Screening for thyroid dysfunction and treatment of screen-detected thyroid dysfunction in asymptomatic, community-dwelling adults: a systematic review

Abstract

BackgroundThis systematic review was conducted to inform the Canadian Task Force on Preventive Health Care recommendations on screening for thyroid dysfunction (TD). The review sought to answer key questions on the benefits and harms of screening for TD, patients’ values and preferences for screening, and the benefits and harms of treating screen-detected TD.MethodsThis review followed Canadian Task Force on Preventive Health Care methods, which include the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The search strategy used for benefits and harms of screening and treatment was an update to the 2014 review by the US Preventive Services Task Force and searched MEDLINE and the Cochrane Library. MEDLINE, Embase, ProQuest Public Health, and SCOPUS were searched for patients’ values and preferences for screening. Outcomes of interest included all-cause mortality, deaths due to cardiovascular diseases, fatal and non-fatal cardiovascular events, atrial fibrillation, fractures, quality of life, cognitive function, and harms due to TD treatment. Two reviewers independently screened abstracts and full texts according to pre-determined inclusion criteria and assessed the risk of bias for each study included. Strength and quality of the evidence was assessed for each outcome. A narrative synthesis was conducted due to heterogeneity of the included studies.ResultsNo studies were found on screening for TD, treatment of subclinical hyperthyroidism, or patients’ values and preferences for screening for TD. Twenty-two studies (from 24 publications) on the treatment of TD in patients with screen-detected subclinical hypothyroidism were included. Results from the included randomized controlled trials suggested no benefit of treatment for subclinical hypothyroidism for the large majority of outcomes. We found very low-quality evidence (from two cohort studies) for a small reduction in all-cause mortality among adults < 65 or 40–70 years who were treated for TD compared to those who were not.ConclusionsThis review found moderate to very low-quality evidence on the benefits and harms of treatment for subclinical hypothyroidism, with most of the evidence showing no benefit of treatment.

The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular complications

“…Therefore, the results from these studies have not resolved the debate as to the appropriateness of treatment in subjects with SCH. Some of the reasons for this debate are new findings showing a shifting of normal TSH values to higher levels with the advancement of age 15,54‐59 . The problem with deciding treatment for patients with SCH are the changes in the circadian rhythm of thyroid hormones and their normal reference values based on age, sex, race, ethnicity and time of day the blood sample is drawn 60 .…”

“…In addition, several other studies have also shown that age, sex, ethnicity, iodine status, BMI, reproductive status and assay method are independent factors that modify the TSH range 61‐64 . All these factors contribute to the uncertainty of treatment of SCH and a recent large review and meta‐analysis found no credible evidence that treatment of patients with SCH, especially in older individuals was not beneficial, and therefore, is not indicated and it could cause adverse CV effects including cardiac arrhythmias 57 . Also, controversial statements from some studies that “subclinical hypothyroidism is a mild thyroid failure and should be treated”, 65 and from other that “the treatment of subclinical hypothyroidism is seldom necessary”, 66 make the decision to treat or not to treat these patients difficult.…”

Recommendation on screening adults for asymptomatic thyroid dysfunction in primary care

“…The recommendation is based on systematic reviews 17 on the effectiveness (i.e., benefits and harms) of screening for thyroid dysfunction in asymptomatic, nonpregnant adults; the effectiveness of treating screen-detected thyroid dysfunction in asymptomatic, nonpregnant adults; and patient values and preferences related to screening (see analytic framework, Appendix 1, available at www. cmaj.ca/lookup/suppl/doi:10.1503/cmaj.190395/-/DC2).…”

“…The protocol (PROSPERO: CRD42016033622), systematic reviews 17 and draft guideline were externally peer reviewed. Two clinical experts engaged with Public Health Agency of Canada staff to address technical and clinical considerations.…”

“…Intermediate outcomes (i.e., physiologic measures related to the screening intervention but not clinical outcomes in and of themselves 20 ) rated as important were blood pressure, bone mineral density, cholesterol and weight change. 17 We also used the GRADE approach to determine the certainty of the evidence and strength of the recommendation (Box 1). 19 Appendix 2 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/ cmaj.190395/-/DC2) provides the evidence-to-decision framework that the task force used to assess the balance between benefits and harms, patient values, resource use, feasibility, acceptability and equity in order to develop the recommendation.…”