Skip to main content
SpringerLink
Log in

Hypothyroidism

  • Chapter
  • First Online:
Thyroid Disorders

  • 2140 Accesses

Abstract

Hypothyroidism can be defined by a decrease in thyroid hormone production and/or by an impaired action of thyroid hormones on target tissues. It is a common condition with multiple etiologies and clinical manifestations. Currently, hypothyroidism is usually diagnosed at early stages which allow a timely treatment. Levothyroxine is still the modality of choice and other therapeutic options are not recommended. The administration of an appropriate hormone replacement dose leads to a normalization of thyroid function in virtually all cases. However, patients with severe long-standing hypothyroidism can develop life-threatening complications. Therefore, physicians must be aware of the typical clinical findings in order to promptly evaluate patients with suspected hypothyroidism. In addition, infants with congenital hypothyroidism should be properly managed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Curling TB. Two cases of absence of the thyroid body, and symmetrical swellings of fat tissue at the sides of the neck, connected with defective cerebral development. Med Chir Trans. 1850;33:303–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gull WW. On a cretinoid state supervening in adult life in women. Trans Clin Soc Lond. 1873/1874;7:180–5.

    Google Scholar 

  3. Ord WM. On myxœdema, a term proposed to be applied to an essential condition in the “cretinoid” affection occasionally observed in middle-aged women. Med Chir Trans. 1878;61:57–78.5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kocher T. Ueber kropfexstirpation und ihre folgen. Arch Klin Chir. 1883;29:254–337.

    Google Scholar 

  5. Ord WM. Report of a committee of the Clinical Society of London nominated December 14, 1883, to investigate the subject of myxoedema. Trans Clin Soc Lond. 1888;21:1–215.

    Google Scholar 

  6. Murray GR. Note on the treatment of myxoedema by hypodermic injections of an extract of the thyroid gland of a sheep. Br Med J. 1891;2:796–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hashimoto H. Zur kenntnis der lymphömatosen Veränderung der schilddrüse (Struma lymphomatosa). Archiv für Klinische Chirurgie. 1912;97:219–48.

    Google Scholar 

  8. Kendall E. The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid. JAMA. 1915;64:2042–3.

    Article  CAS  Google Scholar 

  9. Harington CR, Barger G. Chemistry of thyroxine: constitution and synthesis of thyroxine. Biochem J. 1927;21:169–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gross J, Pitt-Rivers R. The identification of 3:5:3’-L-triiodothyronine in human plasma. Lancet. 1952;1:439–41.

    Article  CAS  PubMed  Google Scholar 

  11. Roitt IM, Doniach D, Campbell PN, et al. Auto-antibodies in Hashimoto’s disease (lymphadenoid goitre). Lancet. 1956;271:820–1.

    Article  CAS  PubMed  Google Scholar 

  12. Condliffe PG. Purification of human thyrotrophin. Endocrinology. 1963;72:893–6.

    Article  CAS  PubMed  Google Scholar 

  13. Braverman LE, Ingbar SH, Sterling K. Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. J Clin Invest. 1970;49:855–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Brent GA, Davies TF. Hypothyroidism and thyroiditis. In: Melmed S, editor. Williams textbook of endocrinology. 12th ed. Philadelphia: Elsevier Health Sciences; 2011. p. 406–39.

    Chapter  Google Scholar 

  15. Roberts CG, Ladenson PW. Hypothyroidism. Lancet. 2004;363:793–803.

    Article  CAS  PubMed  Google Scholar 

  16. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22:1200–35.

    Article  CAS  PubMed  Google Scholar 

  17. Wiersinga WM. Adult hypothyroidism. In: Endotext. 2014. http://www.thyroidmanager.org. Accessed 21 Apr 2015.

  18. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–99.

    Article  CAS  PubMed  Google Scholar 

  19. Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526–34.

    Article  CAS  PubMed  Google Scholar 

  20. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf). 1977;7:481–93.

    Article  CAS  Google Scholar 

  21. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43:55–68.

    Article  CAS  Google Scholar 

  22. Aoki Y, Belin RM, Clickner R, et al. Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002). Thyroid. 2007;17:1211–23.

    Article  PubMed  Google Scholar 

  23. Walsh JP, Bremner AP, Feddema P, et al. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: a 13-year, longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab. 2010;95:1095–104.

    Article  CAS  PubMed  Google Scholar 

  24. Persani L. Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. J Clin Endocrinol Metab. 2012;97:3068–78.

    Article  CAS  PubMed  Google Scholar 

  25. Skordis N, Toumba M, Savva SC, et al. High prevalence of congenital hypothyroidism in the Greek Cypriot population: results of the neonatal screening program 1990–2000. J Pediatr Endocrinol Metab. 2005;18:453–61.

    PubMed  Google Scholar 

  26. Harris KB, Pass KA. Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metab. 2007;91:268–77.

    Article  CAS  PubMed  Google Scholar 

  27. Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull. 2011;99:39–51.

    Article  PubMed  Google Scholar 

  28. Zimmermann MB. Iodine deficiency. Endocr Rev. 2009;30:376–408.

    Article  CAS  PubMed  Google Scholar 

  29. Andersson M, Karumbunathan V, Zimmermann MB. Global iodine status in 2011 and trends over the past decade. J Nutr. 2012;142:744–50.

    Article  CAS  PubMed  Google Scholar 

  30. Pearce EN, Andersson M, Zimmermann MB. Global iodine nutrition: where do we stand in 2013? Thyroid. 2013;23:523–8.

    Article  CAS  PubMed  Google Scholar 

  31. Böttcher Y, Eszlinger M, Tönjes A, et al. The genetics of euthyroid familial goiter. Trends Endocrinol Metab. 2005;16:314–9.

    Article  PubMed  CAS  Google Scholar 

  32. Bourdoux P, Delange F, Gerard M, et al. Evidence that cassava ingestion increases thiocyanate formation: a possible etiologic factor in endemic goiter. J Clin Endocrinol Metab. 1978;46:613–21.

    Article  CAS  PubMed  Google Scholar 

  33. Eastman CJ, Zimmermann M. The iodine deficiency disorders. In: Endotext. 2014. http://www.thyroidmanager.org. Accessed 21 Apr 2015.

  34. Boyages SC. Clinical review 49: iodine deficiency disorders. J Clin Endocrinol Metab. 1993;77:587–91.

    CAS  PubMed  Google Scholar 

  35. Boyages SC, Halpern JP, Maberly GF, et al. A comparative study of neurological and myxedematous endemic cretinism in western China. J Clin Endocrinol Metab. 1988;67:1262–71.

    Article  CAS  PubMed  Google Scholar 

  36. Burgi H. Iodine excess. Best Pract Res Clin Endocrinol Metab. 2010;24:107–15.

    Article  PubMed  CAS  Google Scholar 

  37. McHenry CR, Slusarczyk SJ. Hypothyroidisim following hemithyroidectomy: incidence, risk factors, and management. Surgery. 2000;128:994–8.

    Article  CAS  PubMed  Google Scholar 

  38. Verloop H, Louwerens M, Schoones JW, et al. Risk of hypothyroidism following hemithyroidectomy: systematic review and meta-analysis of prognostic studies. J Clin Endocrinol Metab. 2012;97:2243–55.

