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Cited by 14Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences

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Benvenga, Salvatore, Pantano, Rachele, Saraceno, Giovanna, Lipari, Luigi, Alibrando, Antonio, Inferrera, Santi, Pantano, Giuseppe, Simone, Giuseppe +6 more·2019·Journal of Clinical & Translational Endocrinology
DOI 10.1016/j.jcte.2019.100189PMC PMC6462542
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Abstract

Objective Cross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism ( viz . failure of serum TSH to reach target levels, if hypothyroidism is primary). Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. Method In this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). Result A total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10 −20 ) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10 −7 ). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). Conclusion During a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management.

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  • In a study of 10,496 persons, 730 (7.0%) had L-T4-treated primary hypothyroidism, of whom 391 (5.4%; 3.7% of 10,496) were taking interfering medications, with 114 enrolled; proton-pump inhibitors were the leading interfering medication (95/114 [83%]), followed by calcium salts (18/114 [16%]).

    “Of 10,496 persons, 730 (7.0%) had L-T4-treated PH, of whom 391 (5.4%; 3.7% of 10,496) were taking those IM, with 114 enrolled (age 65.6 ± 12.7 years). PPIs were the leading IM (95/114 [83%]), either alone (n = 71 [62%]) or associated with other IM (n = 24 [21%]), followed by calcium salts (18/114 [16%]).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [23]

  • Concerning interfering medication-induced undertreated hypothyroidism, few data are available on metabolic/cardiovascular complications and costs of frequent assays to monitor L-T4 therapy.

    “Concerning IM-induced UTH, few data are available on two issues (23, 44, 98, 99): (i) metabolic/cardiovascular complications, (ii) costs of frequent assays to monitor L-T4 therapy.”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [23]

  • In 114 L-T4-treated primary hypothyroidism patients, exposure to interfering medications (32.1 ± 6.9 months) significantly increased TSH from 1.27 ± 1.34 to 2.81 ± 3.62 mU/L (+121%), and proportions of TSH >4.12 mU/L from 4.7 to 18.5% and >2.50 mU/L from 20.2 to 53.5% compared to the non-exposure period (35.4 ± 9.7 months).

    “In the aforementioned study on 114 L-T4-treated PH patients (23), exposure to IM (32.1 ± 6.9 months) significantly increased TSH from 1.27 ± 1.34 to 2.81 ± 3.62 mU/L (+121%), and proportions of TSH >4.12 mU/L from 4.7 to 18.5% and >2.50 mU/L from 20.2 to 53.5% compared to the non-exposure period (35.4 ± 9.7 months).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [23]

  • In the same study, 76 patients (67%) had complications (aggravation of pre-existing or de novo onset of metabolic syndrome, impaired fasting glycemia, diabetes, dyslipidemia, hypertension, cardiovascular disease), whose rates of TSH >4.12 or >2.50 mU/L were significantly greater than in the 36 complication-free patients (22 vs. 11%, or 35 vs. 17%); TSH in patients with complications vs. 1.58 ± 1.9

    “Some complications ensued: aggravation of pre-existing or de novo onset of any of metabolic syndrome (MS), impaired fasting glycemia (IFG), diabetes, dyslipidemia, hypertension, cardiovascular disease (CVD). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 or >2.50 mU/L were significantly greater than in the 36 complication-free patients (22 vs. 11%, or 35 vs. 17%). TSH in”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [23]

  • A high proportion of LT4-treated patients ingest medications, foodstuffs, and food supplements that selectively or specifically reduce intestinal absorption of LT4.

    “Furthermore, a high proportion of LT4-treated patients ingest medications, foodstuffs and food supplements that selectively or specifically reduce the intestinal absorption of LT4.”

    From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [61]

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Authors
Benvenga, S., Pantano, R., Saraceno, G., Lipari, L., Alibrando, A., Inferrera, S., Pantano, G., Simone, G., Tamà, S., Scoglio, R., Ursino, M. G., Simone, C., Catalano, A., & Alecci, U.
Affiliations
  • University of Messina (IT)
  • IRCCS Istituto Auxologico Italiano (IT)
  • Società Italiana di Medicina Generale (IT)
Corresponding author
Catalano, Antonino
ORCID
Venue
Journal of Clinical & Translational Endocrinology
Publisher
Elsevier BV
Published
2019-06
Volume
16
Pages
100189
ISSN
2214-6237 (ISSN-L)
DOI
10.1016/j.jcte.2019.100189
PMC
PMC6462542
OpenAlex
W2938214314
Cited by
14
References
33
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical & Translational Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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
primary hypothyroidism, levothyroxine, hyperthyrotropinemia, thyroid-stimulating hormone, polypharmacy, metabolic syndrome, dyslipidemia, hypertension, coronary artery disease, cerebrovascular disease, diabetes mellitus, impaired fasting glucose, cardiovascular complications, duration of exposure, thyroid hormone replacement

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