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Central Hypothyroidism

  • Chapter
Thyroid Diseases in Childhood

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Abstract

Central Hypothyrodism (CeH) is the hypothyroid condition due to an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. CeH is about 1,000-fold more rare than primary hypothyroidism and raises several challenges for the clinicians, mainly because they cannot rely on the systematic use of the “reflex TSH strategy” for diagnosis or therapy monitoring. Therefore, CeH diagnosis is suspected and detectable in patients with known hypothalamic-pituitary diseases, whereas it can be frequently missed in those with a previously unknown pituitary involvement. L-thyroxine replacement in CeH should rely on the combined evaluation of several biochemical and clinical parameters in order to overcome the lack of accuracy of the single index. The management of CeH patients is further complicated by the frequent combination with other pituitary deficiencies and their specific replacement.

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References

  1. Persani L (2012) Central hypothyroidism: pathogenic, diagnostic and therapeutic challenges. J Clin Endocrinol Metab 97:3068–3078

    Article  CAS  PubMed  Google Scholar 

  2. Persani L, Beck-Peccoz P (2012) Chapter 38: Central hypothyroidism. In: Braverman LE, Cooper D (eds) Werner & Ingbar’s the thyroid: a fundamental and clinical text, 10th edn. Lippincott Williams & Wilkins/Wolters Kluwer Health, Philadelphia, pp 560–568

    Google Scholar 

  3. Price A, Weetman AP (2001) Screening for central hypothyroidism is unjustified. Br Med J 322:798

    Article  CAS  Google Scholar 

  4. Nebesio TD, McKenna MP, Nabhan ZM et al (2010) Newborn screening results in children with central hypothyroidism. J Pediatr 156:990–993

    Article  PubMed  Google Scholar 

  5. Kempers MJ, Lanting CI, van Heijst AF et al (2006) Neonatal screening for congenital hypothyroidism based on thyroxine, thyrotropin, and thyroxine-binding globulin measurement: potentials and pitfalls. J Clin Endocrinol Metab 91:3370–3376

    Article  CAS  PubMed  Google Scholar 

  6. Miyai K (2007) Congenital thyrotropin deficiency–from discovery to molecular biology, postgenome and preventive medicine. Endocr J 54:191–203

    Article  CAS  PubMed  Google Scholar 

  7. LaFranchi SH (2010) Newborn screening strategies for congenital hypothyroidism: an update. J Inherit Metab Dis 33(Suppl 2):S225–S233

    Article  PubMed  Google Scholar 

  8. van Tijn DA, de Vijlder JJ, Vulsma T (2008) Role of the thyrotropin-releasing hormone stimulation test in diagnosis of congenital central hypothyroidism in infants. J Clin Endocrinol Metab 93:410–419

    Article  PubMed  Google Scholar 

  9. Pfäffle R, Klammt J (2011) Pituitary transcription factors in the aetiology of combined pituitary hormone deficiency. Best Pract Res Clin Endocrinol Metab 25:43–60

    Article  PubMed  Google Scholar 

  10. Raivio T, Avbelj M, McCabe MJ et al (2012) Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab 97:E694–E699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Bonomi M, Proverbio MC, Weber G et al (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

    CAS  PubMed  Google Scholar 

  12. Ramos HE, Labedan I, Carré A et al (2010) New cases of isolated congenital central hypothyroidism due to homozygous thyrotropin beta gene mutations: a pitfall to neonatal screening. Thyroid 20:639–645

    Article  PubMed  Google Scholar 

  13. Collu R, Tang J, Castagnè 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

    CAS  PubMed  Google Scholar 

  14. Bonomi M, Busnelli M, Beck-Peccoz P et al (2009) A family with complete resistance to thyrotropin-releasing hormone. N Engl J Med 360:731–734

    Article  CAS  PubMed  Google Scholar 

  15. Sun Y, Bak B, Schoenmakers N et al (2012) Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nat Genet 44:1375–1381

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Joustra SD, Schoenmakers N, Persani L et al (2013) The IGSF1 deficiency syndrome: characteristics of male and female patients. J Clin Endocrinol Metab 98:4942–5492

