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Cited by 51Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine

Benvenga, Salvatore, Di Bari, Flavia, Vita, Roberto·2017·Endocrine
DOI 10.1007/s12020-017-1244-2
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Abstract

Purpose The aim of this study was to assess whether oral liquid levothyroxine would correct tablet levothyroxine malabsorption induced by calcium or iron, two sequestrants of levothyroxine.Methods Nineteen adult hypothyroid patients with tablet levothyroxine malabsorption caused by calcium and/or iron supplements were switched from tablet to liquid levothyroxine at the same dose. Primary outcomes were: (1) significantly lower mean serum thyroid-stimulating hormone with the liquid compared with the tablet formulation, and (2) significantly greater rate of serum thyroid-stimulating hormone less than or equal to 4.12 or 2.5 mU/L.The mean follow-up was 25.2 ± 16.5 weeks.Results TSH was lower with liquid levothyroxine compared with tablet levothyroxine (7.48 ± 5.8 vs. 1.95 ± 1.3 mU/L, P < 0.001), both in the calcium group (8.74 ± 7.2 vs. 2.15 ± 1.4, P < 0.001) and iron group (8.74 ± 7.2 vs. 1.68 ± 0.9, P < 0.001). Thyroid-stimulating hormone levels ≤4.12 mU/L in all patients, calcium group and iron group were more frequent post-switch (95, 87 and 100%) compared to pre-switch (26, 22 and 29%, P < 0.001), and so were thyroid-stimulating hormone levels ≤2.50 mU/L (66, 59 and 76% compared to 5, 9 and 0%, P < 0.001). The pattern held comparing the first liquid levothyroxine thyroid-stimulating hormone levels and the first tablet levothyroxine thyroid-stimulating hormone levels or the corresponding rates of thyroid-stimulating hormone levels below the target.Conclusions Liquid levothyroxine is resistant to the sequestration by calcium or iron. The high rate of thyroid-stimulating hormone normalization already at the first check (6-8 weeks) should avoid frequent adjustments in levothyroxine doses and assays of thyroid-stimulating hormone, with consequent financial savings.

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Crossref · 10.1007/s12020-017-1244-2

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  • In a 2017 prospective, pre-post study of 19 hypothyroid patients with malabsorption due to coingestion of calcium and iron supplements, a follow-up of at least 16 weeks showed a significantly reduced TSH level in the solution group compared with the tablet group (7.48 ± 5.8 vs 1.95 ± 1.3 mU/L, P < .001).

    “In 2017, Benvenga et al conducted a prospective, pre–post study of 19 hypothyroid patients with malabsorption due to the coingestion of calcium and iron supplements (196). A follow-up of at least 16 weeks showed a significantly reduced TSH level in the solution group compared with the tablet group (7.48 ± 5.8 vs 1.95 ± 1.3 mU/L, P < .001).”

    From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [196]

  • 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 [98]

  • At euro 20 per TSH test, the total cost for five TSH tests in 125,840 or 1,031,888 patients with calcium-related or iron-related undertreated hypothyroidism ranges from euro 12,584,000 to 103,188,800.

    “At euro 20 for one TSH test, the total cost for five TSH tests in these 125,840 or 1,031,888 patients ranged euro 12,584,000 to 103,188,800.”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [98]

  • L-T4 formulations (liquid, softgel) are refractory or much more resistant to interacting medications than tablet L-T4.

    “the availability of L-T4 formulations (liquid, softgel) that are refractory or much more resistant to IM than tablet L-T4 (9, 14, 98, 100, 109–114).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [98]

  • Orally administered liquid and soft-gel LT4 formulations are associated with higher serum FT4 levels and lower TSH levels than tablet formulations, even when the overall LT4 dose level is the same.

    “Other reports from both retrospective and prospective observational studies indicate that orally administered liquid and soft-gel formulations of LT4 are associated with higher serum FT4 levels and lower TSH levels than tablet formulations, even when the overall LT4 dose level is the same – perhaps due to the absence of gastric disintegration [ 38 – 44 ].”

    From Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults (2022) · cites this paper as [39]

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Authors
Benvenga, S., Di Bari, F., & Vita, R.
Affiliations
University of Messina (IT)
Corresponding author
Vita, Roberto
ORCID
Venue
Endocrine
Publisher
Springer Science and Business Media LLC
Published
2017-02-03
Volume
56
Issue
1
Pages
138-145
ISSN
  • 0969-711X (ISSN-L)
  • 1355-008X
  • 1559-0100
DOI
10.1007/s12020-017-1244-2
OpenAlex
W2584823620
Cited by
51
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 10 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 8 · 2017: 1
FWCI
4.53
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • Endocrine (publishedVersion)
  • PubMed (publishedVersion)
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
hypothyroidism, levothyroxine, calcium supplementation, iron supplementation, thyroid-stimulating hormone, drug sequestration
MeSH terms
Adult, Aged, Calcium, Female, Humans, Hypothyroidism, Iron, Male, Middle Aged, Thyrotropin, Thyroxine, Treatment Outcome, Dietary Supplements

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