Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Figures/Tables List    Related articles in Annals  Services    Send comment/rapid response letter    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Hussein, W. I.    Faiman, C.    Related Articles in PubMed    PubMed Citation    PubMed

BRIEF COMMUNICATION

Normalization of Hyperhomocysteinemia with L-thyroxine in Hypothyroidism

Wiam I. Hussein, MD; Ralph Green, MD; Donald W. Jacobsen, PhD; and Charles Faiman, MD

7 September 1999 | Volume 131 Issue 5 | Pages 348-351

Background: Hyperhomocysteinemia is an independent risk factor for coronary, peripheral, and cerebrovascular disease. Elevated plasma homocysteine levels were described in a preliminary report on primary hypothyroidism.

Objective: To determine whether restoration of euthyroidism by L-thyroxine replacement therapy would reduce or normalize plasma homocysteine levels.

Design: Prospective cohort study.

Setting: Outpatient endocrinology department of a tertiary center.

Patients: 14 patients (10 women and 4 men; 25 to 77 years of age): 4 with newly diagnosed chronic (Hashimoto) hypothyroidism and 10 who had been rendered acutely hypothyroid (thyroid-stimulating hormone level > 25 mU/L) by total thyroidectomy for thyroid carcinoma.

Measurements: Total plasma homocysteine levels were measured at baseline and 3 to 9 months later, after euthyroidism had been attained by L-thyroxine replacement therapy.

Results: Median baseline plasma homocysteine levels in both sexes (women, 11.65 µmol/L [range, 7.2 to 26.5 µmol/L]; men, 15.1 µmol/L [range, 14.1 to 16.3 µmol/L]) were higher (P = 0.002) than those in healthy female (n = 35) and male (n = 36) volunteers (women, 7.52 µmol/L [range, 4.3 to 14.0 µmol/L]; men, 8.72 µmol/L [range, 5.94 to 14.98 µmol/L]). Eight patients (57%) had baseline plasma homocysteine levels that exceeded the upper limit of sex-specific reference ranges. Upon attainment of euthyroidism, all patients had a diminution in plasma homocysteine levels. The median overall change of –5.5 µmol/L (range, –15.4 to –1.8 µmol/L) corresponds to a difference of –44% (range, –58% to –13%) (P < 0.001). Homocysteine levels returned to normal in 7 of the 8 patients with elevated pretreatment values.

Conclusions: Hypothyroidism may be a treatable cause of hyperhomocysteinemia, and elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in primary hypothyroidism.

Author and Article Information

From The Cleveland Clinic Foundation, Cleveland, Ohio, and the University of California, Davis, Davis, California.

Presented in part at the Seventh Annual Meeting of the American Association of Clinical Endocrinologists, Orlando, Florida, April 1998, and the Second International Conference on Homocysteine Metabolism, Nijmegen, the Netherlands, April 1998.

Acknowledgments: The authors thank S.S. Reddy, MD, for recruiting patients and for support for the study; Jacob Selhub, PhD, Tufts University, for kindly doing the vitamin B₆ assays; and Jeff Hammel for statistical analysis and advice.

Grant Support: By a research grant (Research Program Council #5669) from The Cleveland Clinic Foundation and grant HL52234 from the National Institutes of Health (Dr. Jacobsen).

Requests for Reprints: Charles Faiman, MD, Department of Endocrinology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A30, Cleveland, OH 44195; e-mail, faimanc1{at}cesmtp.ccf.org.

Current Author Addresses: Dr. Hussein: Saad Medical Center, PO Box 1991, Alkhobar, 31952, Saudi Arabia.

Dr. Green: Department of Pathology, University of California, Davis, Medical Center, 4400 V Street, Sacramento, CA 95817.

Dr. Jacobsen: Department of Cell Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, NC10, Cleveland, OH 44195.

Dr. Faiman: Department of Endocrinology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A30, Cleveland, OH 44195.

