THERAPY OF ENDOCRINE DISEASE: The challenges in managing giant prolactinomas

Abstract

Giant prolactinomas are rare tumours, representing only 2-3% of all prolactin (PRL)-secreting tumours and raising special diagnostic and therapeutic challenges. Based on several considerations developed in this review, their definition should be restricted to pituitary adenomas with a diameter of 40 mm or more, significant extrasellar extension, very high PRL concentrations (usually above 1000 mg/l) and no concomitant GH or ACTH secretion. Giant prolactinomas are much more frequent in young to middle-aged men than in women, with a male to female ratio of about 9:1. Endocrine symptoms are often present but overlooked for a long period of time, and diagnosis is eventually made when neurologic complications arise from massive extension into the surrounding structures, leading to cranial nerve palsies, hydrocephalus, temporal epilepsy or exophthalmos. PRL concentrations are usually in the range of 1000-100 000 mg/l, but may be underestimated by the so-called 'high-dose hook effect'. As in every prolactinoma, dopamine agonists are the first-line treatment allowing rapid alleviation of neurologic symptoms in the majority of the cases, a significant reduction in tumour size in three-fourths of the patients and PRL normalization in 60-70%. These extensive tumours are usually not completely resectable and neurosurgery has significant morbidity and mortality. It should therefore be restricted to acute complications such as apoplexy or leakage of cerebrospinal fluid (often induced by medical treatment) or to patients with insufficient tumoural response or progression. Irradiation and temozolomide are useful adjuvant therapies in a subset of patients with aggressive/invasive tumours, which are not controlled despite combined medical and surgical treatments. Because of these various challenges, we advocate a multidisciplinary management of these giant tumours in expert centres.

Cerebrospinal fluid rhinorrhoea in young women after 6.5 years of therapy giant prolactinoma with Cabergolin

“…В настоящее время основным методом лечения пролактином, в том числе гигант-ских размеров, является терапия каберголи-ном [4,5]. Каберголин снижает/нормализует уровень ПРЛ в крови и уменьшает размеры опухоли, что приводит к регрессу зритель-ных и неврологических симптомов заболева-ния [6,7].…”

Management of resistant prolactinoma in infertile lady with successful maternal and perinatal outcome

“…10, 11 Maiter D et al in 2014 reviewed the management of giant prolactinoma cases and found that the extensive tumours are usually not completely resectable and neurosurgery has significant morbidity and mortality. 12 So additional therapy after operation using conventional external radiation may be needed, but it takes several years to achieve endocrinological remission and risk for panhypopituitarism or visual disturbances exists.…”

Giant prolactinomas: Multi-modal approach to achieve tumor control

“…Six (13%) and nine (50%) of the patients included in these two cohorts had pituitary surgery compared to 69% in the current series [5]. Maiter D & Delgrange E summarized the efficacy of primary treatment with dopamine agonists in 13 other cohorts of patients with giant prolactinomas including 140 subjects (86% males) [1]. PRL normalized in 60% of the patients treated with cabergoline, bromocriptine, or pergolide, and the tumors have shrunk (>30% decrease in tumor diameter, or >65% reduction in tumor volume) in 74% of the subjects.…”

“…Among the affected patient population, females usually harbor microadenomas, whereas the larger macroadenomas are diagnosed in males and post-menopausal women. The very large and invasive prolactin (PRL)-secreting tumors measuring >40 mm in diameter with baseline PRL levels >1000 ng/ml but typically much higher, the giant prolactinomas, represent 3-5% of all PRL-adenomas, and appear with a male to female ratio of about 9:1 [1,2]. Usually, there is an association between tumor size and baseline serum PRL level, but this association is not always kept.…”