    Article  CAS  PubMed  Google Scholar 

  39. Kandil E, Krishnan B, Noureldine SI, et al. Hemithyroidectomy: a meta-analysis of postoperative need for hormone replacement and complications. ORL J Otorhinolaryngol Relat Spec. 2013;75:6–17.

    Article  CAS  PubMed  Google Scholar 

  40. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21:593–646.

    Article  CAS  Google Scholar 

  41. Von Hofe SE, Dorfman SG, Carretta RF, et al. The increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter. J Nucl Med. 1978;19:180–4.

    Google Scholar 

  42. Nofal MM, Beierwaltes WH, Patno ME. Treatment of hyperthyroidism with sodium iodide I-131. JAMA. 1966;197:605–10.

    Article  CAS  PubMed  Google Scholar 

  43. Metso S, Jaatinen P, Huhtala H, et al. Long-term follow-up study of radioiodine treatment of hyperthyroidism. Clin Endocrinol (Oxf). 2004;61:641–8.

    Article  CAS  Google Scholar 

  44. Nygaard B, Hegedüs L, Nielsen KG, et al. Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules. Clin Endocrinol (Oxf). 1999;50:197–202.

    Article  CAS  Google Scholar 

  45. Hancock SL, Cox RS, McDougall IR. Thyroid diseases after treatment of Hodgkin’s disease. N Engl J Med. 1991;325:599–605.

    Article  CAS  PubMed  Google Scholar 

  46. Smolarz K, Malke G, Voth E, et al. Hypothyroidism after therapy for larynx and pharynx carcinoma. Thyroid. 2000;10:425–9.

    Article  CAS  PubMed  Google Scholar 

  47. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000;85:3227–32.

    CAS  PubMed  Google Scholar 

  48. Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab. 2010;95:2529–35.

    Google Scholar 

  49. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Med. 2005;118:706–14.

    Article  CAS  PubMed  Google Scholar 

  50. Martino E, Bartalena L, Bogazzi F, et al. The effects of amiodarone on the thyroid. Endocr Rev. 2001;22:240–54.

    CAS  PubMed  Google Scholar 

  51. Batcher EL, Tang XC, Singh BN, et al. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med. 2007;120:880–5.

    Article  CAS  PubMed  Google Scholar 

  52. Martino E, Safran M, Aghini-Lombardi F, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101:28–34.

    Article  CAS  PubMed  Google Scholar 

  53. Martino E, Aghini-Lombardi F, Mariotti S, et al. Amiodarone iodine-induced hypothyroidism: risk factors and follow-up in 28 cases. Clin Endocrinol (Oxf). 1987;26:227–37.

    Article  CAS  Google Scholar 

  54. Yagishita A, Hachiya H, Kawabata M, et al. Amiodarone-induced thyrotoxicosis late after amiodarone withdrawal. Circ J. 2013;77:2898–903.

    Article  CAS  PubMed  Google Scholar 

  55. Barbesino G. Drugs affecting thyroid function. Thyroid. 2010;20:763–70.

    Article  PubMed  Google Scholar 

  56. Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23:723–33.

    Article  CAS  PubMed  Google Scholar 

  57. van Melick EJ, Wilting I, Meinders AE, et al. Prevalence and determinants of thyroid disorders in elderly patients with affective disorders: lithium and nonlithium patients. Am J Geriatr Psychiatry. 2010;18:395–403.

    Article  PubMed  Google Scholar 

  58. Kirov G, Tredget J, John R, et al. A cross-sectional and a prospective study of thyroid disorders in lithium-treated patients. J Affect Disord. 2005;87:313–7.

    Article  CAS  PubMed  Google Scholar 

  59. Bocchetta A, Bernardi F, Burrai C, et al. The course of thyroid abnormalities during lithium treatment: a two-year follow-up study. Acta Psychiatr Scand. 1992;86:38–41.

    Article  CAS  PubMed  Google Scholar 

  60. Spaulding SW, Burrow GN, Bermudez F, et al. The inhibitory effect of lithium on thyroid hormone release in both euthyroid and thyrotoxic patients. J Clin Endocrinol Metab. 1972;35:905–11.

    Article  CAS  PubMed  Google Scholar 

  61. Tomer Y, Blackard JT, Akeno N. Interferon alpha treatment and thyroid dysfunction. Endocrinol Metab Clin North Am. 2007;36:1051–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tran HA, Jones TL, Ianna EA, et al. Thyroid disease in chronic hepatitis C infection treated with combination interferon-a and ribavirin: management strategies and future perspective. Endocr Pract. 2013;19:292–300.

    Article  PubMed  Google Scholar 

  63. Nadeem A, Hussain MM, Aslam M, et al. Interferon-alpha induced and ribavirin induced thyroid dysfunction in patients with chronic hepatitis C. Hepat Mon. 2010;10:132–40.

    PubMed  PubMed Central  Google Scholar 

  64. Tomer Y. Hepatitis C, and interferon induced thyroiditis. J Autoimmun. 2010;34:J322–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bini EJ, Mehandru S. Incidence of thyroid dysfunction during interferon alfa-2b and ribavirin therapy in men with chronic hepatitis C: a prospective cohort study. Arch Intern Med. 2004;164:2371–6.

    Article  PubMed  Google Scholar 

  66. Weijl NI, Van der Harst D, Brand A, et al. Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment. J Clin Oncol. 1993;11:1376–83.

    CAS  PubMed  Google Scholar 

  67. Atkins MB, Mier JW, Parkinson DR, et al. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med. 1988;318:1557–63.

    Article  CAS  PubMed  Google Scholar 

  68. Mattijssen VJ, De Mulder PH, Van Liessum PA, et al. Hypothyroidism and goiter in a patient during treatment with interleukin-2. Cancer. 1990;65:2686–8.

    Article  CAS  PubMed  Google Scholar 

  69. Vialettes B, Guillerand MA, Viens P, et al. Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies. Acta Endocrinol (Copenh). 1993;129:31–8.

    CAS  Google Scholar 

  70. Ahmadieh H, Salti I. Tyrosine kinase inhibitors induced thyroid dusfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment. Biomed Res Int. 2013;2013:725410.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Wong E, Rosen LS, Mulay M, et al. Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid. 2007;17:351–5.

    Article  CAS  PubMed  Google Scholar 

  72. Rini BI, Tamaskar I, Shaheen P, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2007;99:81–3.

    Article  CAS  PubMed  Google Scholar 

  73. Papi G, LiVolsi VA. Current concepts on Riedel thyroiditis. Am J Clin Pathol. 2004;121:S50–63.

    PubMed  Google Scholar 

  74. Hennessey JV. Clinical review: Riedel’s thyroiditis: a clinical review. J Clin Endocrinol Metab. 2011;96:3031–41.

    Article  CAS  PubMed  Google Scholar 

  75. Villa F, Dionigi G, Tanda ML, et al. Amyloid goiter. Int J Surg. 2008;6:S16–8.

    Article  PubMed  Google Scholar 

  76. Antonelli A, Fazzi P, Fallahi P, et al. Prevalence of hypothyroidism and Graves disease in sarcoidosis. Chest. 2006;130:526–32.

    Article  PubMed  Google Scholar 

  77. Oerter KE, Kamp GA, Munson PJ, et al. Multiple hormone deficiencies in children with hemochromatosis. J Clin Endocrinol Metab. 1993;76:357–61.

