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



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.


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.


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.


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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This was an independent study, and, thus, we did not receive any funds to perform it.

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Correspondence to Roberto Vita.

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S.B. was an invited speaker at symposia organized by IBSA. The other authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Benvenga, S., Di Bari, F. & Vita, R. Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrine 56, 138–145 (2017).

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  • Hypothyroidism
  • Undertreated hypothyroidism
  • Levothyroxine replacement therapy
  • Malabsorption of levothyroxine