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Central hypothyroidism

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Abstract

Central hypothyroidism (CH) is a rare cause of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland and it is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects. The diagnosis of CH is usually suggested by the finding of lowered thyroid hormone concentrations, associated with inappropriately low/normal TSH levels. Restoration and maintenance of euthyroidism represent the therapeutic goals in all forms of CH. On these basis, the vast majority of patients with CH is treated with standard levo-thyroxine (L-T4) therapy which is tailored according to FT4 circulating levels that should be maintained in the normal range.

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References

  1. Horimoto M, Nishikawa M, Ishihara T, Yoshikawa N, Yoshimura M, Inada M (1995) Bioactivity of thyrotropin (TSH) in patients with central hypothyroidism: comparison between in vivo 3, 5, 3 -triiodothyronine response to TSH and in vitro bioactivity of TSH. J Clin Endocrinol Metab 80:1124–1128. doi:10.1210/jc.80.4.1124

    Article  PubMed  CAS  Google Scholar 

  2. Persani L, Ferretti E, Borgato S, Faglia G, Beck-Peccoz P (2000) Circulating TSH bioactivity in sporadic central hypothyroidism. J Clin Endocrinol Metab 85:3631–3635. doi:10.1210/jc.85.10.3631

    Article  PubMed  CAS  Google Scholar 

  3. Beck-Peccoz P, Amr S, Menezes-Ferreira MM, Faglia G, Weintraub BD (1985) Decreased receptor binding of biologically inactive thyrotropin in central hypothyroidism. Effect of treatment with thyrotropin-releasing hormone. N Engl J Med 312:1085–1090

    PubMed  CAS  Google Scholar 

  4. Beck-Peccoz P, Persani L (1994) Variable biological activity of thyroid-stimulating hormone. Eur J Endocrinol 131:331–340

    PubMed  CAS  Google Scholar 

  5. Sherman SI, Gopal J, Haugen BR et al (1999) Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med 340:1075–1079. doi:10.1056/NEJM199904083401404

    Article  PubMed  CAS  Google Scholar 

  6. Medeiros-Neto G, Herodotou DT, Rajan S et al (1996) A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene. J Clin Invest 97:1250–1256. doi:10.1172/JCI118540

    Article  PubMed  CAS  Google Scholar 

  7. Bonomi M, Proverbio MC, Weber G, Chiumello G, Beck-Peccoz P, Persani L (2001) 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 86:1600–1604. doi:10.1210/jc.86.4.1600

    Article  PubMed  CAS  Google Scholar 

  8. Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (2002) Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol Rev 82:473–502

    PubMed  CAS  Google Scholar 

  9. Collu R, Tang J, Castagne J et al (1997) A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab 82:1561–1565. doi:10.1210/jc.82.5.1561

    Article  PubMed  CAS  Google Scholar 

  10. Dattani MT, Robison IC (2000) The molecular basis for developmental disorders of the pituitary gland. Clin Genet 57:337–346. doi:10.1034/j.1399-0004.2000.570503.x

    Article  PubMed  CAS  Google Scholar 

  11. Cohen LE, Radovick S (2002) Molecular basis of combined pituitary hormone deficiencies. Endocr Rev 23:431–442. doi:10.1210/er.2001-0030

    Article  PubMed  CAS  Google Scholar 

  12. Clement K, Vaisse C, Lahlou N et al (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398–401. doi:10.1038/32911

    Article  PubMed  CAS  Google Scholar 

  13. Nillni EA, Vaslet C, Harris M, Hollenberg A, Bjorbak C, Flier JS (2000) Leptin regulates prothyrotropin-releasing hormone biosynthesis. Evidence for direct and indirect pathways. J Biol Chem 275:36124–36133. doi:10.1074/jbc.M003549200

    Article  PubMed  CAS  Google Scholar 

  14. Baloch Z, Carayon P, Conte-Devolx B et al (2003) Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 13:3–126

    Article  PubMed  Google Scholar 

  15. van Tijn DA, de Vijlder JJ, Verbeeten B Jr, Verkerk PH, Vulsma T (2005) Neonatal detection of congenital hypothyroidism of central origin. J Clin Endocrinol Metab 90:3350–3359. doi:10.1210/jc.2004-2444

