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Central Hypothyroidism

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Abstract

Central hypothyroidism is a rare and heterogeneous disorder caused by anatomical and/or functional alterations affecting the pituitary or the hypothalamus or both. This condition may be acquired (e.g., secondary to head trauma, pituitary tumors, neurosurgical procedures, radiotherapy) or congenital, and the clinical picture is usually milder than that observed in patients with primary hypothyroidism and similar levels of circulating thyroid hormones. In this chapter we will focus on the clinical aspects of central hypothyroidism and in particular on the diagnostic workup and treatment.

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References

  1. Asakura Y, Tachibana K, Adachi M, Suwa S, Yamagami Y. Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine. Acta Paediatr. 2002;91:172–7.

    Article  CAS  Google Scholar 

  2. Nebesio TD, McKenna MP, Nabhan ZM, Eugster EA. Newborn screening results in children with central hypothyroidism. J Pediatr. 2010;156:990–3.

    Article  Google Scholar 

  3. Kempers MJ, Lanting CI, van Heijst AF, van Trotsenburg AS, Wiedijk BM, de Vijlder JJ, Vulsma T. Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol Metab. 2006;91:3370–6.

    Article  CAS  Google Scholar 

  4. Beck-Peccoz P, Persani L, Calebiro D, Bonomi M, Mannavola D, Campi I. Syndromes of hormone resistance in the hypothalamic-pituitary-thyroid axis. Best Pract Res Clin Endocrinol Metab. 2006;20:529–46.

    Article  CAS  Google Scholar 

  5. Bonomi M, Proverbio MC, Weber G, Chiumello G, Beck-Peccoz P, Persani L. Hyperplastic pituitary gland, high serum glycoprotein hormone α-subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSHβ gene. J Clin Endocrinol Metab. 2001;86:1600–4.

    CAS  PubMed  Google Scholar 

  6. Persani L, Ferretti E, Borgato S, Faglia G, Beck-Peccoz P. Circulating thyrotropin bioactivity in sporadic central hypothyroidism. J Clin Endocrinol Metab. 2000;85:3631–5.

    CAS  PubMed  Google Scholar 

  7. Beck-Peccoz P, Amr S, Menezes-Ferreira MM, Faglia G, Weintraub BD. Decreased receptor binding of biologically inactive thyrotropin central hypothyroidism: effect of treatment with thyrotropin- releasing hormone. N Engl J Med. 1985;312:1085–90.

    Article  CAS  Google Scholar 

  8. Papandreou MJ, Persani L, Asteria C, Ronin C, Beck-Peccoz P. Variable carbohydrate structures of circulating thyrotropin as studied by lectin affinity chromatography in different clinical conditions. J Clin Endocrinol Metab. 1993;77:393–8.

    CAS  PubMed  Google Scholar 

  9. Persani L, Borgato S, Romoli R, Asteria C, Pizzocaro A, Beck-Peccoz P. Changes in the degree of sialylation of carbohydrate chains modify the biological properties of circulating thyrotropin isoforms in various physiological and pathological states. J Clin Endocrinol Metab. 1998;83:2486–92.

    CAS  PubMed  Google Scholar 

  10. Joustra SD, Schoenmakers N, Persani L, Campi I, Bonomi M, Radetti G, Beck-Peccoz P, Zhu H, Davis TM, Sun Y, Corssmit EP, Appelman-Dijkstra NM, Heinen CA, Pereira AM, Varewijck AJ, Janssen JA, Endert E, Hennekam RC, Lombardi MP, Mannens MM, Bak B, Bernard DJ, Breuning MH, Chatterjee K, Dattani MT, Oostdijk W, Biermasz NR, Wit JM, van Trotsenburg AS. The IGSF1 deficiency syndrome: characteristics of male and female patients. J Clin Endocrinol Metab. 2013;98:4942–52.

    Article  CAS  Google Scholar 

  11. Shoenmakers N, Alatzoglou KS, Chatterjee VK, Dattani MT. Recent advances in central congenital hypothyroidism. J Endocrinol. 2015;227:R51–71.

