Concomitant Use of Levothyroxine and Proton Pump Inhibitors in Patients with Primary Hypothyroidism: a Systematic Review

Background The aim of this study was to assess the effect of concomitant use of levothyroxine (LT4) and proton pump inhibitors (PPIs) on thyroid-stimulating hormone (TSH) levels in patients with primary hypothyroidism. Methods A systematic review of interventional and observational studies that compared the TSH levels before and after concomitant use of LT4 and PPI was performed. Articles published in English up to September 1, 2019, were included. PubMed, EMBASE, and Cochrane Library databases. Gray literature was also searched in repositories, websites OpenGrey and Google Scholar, and abstracts of major international congresses. Study quality was assessed with the Newcastle-Ottawa quality assessment scale for observational studies and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool was used. Results Five thousand twelve discrete articles were identified. Following assessment and application of eligibility criteria, seven studies were included. There was a considerable heterogeneity among the included studies in design, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics. Each of the included studies showed an increase in TSH levels following LT4 and PPI consumption, and in the majority of these, the increase was statistically significant. Discussion The concomitant use of LT4 and PPI showed a significant increase in TSH concentration. However, given the small number of studies, further research is needed to clarify the interfering role of PPI on LT4 intestinal absorption. PROSPERO Registration Number CRD42020047084.