Endocrine Abstracts

Acute lymphoblastic leukaemia is the commonest malignancy to occur during childhood. Treatment protocols included prophylactic cranial radiotherapy at doses of 18-24Gy. Radiation to the hypothalamic-pituitary axis causes hypopituitarism, the severity of which depends upon the dose and time from treatment. Adults who received 24Gy up to 25 years ago have been shown to be GH deficient, those who received 18Gy were not. Other pituitary function was reported be normal. The purpose of this study was to determine whether patients are at risk of hypopituitarism up to 30 years after treatment for ALL.

We studied 29 adults (17F) treated for ALL between 1972-1989; 13 received 24Gy and 16 received 18Gy of prophylactic cranial irradiation. Blood was drawn for assessment of gonadotrophins, sex steroids, prolactin, TSH, fT₄, and IGF-I. All patients underwent an arginine stimulation test and either an insulin tolerance test (ITT) (n=27) or a glucagon stimulation test (GST) (n=2).

At the time of testing the median age of the patients was 27.5 years (range 19.1-40.4), body mass index 26.2kg/m² (17.5-45.2) and time since irradiation was 22.0 years (13.7-31.3). Thyroid function and prolactin levels were normal in all patients. One woman developed amenorrhoea aged 15, otherwise there was no evidence of gonadotrophin deficiency. Ten patients had a peak GH response consistent with severe GH deficiency; two had received 18Gy of radiation 17.5 and 21 years following treatment. Serum IGF-I correlated with GH response to ITT (r=-0.57, P=0.002) and was lower in those with GH deficiency. Two patients that received 24Gy had suboptimal cortisol responses 27.6 and 28.5 years following treatment.

These findings suggest that patients who received low dose cranial irradiation (18Gy) during childhood are at risk of GH deficiency, while those treated earlier (24Gy) may be at risk of other pituitary hormone deficiencies, particularly ACTH deficiency.