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

Drug interactions with thyroid hormones

Author
Martin I Surks, MD
Section Editor
Douglas S Ross, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Many patients whose thyroid function is evaluated also take medications for a variety of nonthyroidal illnesses. As a result, clinicians must be aware of the interactions between various drugs and thyroid function, including measurements of serum thyroid hormones and thyroid-stimulating hormone (TSH).

Issues relating to the major drug-induced or drug-related abnormalities in thyroid hormone secretion, transport, and metabolism will be reviewed here (table 1). Many of these interactions are discussed in detail separately.

THYROID HORMONE METABOLISM

Before discussing the different drug interactions with thyroid hormones, it is helpful to review briefly thyroid hormone metabolism and the pathways that may be affected by the administration of drugs.

Thyroidal synthesis and secretion of thyroxine (T4) and triiodothyronine (T3) are dependent on thyroid-stimulating hormone (TSH) (figure 1). Under the influence of TSH, thyroid follicular cells sequentially perform the following functions:

Transport of iodide from serum into the cells

                  

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 Aug 06 00:00:00 GMT 2015.
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. Curran PG, DeGroot LJ. The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr Rev 1991; 12:135.
  2. Brabant G, Brabant A, Ranft U, et al. Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration. J Clin Endocrinol Metab 1987; 65:83.
  3. Brabant G, Prank K, Hoang-Vu C, et al. Hypothalamic regulation of pulsatile thyrotopin secretion. J Clin Endocrinol Metab 1991; 72:145.
  4. Lee E, Chen P, Rao H, et al. Effect of acute high dose dobutamine administration on serum thyrotrophin (TSH). Clin Endocrinol (Oxf) 1999; 50:487.
  5. Cooper DS, Klibanski A, Ridgway EC. Dopaminergic modulation of TSH and its subunits: in vivo and in vitro studies. Clin Endocrinol (Oxf) 1983; 18:265.
  6. Agner T, Hagen C, Andersen AN, Djursing H. Increased dopaminergic activity inhibits basal and metoclopramide-stimulated prolactin and thyrotropin secretion. J Clin Endocrinol Metab 1986; 62:778.
  7. Bertherat J, Brue T, Enjalbert A, et al. Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison with the inhibitory effects of octreotide upon in vivo and in vitro hormonal secretions. J Clin Endocrinol Metab 1992; 75:540.
  8. Braverman LE. Iodine induced thyroid disease. Acta Med Austriaca 1990; 17 Suppl 1:29.
  9. Sherman SI, Gopal J, Haugen BR, et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med 1999; 340:1075.
  10. Vigersky RA, Filmore-Nassar A, Glass AR. Thyrotropin suppression by metformin. J Clin Endocrinol Metab 2006; 91:225.
  11. Martin FI, Tress BW, Colman PG, Deam DR. Iodine-induced hyperthyroidism due to nonionic contrast radiography in the elderly. Am J Med 1993; 95:78.
  12. Figge HL, Figge J. The effects of amiodarone on thyroid hormone function: a review of the physiology and clinical manifestations. J Clin Pharmacol 1990; 30:588.
  13. Trip MD, Wiersinga W, Plomp TA. Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. Am J Med 1991; 91:507.
  14. Bartalena L, Grasso L, Brogioni S, et al. Serum interleukin-6 in amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 1994; 78:423.
  15. Bartalena L, Brogioni S, Grasso L, et al. Treatment of amiodarone-induced thyrotoxicosis, a difficult challenge: results of a prospective study. J Clin Endocrinol Metab 1996; 81:2930.
