A liquid formulation of L-thyroxine (L-T4) solves problems of incomplete normalization/suppression of serum TSH caused by proton pump inhibitors (PPI) on conventional tablet formulations of L-T4
G. Saraceno1, R. Vita1, F. Trimarchi1 & S. Benvenga1,2,3
Background: PPI are known to diminish the intestinal absorption of L-T4, which is commonly ingested as tablets of L-T4 sodium salt. However, a liquid formulation is available (Tirosint, oral solution, IBSA Farmaceutici Italia s.r.l., Italy), in which the hormone is solubilized in 28.8% ethyl alcohol. One ml of this formulation (=28 drops) contains 100 mcg L-T4 sodium salt in 243 mg ethanol. Because this formulation contains L-T4 (which is a lipophilic hormone) already solubilized in an organic solvent, as opposed to L-T4 contained in a powder within a tablet, there could be the advantage of virtually skipping the dissolution in the stomach, and subsequent quick, direct arrival of L-T4 in the upper intestine segments (duodenum, jejunum) where most of it is absorbed.
Patients & methods: Upon consent, 1 woman under replacement therapy [100125 mcg/day] and 9 patients (7 women and 2 men) under TSH suppressive therapy [82135 mcg/day], all 10 with PPI-induced malabsorption of LT4, were switched to Tirosint oral solution while maintaining the daily dose of L-T4 and continuing ingesting the PPI as before. The PPI were: lansoprazole, omeprazole or pantoprazole. Post-switch serum TSH was re-assayed after a minimum of 2 months.
Results: In the hypothyroid woman, TSH fell to 2.02.7 mU/L down from 5.07.3. In the other 9 patients, TSH fell to <0.01 to 1.97 mU/L (median: 0.10; mean ±SD: 0.68±0.91), down from 0.282.95 (median: 0.81; mean ±SD 1.02±0.74; P=0.0004 by ANOVA after log10-transformation), and with 65% of the post-switch TSH levels at 0.10 mU/L or below compared to 0% (zero%) of the pre-switch levels (P< 0.0001 by Fishers exact test).
Conclusion: The liquid formulation of L-T4 is an extremely effective means to circumvent the problem of incomplete absorption of the L-T4 caused by the PPI-induced increase of the gastric pH.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector