Levothyroxine treatment and gastric juice pH in humans: the proof of concept

Abstract

Purpose Despite the absorption of oral thyroxine (T4) occurs in the small bowel, several patients with gastric disorders show an increased need for T4. In vitro evidence suggested that medium pH variations interfere with T4 dissolution. This study was aimed at finding the proof of concept of a direct relationship between the minimal effective dose of T4 and the actual gastric juice pH. Patients and methods Among 311 consecutively thyroxine-treated patients, 61 bearing Hashimoto’s thyroiditis (52 F/9 M; median age = 51 years) who complained persistent dyspepsia and/or upper abdominal symptoms following a noninvasive workup for gastrointestinal disorders, underwent EGDS with multiple biopsies and gastric juice pH measurement. All patients accepted to take thyroxine in fasting conditions, abstaining from eating or drinking for one hour. Results Thyroxine requirement increased along with the rising gastric pH (ρ = 0.4229; p = 0.0007). A multivariate analysis revealed that gastric pH was, beside body mass index, the far more important independent variable in determining the effective dose of T4 (p = 0.001). The ROC curve revealed that the pH threshold for an increased thyroxine requirement was at 2.28, being the AUC by 78%. Subdividing patients by the histologic findings, it appeared a significant increase (p = 0.0025) along with the progressive damage of gastric mucosa. Conclusion The in vivo measurement of gastric pH highlighted its key role in determining the minimal effective dose of oral T4 and may explain the interference of food, of some drugs and gut disorders on levothyroxine treatment

Daily requirement of softgel thyroxine is independent from gastric juice pH

“…The study group was a follow up of a previously published study ( 8 ) in which we correlated the actual gastric juice pH of 61 patients to their tablet LT4 requirement of a single brand. As described in ( 8 ), these were hypothyroid patients with Hashimoto’s thyroiditis in need for thyroxine treatment.…”

“…The study group was a follow up of a previously published study ( 8 ) in which we correlated the actual gastric juice pH of 61 patients to their tablet LT4 requirement of a single brand. As described in ( 8 ), these were hypothyroid patients with Hashimoto’s thyroiditis in need for thyroxine treatment. These 61 patients underwent upper endoscopy with multiple biopsies and gastric juice pH evaluation, as suggested by the gastroenterologist, because of long lasting dyspepsia or suspicion of gastritis.…”

“…All patients underwent upper endoscopy in the morning, as described in ( 8 ), fasting from at least eight hours. Briefly, all subjects were sedate using intravenous midazolam (range to 2-5 mg).…”

“…The key of thyroxine treatment efficacy is the absorption process (6) which in turn depends on the gastrointestinal status of patient (gastric acidity, motility, drugs and nutritional interferences, comorbidity etc.) (7)(8)(9). At gastric level, the absorption of LT4 is negligible but disaggregation and dissolution of the tablet occur in the stomach (10)(11)(12), thus influencing the amount of the hormone available to be absorbed at the intestinal level (7).…”

“…In the remaining third, the requirement of tablet and softgel formulation was substantially the same and we suggested the usefulness of direct measurement of the gastric juice pH ( 23 ). Subsequently, evidence has been provided in vivo , that gastric juice pH is one of the major determinants of the minimal effective dose of tablet LT4 ( 8 ). Therefore, we decided to assess the relationship between softgel LT4 requirement and the actual gastric juice pH in oral thyroxine treated patients.…”