  16. Hamnvik OP, Larsen PR, Marqusee E. Thyroid dysfunction from antineoplastic agents. J Natl Cancer Inst 2011; 103:1572.
  17. Aranha AA, Amer S, Reda ES, et al. Autoimmune thyroid disease in the use of alemtuzumab for multiple sclerosis: a review. Endocr Pract 2013; 19:821.
  18. Daniels GH, Vladic A, Brinar V, et al. Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis. J Clin Endocrinol Metab 2014; 99:80.
  19. Philippou G, Koutras DA, Piperingos G, et al. The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement. Clin Endocrinol (Oxf) 1992; 36:573.
  20. Spaulding SW, Burrow GN, Bermudez F, Himmelhoch JM. The inhibitory effect of lithium on thyroid hormone release in both euthyroid and thyrotoxic patients. J Clin Endocrinol Metab 1972; 35:905.
  21. Perrild H, Hegedüs L, Baastrup PC, et al. Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment. Am J Psychiatry 1990; 147:1518.
  22. Shinohara N, Takahashi M, Kamishima T, et al. The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma. Br J Cancer 2011; 104:241.
  23. de Groot JW, Zonnenberg BA, Plukker JT, et al. Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther 2005; 78:433.
  24. Brassard M, Neraud B, Trabado S, et al. Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer. J Clin Endocrinol Metab 2011; 96:2741.
  25. Abdulrahman RM, Verloop H, Hoftijzer H, et al. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab 2010; 95:3758.
  26. Makita N, Iiri T. Tyrosine kinase inhibitor-induced thyroid disorders: a review and hypothesis. Thyroid 2013; 23:151.
  27. Desai J, Yassa L, Marqusee E, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 2006; 145:660.
  28. Mannavola D, Coco P, Vannucchi G, et al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab 2007; 92:3531.
  29. Wong E, Rosen LS, Mulay M, et al. Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid 2007; 17:351.
  30. Verloop H, Smit JW, Dekkers OM. Sorafenib therapy decreases the clearance of thyrotropin. Eur J Endocrinol 2013; 168:163.
  31. Dowsett M, Mehta A, Cantwell BM, Harris AL. Low-dose aminoglutethimide in postmenopausal breast cancer: effects on adrenal and thyroid hormone secretion. Eur J Cancer 1991; 27:846.
  32. Figg WD, Thibault A, Sartor AO, et al. Hypothyroidism associated with aminoglutethimide in patients with prostate cancer. Arch Intern Med 1994; 154:1023.
  33. Smit JW, Stokkel MP, Pereira AM, et al. Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral metabolism of thyroid hormones. J Clin Endocrinol Metab 2007; 92:2496.
  34. Badros AZ, Siegel E, Bodenner D, et al. Hypothyroidism in patients with multiple myeloma following treatment with thalidomide. Am J Med 2002; 112:412.
  35. Stockigt JR, Lim CF, Barlow JW, et al. Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors. J Clin Endocrinol Metab 1985; 60:1025.
  36. Faber J, Waetjen I, Siersbaek-Nielsen K. Free thyroxine measured in undiluted serum by dialysis and ultrafiltration: effects of non-thyroidal illness, and an acute load of salicylate or heparin. Clin Chim Acta 1993; 223:159.
  37. McConnell RJ. Abnormal thyroid function test results in patients taking salsalate. JAMA 1992; 267:1242.
  38. Samuels MH, Pillote K, Asher D, Nelson JC. Variable effects of nonsteroidal antiinflammatory agents on thyroid test results. J Clin Endocrinol Metab 2003; 88:5710.
  39. Jaume JC, Mendel CM, Frost PH, et al. 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 dialysis. Thyroid 1996; 6:79.
  40. Harmon SM, Seifert CF. Levothyroxine-cholestyramine interaction reemphasized. Ann Intern Med 1991; 115:658.
