OBJECTIVE To determine the long-term effects of external beam megavoltage
radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in
prolactinomas. DESIGN Longitudinal study following
radiotherapy with periodic re-assessment at regular intervals, at least 2 months off
dopamine agonist therapy. PATIENTS Thirty-six female patients, age range 19-50 years, with either
macroprolactinomas (12 patients) or
microprolactinomas (24 patients), but without significant suprasellar extensions. MEASUREMENTS Clinical appraisal, and anterior and posterior pituitary assessment: basal levels at yearly intervals or less, with dynamic screening with TRH,
LHRH and hypoglycaemic stimulation every 2-3 years. RESULTS Before RT, serum
prolactin (PRL) levels ranged from 1150 to 34,000 mU/l; after RT (mean 8.5 years, range 3-14), serum PRL fell to normal (i.e. less than 360 mU/l) in 18 of the 36 patients (50%), and to just above the normal range (378-780 mU/l) in a further 10 (28%). Two patients had PRL levels at their last follow-up higher than those at presentation, with one patient showing evidence of tumour recurrence on CT scan. A total of eight of the 36 patients (23%) developed post-RT gonadal deficiency by the end of follow-up at 8 +/- 3.1 years (+/- SD, range 3-11), but six were aged over 40 years at that time. GH deficiency was frequent, occurring in 94% of patients, usually from 2 to 3 years post-RT, while
TSH deficiency and reduced
ACTH reserve was uncommon (each 14%), and occurred later. In the subgroup of 12 patients with
macroprolactinomas, results were broadly comparable. CONCLUSIONS Megavoltage RT produces a progressive fall in serum
prolactin in the great majority of patients with
prolactinomas, with a relatively low incidence of TSH or
ACTH deficiency. As it is now clear that
dopamine agonist therapy alone provides sufficient management for
microprolactinomas, RT may be used for the long-term control of
macroprolactinomas, together with interim
dopamine agonist therapy. It allows pregnancy to be safely undertaken but, in view of the delayed onset of gonadal deficiency, its administration should be timed with respect to the desired onset of conception in women.