SummaryBackgroundAcute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population.ObjectiveTo study the long‐term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients and the prevalence of lactation failure.DesignCase–control study.PatientsWe examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range: 8–27) after ALL diagnosis and 44 matched population controls.MeasurementsPRL secretion (area under the curve; AUC) after GHRH‐arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH‐test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy.ResultsCompared with controls, ALL patients had significantly lower basal and AUC PRL after GHRH‐Arginine (P = 0·03, P = 0·02), and AUC PRL after TRH (P = 0·001). After 5 and 8 years, PRL levels decreased further (P = 0·01, P = 0·03), but thyroid hormones remained normal at baseline and at follow‐up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure.ConclusionsLong‐term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk.