Giant prolactinomas in women

E Delgrange, Endocrinology, Université Catholique de Louvain, Mont-sur-Meuse, 5530, Belgium.
European Journal of Endocrinology (Impact Factor: 4.07). 10/2013; 170(1). DOI: 10.1530/EJE-13-0503
Source: PubMed


to characterize distinctive clinical features of giant prolactinomas in women.
a multicentre retrospective case series and literature review.
we collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1,000 µg/L, and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review.
the initial Pubmed search using the term "giant prolactinomas" identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another 6 female patients were found by extending the literature search while our own series added 15 patients. The median age at diagnosis was 44 years in women compared to 35 years in men (p<0.05). All cases diagnosed before the age of 15 were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with 7 cases of primary amenorrhoea. In 8 women with onset of secondary amenorrhoea before age 40, the diagnosis was made 2 to 31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10,000 µg/L in 15/34 and misdiagnosis due to "hook effect" occurred in 2 of them. Eighteen patients were treated with cabergoline; standard doses (< 2.0 mg/week) were able to normalize prolactin in only 4/18 patients, and 7/18 were resistant to weekly doses ranging from 3.0 to 7.0 mg.
giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.

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Available from: Gérald Raverot, Oct 09, 2015
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    ABSTRACT: Giant prolactinoma are rare tumours, representing only 2-3 % of all prolactin-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 prolactin concentrations (usually above 1000 µg/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 neurological complications arise from massive extension into the surrounding structures, leading to cranial nerve palsies, hydrocephalus, temporal epilepsy or exophthalmos. Prolactin concentrations are usually in the range of 1,000 to 100,000 µg/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 of tumour size in &frac34; 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 tumoral 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.
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