, Volume 17, Issue 1, pp 7–12 | Cite as

Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia

  • C. Follin
  • T. Wiebe
  • C. Moëll
  • E. M. Erfurth


Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. The survival rate in the Scandinavian countries is now around 85 %. ALL patients treated with cranial radiotherapy (CRT) are at risk for growth hormone deficiency (GHD), but little is known about other pituitary insufficiencies, e.g. ACTH. Adult ALL patients (median age at study 25 years), treated with 24 Gy (18–30) of CRT during childhood were investigated. We performed an insulin tolerance test (ITT) to evaluate cortisol secretion. We measured basal serum ACTH and cortisol levels before and after 5 years of GH therapy. 14 out of 37 (38 %) ALL patients had a subnormal cortisol response to an ITT (257–478 nmol/L) while there was no significant difference in basal cortisol levels between 44 patients and controls (P > 0.3). Female, but not male ALL patients had significantly lower ACTH levels compared to controls (P = 0.03). After 5 years of GH therapy only male ALL patients had significantly lowered basal plasma cortisol (P = 0.02). ALL survivors, treated with a moderate dose CRT, have a central adrenal insufficiency 20 years after diagnosis. An increased awareness of the risk for an adrenal insufficiency is of importance and life-long surveillance of the entire hypothalamic–pituitary axis is recommended in these patients.


Childhood acute lymphoblastic leukaemia Cranial radiotherapy GH deficiency Central adrenal insufficiency 



Authors received grants from the Swedish Children’s Cancer Foundation, and the Medical Faculty, Lund University, Sweden.

Conflict of interest

Eva Marie Erfurth is a member of Eli Lilly & Company Advisory Board, all other authors have nothing to disclose.


