Giant prolactinomas in men: efficacy of cabergoline treatment.
OBJECTIVE
The term 'giant prolactinoma' can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long-lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro- and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas.


METHODS
Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage.


RESULTS
In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy.


CONCLUSIONS
These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.
Corsello
S M
SM
Institute of Endocrinology, Catholic University School of Medicine, Rome, Italy. corsello.sm@mclink.it
Ubertini
G
G
Altomare
M
M
Lovicu
R M
RM
Migneco
M G
MG
Rota
C A
CA
Colosimo
C
C
D000311:Adrenal Glands / Q000187:drug effects; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077465:Cabergoline; D007172:Erectile Dysfunction / Q000188:drug therapy; D004873:Ergolines / Q000627:therapeutic use*; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000209:etiology; D007989:Libido / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000503:physiopathology; D010911:Pituitary Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014786:Vision Disorders / Q000150:complications / Q000188:drug therapy
D000970:Antineoplastic Agents; D004873:Ergolines; D011388:Prolactin; D000077465:Cabergoline