    CAS  PubMed  Google Scholar 

  78. Gordon MB, Klein I, Dekker A, et al. Thyroid disease in progressive systemic sclerosis: increased frequency of glandular fibrosis and hypothyroidism. Ann Intern Med. 1981;95:431–5.

    Article  CAS  PubMed  Google Scholar 

  79. Chan AM, Lynch MJ, Bailey JD, et al. Hypothyroidism in cystinosis. A clinical, endocrinologic and histologic study involving sixteen patients with cystinosis. Am J Med. 1970;48:678–92.

    Article  CAS  PubMed  Google Scholar 

  80. Luiz HV, Pereira BD, Silva TN, et al. Thyroid tuberculosis with abnormal thyroid function – case report and review of the literature. Endocr Pract. 2013;19:e44–9.

    Article  PubMed  Google Scholar 

  81. Fisher DA. Second International Conference on Neonatal Thyroid Screening: progress report. J Pediatr. 1983;102:653–4.

    Article  CAS  PubMed  Google Scholar 

  82. Narumi S, Muroya K, Asakura Y, et al. Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients. J Clin Endocrinol Metab. 2010;95:1981–5.

    Article  CAS  PubMed  Google Scholar 

  83. Grasberger H, Refetoff S. Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr. 2011;23:421–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, et al. Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N Engl J Med. 1995;332:155–60.

    Article  CAS  PubMed  Google Scholar 

  85. Delange F, Dalhem A, Bourdoux P, et al. Increased risk of primary hypothyroidism in preterm infants. J Pediatr. 1984;105:462–9.

    Article  CAS  PubMed  Google Scholar 

  86. Bartalena L, Bogazzi F, Braverman LE, et al. Effects of amiodarone administration during pregnancy on neonatal thyroid function and subsequent neurodevelopment. J Endocrinol Invest. 2001;24:116–30.

    Article  CAS  PubMed  Google Scholar 

  87. Zakarija M, McKenzie JM, Eidson MS. Transient neonatal hypothyroidism: characterization of maternal antibodies to the thyrotropin receptor. J Clin Endocrinol Metab. 1990;70:1239–46.

    Article  CAS  PubMed  Google Scholar 

  88. Luiz HV, Silva TN, Pereira BD, et al. Intrasellar plasmacytoma: an entity to be considered in the differential diagnosis of a pituitary mass lesion. In: Abstracts of the 97th annual meeting & expo of The Endocrine Society, San Diego, 5–8 March 2015. 2015.

    Google Scholar 

  89. Yamada M, Mori M. Mechanisms related to the pathophysiology and management of central hypothyroidism. Nat Clin Pract Endocrinol Metab. 2008;4:683–94.

    Article  CAS  PubMed  Google Scholar 

  90. Collu R, Tang J, Castagne J, et al. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab. 1997;82:1561–5.

    CAS  PubMed  Google Scholar 

  91. Bonomi M, Proverbio MC, Weber G, et al. Hyperplastic pituitary gland, high serum glycoprotein hormone alpha-subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSH beta gene. J Clin Endocrinol Metab. 2001;86:1600–4.

    CAS  PubMed  Google Scholar 

  92. Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23:793–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Olateju TO, Vanderpump MP. Thyroid hormone resistance. Ann Clin Biochem. 2006;43:431–40.

    Article  CAS  PubMed  Google Scholar 

  94. Agrawal NK, Goyal R, Rastogi A, et al. Thyroid hormone resistance. Postgrad Med J. 2008;84:473–7.

    Article  CAS  PubMed  Google Scholar 

  95. Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 1830;2013:3987–4003.

    Google Scholar 

  96. Luiz HV, Silva TN, Pereira BD, et al. Management of differentiated thyroid carcinoma in a patient with thyroid hormone resistance: difficulties and challenges. In: Abstracts of the 16th international congress of endocrinology and 96th annual meeting & expo of The Endocrine Society, Chicago, 21–24 June 2014. 2014.

    Google Scholar 

  97. Huang SA, Tu HM, Harney JW, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000;343:185–9.

    Article  CAS  PubMed  Google Scholar 

  98. Ruppe MD, Huang SA, Jan de Beur SM. Consumptive hypothyroidism caused by paraneoplastic production of type 3 iodothyronine deiodinase. Thyroid. 2005;15:1369–72.

    Article  CAS  PubMed  Google Scholar 

  99. Smith TJ, Bahn RS, Gorman CA. Connective tissue, glycosaminoglycans, and diseases of the thyroid. Endocr Rev. 1989;10:366–91.

    Article  CAS  PubMed  Google Scholar 

  100. Hall R, Scanlon MF. Hypothyroidism: clinical features and complications. Clin Endocrinol Metab. 1979;8:29–38.

    Article  CAS  PubMed  Google Scholar 

  101. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344:501–9.

    Article  CAS  PubMed  Google Scholar 

  102. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116:1725–35.

    Article  PubMed  Google Scholar 

  103. Becker C. Hypothyroidism and atherosclerotic heart disease: pathogenesis, medical management, and the role of coronary artery bypass surgery. Endocr Rev. 1985;6:432–40.

    Article  CAS  PubMed  Google Scholar 

  104. Hussein WI, Green R, Jacobsen DW, et al. Normalization of hyperhomocysteinemia with L-thyroxine in hypothyroidism. Ann Intern Med. 1999;131:348–51.

    Article  CAS  PubMed  Google Scholar 

  105. Catargi B, Parrot-Roulaud F, Cochet C, et al. Homocysteine, hypothyroidism, and effect of thyroid hormone replacement. Thyroid. 1999;9:1163–6.

    Article  CAS  PubMed  Google Scholar 

  106. Klein I, Mantell P, Parker M, et al. Resolution of abnormal muscle enzyme studies in hypothyroidism. Am J Med Sci. 1980;279:159–62.

    Article  CAS  PubMed  Google Scholar 

  107. O’Brien T, Dinneen SF, O’Brien PC, et al. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc. 1993;68:860–6.

    Article  PubMed  Google Scholar 

  108. Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of “torsade de pointe” type in hypothyroidism. Acta Med Scand. 1983;213:231–5.

    Article  CAS  PubMed  Google Scholar 

  109. Hardisty CA, Naik DR, Munro DS. Pericardial effudion in hypothyroidism. Clin Endocrinol (Oxf). 1980;13:349–54.

    Article  CAS  Google Scholar 

  110. Santos AD, Miller RP, Mathew PK, et al. Echocardiographic characterization of the reversible cardiomyopathy of hypothyroidism. Am J Med. 1980;68:675–82.

    Article  CAS  PubMed  Google Scholar 

  111. Biondi B. Mechanisms in endocrinology: heart failure and thyroid dysfunction. Eur J Endocrinol. 2012;167:609–18.

    Article  CAS  PubMed  Google Scholar 

  112. Nordqvist P, Dhuner KG, Stenberg K, et al. Myxoedema coma and carbon dioxide-retention. Acta Med Scand. 1960;166:189–94.

