Use of the Leksell Gamma Knife in the Treatment of Prolactinoma Patients

Abstract

The current treatment of choice for prolactinomas is pharmacologic therapy with dopamine agonists (DA). However, these drugs must be taken long-term or even life-long, and they are unsuccessful in adenoma patients who are resistant to or intolerant of DA. Other options in such patients include surgical treatment or radiosurgery with the Leksell gamma knife (LGK). This non-randomized trial was designed to examine the effectiveness of LGK irradiation in treating prolactinoma patients who were resistant to or intolerant of DA. A secondary aim was to investigate the effect of LGK in improving the effects of DA on the size of adenomas, shortening the length of administration of DA, and normalizing prolactin levels permanently. The study population was comprised of 35 patients with prolactin secreting pituitary adenomas (27 females and 8 males), with an average age of 40.3 years (range: 18-71). Nine of the 35 patients (25.7%) had microprolactinomas and 26 of the 35 (74.3%) had macroprolactinomas. The mean ± SD follow-up period was 75.5 ± 34.4 months. Twenty-five patients (71.4%) received only pharmacologic therapy with DA before LGK and 10 patients (28.6%) underwent pituitary adenoma surgery in addition to DA therapy. LGK irradiation was indicated because of drug intolerance (31.4%), partial or complete DA resistance (45.7%), and attempts to shorten the period of treatment with DA or reduce the dosage (22.9%). Pituitary function was monitored regularly by measuring hormone levels at 6-month intervals. The median central radiation dose was 70 Gy (range: 40-80 Gy) and the median minimal peripheral dose was 34 Gy (range: 20-49 Gy). Normoprolactinemia was achieved in 80% (28/35) of the study patients. This included 37.1% (13/35 patients) who discontinued DA treatment and 42.9% (15/35 patients) who continued DA treatment after irradiation. After discontinuation of DA in the study subjects, the median time for hormonal normalization was 96 months. None of the patients achieving normoprolactinemia with LGK experienced any disease relapse. Only 1 patient (2.5%) experienced further growth of the adenoma after LGK irradiation. These findings suggest that LGK may achieve normoprolactinemia in 80.0% of the patients with pituitary adenomas who fail pharmacological therapy due to resistance to, or intolerance of, DAs and insufficient response to DA before radiation. The absence of relapse after normalization with LGK contrasts with DA therapy which produces a permanent remission in less than 50% of patients after discontinuation.