UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Lipid abnormalities in thyroid disease

Author
Douglas S Ross, MD
Section Editor
David S Cooper, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

A relationship between hypothyroidism, lipid disorders, and coronary artery disease was first suggested in the 1960s [1]. This was at a time when the diagnosis of hypothyroidism was based upon symptoms and signs, and sometimes serum cholesterol measurements, rather than measurements of serum thyroxine (T4) and thyroid-stimulating hormone (TSH). In some cases, a high serum cholesterol concentration was regarded as evidence for “premyxoedema” in the absence of symptoms of hypothyroidism [2]. How many of these patients in fact had hypothyroidism is not known. While there is no doubt that many hypothyroid patients have abnormal serum lipid concentrations, the increased risk of coronary artery disease seen in hypothyroid patients is likely multifactorial in etiology. (See "Cardiovascular effects of hypothyroidism".)

OVERT HYPOTHYROIDISM

Many hypothyroid patients have high serum concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol [3], and some have high serum concentrations of triglycerides [4], intermediate-density lipoproteins [5], apoprotein A-1 [6] and apoprotein B [6-8]. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)

In one study of 295 hypothyroid patients, the following patterns of serum lipids were noted, using the Frederickson classification [9]:

Type IIa (hypercholesterolemia) – 56 percent

Type IIb (hypercholesterolemia and hypertriglyceridemia) – 34 percent

       