    Google Scholar 

  113. Weg JG, Calverly JR, Johnson C. Hypothyroidism and alveolar hypoventilation. Arch Intern Med. 1965;115:302–6.

    Article  CAS  PubMed  Google Scholar 

  114. Rosenow F, McCarthy V, Caruso AC. Sleep apnoea in endocrine diseases. J Sleep Res. 1998;7:3–11.

    Article  CAS  PubMed  Google Scholar 

  115. Pelttari L, Rauhala E, Polo O, et al. Upper airway obstruction in hypothyroidism. J Intern Med. 1994;236:177–81.

    Article  CAS  PubMed  Google Scholar 

  116. Karmisholt J, Andersen S, Laurberg P. Weight loss after therapy of hypothyroidism is mainly caused by excretion of excess body water associated with myxoedema. J Clin Endocrinol Metab. 2011;96:E99–103.

    Article  CAS  PubMed  Google Scholar 

  117. Ebert EC. The thyroid and the gut. J Clin Gastroenterol. 2010;44:402–6.

    CAS  PubMed  Google Scholar 

  118. Shafer RB, Prentiss RA, Bond JH. Gastrointestinal transit in thyroid disease. Gastroenterology. 1984;86:852–5.

    CAS  PubMed  Google Scholar 

  119. Hohl RD, Nixon RK. Myxedema ileus. Arch Intern Med. 1965;115:145–50.

    Article  CAS  PubMed  Google Scholar 

  120. Rahman Q, Haboubi NY, Hudson PR, et al. The effect of thyroxine on small intestinal motility in the elderly. Clin Endocrinol (Oxf). 1991;35:443–6.

    Article  CAS  Google Scholar 

  121. Kocen RS, Atkinson M. Ascites in hypothyroidism. Lancet. 1963;1:527–30.

    Article  CAS  PubMed  Google Scholar 

  122. Bellini MA, Cervino JM, De Buno RB, et al. Hypotonia of the gall bladder, of myxedematous origin. J Clin Endocrinol Metab. 1957;17:133–42.

    Article  CAS  PubMed  Google Scholar 

  123. Saha B, Maity C. Alteration of serum enzymes in primary hypothyroidism. Clin Chem Lab Med. 2002;40:609–11.

    Article  CAS  PubMed  Google Scholar 

  124. Amino N, Kuro R, Yabu Y, et al. Elevated levels of circulating carcinoembryonic antigens in hypothyroidism. J Clin Endocrinol Metab. 1981;52:457–62.

    Article  CAS  PubMed  Google Scholar 

  125. Elfström P, Montgomery SM, Kämpe O, et al. Risk of thyroid disease in individuals with celiac disease. J Clin Endocrinol Metab. 2008;93:3915–21.

    Article  PubMed  CAS  Google Scholar 

  126. Bernal J, Guadano-Ferraz A, Morte B. Perspectives in the study of thyroid hormone action on brain development and function. Thyroid. 2003;13:1005–12.

    Article  CAS  PubMed  Google Scholar 

  127. Williams GR. Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008;20:784–94.

    Article  CAS  PubMed  Google Scholar 

  128. Halpern JP, Boyages SC, Maberly GF, et al. The neurology of endemic cretinism. A study of two endemias. Brain. 1991;114:825–41.

    Article  PubMed  Google Scholar 

  129. Moreau T, Manceau E, Giroud-Baleydier F, et al. Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy. Cephalalgia. 1998;18:687–9.

    Article  CAS  PubMed  Google Scholar 

  130. Duyff RF, Van den Bosch J, Laman DM, et al. Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study. J Neurol Neurosurg Psychiatry. 2000;68:750–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Kececi H, Degirmenci Y. Hormone replacement therapy in hypothyroidism and nerve conduction study. Neurophysiol Clin. 2006;36:79–83.

    Article  CAS  PubMed  Google Scholar 

  132. Jellinek EH, Kelly RE. Cerebellar syndrome in myxoedema. Lancet. 1960;2:225–7.

    Article  CAS  PubMed  Google Scholar 

  133. Beghi E, Delodovici ML, Bogliun G, et al. Hypothyroidism and polyneuropathy. J Neurol Neurosurg Psychiatry. 1989;52:1420–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Anand VT, Mann SB, Dash RJ, et al. Auditory investigations in hypothyroidism. Acta Otolaryngol. 1989;108:83–7.

    Article  CAS  PubMed  Google Scholar 

  135. Heinrich TW, Grahm G. Hypothyroidism presenting as psychosis: myxedema madness revisited. Prim Care Companion J Clin Psychiatry. 2003;5:260–6.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Tan ZS, Vasan RS. Thyroid function and Alzheimer’s disease. J Alzheimers Dis. 2009;16:503–7.

    CAS  PubMed  Google Scholar 

  137. van der Cammen TJ, Mattace-Raso F, van Harskamp F, et al. Lack of association between thyroid disorders and Alzheimer’s disease in older persons: a cross-sectional observational study in a geriatric outpatient population. J Am Geriatr Soc. 2003;51:884.

    Article  PubMed  Google Scholar 

  138. Constant EL, de Volder AG, Ivanoiu A, et al. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J Clin Endocrinol Metab. 2001;86:3864–70.

    Article  CAS  PubMed  Google Scholar 

  139. Ferracci F, Carnevale A. The neurological disorder associated with thyroid autoimmunity. J Neurol. 2006;253:975–84.

    Article  CAS  PubMed  Google Scholar 

  140. Kothbauer-Margreiter I, Sturzenegger M, Komor J, et al. Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment. J Neurol. 1996;243:585–93.

    Article  CAS  PubMed  Google Scholar 

  141. Chong JY, Rowland LP, Utiger RD. Hashimoto encephalopathy: syndrome or myth? Arch Neurol. 2003;60:164–71.

    Article  PubMed  Google Scholar 

  142. Murphy E, Williams GR. The thyroid and the skeleton. Clin Endocrinol (Oxf). 2004;61:285–98.

    Article  CAS  Google Scholar 

  143. Rivkees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: the failure to achieve normal adult stature. N Engl J Med. 1988;318:599–602.

    Article  CAS  PubMed  Google Scholar 

  144. Bland JH, Frymoyer JW. Rheumatic syndromes of myxedema. N Engl J Med. 1970;282:1171–4.

    Article  CAS  PubMed  Google Scholar 

  145. Shaw C, Shaw P. Kocher-Debre-Semelaigne syndrome: hypothyroid muscular pseudohypertrophy – a rare report of two cases. Case Rep Endocrinol. 2012;2012:153143.

    PubMed  PubMed Central  Google Scholar 

  146. Najjar SS, Nachman HS. The Kocher-Debre-Semelaigne syndrome; hypothyroidism with muscular “hypertrophy”. J Pediatr. 1965;66:901–8.

    Article  CAS  PubMed  Google Scholar 

  147. Klein I, Parker M, Shebert R, et al. Hypothyroidism presenting as muscle stiffness and pseudohypertrophy: Hoffmann’s syndrome. Am J Med. 1981;70:891–4.

    Article  CAS  PubMed  Google Scholar 

  148. Sekine N, Yamamoto M, Michikawa M, et al. Rhabdomyolysis and acute renal failure in a patient with hypothyroidism. Intern Med. 1993;32:269–71.

    Article  CAS  PubMed  Google Scholar 

  149. Lowe CE, Bird ED, Thomas Jr JC. Hypercalcemia in myxedema. J Clin Endocrinol Metab. 1962;22:261–7.

    Article  CAS  PubMed  Google Scholar 

  150. Discala VA, Kinney MJ. Effects of myxedema on the renal diluting and concentrating mechanism. Am J Med. 1971;50:325–35.

    Article  CAS  PubMed  Google Scholar 

  151. Iglesias P, Diez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol. 2009;160:503–15.

    Article  CAS  PubMed  Google Scholar 

  152. Watanakunakorn C, Hodges RE, Evans TC. Myxedema; a study of 400 cases. Q J Med. 1960;29:513–37.

    Google Scholar 

  153. Tudhope GR, Wilson GM. Anaemia in hypothyroidism. Incidence, pathogenesis, and response to treatment. Q J Med. 1960;29:513–37.

    CAS  PubMed  Google Scholar 

  154. Squizzato A, Romualdi E, Buller HR, et al. Clinical review: thyroid dysfunction and effects on coagulation and fibrinolysis: a systematic review. J Clin Endocrinol Metab. 2007;92:2415–20.

    Article  CAS  PubMed  Google Scholar 

  155. Manfredi E, van Zaane B, Gerdes VE, et al. Hypothyroidism and acquired von Willebrand’s syndrome: a systematic review. Haemophilia. 2008;14:423–33.

    Article  CAS  PubMed  Google Scholar 

  156. Yamada T, Tsukui T, Ikejiri K, et al. Volume of sella turcica in normal subjects and in patients with primary hypothyroidism and hyperthyroidism. J Clin Endocrinol Metab. 1976;42:817–22.

    Article  CAS  PubMed  Google Scholar 

  157. Vagenakis AG, Dole K, Braverman LE. Pituitary enlargement, pituitary failure, and primary hypothyroidism. Ann Intern Med. 1976;85:195–8.

    Article  CAS  PubMed  Google Scholar 

  158. Yamamoto K, Saito K, Takai T, et al. Visual field defects and pituitary enlargement in primary hypothyroidism. J Clin Endocrinol Metab. 1983;57:283–7.

    Article  CAS  PubMed  Google Scholar 

  159. Honbo KS, van Herle AJ, Kellett KA. Serum prolactin levels in untreated primary hypothyroidism. Am J Med. 1978;64:782–7.

    Article  CAS  PubMed  Google Scholar 

  160. Onishi T, Miyai K, Aono T, et al. Primary hypothyroidism and galactorrhea. Am J Med. 1977;63:373–8.

    Article  CAS  PubMed  Google Scholar 

  161. Valcavi R, Valente F, Dieguez C, et al. Evidence against depletion of the growth hormone (GH)-releasable pool in human primary hypothyroidism: studies with GH-releasing hormone, pyridostigmine, and arginine. J Clin Endocrinol Metab. 1993;77:616–20.

    Google Scholar 

  162. Gordon GG, Southren AL. Thyroid – hormone effects on steroid – hormone metabolism. Bull N Y Acad Med. 1977;53:241–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Christensen NJ. Increased levels of plasma noradrenaline in hypothyroidism. J Clin Endocrinol Metab. 1972;35:359–63.

    Article  CAS  PubMed  Google Scholar 

  164. Polikar R, Kennedy B, Maisel A, et al. Decreased adrenergic sensitivity in patients with hypothyroidism. J Am Coll Cardiol. 1990;15:94–8.

    Article  CAS  PubMed  Google Scholar 

  165. Costin G, Kershnar AK, Kogut MD, et al. Prolactin activity in juvenile hypothyroidism and precocious puberty. Pediatrics. 1972;50:881–9.

    CAS  PubMed  Google Scholar 

  166. Louvet JP, Gouarre M, Salandini AM, et al. Hypothyroidism and anovulation. Lancet. 1979;1:1032.

    Article  CAS  PubMed  Google Scholar 

  167. Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50:655–9.

    Article  CAS  Google Scholar 

  168. Smallridge RC, Ladenson PW. Hypothyroidism in pregnancy: consequences to neonatal health. J Clin Endocrinol Metab. 2001;86:2349–53.

    Article  CAS  PubMed  Google Scholar 

  169. Montoro M, Collea JV, Frasier SD, et al. Successful outcome of pregnancy in women with hypothyroidism. Ann Intern Med. 1981;94:31–4.

    Article  CAS  PubMed  Google Scholar 

  170. Carani C, Isidori AM, Granata A, et al. Multicenter study on the prevalence of sexual symptoms in male hypo- and hyperthyroid patients. J Clin Endocrinol Metab. 2005;90:6472–9.

    Article  CAS  PubMed  Google Scholar 

  171. Krassas GE, Papadopoulou F, Tziomalos K, et al. Hypothyroidism has an adverse effect on human spermatogenesis: a prospective, controlled study. Thyroid. 2008;18:1255–9.

    Article  CAS  PubMed  Google Scholar 

  172. Maratou E, Hadjidakis DJ, Kollias A, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160:785–90.

    Article  CAS  PubMed  Google Scholar 

  173. Dimitriadis G, Mitrou P, Lambadiari V, et al. Insulin action in adipose tissue and muscle in hypothyroidism. J Clin Endocrinol Metab. 2006;91:4930–7.

    Article  CAS  PubMed  Google Scholar 

  174. Hecht A, Gershberg H. Diabetes mellitus and primary hypothyroidism. Metabolism. 1968;17:108–13.

    Article  CAS  PubMed  Google Scholar 

  175. Thvilum M, Brandt F, Brix TH, et al. Hypothyroidism is a predictor of disability pension and loss of labor market income: a Danish register-based study. J Clin Endocrinol Metab. 2014;99:3129–35.

    Article  CAS  PubMed  Google Scholar 

  176. Lania A, Persani L, Beck-Peccoz P. Central hypothyroidism. Pituitary. 2008;11:181–6.

    Article  CAS  PubMed  Google Scholar 

  177. Alexopoulou O, Beguin C, De Nayer P, et al. Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol. 2004;150:1–8.

    Article  CAS  PubMed  Google Scholar 

  178. Vulsma T, Gons MH, de Vijlder JJ. Maternal-fetal transfer of thyroxine in congenital hypothyroidism due to a total organification defect or thyroid agenesis. N Engl J Med. 1989;321:13–6.

    Article  CAS  PubMed  Google Scholar 

  179. LaFranchi SH, Murphey WH, Foley Jr TP, et al. Neonatal hypothyroidism detected by the Northwest Regional Screening Program. Pediatrics. 1979;63:180–91.

    CAS  PubMed  Google Scholar 

  180. Olivieri A, Stazi MA, Mastroiacovo P, et al. A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (19911998). J Clin Endocrinol Metab. 2002;87:557–62.

    CAS  PubMed  Google Scholar 

  181. Rastogi MV, LaFranchi SH. Congenital hypothyroidism. Orphanet J Rare Dis. 2010;5:17.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Pantsiouou S, Stanhope R, Uruena M, et al. Growth prognosis and growth after menarche in primary hypothyroidism. Arch Dis Child. 1991;66:838–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94:33–7.

    Article  PubMed  Google Scholar 

  184. Léger J, Olivieri A, Donaldson M, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr. 2014;81:80–103.

    Article  PubMed  CAS  Google Scholar 

  185. Rose SR, Brown RS, Foley T, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117:2290–303.

    Article  PubMed  Google Scholar 

  186. LaFranchi SH. Newborn screening strategies for congenital hypothyroidism: an update. J Inherit Metab Dis. 2010;33:S225–33.

    Article  PubMed  CAS  Google Scholar 

  187. Muir A, Daneman D, Daneman A, et al. Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism. Am J Dis Child. 1988;142:214–6.

