Surgical Indication after Bromocriptine Therapy on Giant Prolactinomas: Effects and Limitations of the Medical Treatment.

Abstract

Abstract.Bromocriptine (BC) is now an accepted primary therapeutic agent for patients with microadenoma. But, for patients with large or giant prolactinomas, the treatment choice is controversial. This report focuses on long-term results of the BC effect on 10 giant prolactinomas (maximum diameter more than 40 mm and the serum PRL level more than 1000 ng/mi) with particular emphasis on cases that needed surgical intervention due to unsatisfactory results from BC therapy alone. BC was effective in 6 cases (60%). They had the serum PRL level normalized in less than one year, with BC maintenance doses between 5-15 mg/day.MRI revealed complete or nearly total disappearance of the tumor. Discontinuation of the medicine was achieved in one patient. In the remaining 4 cases, surgery was needed for various reasons: l) BC resistant prolactinomas in 2 cases, 2) large hematomas in one of the previous cases, 3) regrowth of tumor size, despite the nearly normalized PRL level due to bulk increase in non-secretory adenomatous portion in 1 case, and 4) intolerable side effect in 1 case. BC is effective even for giant prolactinomas in 60% of cases. But, this therapy needs surgical intervention more often than microadenomas.Surgical indications and timing should be decided on based on closer follow-up of neuroimaging and visual evaluation as well as the serum PRL level.

THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas

“…We also observed a gender-related difference in the distribution of giant prolactinomas by decades of life (15). In men, the incidence peaks during the fourth decade of life and then decreases sharply, pointing towards a 'frailty' effect, whereas in women, the diagnosis period seems to have a bimodal distribution with an early-onset group of 11 patients with a median age at diagnosis of 25 years (range [15][16][17][18][19][20][21][22][23][24][25][26][27] (15,95) and a later onset group of 27 patients diagnosed at a median age of 50 years (range 37-87) (15,36,96,97). Early onset may reflect a stronger hereditary pathogenesis, and systematic search for MEN1 or AIP mutations would be interesting in this setting.…”

“…The mean time before improvement recorded in one study was 5 days (range 2-15 days) (7). Of note, an improvement of visual field defect can be observed even in the absence of significant tumour response (22,25).…”

“…In 14 cases (48%), the normalization of the visual field was complete. Improvement occurred promptly, sometimes 1 or 2 days after the initial administration of the DA (22). The mean time before improvement recorded in one study was 5 days (range 2-15 days) (7).…”

“…As serum hormone levels generally parallel tumour size, giant prolactinomas are typically associated with very high PRL concentrations, above 1000 mg/l (21 000 mU/l) (4,15,21). While most non-surgical series published in the literature indeed used this criterion of 1000 mg/l (7,12,15,20,22,23,24), higher cut-off levels of 2000 mg/l (25), 3000 mg/l (8) or even 4000 mg/l (11) have also been used. At the opposite, lower and more conservative PRL thresholds of 200 or 250 mg/l, similar to those used for non-giant macroprolactinomas, have also been proposed previously (6,26), although assay problems were mentioned in the latter report and accurate PRL concentrations were not available in some cases.…”

“…Correlation between baseline prolactin concentration (expressed on a log scale) and maximal tumour diameter recorded in 93 patients (data retrieved from references (7,8,15,20,22,23,25,26,76)). Closed triangle, men; closed circle, women.…”