Gastrointestinal Malabsorption of Thyroxine

Levothyroxine, a largely prescribed drug with a narrow therapeutic index, is often a lifelong treatment. The therapeutic efficacy of T4 may be marred by behavioral, pharmacologic, and pathologic issues acting as interfering factors. Despite a continuous search for an optimal T4 treatment, a significant number of patients fail to show a complete chemical and/or clinical response to this reference dose of T4. Gastrointestinal malabsorption of oral T4 represents an emerging cause of refractory hypothyroidism and may be more frequent than previously reputed. In this review, we examine the pharmacologic features of T4 preparations and their linkage with the intestinal absorption of the hormone. We have stressed the major biochemical and pharmacologic characteristics of T4 and its interaction with the putative transporter at the intestinal level. We have examined the interfering role of nutrients, foods, and drugs on T4 absorption at the gastric and intestinal levels. The impact of gastrointestinal disorders on T4 treatment efficacy has been also analyzed, in keeping with the site of action and the interfering mechanisms. Based on the evidence obtained from the literature, we also propose a schematic diagnostic workup for the most frequent and often hidden gastrointestinal diseases impairing T4 absorption.