, Volume 10, Issue 4, pp 365–371 | Cite as

Diagnosis and treatment of pediatric Cushing’s disease

  • Martin O. Savage
  • Helen L. Storr
  • Li F. Chan
  • Ashley B. Grossman


Cushing’s disease (CD) is rare in the pediatric age range, but may present a diagnostic and therapeutic challenge. Most pediatric endocrinologists have limited experience managing children or adolescents with CD and thus benefit from close consultation with adult colleagues. A diagnostic protocol for investigation is required which broadly follows the model for adult patients. Treatment strategies for CD are described and critically appraised. The management of pediatric CD patients after cure also presents challenges for optimizing growth, bone health, reproduction and body composition from childhood into and during adult life


Cushing’s disease Cushing’s syndrome Hypercortisolism Pituitary 


  1. 1.
    Magiakou MA, Chrousos GP (2002) Cushing’s syndrome in children and adolescents: current diagnostic and therapeutic strategies. J Endocrinol Invest 25:181–194PubMedGoogle Scholar
  2. 2.
    Storr HL et al (2007) Paediatric cushing’s syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol Metab 18:167–174PubMedCrossRefGoogle Scholar
  3. 3.
    Magiakou MA et al (1994) Cushing’s syndrome in children and adolescents. Presentation, diagnosis and therapy. New Eng J Med 331:629–636PubMedCrossRefGoogle Scholar
  4. 4.
    Weber A et al (1995) Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing’s syndrome. Clin Endocrinol 43:19–28Google Scholar
  5. 5.
    Fahlbusch R et al (1994) Neurosurgical management of Cushing’s disease in children. In: Savage MO, Bourguignon JP, Grossman AB (eds) Frontiers of paediatric neuroendocrinology. Blackwell Scientific Publications, Oxford, pp 68–72Google Scholar
  6. 6.
    Storr HL et al (2005) Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing’s disease. Eur J Endocrinol 152:825–833PubMedCrossRefGoogle Scholar
  7. 7.
    Khadilkar VV et al (2004) Cushing’s disease in an 11-month-old child. Indian Pediatr 41:274–276PubMedGoogle Scholar
  8. 8.
    Damiani D et al (1998) Pituitary macroadenoma and Cushing’s disease in pediatric patients: patient report and review of the literature. J Ped Endocrinol Metab 11:665–669Google Scholar
  9. 9.
    Stratakis CA et al (2000) Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 85:4776–4780PubMedCrossRefGoogle Scholar
  10. 10.
    Besser GM, Trainer PJ (2002) Cushing’s syndrome. In: Besser GM, Thorner MO (eds) Comprehensive clinical endocrinology, 3rd edn. Edinburgh: Mosby, pp 193–202Google Scholar
  11. 11.
    Giraldi FP et al (2003) Gender-related differences in the presentation and course of Cushing’s disease. J Clin Endocrinol Metab 80:3818–3820Google Scholar
  12. 12.
    Leinung MC et al (1995) Long-term follow-up of transsphenoidal surgery for the treatment of Cushing’s disease in childhood. J Clin Endocrinol Metab 80:2475–2479PubMedCrossRefGoogle Scholar
  13. 13.
    Devoe DJ et al (1997) Long term outcome in children and adolescents after trans-sphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 82:3196–3202PubMedCrossRefGoogle Scholar
  14. 14.
    Storr HL et al (2004) Pre-pubertal Cushing’s is more common in males, but there is no increase in severity at diagnosis. J Clin Endocrinol Metab 89:3818–3820PubMedCrossRefGoogle Scholar
  15. 15.
    Greening JE et al (2006) Linear growth and body mass index in paediatric patients with Cushing’s disease or simple obesity. J Endocrinol Invest 29:885–887PubMedGoogle Scholar
  16. 16.
    Peters CJ et al (2007) Factors influencing skeletal maturation at diagnosis of paediatric Cushing’s disease. Horm Res 68:231–235CrossRefGoogle Scholar
  17. 17.
    Dupuis C et al (2007) Abnormal puberty in paediatric Cushing’s disease; relationships with adrenal androgens, sex hormone binding globulin and gonadotrophin concentrations. Clin Endocrinol 66:838–843CrossRefGoogle Scholar
  18. 18.
    Hauffa B et al (1984) Dissociation between plasma adrenal androgens and cortisol in Cushing’s disease and ectopic ACTH-producing tumour: relation to adrenarche. Lancet 1:1373–1376PubMedCrossRefGoogle Scholar
  19. 19.
    Newell-Price J et al (1998) The diagnosis and differential diagnosis of Cushing’s and pseudo-Cushing;s syndrome. Endocrin Rev 19:647–672CrossRefGoogle Scholar
  20. 20.
    Arnaldi G et al (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88:5593–5602PubMedCrossRefGoogle Scholar
  21. 21.
    Peters CJ et al (2006) The role of corticotrophin-releasing hormone in the diagnosis of Cushing’s syndrome. Eur J Endocrinol 155:S93–S98CrossRefGoogle Scholar
  22. 22.
    Isidori A et al (2003) Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 88:5299–5306PubMedCrossRefGoogle Scholar
  23. 23.
    Dias R et al (2006) The discriminatory value of the low-dose dexamethasone suppression test in the investigation of paediatric Cushing’ syndrome. Horm Res 65:159–162PubMedCrossRefGoogle Scholar
  24. 24.
    Oldfield EH et al (1991) Petrosal sinus sampling with corticotropin-releasing hormone to distinguish Cushing’s disease from pseudo-Cushing’s states or normal physiology. New Eng J Med 325:897–905PubMedCrossRefGoogle Scholar
  25. 25.
    Lienhardt A et al (2001) Relative contributions of inferior petrosal sinus sampling and pituitary imaging in the investigation of children and adolescents with ACTH-dependent Cushing’s syndrome. J Clin Endocrinol Metab 86:5711–5714PubMedCrossRefGoogle Scholar
  26. 26.
    Batista D et al (2006) An assessment of petrosal sinus sampling for localisation of pituitary microadenomas in children with Cushing disease. J Clin Endocrinol Metab 91:221–224PubMedCrossRefGoogle Scholar
  27. 27.
    Hopwood NJ, Kenny FM (1977) Incidence of Nelson’s syndrome after adrenalectomy for Cushing’s disease in children: results of a nationwide survey. Am J Dis Child 131:1353–1356PubMedGoogle Scholar
  28. 28.
    McArthur RG et al (1979) Childhood Cushing disease: results of bilateral adrenalectomy. J Pediatr 95:214–219PubMedCrossRefGoogle Scholar
  29. 29.
    Greening JE et al (2005) Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing’s syndrome. Horm Res 64:140–143PubMedCrossRefGoogle Scholar
  30. 30.
    Massoud AF et al (1997) Transsphenphoidal surgery for pituitary tumours. Arch Dis Child 76:398–404PubMedCrossRefGoogle Scholar
  31. 31.
    Knappe UJ, Ludecke DK (1996) Transnasal microsurgery in children and adolescents with Cushing’s disease. Neurosurgery 39:484–493PubMedCrossRefGoogle Scholar
  32. 32.
    Kanter AS et al (2005) Single-center experience with pediatric Cushing’s disease. J Neurosurgery 103(5 Suppl):413–420Google Scholar
  33. 33.
    Joshi SM et al (2005) Cushing’s disease in children and adolescents: 20 years of experience in a single neurosurgical centre. Neurosurgery 57:281–285PubMedCrossRefGoogle Scholar
  34. 34.
    Trainer PJ et al (1993) Transsphenoidal resection in Cushing’s disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol 56:25–31Google Scholar
  35. 35.
    Magiakou MA et al (1994) Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure. J Clin Endocrinol Metab 78:131–137PubMedCrossRefGoogle Scholar
  36. 36.
    Linglart A, Visot A (2002) Cushing’s disease in children and adolescents. Neurochirurgie 48:271–280PubMedGoogle Scholar
  37. 37.
    Styne DM et al (1984) Treatment of Cushing’s syndrome in childhood and adolescence by transsphenoidal microadenomectomy. New Eng J Med 310:889–893PubMedCrossRefGoogle Scholar
  38. 38.
    Jennings AS et al (1977) Results of treating childhood Cushing’s disease with pituitary irradiation. New Eng J Med 297:957–962PubMedCrossRefGoogle Scholar
  39. 39.
    Thoren M et al (1986) Treatment of Cushing’s disease in childhood and adolescence by stereotactic pituitary irradiation. Acta Pæd Scand 75:388–395Google Scholar
  40. 40.
    Storr HL et al (2003) Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing’s disease. J Clin Endocrinol Metab 88:34–37PubMedCrossRefGoogle Scholar
  41. 41.
    Plowman PN (1997) Pituitary radiotherapy: techniques and potential complications. In Jenkins PJ, Wass JAH, Sheaves R (eds) Clinical endocrine oncology. Blackwell Scientific Publications, Oxford, pp 185–188Google Scholar
  42. 42.
    Chan L et al (2007) Long-term anterior pituitary function in patients with paediatric Cushing’s disease treated with pituitary radiotherapy. Eur J Endocrinol 156:477–482PubMedCrossRefGoogle Scholar
  43. 43.
    Nicholl RM et al (1993) Acceleration of pubertal development following pituitary radiotherapy for Cushing’s disease. Clin Oncol 3:393–394CrossRefGoogle Scholar
  44. 44.
    Lebrethon MC et al (2000) Linear growth and final height after treatment of Cushing’s disease in childhood. J Clin Endocrinol Metab 85:3262–3265PubMedCrossRefGoogle Scholar
  45. 45.
    Magiakou MA et al (1994) Final stature in patients with endogenous Cushing’s syndrome. J Clin Endocrinol Metab 79:1082–1085PubMedCrossRefGoogle Scholar
  46. 46.
    Davies JH et al (2005) Final adult height and body mass index after cure of paediatric Cushing’s disease. Clin Endocrinol 62:466–472CrossRefGoogle Scholar
  47. 47.
    Carroll PV et al (2005) Successful treatment of childhood-onset Cushing’s disease is associated with persistent reduction in growth hormone secretion. Clin Endocrinol 60:169–174CrossRefGoogle Scholar
  48. 48.
    Leong GM et al (2007) 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 22:110–118PubMedCrossRefGoogle Scholar
  49. 49.
    Scommegna S et al (2005) Bone mineral density at diagnosis and following successful treatment of disease. J Endocrinol Invest 28:231–235PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Martin O. Savage
    • 1
  • Helen L. Storr
    • 1
  • Li F. Chan
    • 1
  • Ashley B. Grossman
    • 1
  1. 1.Department of Endocrinology, William Harvey Research InstituteBarts and the London School of Medicine and DentistryLondonUK

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