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Evaluating Thyroid Function Tests in Patients with Kidney Disease

  • Stephanie Smooke PrawEmail author
  • Jennifer Sue An Way
  • Rebecca Weiss
Chapter

Abstract

Disorders of thyroid function, especially hypothyroidism, are more prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), compared to the general population. While tests for thyroid function are among the most common hormonal tests ordered, the interpretation of thyroid function tests can be obscured by multiple entities in patients with renal disease, including non-thyroidal illness syndrome (NTI), malnutrition, inflammation, iodine retention, metabolic acidosis, medications, mineral deficiencies, and dialysis. Several studies have shown that both hypothyroidism and hyperthyroidism are associated with increased cardiovascular morbidity and mortality in CKD and ESRD. It is important, then, to understand which thyroid function test results represent authentic thyroid dysfunction, rather than changes secondary to renal disease.

In this chapter, we will review commonly ordered tests of thyroid function, alterations associated with renal disease, testing for thyroid autoimmunity, and the impact of medications on thyroid hormone measurements and thyroid hormone absorption, relevant for the many kidney disease patients that take levothyroxine therapy.

Keywords

Thyroid function tests Chronic kidney disease Thyroid dysfunction Thyroid autoimmunity Medication and thyroid hormone measurement 

References

  1. 1.
    Rhee CM. The interaction between thyroid and kidney disease: an overview of the evidence. Curr Opin Endocrinol Diabetes Obes. 2016;23(5):407–15.CrossRefGoogle Scholar
  2. 2.
    Brent GA. Thyroid function testing. New York: Springer; 2010. Available from: SpringerLink. Restricted to UC campuses  https://doi.org/10.1007/978-1-4419-1485-9.
  3. 3.
    Hershman JM. Regulation of thyroid hormone production and measurement of thyrotropin. In: Brent GA, editor. Thyroid function testing. New York: Springer; 2010. p. 79–90.Google Scholar
  4. 4.
    Spencer CA. Assay of thyroid hormones and related substances. South Dartmouth: MDText.com, Inc. Updated Jan 2013.
  5. 5.
    Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, et al. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab. 1990;70(2):453–60.CrossRefGoogle Scholar
  6. 6.
    Kaptein EM. Thyroid hormone metabolism and thyroid diseases in chronic renal failure. Endocr Rev. 1996;17(1):45–63.CrossRefGoogle Scholar
  7. 7.
    Beckers C, Machiels J, Soyez C, Cornette C. Metabolic clearance rate and production rate of thyroid-stimulating hormone in man. Horm Metab Res. 1971;3(1):34–6.CrossRefGoogle Scholar
  8. 8.
    Kaptein EM, Quion-Verde H, Chooljian CJ, Tang WW, Friedman PE, Rodriquez HJ, et al. The thyroid in end-stage renal disease. Medicine (Baltimore). 1988;67(3):187–97.CrossRefGoogle Scholar
  9. 9.
    Lo JC, Chertow GM, Go AS, Hsu CY. Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int. 2005;67(3):1047–52.CrossRefGoogle Scholar
  10. 10.
    Asvold BO, Bjøro T, Vatten LJ. Association of thyroid function with estimated glomerular filtration rate in a population-based study: the HUNT study. Eur J Endocrinol. 2011;164(1):101–5.CrossRefGoogle Scholar
  11. 11.
    Woodward A, McCann S, Al-Jubouri M. The relationship between estimated glomerular filtration rate and thyroid function: an observational study. Ann Clin Biochem. 2008;45(Pt 5):515–7.CrossRefGoogle Scholar
  12. 12.
    Chaker L, Sedaghat S, Hoorn EJ, Elzen WP, Gussekloo J, Hofman A, et al. The association of thyroid function and the risk of kidney function decline: a population-based cohort study. Eur J Endocrinol. 2016;175(6):653–60.CrossRefGoogle Scholar
  13. 13.
    Zhang Y, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, et al. Thyroid hormone levels and incident chronic kidney disease in euthyroid individuals: the Kangbuk Samsung Health Study. Int J Epidemiol. 2014;43(5):1624–32.CrossRefGoogle Scholar
  14. 14.
    Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab. 2013;27(6):745–62.CrossRefGoogle Scholar
  15. 15.
    Kaptein EM, LoPresti JS, Kaptein MJ. Is an isolated TSH elevation in chronic nonthyroidal illness “subclinical hypothyroidism”. J Clin Endocrinol Metab. 2014;99(11):4015–26.CrossRefGoogle Scholar
  16. 16.
    Paudel K. Prevalence and clinical characteristics of hypothyroidism in a population undergoing maintenance hemodialysis. J Clin Diagn Res. 2014;8(4):MC01–4.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Kalk WJ, Morley JE, Gold CH, Meyers A. Thyroid function tests in patients on regular hemodialysis. Nephron. 1980;25(4):173–8.CrossRefGoogle Scholar
  18. 18.
    Hardy MJ, Ragbeer SS, Nascimento L. Pituitary-thyroid function in chronic renal failure assessed by a highly sensitive thyrotropin assay. J Clin Endocrinol Metab. 1988;66(1):233–6.CrossRefGoogle Scholar
  19. 19.
    Du X, Pan B, Li W, Zou Y, Hua X, Huang W, et al. Albuminuria is an independent risk factor of T4 elevation in chronic kidney disease. Sci Rep. 2017;7:41302.CrossRefGoogle Scholar
  20. 20.
    Klee G. Laboratory techniques for recognition of endocrine disorders. In: Melmed S, Polonsky K, Larson PR, Kronenberg HM, editors. Williams textbook of endocrinology. 13th ed. Philadelphia: Elsevier; 2015. p. 83–99.Google Scholar
  21. 21.
    Midgley JE. Direct and indirect free thyroxine assay methods: theory and practice. Clin Chem. 2001;47(8):1353–63.PubMedGoogle Scholar
  22. 22.
    Iitaka M, Kawasaki S, Sakurai S, Hara Y, Kuriyama R, Yamanaka K, et al. Serum substances that interfere with thyroid hormone assays in patients with chronic renal failure. Clin Endocrinol. 1998;48(6):739–46.CrossRefGoogle Scholar
  23. 23.
    d’Herbomez M, Forzy G, Gasser F, Massart C, Beaudonnet A, Sapin R. Clinical evaluation of nine free thyroxine assays: persistent problems in particular populations. Clin Chem Lab Med. 2003;41(7):942–7.PubMedGoogle Scholar
  24. 24.
    Nishikawa M, Ogawa Y, Yoshikawa N, Yoshimura M, Toyoda N, Shouzu A, et al. Plasma free thyroxine (FT4) concentrations during hemodialysis in patients with chronic renal failure: effects of plasma non-esterified fatty acids on FT4 measurement. Endocr J. 1996;43(5):487–93.CrossRefGoogle Scholar
  25. 25.
    Wiederkehr MR, Kalogiros J, Krapf R. Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients. Nephrol Dial Transplant. 2004;19(5):1190–7.CrossRefGoogle Scholar
  26. 26.
    Stevenson HP, Archbold GP, Johnston P, Young IS, Sheridan B. Misleading serum free thyroxine results during low molecular weight heparin treatment. Clin Chem. 1998;44(5):1002–7.PubMedGoogle Scholar
  27. 27.
    Kulkarni DP, Holley JL. Thyroid function tests in end-stage renal disease. Semin Dial. 2014;27(6):552–5.CrossRefGoogle Scholar
  28. 28.
    Fan J, Yan P, Wang Y, Shen B, Ding F, Liu Y. Prevalence and clinical significance of low T3 syndrome in non-dialysis patients with chronic kidney disease. Med Sci Monit. 2016;22:1171–9.CrossRefGoogle Scholar
  29. 29.
    Song SH, Kwak IS, Lee DW, Kang YH, Seong EY, Park JS. The prevalence of low triiodothyronine according to the stage of chronic kidney disease in subjects with a normal thyroid-stimulating hormone. Nephrol Dial Transplant. 2009;24(5):1534–8.CrossRefGoogle Scholar
  30. 30.
    Malyszko J, Malyszko JS, Pawlak K, Mysliwiec M. Thyroid function, endothelium, and inflammation in hemodialyzed patients: possible relations? J Ren Nutr. 2007;17(1):30–7.CrossRefGoogle Scholar
  31. 31.
    Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol. 2009;160(4):503–15.CrossRefGoogle Scholar
  32. 32.
    Horáček J, Dusilová Sulková S, Kubišová M, Safránek R, Malířová E, Kalousová M, et al. Thyroid hormone abnormalities in hemodialyzed patients: low triiodothyronine as well as high reverse triiodothyronine are associated with increased mortality. Physiol Res. 2012;61(5):495–501.PubMedGoogle Scholar
  33. 33.
    Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams textbook of endocrinology. 13th ed. Philadelphia: Elsevier; 2016. PrintGoogle Scholar
  34. 34.
    Kraiem Z, Lahat N, Glaser B, Baron E, Sadeh O, Sheinfeld M. Thyrotrophin receptor blocking antibodies: incidence, characterization and in-vitro synthesis. Clin Endocrinol. 1987;27:409–21.CrossRefGoogle Scholar