Related articles in Annals:

Letters
Hyperhomocysteinemia in Hypothyroidism
Daniel Weiss

Annals 2000 132: 677. [Full Text]  

Letters
Hyperhomocysteinemia in Hypothyroidism
Charles Faiman, Donald W. Jacobsen, AND Ralph Green

Annals 2000 132: 677. [Full Text]  

This article has been cited by other articles:

				A. Squizzato, V.E.A. Gerdes, D.P.M. Brandjes, H.R. Buller, and J. Stam Thyroid Diseases and Cerebrovascular Disease Stroke, October 1, 2005; 36(10): 2302 - 2310. [Abstract] [Full Text] [PDF]

				H.-K. Kuo, F. A. Sorond, J.-H. Chen, A. Hashmi, W. P. Milberg, and L. A. Lipsitz The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2005; 60(9): 1190 - 1201. [Abstract] [Full Text] [PDF]

				F. Monzani, N. Caraccio, M. Kozakowa, A. Dardano, F. Vittone, A. Virdis, S. Taddei, C. Palombo, and E. Ferrannini Effect of Levothyroxine Replacement on Lipid Profile and Intima-Media Thickness in Subclinical Hypothyroidism: A Double-Blind, Placebo- Controlled Study J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2099 - 2106. [Abstract] [Full Text] [PDF]

				A. R. Cappola and P. W. Ladenson Hypothyroidism and Atherosclerosis J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2438 - 2444. [Full Text] [PDF]

				M. Coffey, G. K. Crowder, and D. J. Cheek Reducing Coronary Artery Disease by Decreasing Homocysteine Levels Crit. Care Nurse, February 1, 2003; 23(1): 25 - 30. [Full Text] [PDF]

				R. Carmel, R. Green, D. S. Rosenblatt, and D. Watkins Update on Cobalamin, Folate, and Homocysteine Hematology, January 1, 2003; 2003(1): 62 - 81. [Abstract] [Full Text] [PDF]

				B. Biondi, E. A. Palmieri, G. Lombardi, and S. Fazio Effects of Subclinical Thyroid Dysfunction on the Heart Ann Intern Med, December 3, 2002; 137(11): 904 - 914. [Abstract] [Full Text] [PDF]

				R. L. Jacobs, L. M. Stead, M. E. Brosnan, and J. T. Brosnan Hyperglucagonemia in Rats Results in Decreased Plasma Homocysteine and Increased Flux through the Transsulfuration Pathway in Liver J. Biol. Chem., November 16, 2001; 276(47): 43740 - 43747. [Abstract] [Full Text] [PDF]

				J. W. Chu and L. M. Crapo The Treatment of Subclinical Hypothyroidism Is Seldom Necessary J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4591 - 4599. [Full Text] [PDF]

				B. G. Nedrebo, O. Nygard, P. M. Ueland, and E. A. Lien Plasma Total Homocysteine in Hyper- and Hypothyroid Patients before and during 12 Months of Treatment Clin. Chem., September 1, 2001; 47(9): 1738 - 1741. [Full Text] [PDF]

				G. Sesmilo, B. M. K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski Effects of Growth Hormone (GH) Administration on Homocyst(e)ine Levels in Men with GH Deficiency: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1518 - 1524. [Abstract] [Full Text]

				F. Barbé, M. Klein, A. Chango, S. Frémont, P. Gérard, G. Weryha, J.-L. Guéant, and J.-P. Nicolas Homocysteine, Folate, Vitamin B12, and Transcobalamins in Patients Undergoing Successive Hypo- and Hyperthyroid States J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1845 - 1846. [Full Text]

				E. A. Lien, S. Hustad, B. G. Nedrebø, O. Nygård, and P. M. Ueland Total Plasma Homocysteine in Hypo- and Hyperthyroidism: Covariations and Causality J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1846 - 1846. [Full Text]

				D. Weiss Hyperhomocysteinemia in Hypothyroidism Ann Intern Med, April 18, 2000; 132(8): 677 - 677. [Full Text] [PDF]