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Mar 24 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Bastenie PA, Vanhaelst L, Neve P. Coronary-artery disease in hypothyroidism. Lancet 1967; 2:1221.
  2. Fowler PS, Swale J. Premyxoedema and coronary-artery disease. Lancet 1967; 1:1077.
  3. Lithell H, Boberg J, Hellsing K, et al. Serum lipoprotein and apolipoprotein concentrations and tissue lipoprotein-lipase activity in overt and subclinical hypothyroidism: the effect of substitution therapy. Eur J Clin Invest 1981; 11:3.
  4. Nikkila E, Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest 1973; 51:203.
  5. Hazzard WR, Bierman EL. Aggravation of broad- disease (type 3 hyperlipoproteinemia) by hypothyroidism. Arch Intern Med 1972; 130:822.
  6. Arem R, Escalante DA, Arem N, et al. Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a). Metabolism 1995; 44:1559.
  7. de Bruin TW, van Barlingen H, van Linde-Sibenius Trip M, et al. Lipoprotein(a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid, and hyperthyroid subjects. J Clin Endocrinol Metab 1993; 76:121.
  8. Pazos F, Alvarez JJ, Rubiés-Prat J, et al. Long-term thyroid replacement therapy and levels of lipoprotein(a) and other lipoproteins. J Clin Endocrinol Metab 1995; 80:562.
  9. O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc 1993; 68:860.
  10. Muls E, Rosseneu M, Blaton V, et al. Serum lipids and apolipoproteins A-I, A-II and B in primary hypothyroidism before and during treatment. Eur J Clin Invest 1984; 14:12.
  11. Agdeppa D, Macaron C, Mallik T, Schnuda ND. Plasma high density lipoprotein cholesterol in thyroid disease. J Clin Endocrinol Metab 1979; 49:726.
  12. Verdugo C, Perrot L, Ponsin G, et al. Time-course of alterations of high density lipoproteins (HDL) during thyroxine administration to hypothyroid women. Eur J Clin Invest 1987; 17:313.
  13. Pearce EN, Wilson PW, Yang Q, et al. Thyroid function and lipid subparticle sizes in patients with short-term hypothyroidism and a population-based cohort. J Clin Endocrinol Metab 2008; 93:888.
  14. Martínez-Triguero ML, Hernández-Mijares A, Nguyen TT, et al. Effect of thyroid hormone replacement on lipoprotein(a), lipids, and apolipoproteins in subjects with hypothyroidism. Mayo Clin Proc 1998; 73:837.
  15. Tzotzas T, Krassas GE, Konstantinidis T, Bougoulia M. Changes in lipoprotein(a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 2000; 10:803.
  16. Spandrio S, Sleiman I, Scalvini T, et al. Lipoprotein (a) in thyroid dysfunction before and after treatment. Horm Metab Res 1993; 25:586.
  17. Klausen IC, Nielsen FE, Hegedüs L, et al. Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a). Metabolism 1992; 41:911.
  18. Tanis BC, Westendorp GJ, Smelt HM. Effect of thyroid substitution on hypercholesterolaemia in patients with subclinical hypothyroidism: a reanalysis of intervention studies. Clin Endocrinol (Oxf) 1996; 44:643.
  19. Ito M, Takamatsu J, Matsuo T, et al. Serum concentrations of remnant-like particles in hypothyroid patients before and after thyroxine replacement. Clin Endocrinol (Oxf) 2003; 58:621.
  20. Ito M, Arishima T, Kudo T, et al. Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients. J Clin Endocrinol Metab 2007; 92:608.
  21. Thompson GR, Soutar AK, Spengel FA, et al. Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci U S A 1981; 78:2591.
  22. Hoogerbrugge N, Jansen H, Staels B, et al. Growth hormone normalizes low-density lipoprotein receptor gene expression in hypothyroid rats. Metabolism 1996; 45:680.
  23. Wiseman SA, Powell JT, Humphries SE, Press M. The magnitude of the hypercholesterolemia of hypothyroidism is associated with variation in the low density lipoprotein receptor gene. J Clin Endocrinol Metab 1993; 77:108.
  24. Costantini F, Pierdomenico SD, De Cesare D, et al. Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vasc Biol 1998; 18:732.
  25. FRIEDMAN M, BYERS SO, ROSENMAN RH. Changes in excretion of intestinal cholesterol and sterol digitonides in hyper and hypothyroidism. Circulation 1952; 5:657.
  26. Ritter MC, Kannan CR, Bagdade JD. The effects of hypothyroidism and replacement therapy on cholesteryl ester transfer. J Clin Endocrinol Metab 1996; 81:797.
  27. Pykälistö O, Goldberg AP, Brunzell JD. Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism. J Clin Endocrinol Metab 1976; 43:591.
  28. Gjedde S, Gormsen LC, Rungby J, et al. Decreased lipid intermediate levels and lipid oxidation rates despite normal lipolysis in patients with hypothyroidism. Thyroid 2010; 20:843.
  29. Weintraub M, Grosskopf I, Trostanesky Y, et al. Thyroxine replacement therapy enhances clearance of chylomicron remnants in patients with hypothyroidism. J Clin Endocrinol Metab 1999; 84:2532.
  30. Willard DL, Leung AM, Pearce EN. Thyroid function testing in patients with newly diagnosed hyperlipidemia. JAMA Intern Med 2014; 174:287.
  31. Tsimihodimos V, Bairaktari E, Tzallas C, et al. The incidence of thyroid function abnormalities in patients attending an outpatient lipid clinic. Thyroid 1999; 9:365.
  32. Illingworth DR, McClung MR, Connor WE, Alaupovic P. Familial hypercholesterolaemia and primary hypothyroidism: coexistence of both disorders in a young woman with severe hypercholesterolaemia. Clin Endocrinol (Oxf) 1981; 14:145.
  33. Chait A, Brunzell JD. Severe hypertriglyceridemia: role of familial and acquired disorders. Metabolism 1983; 32:209.
  34. Tièche M, Lupi GA, Gutzwiller F, et al. Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease? Br Heart J 1981; 46:202.
  35. Lotz H, Salabè GB. Lipoprotein(a) increase associated with thyroid autoimmunity. Eur J Endocrinol 1997; 136:87.
  36. Kung AW, Pang RW, Janus ED. Elevated serum lipoprotein(a) in subclinical hypothyroidism. Clin Endocrinol (Oxf) 1995; 43:445.
  37. 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; 85:2993.
  38. Caraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab 2002; 87:1533.
  39. Nakajima Y, Yamada M, Akuzawa M, et al. Subclinical hypothyroidism and indices for metabolic syndrome in Japanese women: one-year follow-up study. J Clin Endocrinol Metab 2013; 98:3280.
  40. Zhao M, Yang T, Chen L, et al. Subclinical hypothyroidism might worsen the effects of aging on serum lipid profiles: a population-based case-control study. Thyroid 2015; 25:485.
  41. Meier C, Staub JJ, Roth CB, et al. TSH-controlled L-thyroxine therapy reduces cholesterol levels and clinical symptoms in subclinical hypothyroidism: a double blind, placebo-controlled trial (Basel Thyroid Study). J Clin Endocrinol Metab 2001; 86:4860.
  42. Michalopoulou G, Alevizaki M, Piperingos G, et al. High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism? Eur J Endocrinol 1998; 138:141.
  43. Yildirimkaya M, Ozata M, Yilmaz K, et al. Lipoprotein(a) concentration in subclinical hypothyroidism before and after levo-thyroxine therapy. Endocr J 1996; 43:731.
  44. Ganotakis ES, Mandalaki K, Tampakaki M, et al. Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy. Angiology 2003; 54:569.
  45. Althaus BU, Staub JJ, Ryff-De Lèche A, et al. LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol (Oxf) 1988; 28:157.
  46. Caron P, Calazel C, Parra HJ, et al. Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy. Clin Endocrinol (Oxf) 1990; 33:519.
  47. Parle JV, Franklyn JA, Cross KW, et al. Circulating lipids and minor abnormalities of thyroid function. Clin Endocrinol (Oxf) 1992; 37:411.
  48. Bogner U, Arntz HR, Peters H, Schleusener H. Subclinical hypothyroidism and hyperlipoproteinaemia: indiscriminate L-thyroxine treatment not justified. Acta Endocrinol (Copenh) 1993; 128:202.
  49. Staub JJ, Althaus BU, Engler H, et al. Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. Am J Med 1992; 92:631.
  50. Ito M, Takamatsu J, Sasaki I, et al. Disturbed metabolism of remnant lipoproteins in patients with subclinical hypothyroidism. Am J Med 2004; 117:696.
  51. Brenta G, Berg G, Miksztowicz V, et al. Atherogenic Lipoproteins in Subclinical Hypothyroidism and Their Relationship with Hepatic Lipase Activity: Response to Replacement Treatment with Levothyroxine. Thyroid 2016; 26:365.
  52. Zhao M, Tang X, Yang T, et al. Lipotoxicity, a potential risk factor for the increasing prevalence of subclinical hypothyroidism? J Clin Endocrinol Metab 2015; 100:1887.
  53. Hoppichler F, Sandholzer C, Moncayo R, et al. Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels. Atherosclerosis 1995; 115:65.