Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-Analysis.

CONTEXT Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. OBJECTIVE The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. DATA SOURCES We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through April 5, 2018. STUDY SELECTION Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. DATA EXTRACTION Pairs of independent reviewers extracted data and appraised studies. DATA SYNTHESIS Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI], 37.99, 51.02), low-density lipoprotein (LDL-C) by 31.13 mg/dL (95% CI 24.33, 37.93), high-density lipoprotein (HDL-C) by 5.52 mg/dL (95% CI 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI 22.67, 29.57) and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI -5.67, -2.61), TGs by -27.25 mg/dL (95% CI -36.63, 17.87), apo A by -12.59 mg/dL (95% CI -17.98, -7.19), apo B by -33.96 mg/dL (95% CI 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. CONCLUSIONS Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.

[1]  J. Higgins,et al.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, International Coaching Psychology Review.

[2]  Daniel E Forman,et al.  2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2019, Journal of the American College of Cardiology.

[3]  N. Rodondi,et al.  Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline , 2019, BMJ.

[4]  D. Bauer,et al.  Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis , 2018, JAMA.

[5]  H. Yoo,et al.  Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. , 2018, Thyroid : official journal of the American Thyroid Association.

[6]  A. Bianco,et al.  Systemic Thyroid Hormone Status During Levothyroxine Therapy in Hypothyroidism: A Systematic Review and Meta-Analysis , 2018, The Journal of clinical endocrinology and metabolism.

[7]  B. Biondi,et al.  Thyroid Hormones and Cardiovascular Function and Diseases. , 2018, Journal of the American College of Cardiology.

[8]  B. Cho,et al.  Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function. , 2017, Journal of clinical lipidology.

[9]  Xia Li,et al.  The lipid‐lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta‐analysis of randomized controlled trials , 2017, Clinical endocrinology.

[10]  D. Carvalho,et al.  Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile , 2017, Endocrine connections.

[11]  B. Corvilain,et al.  Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism? , 2017, Clinical endocrinology.

[12]  S. Rivkees,et al.  2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. , 2016, Thyroid : official journal of the American Thyroid Association.

[13]  G. Paz-Filho,et al.  Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study , 2016, Archives of endocrinology and metabolism.

[14]  Mingzhu Lin,et al.  Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism. , 2015, The Journal of clinical endocrinology and metabolism.

[15]  B. Angelin,et al.  Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans[S] , 2014, Journal of Lipid Research.

[16]  J. Olesen,et al.  Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. , 2014, The Journal of clinical endocrinology and metabolism.

[17]  Irwin Klein,et al.  Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[18]  Byron C. Wallace,et al.  Closing the Gap between Methodologists and End-Users: R as a Computational Back-End , 2012 .

[19]  L. Duntas,et al.  The effect of thyroid disorders on lipid levels and metabolism. , 2012, The Medical clinics of North America.

[20]  L. Hegedüs,et al.  A critical review and meta-analysis of the association between overt hyperthyroidism and mortality. , 2011, European journal of endocrinology.

[21]  G. Melnichenko,et al.  Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism , 2010, Hormones.

[22]  G. Brent,et al.  Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation , 2010, Trends in Endocrinology & Metabolism.

[23]  Stephen Kaptoge,et al.  Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. , 2009, JAMA.

[24]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[25]  S. Momtazi,et al.  Efficacy of Combined Levothyroxine and Liothyronine as Compared with Levothyroxine Monotherapy in Primary Hypothyroidism: A Randomized Controlled Trial , 2009, Endocrine research.

[26]  B. Angelin,et al.  Dramatically increased intestinal absorption of cholesterol following hypophysectomy is normalized by thyroid hormone. , 2008, Gastroenterology.

[27]  A. Costa,et al.  Lipid profile in different degrees of hypothyroidism and effects of levothyroxine replacement in mild thyroid failure. , 2008, Translational research : the journal of laboratory and clinical medicine.

[28]  J. Manson,et al.  Multivariate Assessment of Lipid Parameters as Predictors of Coronary Heart Disease Among Postmenopausal Women: Potential Implications for Clinical Guidelines , 2004, Circulation.

[29]  C. Palombo,et al.  Effect of levothyroxine replacement on lipid profile and intima-media thickness in subclinical hypothyroidism: a double-blind, placebo- controlled study. , 2004, The Journal of clinical endocrinology and metabolism.

[30]  G. Walldius,et al.  Apolipoprotein B and apolipoprotein A‐I: risk indicators of coronary heart disease and targets for lipid‐modifying therapy , 2004, Journal of internal medicine.

[31]  A. Harari,et al.  Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism: a randomized controlled trial. , 2003, JAMA.

[32]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[33]  E. Hawe,et al.  Nonfasting Apolipoprotein B and Triglyceride Levels as a Useful Predictor of Coronary Heart Disease Risk in Middle-Aged UK Men , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[34]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[35]  E. Ferrannini,et al.  Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. , 2002, The Journal of clinical endocrinology and metabolism.

[36]  I. Holme,et al.  High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study , 2001, The Lancet.

[37]  A. Moss,et al.  Thrombogenic factors and recurrent coronary events. , 1999, Circulation.

[38]  A. Kung,et al.  Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein. , 1998, The Journal of clinical endocrinology and metabolism.

[39]  A. Çorakçı,et al.  The effects of thyroid status on serum apolipoprotein A-I-containing lipoprotein particles. , 1998, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[40]  J. Louvet,et al.  DECREASED HDL CHOLESTEROL IN SUBCLINICAL HYPOTHYROIDISM: THE EFFECT OF L‐THYROXINE THERAPY , 1990, Clinical endocrinology.

[41]  J. Neaton,et al.  Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). , 1986, JAMA.

[42]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[43]  H. Lithell,et al.  Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein‐lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy , 1981, European journal of clinical investigation.

[44]  A. Goldberg,et al.  Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism. , 1976, The Journal of clinical endocrinology and metabolism.

[45]  M. Vaisman,et al.  Treatment of Subclinical Hypothyroidism Reduces Atherogenic Lipid Levels in a Placebo-controlled Double-blind Clinical Trial , 2007, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.