  35. 35.
    Barbesino G, Tomer Y. Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab. 2013;98:2247–55.CrossRefGoogle Scholar
  36. 36.
    Tozolli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with Graves’ disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis. Autoimmun Rev. 2012;12:107–13.CrossRefGoogle Scholar
  37. 37.
    Lukinac L, Kusic Z, Kes P. False-positive titers of thyroid autoantibodies in patients undergoing hemodialysis? Clin Chem. 1991;37:2153–4.PubMedGoogle Scholar
  38. 38.
    Targher G, Chonchol M, Zoppini G, Salvagno G, Pichiri I, Franchini M, Lippi G. Prevalence of thyroid autoimmunity and subclinical hypothyroidism in persons with chronic kidney disease not requiring chronic dialysis. Clin Chem Lab Med. 2009;47:1367–71.PubMedGoogle Scholar
  39. 39.
    Christofides ND. Furosemide interference in newer free thyroxine assays. Clin Chem. 1999;45:1315.PubMedGoogle Scholar
  40. 40.
    Jaume JC, Mendel CM, Frost PH, Greenspan FS, Laughton CW. Extremely low doses of heparin release lipase activity into the plasma and can thereby cause artifactual elevations in the serum-free thyroxine concentration as measured by equilibrium. Thyroid. 1996;6:79–83.CrossRefGoogle Scholar
  41. 41.
    Samuels MH, Pillote K, Asher D, Nelson JC. Variable effects of nonsteroidal anti-inflammatory agents on thyroid test results. J Clin Endocrinol Metab. 2003;88:5710–6.CrossRefGoogle Scholar
  42. 42.
    Pabla D, Akhlaghi F, Zia H. A comparative pH-dissolution profile study of selected commercial levothyroxine products using induc- tively coupled plasma mass spectrometry. Eur J Pharm Biopharm. 2009;72:105–10.CrossRefGoogle Scholar
  43. 43.
    Liwanpo L, Hershman JM. Conditions and drugs interfering with thyroxine absorption. Best Pract Res Clin Endocrinol Metab. 2009;23:781–92.CrossRefGoogle Scholar
  44. 44.
    Diskin CJ, Stokes TJ, Dansby LM, et al. Effect of phosphate binders upon TSH and L-thyroxine dose in patients on thyroid replacement. Int Urol Nephrol. 2007;39:599–602.CrossRefGoogle Scholar
  45. 45.
    Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283:2822.CrossRefGoogle Scholar
  46. 46.
    Sachmechi I, Reich DM, Aninyei M, Wibowo F, Gupta G, Kim PJ. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007;13:345–9.CrossRefGoogle Scholar
  47. 47.
    Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354:1787.CrossRefGoogle Scholar
  48. 48.
    Dietrich JW, Gieselbrecht K, Holl RW, Boehm BO. Absorption kinetics of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res. 2006;38:57–9.CrossRefGoogle Scholar
  49. 49.
    Ananthakrishnan S, Braverman LE, Levin RM, Magnani B, Pearce EN. The effect of famotidine, esomeprazole, and ezetimibe on levothyroxine absorption. Thyroid. 2008;18:493–8.CrossRefGoogle Scholar
  50. 50.
    Vita R, Saraceno G, Trimarchi F, Benvenga S. Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors. J Clin Endocrinol Metab. 2014;99:4481–6.CrossRefGoogle Scholar
  51. 51.
    Campbell RC, Hasinoff BB, Stalts H, Rao B, Wong NC. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117:1010–3.CrossRefGoogle Scholar
  52. 52.
    Liel Y, Harman-Boehm I, Shany S. Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J Clin Endocrinol Metab. 1996;81:857–9.PubMedGoogle Scholar
  53. 53.
    Kisch E, Segall HS. Interaction between simvastatin and L-thyroxine. Ann Intern Med. 2005;143:547.CrossRefGoogle Scholar
  54. 54.
    Kiernan TJ. Simvastatin induced rhabdomyolysis and an important clinical link with hypothyroidism. Int J Cardiol. 2007;119(3):374–6.CrossRefGoogle Scholar
  55. 55.
    Product Information: Synthroid(R) oral tablets, levothyroxine sodium oral tablets. Abbott Laboratories (per DailyMed), North Chicago, IL, June 2011.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Stephanie Smooke Praw
    • 1
    Email author
  • Jennifer Sue An Way
    • 1
  • Rebecca Weiss
    • 2
  1. 1.Division of Endocrinology, Diabetes, and Metabolism, Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Department of Endocrinology, Kaiser Permanente—Woodland HillsWoodland HillsUSA

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