Effect of Levothyroxine on Older Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis

Abstract

Background: Subclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The aim of the systematic review and meta-analysis was to evaluate whether levothyroxine has a beneficial or harmful effect on older patients with SCH.

Methods: Databases including PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Weipu and China National Knowledge Infrastructure were searched from inception until December 21, 2021. Subjects must be diagnosed with SCH, and older than or equal to 60 years of age. Interventions should be thyroid hormone therapy (e.g. levothyroxine). The literature was independently screened by 2 researchers. Statistical analysis was performed using RevMan5.3 software.

Results: A total of 13 articles were included. Meta-analysis results showed that in older SCH patients, levothyroxine can significantly reduce cholesterol (TC) (p < 0.00001), triglyceride (TG) (p < 0.00001), low-density lipoprotein cholesterol (LDL-C) (p = 0.03) and apolipoprotein B (ApoB) (p < 0.00001). In addition, levothyroxine had no significant effect on bone mineral density, fatigue, hypothyroidism symptoms, quality of life, BMI, cognitive function, depression, blood pressure, etc. in older SCH patients, and also did not significantly increase the incidence of adverse events.

Conclusions: Among older SCH patients, levothyroxine treatment may reduce TC, TG, LDL-C, and ApoB.

Keywords: apolipoprotein B; cholesterol; levothyroxine; low-density lipoprotein cholesterol; older; subclinical hypothyroidism; triglyceride.

Figure 1

Meta-analysis flowchart. This meta-analysis included a total of four steps: Identification, Screening, Eligibility and Included. CNKI, China National Knowledge Infrastructure.

Figure 2

Forest plots depicting the effect of levothyroxine on the bone mineral density, fatigue, hypothyroidism symptoms and quality of life in older patients. (A) Association between levothyroxine and bone mineral density. (B) Association between levothyroxine and fatigue. (C) Association between levothyroxine and hypothyroidism symptoms. (D) Association between levothyroxine and quality of life.

Figure 3

Forest plots depicting the effect of levothyroxine on the BMI, cognitive function, depression and serum creatinine in older patients. (A) Association between levothyroxine and BMI. (B) Association between levothyroxine and cognitive function. (C) Association between levothyroxine and depression. (D) Association between levothyroxine and serum creatinine. BMI, Body Mass Index.

Figure 4

Forest plots depicting the effect of levothyroxine on the systolic blood pressure, diastolic blood pressure, fasting blood glucose, HDL-C and apolipoprotein A in older patients. (A) Association between levothyroxine and systolic blood pressure. (B) Association between levothyroxine and diastolic blood pressure. (C) Association between levothyroxine and fasting blood glucose. (D) Association between levothyroxine and HDL-C. (E) Association between levothyroxine and apolipoprotein A. HDL-C, High-Density Lipoprotein Cholesterol.

Figure 5

Forest plots depicting the effect of levothyroxine on the cholesterol, triglyceride, LDL-C and apolipoprotein B in older patients. (A) Association between levothyroxine and cholesterol. (B) Association between levothyroxine and triglyceride. (C) Association between levothyroxine and LDL-C. (D) Association between levothyroxine and apolipoprotein B. LDL-C, Low-Density Lipoprotein Cholesterol.

Figure 6

Forest plots depicting the effect of levothyroxine on the fatal or nonfatal cardiovascular event, cardiovascular death, all-cause death, atrial fibrillation, heart failure and number of patients with ≥1 serious adverse event in older patients. (A) Association between levothyroxine and fatal or nonfatal cardiovascular event. (B) Association between levothyroxine and cardiovascular death. (C) Association between levothyroxine and all-cause death. (D) Association between levothyroxine and atrial fibrillation. (E) Association between levothyroxine and heart failure. (F) Association between levothyroxine and number of patients with ≥1 serious adverse event.