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

Abstract

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 25years), treated with 24Gy (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 5years of GH therapy. 14 out of 37 (38%) ALL patients had a subnormal cortisol response to an ITT (257-478nmol/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 5years 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 20years 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.