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Endocrine. 2017 Apr;56(1):138-145. doi: 10.1007/s12020-017-1244-2. Epub 2017 Feb 3.

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

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Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi,, 98125, Messina, Italy.
Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina, Viale Gazzi,, 98125, Messina, Italy.
Interdepartmental Program of Molecular & Clinical Endocrinology, and Women's Endocrine Health, University Hospital, Policlinico Universitario G. Martino, Viale Gazzi,, 98125, Messina, Italy.
Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi,, 98125, Messina, Italy.



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.


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

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