AUTHOR=Virili Camilla , Capriello Silvia , Stramazzo Ilaria , Brusca Nunzia , Santaguida Maria Giulia , Gargano Lucilla , Bagaglini Maria Flavia , Bruno Giovanni , Severi Carola , Centanni Marco TITLE=Daily requirement of softgel thyroxine is independent from gastric juice pH JOURNAL=Frontiers in Endocrinology VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1002583 DOI=10.3389/fendo.2022.1002583 ISSN=1664-2392 ABSTRACT=Background: Softgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better perfor-mance of softgel LT4 preparation in patients with gastric disorders but whether this finding is relat-ed to gastric juice pH variation in vivo is not known. Methods: Twenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 µg/kg/day) and with stable TSH values on target (<0.8-2.5> mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar in-dividual serum TSH value. All subjects followed a specific treatment schedule, taking levothyroxine in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent en-doscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gas-tric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. Results: Upon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly re-duced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction >20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no patients showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p<0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p<0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman’s ρ =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman’s ρ =1.952; p = 0.3194). Conclusions: These findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with in-creased LT4 requirement, owed to disorders impairing the gastric acidic output.