Skip to main content
SpringerLink
Log in
Book cover

Cushing's Disease pp 197–210Cite as

Diagnosis and Treatment of Pediatric Cushing’s Disease

  • Chapter
  • First Online:

  • 1511 Accesses

Part of the book series: Endocrine Updates ((ENDO,volume 31))

Abstract

Cushing’s disease (CD), which is caused by an ACTH-secreting pituitary corticotroph adenoma, is the commonest cause of Cushing’s syndrome in children over 5 years of age. However, it remains rare in the pediatric age range and may present a difficult diagnostic and therapeutic challenge. Key presenting features include weight gain associated with growth failure. Parents and general practitioners frequently fail to appreciate the nature of the pathology, significantly delaying diagnosis. Most pediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. We describe a diagnostic protocol for investigation that broadly follows the model for adult patients. Treatment strategies for CD are examined and critically appraised. The management of pediatric CD patients after cure is also discussed, as it presents unique challenges for optimizing growth, bone health, reproduction, and body composition from childhood into and during adult life.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

References

  1. Magiakou MA, Chrousos GP. Cushing’s syndrome in children and adolescents: current diagnostic and therapeutic strategies. J Endocrinol Invest. 2002;25(2):181–94.

    PubMed  CAS  Google Scholar 

  2. Savage MO, Besser GM. Cushing’s disease in childhood. Trends Endocrinol Metab. 1996;7(6):213–6.

    Article  PubMed  CAS  Google Scholar 

  3. Magiakou MA et al. Cushing’s syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med. 1994;331(10):629–36.

    Article  PubMed  CAS  Google Scholar 

  4. Weber A et al. Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing’s syndrome. Clin Endocrinol (Oxf). 1995;43(1):19–28.

    Article  CAS  Google Scholar 

  5. Fahlbusch R. Neurosurgical management of Cushing’s disease in children. In: Savage MO, Bourguignon J-P, Grossman AB, editors. Frontiers of pediatric neuroendocrinology. Oxford: Blackwell Scientific; 1995. p. 68–72.

    Google Scholar 

  6. Storr HL et al. Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing’s disease. Eur J Endocrinol. 2005;152(6):825–33.

    Article  PubMed  CAS  Google Scholar 

  7. Khadilkar VV, Khadilkar AV, Navrange JR. Cushing’s disease in an 11-month-old child. Indian Pediatr. 2004;41(3):274–6.

    PubMed  CAS  Google Scholar 

  8. Damiani D et al. Pituitary macroadenoma and Cushing’s disease in pediatric patients: patient report and review of the literature. J Pediatr Endocrinol Metab. 1998;11(5):665–9.

    Article  PubMed  CAS  Google Scholar 

  9. Stratakis CA et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85(12):4776–80.

    Article  PubMed  CAS  Google Scholar 

  10. Besser G, Trainer PJ. Cushing’s syndrome. In: Besser GM, Thorner MO, editors. Comprehensive clinical endocrinology. 3rd ed. Edinburgh: Mosby; 2002.

    Google Scholar 

  11. Storr HL et al. Prepubertal Cushing’s disease is more common in males, but there is no increase in severity at diagnosis. J Clin Endocrinol Metab. 2004;89(8):3818–20.

    Article  PubMed  CAS  Google Scholar 

  12. Magiakou MA et al. Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure. J Clin Endocrinol Metab. 1994;78(1):131–7.

    Article  PubMed  CAS  Google Scholar 

  13. Magiakou MA, Mastorakos G, Chrousos GP. Final stature in patients with endogenous Cushing’s syndrome. J Clin Endocrinol Metab. 1994;79(4):1082–5.

    Article  PubMed  CAS  Google Scholar 

  14. Greening JE et al. Linear growth and body mass index in pediatric patients with Cushing’s disease or simple obesity. J Endocrinol Invest. 2006;29(10):885–7.

    PubMed  CAS  Google Scholar 

  15. Peters CJ et al. Factors influencing skeletal maturation at diagnosis of paediatric Cushing’s disease. Horm Res. 2007;68(5):231–5.

    Article  PubMed  CAS  Google Scholar 

  16. Dupuis CC et al. Abnormal puberty in paediatric Cushing’s disease: relationship with adrenal androgen, sex hormone binding globulin and gonadotrophin concentrations. Clin Endocrinol (Oxf). 2007;66(6):838–43.

    Article  CAS  Google Scholar 

  17. Hauffa BP, Kaplan SL, Grumbach MM. Dissociation between plasma adrenal androgens and cortisol in Cushing’s disease and ectopic ACTH-producing tumour: relation to adrenarche. Lancet. 1984;1(8391):1373–6.

    Article  PubMed  CAS  Google Scholar 

  18. Newell-Price J et al. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev. 1998;19(5):647–72.

    Article  PubMed  CAS  Google Scholar 

  19. Arnaldi G et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab. 2003;88(12):5593–602.

    Article  PubMed  CAS  Google Scholar 

  20. Nieman LK et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:1526–40.

    Google Scholar 

  21. Batista DL et al. Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics. 2007;120(3):e575–86.

    Article  PubMed  Google Scholar 

  22. Martinelli Jr CE et al. Salivary cortisol for screening of Cushing’s syndrome in children. Clin Endocrinol (Oxf). 1999;51(1):67–71.

    Article  Google Scholar 

  23. Dias R et al. The discriminatory value of the low-dose dexamethasone suppression test in the investigation of paediatric Cushing’s syndrome. Horm Res. 2006;65(3):159–62.

    Article  PubMed  CAS  Google Scholar 

  24. Oldfield EH et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med. 1991;325(13):897–905.

    Article  PubMed  CAS  Google Scholar 

  25. Batista D et al. An assessment of petrosal sinus sampling for localization of pituitary microadenomas in children with Cushing disease. J Clin Endocrinol Metab. 2006;91(1):221–4.

    Article  PubMed  CAS  Google Scholar 

  26. Hopwood NJ, Kenny FM. Incidence of Nelson’s syndrome after adrenalectomy for Cushing’s disease in children: results of a nationwide survey. Am J Dis Child. 1977;131(12):1353–6.

    PubMed  CAS  Google Scholar 

  27. McArthur RG, Hayles AB, Salassa RM. Childhood Cushing disease: results of bilateral adrenalectomy. J Pediatr. 1979;95(2):214–9.

    Article  PubMed  CAS  Google Scholar 

  28. Greening JE et al. Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing’s disease. Horm Res. 2005;64(3):140–3.

    Article  PubMed  CAS  Google Scholar 

  29. Massoud AF et al. Transsphenoidal surgery for pituitary tumours. Arch Dis Child. 1997;76(5):398–404.

    Article  PubMed  CAS  Google Scholar 

  30. Knappe UJ, Ludecke DK. Transnasal microsurgery in children and adolescents with Cushing’s disease. Neurosurgery. 1996;39(3):484–92. discussion 492–3.

    PubMed  CAS  Google Scholar 

  31. Kanter AS et al. Single-center experience with pediatric Cushing’s disease. J Neurosurg. 2005;103(5 Suppl):413–20.

    PubMed  Google Scholar 

  32. Joshi SM et al. Cushing’s disease in children and adolescents: 20 years of experience in a single neurosurgical center. Neurosurgery. 2005;57(2):281–5. discussion 281–5.

    Article  PubMed  Google Scholar 

  33. Linglart A, Visot A. Cushing’s disease in children and adolescents. Neurochirurgie. 2002;48(2–3 Pt 2):271–80.

    PubMed  CAS  Google Scholar 

  34. Trainer PJ et al. Transsphenoidal resection in Cushing’s disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf). 1993;38(1):73–8.

    Article  CAS  Google Scholar 

  35. Leinung MC et al. Long term follow-up of transsphenoidal surgery for the treatment of Cushing’s disease in childhood. J Clin Endocrinol Metab. 1995;80(8):2475–9.

    Article  PubMed  CAS  Google Scholar 

  36. Devoe DJ et al. Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab. 1997;82(10):3196–202.

    Article  PubMed  CAS  Google Scholar 

  37. Styne DM et al. Treatment of Cushing’s disease in childhood and adolescence by transsphenoidal microadenomectomy. N Engl J Med. 1984;310(14):889–93.