    Article  PubMed  CAS  Google Scholar 

  16. Smallridge RC (1996) Metabolic, physiological, and clinical indexes of thyroid function. In: Braverman LE, Utiger RD (eds) The thyroid, 7th edn. Lippincott, Philadelphia, pp 397–405

    Google Scholar 

  17. Ferretti E, Persani L, Jaffrain-Rea ML, Giambona S, Tamburrano G, Beck-Peccoz P (1999) Evaluation of the adequacy of l-T4 replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab 84:924–929. doi:10.1210/jc.84.3.924

    Article  PubMed  CAS  Google Scholar 

  18. Jorgensen JO, Moller J, Laursen T, Orskov H, Christiansen JS, Weeke J (1994) 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 41:609–614. doi:10.1111/j.1365–2265.1994.tb01826.x

    Article  CAS  Google Scholar 

  19. Jorgensen JO, Pedersen SA, Laurberg P, Weeke J, Skakkebaek NE, Christiansen JS (1989) Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism. J Clin Endocrinol Metab 69:1127–1132

    PubMed  CAS  Google Scholar 

  20. Alexopoulou O, Beguin C, De Nayer P, Maiter D (2004) Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol 150:1–8. doi:10.1530/eje.0.1500001

    Article  PubMed  CAS  Google Scholar 

  21. Andersen S, Pedersen KM, Bruun NH, Laurberg P (2002) Narrow individual variations in serum T4 and T3 in normal subjects: a clue to understanding of subclinical thyroid disease. J Clin Endocrinol Metab 87:1068–1072. doi:10.1210/jc.87.3.1068

    Article  PubMed  CAS  Google Scholar 

  22. Rose SR, Lustig RH, Pitukcheewanont P et al (1999) Diagnosis of hidden central hypothyroidism in survivors of child cancer. J Clin Endocrinol Metab 84:4472–4479. doi:10.1210/jc.84.12.4472

    Article  PubMed  CAS  Google Scholar 

  23. Yamakita N, Komaki T, Takao T, Murai T, Hashimoto K, Yasuda K (2001) Usefulness of thyrotropin (TSH)-releasing hormone test and nocturnal surge of TSH for diagnosis of isolated deficit of TSH secretion. J Clin Endocrinol Metab 86:1054–1060. doi:10.1210/jc.86.3.1054

    Article  PubMed  CAS  Google Scholar 

  24. Costom BH, Grumbach MM, Kaplan SL (1971) Effect of thyrotropin-releasing factor on serum thyroid-stimulating hormone. An approach to distinguishing hypothalamic from pituitary forms of idiopathic hypopituitary dwarfism. J Clin Invest 50:2219–2225. doi:10.1172/JCI106717

    Article  PubMed  CAS  Google Scholar 

  25. Faglia G, Beck-Peccoz P, Ferrari C et al (1973) Plasma thyrotropin response to thyrotropin-releasing hormone in patients with pituitary and hypothalamic disorders. J Clin Endocrinol Metab 37:595–601

    PubMed  CAS  Google Scholar 

  26. Mehta A, Hindmarsh PC, Stanhope RG, Brain CE, Preece MA, Dattani MT (2003) Is the thyrotropin-releasing hormone test necessary in the diagnosis of central hypothyroidism in children. J Clin Endocrinol Metab 88:5696–5703. doi:10.1210/jc.2003-030943

    Article  PubMed  CAS  Google Scholar 

  27. Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr (1999) Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 340:424–429. doi:10.1056/NEJM199902113400603

    Article  PubMed  CAS  Google Scholar 

  28. Clyde PW, Harari AE, Getka EJ, Shakir KMM (2003) Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyrodism. A randomized controlled trial. JAMA 290:2952–2958. doi:10.1001/jama.290.22.2952

    Article  PubMed  CAS  Google Scholar 

  29. Helfand M, Crapo LM (1990) Monitoring therapy in patients taking levothyroxine. Ann Intern Med 113:450–454

    PubMed  CAS  Google Scholar 

  30. Oppenheimer JH, Braverman LE, Toft A, Jackson IM, Ladenson PW (1995) A therapeutic controversy. Thyroid hormone treatment: when and what? J Clin Endocrinol Metab 80:2873–2883. doi:10.1210/jc.80.10.2873