    Article  CAS  PubMed  Google Scholar 

  17. Ferretti E, Persani L, Jaffrain-Rea ML et al (1999) Evaluation of the adequacy of l-T4 replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab 84:924–929

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Rose SR, Lustig RH, Pitukcheewanont P et al (1999) Diagnosis of hidden central hypothyroidism in survivors of childhood cancer. J Clin Endocrinol Metab 84:4472–4479

    CAS  PubMed  Google Scholar 

  20. Darzy KH, Shalet SM (2005) Circadian and stimulated thyrotropin secretion in cranially irradiated adult cancer survivors. J Clin Endocrinol Metab 90:6490–6497

    Article  CAS  PubMed  Google Scholar 

  21. Yamakita N, Komaki T, Takao T et al (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

    Article  CAS  PubMed  Google Scholar 

  22. Faglia G (1998) The clinical impact of the thyrotropin-releasing hormone test. Thyroid 8:903–908

    Article  CAS  PubMed  Google Scholar 

  23. Mehta A, Hindmarsh PC, Stanhope RG et al (2003) Is the thyrotropin-releasing hormone test necessary in the diagnosis of central hypothyroidism in children? J Clin Endocrinol Metab 88:5696–5703

    Article  CAS  PubMed  Google Scholar 

  24. Andersen S, Pedersen KM, Bruun NH et al (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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Friesema EC, Visser WE, Visser TJ (2010) Genetics and phenomics of thyroid hormone transport by MCT8. Mol Cell Endocrinol 322:107–113

    Article  CAS  PubMed  Google Scholar 

  27. Refetoff S, Bassett JH, Beck-Peccoz P et al (2014) Classification and proposed nomenclature for inherited defects of thyroid hormone action, cell transport, and metabolism. Eur Thyroid J 3:7–9

    Article  PubMed Central  PubMed  Google Scholar 

  28. Bochukova E, Schoenmakers N, Agostini M et al (2012) A mutation in the thyroid hormone receptor alpha gene. N Engl J Med 366:243–249

    Article  CAS  PubMed  Google Scholar 

  29. van Mullem A, van Heerebeek R, Chrysis D (2012) Clinical phenotype and mutant TRα1. N Engl J Med 366:1451–1453

    Article  PubMed  Google Scholar 

  30. Beck-Peccoz P (2011) Treatment of central hypothyroidism. Clin Endocrinol 74:671–672

    Article  CAS  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  32. Hollowell JG, Staehling NW, Flanders WD et al (2002) 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 87:489–499

    Article  CAS  PubMed  Google Scholar 

  33. Selva KA, Mandel SH, Rien L (2002) Initial treatment dose of L-thyroxine in congenital hypothyroidism. J Pediatrics 141:786–792

    Article  CAS  Google Scholar 

  34. American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK (2006) Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 117:2290–2303

    Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Luca Persani MD, PhD & Marco Bonomi

  2. Division of Endocrine and Metabolic Diseases, San Luca Hospital, IRCCS Istituto Auxologico Italiano, Piazzale Brescia 20, Milan, 20149, Italy

    Luca Persani MD, PhD & Marco Bonomi

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  1. Luca Persani MD, PhD
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  2. Marco Bonomi
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Correspondence to Luca Persani MD, PhD .

Editor information

Editors and Affiliations

  1. Novara, Italy

    Gianni Bona

  2. Messina, Italy

    Filippo De Luca

  3. Division of Pediatrics, Piedemonte Hospital, Novara, Italy

    Alice Monzani

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© 2015 Springer International Publishing Switzerland

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Persani, L., Bonomi, M. (2015). Central Hypothyroidism. In: Bona, G., De Luca, F., Monzani, A. (eds) Thyroid Diseases in Childhood. Springer, Cham. https://doi.org/10.1007/978-3-319-19213-0_9

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  • DOI: https://doi.org/10.1007/978-3-319-19213-0_9

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19212-3

  • Online ISBN: 978-3-319-19213-0

  • eBook Packages: MedicineMedicine (R0)

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