ABSTRACT
BACKGROUND: Levothyroxine (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. METHODS: A systematic search was conducted in March 2022 for randomized controlled trials and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement. RESULTS: A total of 277 articles were reviewed and seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 (±2.8) 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. The two clinical trials with the largest improvement in fatigue scores were the use of ginger and surgery. One observational study comparing thyroidectomy vs observation found no significant difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and quality of life. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group. CONCLUSIONS: There 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.
ABSTRACT
BACKGROUND: Statin intolerance is a key barrier to the effective prevention of atherosclerotic cardiovascular disease (ASCVD). Experts do not agree on what it is and how to respond to this problem clinically. OBJECTIVE: To characterize the range of expert recommendations about the care of patients with statin intolerance. METHODS: Systematic review registered in PROSPERO that searched on April 1 2022 in PubMed, EMBASE, Scopus, Cochrane, online textbooks, and specialty textbooks for expert reviews (e.g., review articles and book chapters), systematic reviews, or clinical practice guidelines published in the past 5 years without language restriction. Authors working in duplicate extracted definitions, management recommendations, and supportive evidence cited. RESULTS: We identified 26 eligible articles, none of which described a systematic method to summarize the evidence or to develop and grade recommendations. Of these, 14 (54%) offered a definition of statin intolerance. A sequenced approach to management of statin intolerance was suggested in 24 (92%) articles describing 12 different approaches without supporting evidence of efficacy. Investigating for other causes was the most common first step. All authors suggested rechallenging after a washout period with either the same or other statin. Few considered nonlipid approaches to reducing ASCVD risk and none recommended involving patients in shared decision making. CONCLUSION: We found substantial variability in the definition and management of statin intolerance among experts. Few focused on ASCVD risk reduction and none promoted the participation of patients in shared decision making about how to address the threat of ASCVD with or without statins.