    Article  PubMed  CAS  Google Scholar 

  31. Carrozza V, Csako G, Yanovski JA et al (1999) Levothyroxine replacement therapy in central hypothyroidism: a practice report. Pharmacotherapy 19:349–355. doi:10.1592/phco.19.4.349.30940

    Article  PubMed  CAS  Google Scholar 

  32. Shimon I, Cohen O, Lubetsky A, Olchovsky D (2002) Thyrotropin suppression by thyroid hormone replacement is correlated with thyroxine level normalization in central hypothyroidism. Thyroid 12:823–827. doi:10.1089/105072502760339406

    Article  PubMed  CAS  Google Scholar 

  33. Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD (1996) Thyrotropin-secreting pituitary tumors. Endocr Rev 17:610–638. doi:10.1210/er.17.6.610

    Article  PubMed  CAS  Google Scholar 

  34. Beck-Peccoz P, Persani L (2001) TSH-producing adenomas. In: DeGroot LJ, Jameson JL (eds) Endocrinology, 4th edn, Chapter 24. WB Saunders, Philadelphia, pp 321–328

    Google Scholar 

  35. Griffin JE (1990) Hypothyroidism in the elderly. Am J Med Sci 299:334–345. doi:10.1097/00000441-199005000-00009

    Article  PubMed  CAS  Google Scholar 

  36. Porretti S, Giavoli C, Ronchi C et al (2002) 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 87:2042–2045. doi:10.1210/jc.87.5.2042

    Article  PubMed  CAS  Google Scholar 

  37. Arafah BM (2001) Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 344:1743–1749. doi:10.1056/NEJM200106073442302

    Article  PubMed  CAS  Google Scholar 

  38. Ain KB, Mori Y, Refetoff S (1987) 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 65:689–696

    PubMed  CAS  Google Scholar 

  39. Grunfeld C, Sherman BM, Cavalieri RR (1988) The acute effects of human growth hormone administration on thyroid function in normal men. J Clin Endocrinol Metab 67:1111–1114

    Article  PubMed  CAS  Google Scholar 

  40. Portes ES, Oliveira JH, Maccagnan P, Abucham J (2000) Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol 53:183–189. doi:10.1046/j.1365-2265.2000.01071.x

    Article  CAS  Google Scholar 

  41. Giavoli C, Porretti S, Ferrante E et al (2003) Recombinant hGH replacement therapy and the hypothalamus-pituitary-thyroid axis in children with GH deficiency: when should we be concerned about the occurrence of central hypothyroidism? Clin Endocrinol 59(806):810. doi:10.1046/j.1365–2265.2003.01892.x

    Google Scholar 

  42. Koch CA, Sarlis NJ (2001) The spectrum of thyroid diseases in childhood and its evolution during transition to adulthood: natural history, diagnosis, differential diagnosis and management. J Endocrinol Invest 24:659–675

    PubMed  CAS  Google Scholar 

  43. Selva KA, Mandel SH, Rien L et al (2002) Initial treatment dose of L-thyroxine in congenital hypothyroidism. J Pediatr 141:786–792. doi:10.1067/mpd.2002.128887

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medical Sciences, Endocrinology and Diabetology Unit, Fondazione Ospedale Maggiore Policlinico IRCCS, University of Milan, Pad. Granelli, Via F. Sforza 35, 20122, Milan, Italy

    Andrea Lania, Luca Persani & Paolo Beck-Peccoz

  2. Lab of Experimental Endocrinology, Istituto Auxologico Italiano IRCCS, Milan, Italy

    Luca Persani

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  1. Andrea Lania
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  2. Luca Persani
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  3. Paolo Beck-Peccoz
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Correspondence to Paolo Beck-Peccoz.

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Lania, A., Persani, L. & Beck-Peccoz, P. Central hypothyroidism. Pituitary 11, 181–186 (2008). https://doi.org/10.1007/s11102-008-0122-6

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