  1. 1.
    Oeffinger KC, Eshelman DA, Tomlinson GE, Tolle M, Schneider GW (2000) Providing primary care for long-term survivors of childhood acute lymphoblastic leukemia. J Fam Pract 49:1133–1146PubMedGoogle Scholar
  2. 2.
    Shalet S, Beardwell CG, Pearson D (1976) The effect of varying doses of cerebral irradiation on growth hormone production in childhood. Clin Endocrinol (Oxf) 5:287–290CrossRefGoogle Scholar
  3. 3.
    Littley M, Shalet S, Beardwell C (1990) Radiation and hypothalamic–pituitary function. Baillieres Clin Endocrin Metab 4:147–175CrossRefGoogle Scholar
  4. 4.
    Brennan BMD, Rahim A, Mackie EM, Eden O, Shalet S (1998) Growth hormone status in adults treated for acute lymphoblastic leukaemia in childhood. Clin Endocrinol 48:777–783CrossRefGoogle Scholar
  5. 5.
    Link K, Moëll C, Garwicz S, Cavallin-Ståhl E, Björk J, Thilén U, Ahrén B, Erfurth EM (2004) Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukaemia in childhood. J Clin Endocrin Metab 89:5005–5012CrossRefGoogle Scholar
  6. 6.
    Follin C, Link K, Wiebe T, Moëll C, Björk J, Erfurth EM (2012) Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia. Clin Endocrinol (Oxf). doi: 10.1111/cen.12111
  7. 7.
    Oberfield SE, Nirenberg A, Allen J, Cohen H, Donahue B, Prasad V, Schiff R, Pang S, Ghavimi F, David R, Chrousos G, Sklar C (1997) Hypothalamic–pituitary–adrenal function following cranial irradiation. Horm Res 47:9–16PubMedCrossRefGoogle Scholar
  8. 8.
    Spoudeas HA, Charmandari E, Brook CGD (2003) Hypothalamo-Pituitary-Adrenal axis integrity after cranial irradiation for childhood posterior fossa tumours. Med Pediatr Oncol 40:224–229PubMedCrossRefGoogle Scholar
  9. 9.
    Rose S, Danish R, Kearny N, Schreiber R, Lustig R, Burghen G, Husdon M (2005) ACTH deficiency in childhood cancer survivors. Pediatr Blood Cancer 45:808–813PubMedCrossRefGoogle Scholar
  10. 10.
    Patterson B, Truxillo L, Wasilewski-Masker K, Mertens A, Meacham L (2009) Adrenal testing in pediatric cancer survivors. Pediatr Blood Cancer 53:1302–1307PubMedCrossRefGoogle Scholar
  11. 11.
    Crowne E, Wallace H, Gibson S, Moore M, White A, Shalet S (1993) Adrenocorticotrophin and cortisol secretion in children after low dose cranial irradiation. Clin Endocrinol 39:297–305CrossRefGoogle Scholar
  12. 12.
    Constine L, Wolf P, Cann D, Mick G, McCormick K, Raubertas R, Rubin P (1993) Hypothalamic–Pituitary dysfunction after radiation for brain tumours. N Engl J Med 328:87–94PubMedCrossRefGoogle Scholar
  13. 13.
    Heikens J, Michiels E, Behrendt H, Endert E, Bakker P, Fliers E (1998) Long-term Neuro-enocrine sequele after treatment for childhood medulloblastoma. Eur J Cancer 34:1592–1597PubMedCrossRefGoogle Scholar
  14. 14.
    Schmiegelow M, Feldt-Rasmussen U, Rasmussen A, Lange M, Poulsen H, Müller J (2003) Assessment of the hypothalamic–pituitary–adrenal axis in patients treated with radiotherapy and chemotherapy for childhood brain tumour. J Clin Endocrinol Metab 88:3149–3154PubMedCrossRefGoogle Scholar
  15. 15.
    Corneli G, Di Soma C, Baldelli R, Rovere S, Gasco V, Croce CG, Grottoli S, Maccario M, Colao A, Lombardi G, Ghigo E, Camanni F, Aimaretti G (2005) The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Euro J Endocrin 153:257–264CrossRefGoogle Scholar
  16. 16.
    Hurel SJ, Thompson CJ, Watson MJ, Harris MM, Baylis PH, Kendall-Taylor P (1996) The short Synacthen and insulin stress tests in the assessment of the hypothalamic–pituitary–adrenal axis. Clin Endocrinol 44:141–146CrossRefGoogle Scholar
  17. 17.
    Stewart PM, Murry BA, Mason JI (1994) Human kidney 11 beta-hydroxysteriod dehydrogenase is a high affinity nicotinamide adenine dinucleotide-dependent enzyme and differs from the cloned type I isoform. J Clin Endocrinol Metab 79:480–484PubMedGoogle Scholar
  18. 18.
    Giavoli C, Bergamaschi Ferrante E, Ronchi C, Lania A, Rusconi R, Spada A, Beck-Peccoz P (2008) 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 68:247–251Google Scholar
  19. 19.
    Giavoli C, Libé R, Corbetta S, Ferrante E, Lania A, Arosio M, Spada A, Beck-Peccoz P (2004) Effect of recombinant human growth hormone (GH) replacement on the hypothalamic–pituitary–adrenal axis in adult GH-deficient patients. J Clin Endocrinol Metab 89:5397–5401PubMedCrossRefGoogle Scholar
  20. 20.
    The growth hormone research society (GRS) (1998) Consensus guidelines for the diagnosis and treatment of adults with GH deficiency: summary statement of the GRS workshop on adults GHD. J Clin Endocrinol Metab 34:379–381Google Scholar
  21. 21.
    Darzy K, Aimaretti W, Gattamaneni R (2003) The usefulness of the combined growth hormone (GH)—releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab 88:95–102PubMedCrossRefGoogle Scholar
  22. 22.
    Children’s Oncology Group Guidelines (2008) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • C. Follin
    • 1
  • T. Wiebe
    • 2
  • C. Moëll
    • 2
  • E. M. Erfurth
    • 1
  1. 1.Department of EndocrinologySkåne University HospitalLundSweden
  2. 2.Department of PaediatricsSkåne University HospitalLundSweden

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