    Article  Google Scholar 

  12. Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab. 2008;93:3717–26.

    Article  CAS  Google Scholar 

  13. Ferrante E, Ferraroni M, Castrignano’ T, Menicatti L, Anagni M, Reimondo G, Del Monte P, Bernasconi D, Loli P, Faustini-Fustini M, Borretta G, Terzolo M, Losa M, Morabito A, Spada A, Beck-Peccoz P, Lania A. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol. 2008;155:823–9.

    Article  Google Scholar 

  14. Karavitaki N, Brufani C, Warner JT, et al. Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up. Clin Endocrinol (Oxf). 2005;62:397–409.

    Article  CAS  Google Scholar 

  15. Karavitaki N, Cudlip S, Adams CB, et al. Craniopharyngiomas. Endocr Rev. 2006;27:371–97.

    Article  Google Scholar 

  16. Muller HL. Craniopharyngioma. Endocr Rev. 2014;35:513–43.

    Article  Google Scholar 

  17. Kanumakala S, Warne GL, Zacharin MR. Evolving hypopituitarism following cranial irradiation. J Paediatr Child Health. 2003;39:232–5.

    Article  CAS  Google Scholar 

  18. Schmiegelow M, Feldt-Rasmussen U, Rasmussen AK, Poulsen HS, Muller J. A population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor. J Clin Endocrinol Metab. 2003;88:136–40.

    Article  CAS  Google Scholar 

  19. Ratnasingam J, Karim N, Paramasivam SS, Ibrahim L, Lim LL, Tan AT, Vethakkan SR, Jalaludin A, Chan SP. Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors. Pituitary. 2015;18(4):448–55.

    Article  CAS  Google Scholar 

  20. Samaan NA, Schultz PN, Yang KP, Vassilopoulou-Sellin R, Maor MH, Cangir A, Goepfert H. Endocrine complications after radiotherapy for tumors of the head and neck. J Lab Clin Med. 1987;109:364–72.

    CAS  PubMed  Google Scholar 

  21. Constine LS, Woolf PD, Cann D, Mick G, McCormick K, Raubertas RF, Rubin P. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med. 1993;328:87–94.

    Article  CAS  Google Scholar 

  22. Kyriakakis N, Lynch J, Orme SM, Gerrard G, Hatfield P, Loughrey C, Short SC, Murray RD. Pituitary dysfunction following cranial radiotherapy for adult-onset nonpituitary brain tumours. Clin Endocrinol (Oxf). 2016;84:372–9.

    Article  CAS  Google Scholar 

  23. Xu Z, Lee Vance M, Schlesinger D, Sheehan JP. Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery. 2013;72:630–7.

    Article  Google Scholar 

  24. Fernandez-Rodriguez E, Bernabeu I, Castro AI, Casanueva FF. Hypopituitarism after traumatic brain injury. Endocrinol Metab Clin North Am Mar. 2015;44(1):151–9.

    Article  Google Scholar 

  25. Klose M, Brennum J, Poulsgaard L, Kosteljanetz M, Wagner A, Feldt-Rasmussen U. Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2010;73:95–101.

    Google Scholar 

  26. Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev. 2008;6(Suppl 1):158–69.

    PubMed  Google Scholar 

  27. Lewis AS, Courtney CH, Atkinson AB. All patients with ‘idiopathic’ hypopituitarism should be screened for hemochromatosis. Pituitary. 2009;12:273–5.

    Article  Google Scholar 

  28. Fukuoka H. Hypophysitis. Endocrinol Metab Clin North Am. 2015;44:143–9.

    Article  Google Scholar 

  29. Lam T, Chan MM, Sweeting AN, De Sousa SM, Clements A, Carlino MS, Long GV, Tonks K, Chua E, Kefford RF, Chipps DR. Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. Intern Med J. 2015;45:1066–73.