    CAS  PubMed  Google Scholar 

  188. Weetman AP. Hypothyroidism: screening and subclinical disease. BMJ. 1997;314:1175–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med. 1998;129:144–58.

    Article  CAS  PubMed  Google Scholar 

  190. Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160:1573–5.

    Article  CAS  PubMed  Google Scholar 

  191. Spencer CA. Clinical utility and cost-effectiveness of sensitive thyrotropin assays in ambulatory and hospitalized patients. Mayo Clin Proc. 1988;63:1214–22.

    Article  CAS  PubMed  Google Scholar 

  192. Tachman ML, Guthrie Jr GP. Hypothyroidism: diversity of presentation. Endocr Rev. 1984;5:456–65.

    Article  CAS  PubMed  Google Scholar 

  193. Billewicz WZ, Chapman RS, Crooks J, et al. Statistical methods applied to the diagnosis of hypothyroidism. Q J Med. 1969;38:255–66.

    CAS  PubMed  Google Scholar 

  194. Zulewski H, Müller B, Exer P, et al. Estimation of tissue hypothyroidism by a new clinical score: evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab. 1997;82:771–6.

    CAS  PubMed  Google Scholar 

  195. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005;90:5483–8.

    Article  CAS  PubMed  Google Scholar 

  196. Boucai L, Hollowell JG, Surks MI. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits. Thyroid. 2011;21:5–11.

    Article  PubMed  PubMed Central  Google Scholar 

  197. Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab. 2007;92:4575–82.

    Article  CAS  PubMed  Google Scholar 

  198. Evered DC, Ormston BJ, Smith PA, et al. Grades of hypothyroidism. Br Med J. 1973;1:657–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Gereben B, Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29:898–938.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Beck-Peccoz P, Amr S, Menezes-Ferreira MM, et al. Decreased receptor binding of biologically inactive thyrotropin in central hypothyroidism. Effect of treatment with thyrotropin-releasing hormone. N Engl J Med. 1985;312:1085–90.

    Article  CAS  PubMed  Google Scholar 

  201. Samuels MH, Lillehei K, Kleinschmidt-Demasters BK, et al. Patterns of pulsatile pituitary glycoprotein secretion in central hypothyroidism and hypogonadism. J Clin Endocrinol Metab. 1990;70:391–5.

    Article  CAS  PubMed  Google Scholar 

  202. Caron PJ, Nieman LK, Rose SR, et al. Deficient nocturnal surge of thyrotropin in central hypothyroidism. J Clin Endocrinol Metab. 1986;62:960–4.

    Article  CAS  PubMed  Google Scholar 

  203. Pedersen OM, Aardal NP, Larssen TB, et al. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid. 2000;10:251–9.

    Article  CAS  PubMed  Google Scholar 

  204. Beck-Peccoz P, Lania A, Beckers A, et al. 2013 European Thyroid Association guidelines for the diagnosis and treatment of thyrotropin-secreting pituitary tumors. Eur Thyroid J. 2013;2:76–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Beck-Peccoz P, Persani L, Mannavola D, et al. Pituitary tumours: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab. 2009;23:597–606.

    Article  CAS  PubMed  Google Scholar 

  206. Burman KD, Wartofsky L. Thyroid function in the intensive care unit setting. Crit Care Clin. 2001;17:43–57.

    Article  CAS  PubMed  Google Scholar 

  207. Adler SM, Wartofsky L. The nonthyroidal illness syndrome. Endocrinol Metab Clin North Am. 2007;36:657–72.

    Article  CAS  PubMed  Google Scholar 

  208. Topliss DJ, White EL, Stockigt JR. Significance of thyrotropin excess in untreated primary adrenal insufficiency. J Clin Endocrinol Metab. 1980;50:52–6.

    Article  CAS  PubMed  Google Scholar 

  209. Kahn BB, Weintraub BD, Csako G, et al. Factitious elevation of thyrotropin in a new ultrasensitive assay: implications for the use of monoclonal antibodies in “sandwich” immunoassay. J Clin Endocrinol Metab. 1988;66:526–33.

    Article  CAS  PubMed  Google Scholar 

  210. Loh TP, Kao SL, Halsall DJ, et al. Macro-thyrotropin: a case report and review of literature. J Clin Endocrinol Metab. 2012;97:1823–8.

    Article  CAS  PubMed  Google Scholar 

  211. Ross DS, Cooper DS, Mulder JE. Central hypothyroidism. In: Post TW, editor. UpToDate. Waltham: UpToDate; 2015. Accessed on 17 May 2015.

    Google Scholar 

  212. Mannavola D, Vannucchi G, Fugazzola L, et al. TBG deficiency: description of two novel mutations associated with complete TBG deficiency and review of the literature. J Mol Med (Berl). 2006;84:864–71.

    Article  CAS  Google Scholar 

  213. Arafah BM. Decreased levothyroxine requirement in women with hypothyroidism during androgen therapy for breast cancer. Ann Intern Med. 1994;12:247–51.

    Article  Google Scholar 

  214. Bános C, Takó J, Salamon F, et al. Effect of ACTH-stimulated glucocorticoid hypersecretion on the serum concentrations of thyroxine-binding globulin, thyroxine, triiodothyronine, reverse triiodothyronine and on the TSH-response to TRH. Acta Med Acad Sci Hung. 1979;36:381–94.

    PubMed  Google Scholar 

  215. Afrasiabi MA, Vaziri ND, Gwinup G. Thyroid function studies in the nephrotic syndrome. Ann Intern Med. 1979;90:335–8.

    Article  CAS  PubMed  Google Scholar 

  216. Garnick MB, Larsen PR. Acute deficiency of thyroxine-binding globulin during L-asparaginase therapy. N Engl J Med. 1979;301:252–3.

    Google Scholar 

  217. Graham RL, Gambrell Jr RD. Changes in thyroid function tests during danazol therapy. Obstet Gynecol. 1980;55:395–7.

    CAS  PubMed  Google Scholar 

  218. Shakir KM, Kroll S, Aprill BS, et al. Nicotinic acid decreases serum thyroid hormone levels while maintaining a euthyroid state. Mayo Clin Proc. 1995;70:556–8.

    Article  CAS  PubMed  Google Scholar 

  219. Connacher AA, Borsey DQ, Browning MC, et al. The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic. Postgrad Med J. 1987;63:841–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Lai EC, Yang YH, Lin SJ, et al. Use of antiepileptic drugs and risk of hypothyroidism. Pharmacoepidemiol Drug Saf. 2013;22:1071–9.

    CAS  PubMed  Google Scholar 

  221. Mai VQ, Burch HB. A stepwise approach to the evaluation and treatment of subclinical hyperthyroidism. Endocr Pract. 2012;18:772–80.

    Article  PubMed  Google Scholar 

  222. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. Thyroid. 2014;24:1670–751.

    Article  PubMed  PubMed Central  Google Scholar 

  223. Wiersinga WM, Duntas L, Fadeyev V, et al. 2012 ETA guidelines: the use of L-T4 + L-T3 in the treatment of hypothyroidism. Eur Thyroid J. 2012;1:55–71.

