Growth hormone releasing hormone plus arginine stimulation testing in young adults treated in childhood with cranio-spinal radiation therapy

Abstract

Summary: Objective Growth hormone deficiency (GHD) secondary to cranio‐spinal radiation therapy (CSRT) is a complication seen in medulloblastoma survivors. The standard for diagnosis of adult GHD is a peak GH < 3 µg/l by the insulin tolerance test (ITT). However, insulin tolerance testing exposes patients to the risks of hypoglycaemia. Recent studies suggest that the GH releasing hormone + arginine (GHRH + ARG) test can identify GHD in cranially irradiated patients at longer time intervals after radiation. We evaluated the GHRH + ARG stimulation test compared to the ITT in young adults diagnosed with medulloblastoma during childhood. Patients We evaluated 10 young adult patients (age range 17–26 years) who were treated with CSRT during childhood for medulloblastoma, and who had resultant childhood‐onset GHD. Measurements Subjects underwent GH provocative testing with the ITT and the GHRH + ARG test. IGF‐I and IGFBP3 levels were also measured at baseline. Results Insulin tolerance testing and GHRH + arginine stimulation were performed at a mean ± SD 14 ± 4·4 years after cranial radiation. All patients failed the ITT with median peak GH 0·40 µg/l (range < 0·05–2·2). GHRH + arginine gave higher peak GH levels with a mean of 7·9 ± 5·7 µg/l (P = 0·003). Four patients had peak GH > 9 µg/l and were between 7·8 and 19·6 years from cranial radiation. There was no correlation of peak GH levels with time interval since CSRT. Thirty‐three per cent of subjects had normal IGF‐I; neither IGF‐I nor IGFBP3 standard deviation scores (SDS) correlated with ITT results. Conclusions Using a GHRH + arginine cut‐off for GHD of 9 µg/l, four patients would have been misclassified as GH sufficient, despite being > 7 years (with two patients being nearly 20 years) out from CSRT. These findings suggest that the pituitary GH‐producing cells of young adults continue to maintain responsiveness to GHRH + arginine more than 5–10 years after cranial irradiation.