Interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms: A systematic review

Abstract

BackgroundLevothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however, 10-15% of patients have persistent hypothyroid symptoms despite normalizing thyroid hormone levels with LT4. This study aims to summarize the best available evidence on interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms. MethodsA systematic search was conducted in March 2022 for randomized controlled trials (RCTs) and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement. ResultsOf 277 articles, seven ful lled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidism related symptoms and general health. Of these clinical trials, the use of ginger and surgery showed the largest improvements in fatigue scores. One observational study comparing thyroidectomy vs observation found no impact difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and QoL. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group. ConclusionsThere is no high-quality evidence supporting any intervention for persistent symptoms in hypothyroidism. Available evidence, limited by the risk of bias, inconsistency, and heterogeneity, suggests that some persistent symptoms, particularly fatigue, could improve with ginger and thyroidectomy.Trial registry number:PROSPERO (CRD42022318720) Author ContributionsAuthor Jessica Hidalgo: Writing of protocol. Screening the titles, abstracts, and full text articles for eligibility. Extracting the study data into a spreadsheet. Analysis and interpretation of the data. Writing original draft. Approval of the version to be published.Author Eddy P. Lincango: Extracting the study data into a spreadsheet. Analysis and interpretation of the data. Approval of the version to be published.Author Sandra Cordova-Madera: Screening the titles, abstracts, and full text articles for eligibility. Approval of the version to be published.Author Kim Ruiz. Screening the titles, abstracts, and full text articles for eligibility. Approval of the version to be published.Author Camila Wenczenovicz: Screening the titles, abstracts, and full text articles for eligibility. Approval of the version to be published.