Moderate dose cranial radiotherapy causes central adrenal insufficiency in long-term survivors of childhood leukaemia
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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.
KeywordsChildhood 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.
- 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
- 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
- 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
- 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.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.Children’s Oncology Group Guidelines (2008) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. www.survivorshipguidlines.org