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Evidence summaries

Effect of Thyroxine Therapy on Serum Lipid Levels in Subclinical Hypothyroidism

Levothyroxine (T4) therapy in individuals with sublinical hypothyroidism may lower mean serum total and LDL cholesterol concentrations. Level of evidence: "C"

The quality of evidence is downgraded by study limitations and by inconsistency (variability in results).

Summary

A systematic review 1 included 13 studies with a total of 247 subjects with mild thyroid failure (i.e. subclinical hypothyroidism). Three studies (23%) were RCTs with 81 participants. The mean decrease in the serum total cholesterol (TC) concentration (13 studies) was -0.20 mmol/l (-7.9 mg/dl, 95% CI -0.09 to 0.34). The decline in serum TC was directly proportional to its baseline concentration. Studies enrolling hypothyroid participants receiving suboptimal T4 doses reported significantly larger decreases in serum TC after thyroid-stimulating hormone normalisation than those enrolling previously untreated individuals with mild thyroid failure. The authors conclude the reduction in serum TC may be larger in individuals with higher pre-treatment cholesterol levels, and in hypothyroid individuals taking suboptimal T4 doses. There seems to be no significant effects of T4 on serum HDL or triglyceride concentrations.

Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 ± 0.8 mIU/liter) were randomly assigned to receive L-thyroxine or placebo for 48 wk 2. In the L-thyroxine group (n = 31) TC and low density lipoprotein cholesterol (LDL-C) were significantly reduced (-0.24 mmol/liter, 3.8%, P = 0.015) and -0.33 mmol/liter, 8.2%, P = 0.004), respectively). LDL-C decrease was more pronounced in patients with TSH levels greater than 12 mIU/liter or elevated LDL-C levels at baseline. Two clinical scores assessing symptoms and signs of hypothyroidism (Billewicz and Zulewski scores) improved significantly (P = 0.02).

A systematic review 3 included 12 studies with a total of 940 subjects with subclinical hypothyroidism. Levothyroxine substitution reduced TC (WMD-0.29 mmol/L, 95% CI -0.42 to -0.16) and LDL-C (WMD -0.22 mmol/L, 95% CI -0.36 to -0.09, statistical heterogeneity I2 =66%), with no significant effects on HDL-C (-0.04 mmol/L, 95% CI -0.08 to 0.01; statistical heterogeneity I2 =64%) or triglycerides (-0.04 mmol/L, 95% CI -0.08 to 0.00). Studies in which only patients with mild subclinical hypothyroidism (TSH <10 mIU/L) were enrolled showed similar results.

    References

    • Danese MD, Ladenson PW, Meinert CL, Powe NR. Clinical review 115: effect of thyroxine therapy on serum lipoproteins in patients with mild thyroid failure: a quantitative review of the literature. J Clin Endocrinol Metab 2000 Sep;85(9):2993-3001. [PubMed]
    • Chu JW, Crapo LM. The treatment of subclinical hypothyroidism is seldom necessary. J Clin Endocrinol Metab 2001 Oct;86(10):4591-9. [PubMed]
    • Li X, Wang Y, Guan Q et al. The lipid-lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf) 2017;87(1):1-9. [PubMed]

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