  41. Witztum JL, Jacobs LS, Schonfeld G. Thyroid hormone and thyrotropin levels in patients placed on colestipol hydrochloride. J Clin Endocrinol Metab 1978; 46:838.
  42. Weitzman SP, Ginsburg KC, Carlson HE. Colesevelam hydrochloride and lanthanum carbonate interfere with the absorption of levothyroxine. Thyroid 2009; 19:77.
  43. Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006; 354:1787.
  44. Sachmechi I, Reich DM, Aninyei M, et al. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract 2007; 13:345.
  45. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000; 283:2822.
  46. Siraj ES, Gupta MK, Reddy SS. Raloxifene causing malabsorption of levothyroxine. Arch Intern Med 2003; 163:1367.
  47. Cooper JG, Harboe K, Frost SK, Skadberg Ø. Ciprofloxacin interacts with thyroid replacement therapy. BMJ 2005; 330:1002.
  48. Liel Y, Sperber AD, Shany S. Nonspecific intestinal adsorption of levothyroxine by aluminum hydroxide. Am J Med 1994; 97:363.
  49. Campbell NR, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med 1992; 117:1010.
  50. Campbell JA, Schmidt BA, Bantle JP. Sucralfate and the absorption of L-thyroxine. Ann Intern Med 1994; 121:152.
  51. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007; 17:763.
  52. Oppenheimer JH, Bernstein G, Surks MI. Increased thyroxine turnover and thyroidal function after stimulation of hepatocellular binding of thyroxine by phenobarbital. J Clin Invest 1968; 47:1399.
  53. Cavlieri RR, Sung LC, Becker CE. Effects of phenobarbital on thyroxine and triiodothyronine kinetics in Graves' disease. J Clin Endocrinol Metab 1973; 37:308.
  54. Isley WL. Effect of rifampin therapy on thyroid function tests in a hypothyroid patient on replacement L-thyroxine. Ann Intern Med 1987; 107:517.
  55. Smith PJ, Surks MI. Multiple effects of 5,5'-diphenylhydantoin on the thyroid hormone system. Endocr Rev 1984; 5:514.
  56. Surks MI, DeFesi CR. Normal serum free thyroid hormone concentrations in patients treated with phenytoin or carbamazepine. A paradox resolved. JAMA 1996; 275:1495.
  57. Miller J, Carney P. Central hypothyroidism with oxcarbazepine therapy. Pediatr Neurol 2006; 34:242.
  58. LoPresti JS, Eigen A, Kaptein E, et al. Alterations in 3,3'5'-triiodothyronine metabolism in response to propylthiouracil, dexamethasone, and thyroxine administration in man. J Clin Invest 1989; 84:1650.
  59. Degroot LJ, Hoye K. Dexamethasone suppression of serum T3 and T4. J Clin Endocrinol Metab 1976; 42:976.
  60. Gamstedt A, Järnerot G, Kågedal B. Dose related effects of betamethasone on iodothyronines and thyroid hormone-binding proteins in serum. Acta Endocrinol (Copenh) 1981; 96:484.
  61. Duick DS, Warren DW, Nicoloff JT, et al. Effect of single dose dexamethasone on the concentration of serum triiodothyronine in man. J Clin Endocrinol Metab 1974; 39:1151.
  62. Chopra IJ, Williams DE, Orgiazzi J, Solomon DH. Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3). J Clin Endocrinol Metab 1975; 41:911.
  63. Kristensen BO, Weeke J. Propranolol-induced increments in total and free serum thyroxine in patients with essential hypertension. Clin Pharmacol Ther 1977; 22:864.
  64. Cooper DS, Daniels GH, Ladenson PW, Ridgway EC. Hyperthyroxinemia in patients treated with high-dose propranolol. Am J Med 1982; 73:867.
  65. Perrild H, Hansen JM, Skovsted L, Christensen LK. Different effects of propranolol, alprenolol, sotalol, atenolol and metoprolol on serum T3 and serum rT3 in hyperthyroidism. Clin Endocrinol (Oxf) 1983; 18:139.
  66. Reeves RA, From GL, Paul W, Leenen FH. Nadolol, propranolol, and thyroid hormones: evidence for a membrane-stabilizing action of propranolol. Clin Pharmacol Ther 1985; 37:157.