Long-term Efficacy of Bromocriptine in Macroprolactinomas and Giant prolactinomas in Men

Abstract

We prospectively analyzed presentations and long-term therapeutic responses to bromocriptine (BRC) in 29 newly diagnosed men with macroprolactinomas including 14 patients with 'giant prolactinoma'. Clinical symptoms, prolactin (PRL) levels and tumor size on MRI were measured before BRC and sequentially thereafter. The duration of follow-up were 6 to 96 (30.7 +/- 14.4) months. Pretreatment PRL ranged between 124 and 29200 ng/mL (1698 +/- 857.1) and tumor volume was between 2.81 and 132 cm(3) (21.1 +/- 24.3). Baseline PRL levels did not correlated with tumor volume (r = 0.45, P > 0.05). Significant decrease (P = 0.0003) in PRL, at least 96% of the pretreatment value from 1698 +/- 857.1 ng/mL to 42.4 +/- 30.6 ng/mL occurred in 26 patients. Persistent normalization of PRL levels (< 16 ng/mL) for at least 6 months was achieved in 12 patients (40.8%). Twenty-two patients (74.8%) achieved significant tumor shrinkage (P = 0.005) at study completion. An improvement in visual field defects (VFD) and restoration of libido and potency was observed in 40% and 33.3%, respectively. Trans-sphenoidal / trans-frontal pituitary surgery was performed in 9 patients (31%) for various reasons: pituitary apoplexy in 1, CSF rhinorrhea in 2, increasing prolactin in spite of BRC therapy in 3, and intolerant /resistant to BRC in 3 patients. These data suggest that, in male macro- and giant prolactinomas, dopamine agonists represent the first-line therapy effective in reducing PRL, restoration of libido and potency, improvement of VFD and determining tumor shrinkage.

THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas

“…When very large prolactinomas extend laterally in the cavernous sinus, they will frequently cause cranial nerve palsies (30,47,48,49). The VI (or abducens) nerve is usually involved first, typically resulting in a binocular horizontal diplopia that worsens with gaze.…”

“…Spontaneous CSF rhinorrhoea may occur but is rather uncommon in untreated giant prolactinomas, being most often induced by surgery or by a too effective medical treatment causing rapid tumour shrinkage (8,47,50). In a review of existing literature, Lam et al (51) recently reported 52 patients with non-surgically induced CSF leaks in the setting of a pituitary adenoma.…”

“…By comparison, hormone resistance rates previously reported in invasive macroprolactinomas were 33% with BRC (78) and 24% with CAB (75). Tumour shrinkage and hormonal response being independent of tumour size or pretreatment PRL levels, the treatment protocol used for macroprolactinomas (79) can be applied to giant prolactinomas, and it is not advised to start with a higher dose and/or to increase it more rapidly as some patients may normalize PRL levels rapidly and show massive tumour size reduction, which may favour CSF leakage or apoplexia (47). Regarding the type of DA, even though there is no proof of a higher efficacy of CAB over BRC in the management of giant prolactinomas, CAB is certainly better tolerated and generally recommended as first-line treatment.…”

“…Hormonal resistance was defined by the absence of normalization of serum prolactin levels despite a cabergoline dose R2.0 mg/week or a bromocriptine dose R15 mg/day. surgical indication in this selected series but may occur either in the natural course of the disease or as a complication of medical treatment (47,58,84,85). Debulking surgery was carried out because of insufficient tumour response in six patients, after 3-48 months of treatment.…”

Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment

“…Medical treatment with dopamine agonists (DA) corrects hyperprolactinemia, decreases tumor size, and restores gonadal function in most patients (1). However, 30-50% of male patients with prolactinomas under DA treatment, both with normal and with high prolactin levels, still remain hypogonadal (2)(3)(4)(5)(6)(7). Persistent hypogonadism in these patients is treated with testosterone replacement, most often with intramuscular injections that require frequent applications and induce large fluctuations in serum testosterone levels with corresponding fluctuations in patients' energy, libido, sexual performance, and mood (8,9).…”