    Article  PubMed  PubMed Central  Google Scholar 

  224. Jonklaas J, Davidson B, Bhagat S, et al. Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA. 2008;299:769–77.

    Article  CAS  PubMed  Google Scholar 

  225. Hays MT. Localization of human thyroxine absorption. Thyroid. 1991;1:241–8.

    Article  CAS  PubMed  Google Scholar 

  226. Wenzel KW, Kirschsieper HE. Aspects of the absorption of oral L-thyroxine in normal man. Metabolism. 1977;26:1–8.

    Article  CAS  PubMed  Google Scholar 

  227. Perez CL, Araki FS, Graf H, et al. Serum thyrotropin levels following levothyroxine administration at breakfast. Thyroid. 2013;23:779–84.

    Article  CAS  PubMed  Google Scholar 

  228. Bach-Huynh TG, Nayak B, Loh J, et al. Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab. 2009;94:3905–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Bolk N, Visser TJ, Nijman J, et al. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med. 2010;170:1996–2003.

    Article  CAS  PubMed  Google Scholar 

  230. Fish LH, Schwartz HL, Cavanaugh J, et al. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. N Engl J Med. 1987;316:764–70.

    Article  CAS  PubMed  Google Scholar 

  231. Saberi M, Utiger RD. Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy. J Clin Endocrinol Metab. 1974;39:923–7.

    Article  CAS  PubMed  Google Scholar 

  232. Daniels GH. Response to ‘How do you approach the problem of TSH elevation in a patient on high-dose thyroid hormone replacement?’. Clin Endocrinol (Oxf). 2009;71:603.

    Article  Google Scholar 

  233. Walker JN, Shillo P, Ibbotson V, et al. A thyroxine absorption test followed by weekly thyroxine administration: a method to assess non-adherence to treatment. Eur J Endocrinol. 2013;168:913–7.

    Article  CAS  PubMed  Google Scholar 

  234. Grebe SK, Cooke RR, Ford HC, et al. Treatment of hypothyroidism with once weekly thyroxine. J Clin Endocrinol Metab. 1997;82:870–5.

    CAS  PubMed  Google Scholar 

  235. Colucci P, DAngelo P, Mautone G, et al. Pharmacokinetic equivalence of a levothyroxine sodium soft capsule manufactured using the new food and drug administration potency guidelines in healthy volunteers under fasting conditions. Ther Drug Monit. 2011;33:355–61.

    Article  CAS  PubMed  Google Scholar 

  236. Benvenga S. (Soft) capsules of wisdom: preventing myo-inositol malabsorption caused by coffee. Expert Opin Drug Deliv. 2012;9:1177–9.

    Article  CAS  PubMed  Google Scholar 

  237. Vita R, Benvenga S. Tablet levothyroxine (L-T4) malabsorption induced by proton pump inhibitor; a problem that was solved by switching to L-T4 in soft gel capsule. Endocr Pract. 2014;20:e38–41.

    Article  PubMed  Google Scholar 

  238. Santini F, Pinchera A, Marsili A, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab. 2005;90:124–7.

    Article  CAS  PubMed  Google Scholar 

  239. Gordon MB, Gordon MS. Variations in adequate levothyroxine replacement therapy in patients with different causes of hypothyroidism. Endocr Pract. 1999;5:233–8.

    Article  CAS  PubMed  Google Scholar 

  240. Burmeister LA, Goumaz MO, Mariash CN, et al. Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid cancer. J Clin Endocrinol Metab. 1992;75:344–50.

    CAS  PubMed  Google Scholar 

  241. Kabadi UM, Kabadi MM. Serum thyrotropin in primary hypothyroidism: a reliable and accurate predictor of optimal daily levothyroxine dose. Endocr Pract. 2001;7:16–8.

    Article  CAS  PubMed  Google Scholar 

  242. Roos A, Linn-Rasker SP, van Domburg RT, et al. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med. 2005;165:1714–20.

    Google Scholar 

  243. Liewendahl K, Helenius T, Lamberg BA, et al. Free thyroxine, free triiodothyronine, and thyrotropin concentrations in hypothyroid and thyroid carcinoma patients receiving thyroxine therapy. Acta Endocrinol (Copenh). 1987;116:418–24.

    CAS  Google Scholar 

  244. Woeber KA. Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. J Endocrinol Invest. 2002;25:106–9.

    Article  CAS  PubMed  Google Scholar 

  245. Ain KB, Pucino F, Shiver TM, et al. Thyroid hormone levels affected by time of blood sampling in thyroxine-treated patients. Thyroid. 1993;3:81–5.

    Article  CAS  PubMed  Google Scholar 

  246. Karmisholt J, Andersen S, Laurberg P. Variation in thyroid function tests in patients with stable untreated subclinical hypothyroidism. Thyroid. 2008;18:303–8.

    Article  PubMed  Google Scholar 

  247. Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354:1787–95.

    Article  CAS  PubMed  Google Scholar 

  248. Collins D, Wilcox R, Nathan M, et al. Celiac disease and hypothyroidism. Am J Med. 2012;125:278–82.

    Article  PubMed  Google Scholar 

  249. Singh N, Weisler SL, Hershman JM. The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid. 2001;11:967–71.

    Article  CAS  PubMed  Google Scholar 

  250. Weitzman SP, Ginsburg KC, Carlson HE. Colesevelam hydrochloride and lanthanum carbonate interfere with the absorption of levothyroxine. Thyroid. 2009;19:77–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. 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.

    Article  CAS  PubMed  Google Scholar 

  252. Shakir KM, Chute JP, Aprill BS, et al. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J. 1997;90:637–9.

    Article  CAS  PubMed  Google Scholar 

  253. Sperber AD, Liel Y. Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide. Arch Intern Med. 1992;152:183–4.

    Article  CAS  PubMed  Google Scholar 

  254. Sherman SI, Tielens ET, Ladenson PW. Sucralfate causes malabsorption of L-thyroxine. Am J Med. 1994;96:531–5.

    Google Scholar 

  255. 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;13:345–9.

    Article  PubMed  Google Scholar 

  256. Benvenga S, Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid. 2008;18:293–301.

    Google Scholar 

  257. Isley WL. Effect of rifampin therapy on thyroid function tests in a hypothyroid patient on replacement L-thyroxine. Ann Intern Med. 1987;107:517–8.

    Article  CAS  PubMed  Google Scholar 

  258. De Luca F, Arrigo T, Pandullo E, et al. Changes in thyroid function tests induced by 2 month carbamazepine treatment in L-thyroxine-substituted hypothyroid children. Eur J Pediatr. 1986;145:77–9.

    Article  PubMed  Google Scholar 

  259. Faber J, Lumholtz IB, Kirkegaard C, et al. The effects of phenytoin (diphenylhydantoin) on the extrathyroidal turnover of thyroxine, 3,5,3’-triiodothyronine, 3,3’,5’-triiodothyronine, and 3’,5’-diiodothyronine in man. J Clin Endocrinol Metab. 1985;61:1093–9.

    Google Scholar 

  260. McCowen KC, Garber JR, Spark R. Elevated serum thyrotropin in thyroxine- treated patients with hypothyroidism given sertraline. N Engl J Med. 1997;337:1010–1.

    Article  CAS  PubMed  Google Scholar 

  261. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001;344:1743–9.

    Article  CAS  PubMed  Google Scholar 

  262. Cunningham JJ, Barzel US. Lean body mass is a predictor of the daily requirement for thyroid hormone in older men and women. J Am Geriatr Soc. 1984;32:204–7.

