increased health care resources.

    “It is important to note that patients with RH may also experience thyroid emergencies, such as myxedema coma, and may require increased utilization of health care resources.”

  • The paper relies on this without support.

    No specific guidance exists for managing hypothyroidism in obesity.

    “While there are no specific guidelines for hypothyroidism and obesity, studies suggest lean body mass is a better predictor, with around 2.3 mg/kg per day.97,99,100”
2 of 2

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?

  • Refractory hypothyroidism is due to either malabsorption, increased metabolism of thyroxine, or nonadherence to treatment.

    “Such patients present so called “refractory hypothyroidism” generally because of poor therapeutic compliance, levothyroxine malabsorption syndromes, or accelerated pharmacokinetics of thyroxine [5].”

    From Levothyroxine Absorption Test With the Daily Levothyroxine Dose in Patients With “Refractory Hypothyroidism” (2025) · cites this paper as [5]

    The Clinical Relevance section (page unavailable) identifies nonadherence and gastrointestinal disorders as the main causes of refractory hypothyroidism. The medication-interference section says some drugs alter levothyroxine catabolism, but does not establish accelerated thyroxine metabolism as a general cause alongside those two. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Abstract and Methods name different databases

    Minor

    The abstract says the review searched Scielo, Scopus, and EMBASE, whereas the Methods section names PubMed/Medline, EMBASE, and Scielo. Scopus appears only in the abstract, and PubMed/Medline appears only in Methods.

1 of 1

Cites

Flagged first, then by citations

15 of the 111 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Chaker, 2022, Hypothyroidism, Nat Rev Dis Primers, 8, 1
  2. Ramírez Rentería, 2018, Inappropriate thyrotropin secretion in the presence of a pituitary adenoma: a complex differential diagnosis made easier by thorough clinical evaluation – two teaching case reports, Revista Mexicana de Endocrinología Metabolismo Nutrición, 5, 33
  3. Chiu, 2021, Weekly versus daily levothyroxine tablet replacement in adults with hypothyroidism: a meta-analysis, JASEAN Fed Endocr Soc, 36, 156

Cited by

Sorted by citations

Related

Authors
Quiroz-Aldave, J. E., Concepción-Zavaleta, M. J., Durand-Vásquez, M. D. C., Concepción-Urteaga, L. A., Gamarra-Osorio, E. R., Suárez-Rojas, J., Rafael-Robles, L. D. P., Paz-Ibarra, J., & Román-González, A.
Affiliations
Hospital Santa Rosa (PE)
ORCID
Venue
Endocrine Practice
Publisher
Elsevier BV
Published
2023-12
Volume
29
Issue
12
Pages
1007-1016
ISSN
1530-891X (ISSN-L)
DOI
10.1016/j.eprac.2023.09.003
OpenAlex
W4386701221
Semantic Scholar
bd7b4893226c80c1698598182fd0a888fa855108
Cited by
14
References
111
Citations by year
2026: 7 · 2025: 4 · 2024: 3
FWCI
0.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Practice (publishedVersion)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
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 › Thyroid Cancer Diagnosis and Treatment
Keywords
refractory hypothyroidism, levothyroxine, treatment non-adherence, drug interactions, lactose intolerance, Helicobacter pylori infection, giardiasis, triiodothyronine, thyroid hormone absorption, hyperthyroidism
MeSH terms
Female, Humans, Hypothyroidism, Pregnancy, Thyrotropin, Thyroxine, Helicobacter pylori, Helicobacter Infections

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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