    Article  PubMed  CAS  Google Scholar 

  38. Storr HL et al. Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing’s disease: an effective second-line treatment. J Clin Endocrinol Metab. 2003;88(1):34–7.

    Article  PubMed  CAS  Google Scholar 

  39. Plowman PN. Pituitary radiotherapy: techniques and potential complications. In: Jenkins PJ, Wass JAH, Sheaves R, editors. Clinical endocrine oncology. Oxford: Blackwell Science Publications; 1997. p. 185–8.

    Google Scholar 

  40. Jennings AS, Liddle GW, Orth DN. Results of treating childhood Cushing’s disease with pituitary irradiation. N Engl J Med. 1977;297(18):957–62.

    Article  PubMed  CAS  Google Scholar 

  41. Thoren M et al. Treatment of Cushing’s disease in childhood and adolescence by stereotactic pituitary irradiation. Acta Paediatr Scand. 1986;75(3):388–95.

    Article  PubMed  CAS  Google Scholar 

  42. Lebrethon MC et al. Linear growth and final height after treatment for Cushing’s disease in childhood. J Clin Endocrinol Metab. 2000;85(9):3262–5.

    Article  PubMed  CAS  Google Scholar 

  43. Hayles AB et al. Hormone-secreting tumors of the adrenal cortex in children. Pediatrics. 1966;37(1):19–25.

    PubMed  CAS  Google Scholar 

  44. Davies JH et al. Final adult height and body mass index after cure of paediatric Cushing’s disease. Clin Endocrinol (Oxf). 2005;62(4):466–72.

    Article  CAS  Google Scholar 

  45. Leong GM et al. Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study into young adulthood. J Bone Miner Res. 2007;22(1):110–8.

    Article  PubMed  Google Scholar 

  46. Scommegna S et al. Bone mineral density at diagnosis and following successful treatment of pediatric Cushing’s disease. J Endocrinol Invest. 2005;28(3):231–5.

    PubMed  CAS  Google Scholar 

  47. Chan LF et al. Long-term anterior pituitary function in patients with paediatric Cushing’s disease treated with pituitary radiotherapy. Eur J Endocrinol. 2007;156(4):477–82.

    Article  PubMed  CAS  Google Scholar 

  48. Dorn LD et al. The longitudinal course of psychopathology in Cushing’s syndrome after correction of hypercortisolism. J Clin Endocrinol Metab. 1997;82(3):912–9.

    Article  PubMed  CAS  Google Scholar 

  49. Merke DP et al. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab. 2005;90(5):2531–6.

    Article  PubMed  CAS  Google Scholar 

  50. McEwen BS. Cortisol, Cushing’s syndrome, and a shrinking brain-new evidence for reversibility. J Clin Endocrinol Metab. 2002;87(5):1947–8.

    Article  PubMed  CAS  Google Scholar 

  51. Keil MF et al. Quality of life in children and adolescents 1-year after cure of Cushing syndrome: a prospective study. Clin Endocrinol (Oxf). 2009;71(3):326–33.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK

    Claire R. Hughes, Helen L. Storr & Ashley B. Grossman

  2. Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK

    Martin O. Savage

Authors
  1. Claire R. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Helen L. Storr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashley B. Grossman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin O. Savage
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martin O. Savage .

Editor information

Editors and Affiliations

  1. Massachusetts General Hospital, Dept. Neurosurgery, Harvard Medical School, Parkman St. 15, Boston, 02114, Massachusetts, USA

    Brooke Swearingen

  2. Neuroendocrine Clinical Centre, Massachusetts General Hospital, Fruit St. 55, Boston, 02114, Massachusetts, USA

    Beverly M. K. Biller

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hughes, C.R., Storr, H.L., Grossman, A.B., Savage, M.O. (2011). Diagnosis and Treatment of Pediatric Cushing’s Disease. In: Swearingen, B., Biller, B. (eds) Cushing's Disease. Endocrine Updates, vol 31. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0011-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-0011-0_14

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4614-0010-3

  • Online ISBN: 978-1-4614-0011-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation