Association of Thyroid Hormone Therapy with Mortality in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis

Abstract

Context Benefits of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism remain undetermined. Objective To summarize the impact of thyroid hormone therapy on mortality in adults with subclinical hypothyroidism. Data Sources PubMed, Embase, Scopus, Web of Science, and Clinicaltrials.gov from inception until April 25, 2020. Study Selection Studies comparing the effect of thyroid hormone therapy with that of placebo or no therapy in adults with subclinical hypothyroidism on all-cause and/or cardiovascular mortality. Data Extraction Two reviewers independently extracted data and performed quality assessments. Random-effects models for meta-analyses were used. Data Synthesis Five observational studies and two randomized controlled trials with 21,055 adults were included. Overall, thyroid hormone therapy was not significantly associated with all-cause (pooled relative risk [RR] = 0.95, 95% confidence interval [CI]: 0.75–1.22, p = 0.704) or cardiovascular (pooled RR = 0.99, 95% CI: 0.82–1.20, p = 0.946) mortality. Subgroup analyses revealed that in younger adults (aged < 65–70 years), thyroid hormone therapy was significantly associated with a lower all-cause (pooled RR = 0.50, 95% CI: 0.29–0.85, p = 0.011) and cardiovascular (pooled RR = 0.54, 95% CI: 0.37–0.80, p = 0.002) mortality. However, no significant association between thyroid hormone therapy and mortality was observed in older adults (aged ≥ 65–70 years). Conclusions Use of thyroid hormone therapy does not provide protective effects on mortality in older adults with subclinical hypothyroidism. However, thyroid hormone therapy for subclinical hypothyroidism may show benefits on morality in adults aged < 65–70 years.

Risk of All-Cause Mortality in Levothyroxine-Treated Hypothyroid Patients: A Nationwide Korean Cohort Study

“…Previous studies have suggested that the association between hypothyroidism and mortality is less evident in individuals aged > 65 years (20,32,34,44). Recently, Peng et al found that the use of thyroid hormone replacement was not associated with all-cause mortality in patients aged > 65 years with subclinical hypothyroidism (38). The Leiden 85+ study, which enrolled individuals aged 85 years and older, indicated a decreased risk of cardiovascular and all-cause mortality with higher TSH levels (18), but these findings have not been replicated.…”

“…The risk of mortality in hypothyroidism may differ by age and sex ( 18 , 20 , 24 , 28 , 32 , 34 , 38 ). Previous studies have suggested that the association between hypothyroidism and mortality is less evident in individuals aged > 65 years ( 20 , 32 , 34 , 44 ).…”

“…To date, a number of cohort studies and meta-analyses have investigated the relationship between hypothyroidism and mortality (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). However, most have been restricted to subjects with subclinical hypothyroidism (17,20,21,28,29,33,34,38) and some studies have defined hypothyroidism based on only one TSH level measurement (13,15,22,28,30,37). Therefore, these studies may not represent patients with hypothyroidism who require long-term thyroid hormone replacement.…”

Thyroid and heart, a clinically relevant relationship

“…Five observational studies and two randomized controlled trials (with a total of 21,055 patients) were included. The results showed that LT4 therapy was associated with a significant reduction in all-cause (RR = 0.50, CI 0.29–0.85, p = 0.011) and cardiovascular (RR = 0.54, 95% CI 0.37–0.80, p = 0.002) mortality in patients younger than 65 years, but not in older patients [ 34 ].…”

Autoimmunthyreoiditis

“…Eine aktuelle Metaanalyse mit 21 055 Erwachsenen belegte in einer Subgruppenanalyse bei Erwachsenen < 65-70 Jahre, dass eine Schilddrüsenhormonsubstitution bei subklinischer Hypothyreose signifikant mit einer geringeren kardiovaskulären Mortalität und Gesamtmortalität assoziiert war [15].…”