    Article  CAS  Google Scholar 

  30. Yamamoto M, Iguchi G, Takeno R, Okimura Y, Sano T, Takahashi M, Nishizawa H, Handayaningshi AE, Fukuoka H, Tobita M, Saitoh T, Tojo K, Mokubo A, Morinobu A, Iida K, Kaji H, Seino S, Chihara K, Takahashi Y. Adult combined GH, prolactin, and TSH deficiency associated with circulating PIT-1 antibody in humans. J Clin Invest. 2011;121:113–9.

    Article  CAS  Google Scholar 

  31. Barbesino G, Sluss PM, Caturegli P. Central hypothyroidism in a patient with pituitary autoimmunity: evidence for TSH-independent thyroid hormone synthesis. J Clin Endocrinol Metab. 2012;97:345–50.

    Article  CAS  Google Scholar 

  32. Neumann S, Raaka BM, Gershengorn MC. Constitutively active thyrotropin and thyrotropin-releasing hormone receptors and their inverse agonists. Methods Enzymol. 2010;485:147–60.

    Article  CAS  Google Scholar 

  33. Bonomi M, Busnelli M, Beck-Peccoz P, Costanzo D, Antonica F, Dolci C, Pilotta A, Buzi F, Persani L. A family with complete resistance to thyrotropin-releasing hormone. N Engl J Med. 2009;360:731–4.

    Article  CAS  Google Scholar 

  34. Collu R, Tang J, Castagné J, Lagacé G, Masson N, Huot C, Deal C, Delvin E, Faccenda E, Eidne KA, Van Vliet G. A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab. 1997;82(5):1561–5.

    CAS  PubMed  Google Scholar 

  35. Koulouri O, Nicholas AK, Schoenmakers E, Mokrosinski J, Lane F, Cole T, Kirk J, Farooqi IS, Chatterjee VK, Gurnell M, Schoenmakers N. A novel thyrotropin-releasing hormone receptor missense mutation (p81r) in central congenital hypothyroidism. J Clin Endocrinol Metab. 2016;101:847–51.

    Article  CAS  Google Scholar 

  36. Hulle SV, Craen M, Callewaert B, Joustra S, Oostdijk W, Losekoot M, Wit JM, Turgeon MO, Bernard DJ, Schepper JD. Delayed adrenarche may be an additional feature of immunoglobulin super family member 1 Deficiency syndrome. J Clin Res Pediatr Endocrinol. 2016;8:86–91.

    Article  Google Scholar 

  37. Hughes JN, Aubert M, Heatlie J, Gardner A, Gecz J, Morgan T, Belsky J, Thomas PQ. Identification of an IGSF1-specific deletion in a five generation pedigree with X-linked Central Hypothyroidism without macroorchidism. Clin Endocrinol (Oxf). 2016;85(4):609–15.

    Article  CAS  Google Scholar 

  38. Joustra SD, Andela CD, Oostdijk W, van Trotsenburg AS, Fliers E, Wit JM, Pereira AM, Middelkoop HA, Biermasz NR. Mild deficits in attentional control in patients with the IGSF1 deficiency syndrome. Clin Endocrinol (Oxf). 2016;84:896–903.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. 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;27:745–62.

    Article  CAS  Google Scholar 

  41. Darzy KH, Shalet SM. Circadian and stimulated thyrotropin secretion in cranially irradiated adult cancer survivors. J Clin Endocrinol Metab. 2005;90:6490–7.

    Article  CAS  Google Scholar 

  42. Alexopoulou O, Beguin C, De Nayer P, Maiter D. 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  Google Scholar 

  43. Cassio A, Cacciari E, Cicognani A, Damiani G, Missiroli G, Corbelli E, Balsamo A, Bal M, Gualandi S. Treatment for congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Pediatrics. 2003;111:1055–60.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. Slawik M, Klawitter B, Meiser E, Schories M, Zwermann O, Borm K, Peper M, Lubrich B, Hug MJ, Nauck M, Olschewski M, Beuschlein F, Reincke M. 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  Google Scholar 

  46. Wiersinga WM. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat Rev Endocrinol. 2014;10(3):164–74.

    Article  CAS  Google Scholar 

  47. Ferretti E, Persani L, Jaffrain-Rea ML, Giambona S, Tamburrano G, Beck-Peccoz P. Evaluation of the adequacy of l-T4 replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab. 1999;84:924–9.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  49. Beck-Peccoz P. Treatment of central hypothyroidism. Clin Endocrinol (Oxf). 2011;74:671–2.

    Article  CAS  Google Scholar 

  50. Koulouri O, Auldin MA, Agarwal R, Kieffer V, Robertson C, Falconer Smith J, Levy MJ, Howlett TA. Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of underreplacement with levothyroxine. Clin Endocrinol (Oxf). 2011;74:744–9.

    Article  CAS  Google Scholar 

  51. Iverson JF, Mariash CN. Optimal free thyroxine levels for thyroid hormone replacement in hypothyroidism. Endocr Pract. 2008;14:550–5.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  53. Ain KB, Mori Y, Refetoff S. Reduced clearance rate of thyroxine-binding globulin (TBG) with increased sialylation: a mechanism for estrogen-induced elevation of serum TBG concentration. J Clin Endocrinol Metab. 1987;65:689–96.

    Article  CAS  Google Scholar 

  54. Agha A, Walker D, Perry L, Drake WM, Chew SL, Jenkins PJ, Grossman AB, Monson JP. Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitaric patients. Clin Endocrinol (Oxf). 2007;66:72–7.

    CAS  Google Scholar 

  55. Giavoli C, Bergamaschi S, Ferrante E, Ronchi CL, Lania AG, Rusconi R, Spada A, Beck-Peccoz P. Effect of growth hormone deficiency and recombinant hGH (rhGH) replacement on the hypothalamic-pituitary-adrenal axis in children with idiopathic isolated GH deficiency. Clin Endocrinol (Oxf). 2008;68:247–51.

    CAS  Google Scholar 

  56. Losa M, Scavini M, Gatti E, Rossini A, Madaschi S, Formenti I, Caumo A, Stidley CA, Lanzi R. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency. Thyroid. 2008;18:1249–54.

    Article  CAS  Google Scholar 

  57. Porretti S, Giavoli C, Ronchi C, Lombardi G, Zaccaria M, Valle D, Arosio M, Beck-Peccoz P. Recombinant human GH replacement therapy and thyroid function in a large group of adult GH-deficient patients: when does L-T4 therapy become mandatory? J Clin Endocrinol Metab. 2002;87:2042–5.

    Article  CAS  Google Scholar 

  58. Portes ES, Oliveira JH, MacCagnan P, Abucham J. Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol (Oxf). 2000;53:183–9.

    Article  CAS  Google Scholar 

  59. Jorgensen JO, Moller J, Laursen T, Orskov H, Christiansen JS, Weeke J. Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults. Clin Endocrinol. 1994;41:609–14.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Endocrinology Unit, Department of Biomedical Sciences, Humanitas Research Hospital, Humanitas University, Rozzano, Italy

    Andrea Lania

  2. Endocrinology and Metabolic Diseases Unit, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy

    Claudia Giavoli & Eriselda Profka

  3. University of Milan, Milan, Italy

    Paolo Beck-Peccoz

Authors
  1. Andrea Lania
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  2. Claudia Giavoli
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  3. Eriselda Profka
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  4. Paolo Beck-Peccoz
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Corresponding author

Correspondence to Andrea Lania .

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Editors and Affiliations

  1. Department of Nuclear Medicine, Philipps University Marburg, Marburg, Germany

    Markus Luster

  2. Unit of Endocrinology Diabetes and Metabolism, Evgenidion Hospital, National and Kapodistrian University of Athens, Athens, Greece

    Leonidas H. Duntas

  3. Georgetown University School of Medicine, Washington, DC, USA

    Leonard Wartofsky

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Lania, A., Giavoli, C., Profka, E., Beck-Peccoz, P. (2019). Central Hypothyroidism. In: Luster, M., Duntas, L., Wartofsky, L. (eds) The Thyroid and Its Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-72102-6_17

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  • DOI: https://doi.org/10.1007/978-3-319-72102-6_17

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