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The evolution of radiation-induced growth hormone deficiency in adults is determined by the baseline growth hormone
A A Toogood1, W D Ryder, C G Beardwell
1Department of Endocrinology, Christie Hospital, Withington, Manchester, UK.
Objective:
Recent studies of GH replacement have suggested several beneficial effects for GH deficient adults. It would therefore be helpful to predict the time of onset of GH deficiency after external pituitary irradiation. We have studied the evolution of GH deficiency with time in patients irradiated for pituitary adenomas and other hypothalamic pituitary tumours.
Design:
Analysis of serial peak GH responses to insulin hypoglycaemia following external irradiation to the hypothalamic-pituitary axis using statistical models which allowed for age, sex, previous surgery and the pre-radiotherapy GH peak response.
Patients:
Eighty-five non-acromegalic adults (48 male), 75 of whom had either a pituitary adenoma or a craniopharyngioma and 10 who had other tumours in the hypothalamic-pituitary region. All the patients had received a radiation dose between 37.5 and 45 Gy divided into 15 fractions given over 21 days.
Measurements:
The GH responses to an insulin tolerance test (ITT) performed as part of the regular endocrine follow-up in patients who received irradiation to the hypothalamic-pituitary region.
Results:
Three hundred and forty-five ITTs were performed over a period of 10 years following radiotherapy. There was a decline in the modelled mean peak GH response to an ITT over the first 5 years which then appeared to plateau. Using an extended model, women had higher GH peak responses than men and this difference was maintained throughout the ten-year period. The magnitude of the post-radiotherapy peak GH response at any given time was dependent on the baseline peak GH response, but the rate of the decrease was not affected (P = 0.66). To develop severe GH deficiency (peak GH response less than 5 mU/l) after radiotherapy it took patients with baseline GH peaks of 30, 20 and 10 mU/l approximately 4 years, 3 years and 1 year respectively. Those patients with a baseline GH peak of greater than 50 mU/l are unlikely to develop severe GH deficiency within the first 5 years following radiotherapy.
Conclusion:
These results provide an insight into the pattern of the decline in GH secretion following radiotherapy in patients with pituitary disease and the factors affecting it. This information will help the clinician predict the frequency and timing of GH deficiency in patients irradiated for pituitary disease and the potential need for GH replacement therapy.