Advertisement

Central Hypothyroidism

  • Andrea Lania
  • Claudia Giavoli
  • Eriselda Profka
  • Paolo Beck-Peccoz
Chapter

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.

Keywords

Central hypothyroidism l-thyroxine Hypopituitarism 

References

  1. 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.CrossRefGoogle Scholar
  2. 2.
    Nebesio TD, McKenna MP, Nabhan ZM, Eugster EA. Newborn screening results in children with central hypothyroidism. J Pediatr. 2010;156:990–3.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 11.
    Shoenmakers N, Alatzoglou KS, Chatterjee VK, Dattani MT. Recent advances in central congenital hypothyroidism. J Endocrinol. 2015;227:R51–71.CrossRefGoogle Scholar
  12. 12.
    Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab. 2008;93:3717–26.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 15.
    Karavitaki N, Cudlip S, Adams CB, et al. Craniopharyngiomas. Endocr Rev. 2006;27:371–97.CrossRefGoogle Scholar
  16. 16.
    Muller HL. Craniopharyngioma. Endocr Rev. 2014;35:513–43.CrossRefGoogle Scholar
  17. 17.
    Kanumakala S, Warne GL, Zacharin MR. Evolving hypopituitarism following cranial irradiation. J Paediatr Child Health. 2003;39:232–5.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 23.
    Xu Z, Lee Vance M, Schlesinger D, Sheehan JP. Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery. 2013;72:630–7.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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. 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.PubMedGoogle Scholar
  27. 27.
    Lewis AS, Courtney CH, Atkinson AB. All patients with ‘idiopathic’ hypopituitarism should be screened for hemochromatosis. Pituitary. 2009;12:273–5.CrossRefGoogle Scholar
  28. 28.
    Fukuoka H. Hypophysitis. Endocrinol Metab Clin North Am. 2015;44:143–9.CrossRefGoogle Scholar
  29. 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.CrossRefGoogle Scholar
  30. 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.CrossRefGoogle Scholar
  31. 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.CrossRefGoogle Scholar
  32. 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.CrossRefGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.CrossRefGoogle Scholar
  36. 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.CrossRefGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 39.
    Lania A, Persani L, Beck-Peccoz P. Central hypothyroidism. Pituitary. 2008;11:181–6.CrossRefGoogle Scholar
  40. 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.CrossRefGoogle Scholar
  41. 41.
    Darzy KH, Shalet SM. Circadian and stimulated thyrotropin secretion in cranially irradiated adult cancer survivors. J Clin Endocrinol Metab. 2005;90:6490–7.CrossRefGoogle Scholar
  42. 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.CrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.CrossRefGoogle Scholar
  45. 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.CrossRefGoogle Scholar
  46. 46.
    Wiersinga WM. Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat Rev Endocrinol. 2014;10(3):164–74.CrossRefGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 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.CrossRefGoogle Scholar
  49. 49.
    Beck-Peccoz P. Treatment of central hypothyroidism. Clin Endocrinol (Oxf). 2011;74:671–2.CrossRefGoogle Scholar
  50. 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.CrossRefGoogle Scholar
  51. 51.
    Iverson JF, Mariash CN. Optimal free thyroxine levels for thyroid hormone replacement in hypothyroidism. Endocr Pract. 2008;14:550–5.CrossRefGoogle Scholar
  52. 52.
    Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001;344:1743–9.CrossRefGoogle Scholar
  53. 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.CrossRefGoogle Scholar
  54. 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.Google Scholar
  55. 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.Google Scholar
  56. 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.CrossRefGoogle Scholar
  57. 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.CrossRefGoogle Scholar
  58. 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.CrossRefGoogle Scholar
  59. 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.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Andrea Lania
    • 1
  • Claudia Giavoli
    • 2
  • Eriselda Profka
    • 2
  • Paolo Beck-Peccoz
    • 3
  1. 1.Endocrinology Unit, Department of Biomedical SciencesHumanitas Research Hospital, Humanitas UniversityRozzanoItaly
  2. 2.Endocrinology and Metabolic Diseases UnitFondazione IRCCS Cà Granda-Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.University of MilanMilanItaly

Personalised recommendations