    Article  CAS  PubMed  Google Scholar 

  263. Magner J, Gerber P. Urticaria due to blue dye in synthroid tablets. Thyroid. 1994;4:341.

    Article  CAS  PubMed  Google Scholar 

  264. Somwaru LL, Arnold AM, Joshi N, et al. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J Clin Endocrinol Metab. 2009;94:1342–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  265. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994;331:1249–52.

    Article  CAS  PubMed  Google Scholar 

  266. Bauer DC, Ettinger B, Nevitt MC, et al. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001;134:561–8.

    Article  CAS  PubMed  Google Scholar 

  267. Ladenson PW, Levin AA, Ridgway EC, et al. Complications of surgery in hypothyroid patients. Am J Med. 1984;77:261–6.

    Article  CAS  PubMed  Google Scholar 

  268. Weinberg AD, Brennan MD, Gorman CA, et al. Outcome of anesthesia and surgery in hypothyroid patients. Arch Intern Med. 1983;143:893–7.

    Article  CAS  PubMed  Google Scholar 

  269. Celi FS, Zemskova M, Linderman JD, et al. The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross-over study in thyroidectomized patients. Clin Endocrinol (Oxf). 2010;72:709–15.

    Article  CAS  Google Scholar 

  270. Hoang TD, Olsen CH, Mai VQ, et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab. 2013;98:1982–90.

    Article  CAS  PubMed  Google Scholar 

  271. Kaptein EM, Beale E, Chan LS. Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab. 2009;94:3663–75.

    Article  CAS  PubMed  Google Scholar 

  272. Burch HB, Burman KD, Cooper DS, et al. A 2013 survey of clinical practice patterns in the management of primary hypothyroidism. J Clin Endocrinol Metab. 2014;99:2077–85.

    Article  CAS  PubMed  Google Scholar 

  273. Grozinsky-Glasberg S, Fraser A, Nahshoni E, et al. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2006;91:2592–9.

    Google Scholar 

  274. Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, et al. Review: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J Clin Endocrinol Metab. 2005;90:4946–54.

    Article  CAS  PubMed  Google Scholar 

  275. Joffe RT, Brimacombe M, Levitt AJ, et al. Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: a literature review and metaanalysis. Psychosomatics. 2007;48:379–84.

    Article  CAS  PubMed  Google Scholar 

  276. Ma C, Xie J, Huang X, et al. Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism. Nucl Med Commun. 2009;30:586–93.

    Article  CAS  PubMed  Google Scholar 

  277. Panicker V, Saravanan P, Vaidya B, et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab. 2009;94:1623–9.

    Article  CAS  PubMed  Google Scholar 

  278. Wiersinga WM. Do we need still more trials on T4 and T3 combination therapy in hypothyroidism? Eur J Endocrinol. 2009;161:955–9.

    Article  CAS  PubMed  Google Scholar 

  279. Hennemann G, Docter R, Visser TJ, et al. Thyroxine plus low-dose, slow-release triiodothyronine replacement in hypothyroidism: proof of principle. Thyroid. 2004;14:271–5.

    Article  CAS  PubMed  Google Scholar 

  280. Jackson IM, Cobb WE. Why does anyone still use desiccated thyroid USP? Am J Med. 1978;64:284–8.

    Article  CAS  PubMed  Google Scholar 

  281. Nicoloff JT, Low JC, Dussault JH, et al. Simultaneous measurement of thyroxine and triiodothyronine peripheral turnover kinetics in man. J Clin Invest. 1972;51:473–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  282. Celi FS, Zemskova M, Linderman JD, et al. Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. J Clin Endocrinol Metab. 2011;96:3466–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  283. Blumberg KR, Mayer WJ, Parikh DK, et al. Liothyronine and levothyroxine in Armour thyroid. J Pharm Sci. 1987;76:346–7.

    Article  CAS  PubMed  Google Scholar 

  284. Penny R, Frasier SD. Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid. Am J Dis Child. 1980;134:16–8.

    Article  CAS  PubMed  Google Scholar 

  285. Lev-Ran A. Part-of-the-day hypertriiodothyroninemia caused by desiccated thyroid. JAMA. 1983;250:2790–1.

    Article  CAS  PubMed  Google Scholar 

  286. Jha S, Waghdhare S, Reddi R, et al. Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis. Thyroid. 2012;22:1283–6.

    Article  CAS  PubMed  Google Scholar 

  287. Boulton DW, Fawcett JP, Woods DJ. Stability of an extemporaneously compounded levothyroxine sodium oral liquid. Am J Health Syst Pharm. 1996;53:1157–61.

    CAS  PubMed  Google Scholar 

  288. Zeisel SH. Regulation of “nutraceuticals”. Science. 1999;285:1853–5.

    Article  CAS  PubMed  Google Scholar 

  289. Mechanick JI, Brett EM, Chausmer AB, et al. American Association of Clinical Endocrinologists medical guidelines for the clinical use of dietary supplements and nutraceuticals. Endocr Pract. 2003;9:417–70.

    Article  PubMed  Google Scholar 

  290. Rosen JE, Gardiner P, Saper RB. Complementary and alternative medicine use among patients with thyroid cancer. Thyroid. 2013;23:1238–46.

    Article  PubMed  PubMed Central  Google Scholar 

  291. Slawik M, Klawitter B, Meiser E, et al. Thyroid hormone replacement for central hypothyroidism: a randomized controlled trial comparing two doses of thyroxine (T4) with a combination of T4 and triiodothyronine. J Clin Endocrinol Metab. 2007;92:4115–22.

    Article  CAS  PubMed  Google Scholar 

  292. Shimon I, Cohen O, Lubetsky A, et al. Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism. Thyroid. 2002;12:823–7.

    Article  CAS  PubMed  Google Scholar 

  293. Zeitler P, Solberg P. Food and levothyroxine administration in infants and children. J Pediatr. 2010;157:13–4.

    Article  PubMed  Google Scholar 

  294. Tillotson SL, Fuggle PW, Smith I, et al. Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect. BMJ. 1994;309:440–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  295. Glorieux J, Dussault J, Van Vliet G. Intellectual development at age 12 years of children with congenital hypothyroidism diagnosed by neonatal screening. J Pediatr. 1992;121:581–4.

    Article  CAS  PubMed  Google Scholar 

  296. LaFranchi SH, Austin J. How should we be treating children with congenital hypothyroidism? J Pediatr Endocrinol Metab. 2007;20:559–78.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

We thank Joan Kennedy for the assistance in preparing the chapter.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Diabetology, Hospital Garcia de Orta, Avenida Torrado da Silva, Almada, 2801-951, Portugal

    Henrique Vara Luiz MD, Isabel Manita MD & Jorge Portugal MD

Authors
  1. Henrique Vara Luiz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Isabel Manita MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorge Portugal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henrique Vara Luiz MD .

Editor information

Editors and Affiliations

  1. Internal Medicine, Al-Mouwasat Hospital, Jubail, Saudi Arabia

    Syed Khalid Imam

  2. School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

    Shamim I. Ahmad

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Luiz, H.V., Manita, I., Portugal, J. (2016). Hypothyroidism. In: Imam, S., Ahmad, S. (eds) Thyroid Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-25871-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-25871-3_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-25869-0

  • Online ISBN: 978-3-319-25871-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation