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Journal of Neurosurgery May 2011The authors' object in this paper was to review the definition, epidemiology, biology, resistance mechanisms, and treatment options for dopamine agonist-resistant... (Review)
Review
The authors' object in this paper was to review the definition, epidemiology, biology, resistance mechanisms, and treatment options for dopamine agonist-resistant prolactinomas (DARPs). Prolactinomas are relatively unique among primary brain tumors in that medical treatment alone using dopamine agonists carries a high probability of disease control or even radiographic and endocrine remission, and thus has replaced surgery as the first line of therapy. Unfortunately, slightly less than 10% of patients with prolactinomas do not experience normalization of their prolactin levels in response to dopamine agonists, and harbor tumors that are resistant to dopamine agonist therapy. A literature review underscores that in male patients these DARPs are more likely to be invasive macroadenomas than dopamine agonist-responsive prolactinomas and that they are also more angiogenic, more proliferative, and more likely to exhibit cellular atypia. Estrogen receptor antagonists and temozolomide are the most commonly applied medical therapies in cases in which resection and radiosurgery have not induced remission of the hyperprolactinemia. Dopamine agonist-resistant prolactinomas exhibit aggressive behavior and tend to be large, invasive, hyperangiogenic tumors with high mitotic indices, which makes their management via surgery, radiosurgery, or alternative medical therapies challenging, thus underscoring the need for novel medical therapies or treatment regimens that target these lesions.
Topics: Antineoplastic Agents, Alkylating; Cell Division; Dacarbazine; Dopamine Agonists; Drug Resistance, Neoplasm; Female; Humans; Male; Mitotic Index; Neoplasm Invasiveness; Pituitary Neoplasms; Prolactin; Prolactinoma; Receptors, Estrogen; Sex Factors; Temozolomide
PubMed: 21214334
DOI: 10.3171/2010.11.JNS101369 -
Journal of Endocrinological... Nov 2008(a) To evaluate body fat in men with prolactinoma and healthy controls, using whole body dual energy x-ray absorptiometry (DXA), and (b) to correlate DXA results with...
OBJECTIVE
(a) To evaluate body fat in men with prolactinoma and healthy controls, using whole body dual energy x-ray absorptiometry (DXA), and (b) to correlate DXA results with anthropometry and clinical aspects of male prolactinomas.
MATERIAL AND METHODS
A cross-sectional study was performed in two University referral centers. Eleven newly-diagnosed men with prolactinoma and 9 with normal PRL levels due to dopamine agonist treatment were submitted to DXA and blood analysis (PRL, testosterone, dihydrotestosterone, estradiol, and SHBG) by the time of their clinical evaluation. They were compared with 14 control men of similar age and body mass index distribution.
RESULTS
Newly-diagnosed men with prolactinoma had higher fat percentage in the arms and the total body, when compared with patients treated with dopamine agonists and controls. The former group also presented higher fat percentage in the legs than the controls. Truncal fat percentage of the newly-diagnosed patients was lower than the dopamine agonist treated group. The 3 groups had similar android and gynoid fat contents. Fat percentage of the 6 sites correlated with PRL, testosterone, and dihydrotestosterone levels.
CONCLUSION
Newly-diagnosed men with prolactinomas had higher body fat content. Body fat was linked to disease control, especially to the PRL and androgen levels. Consequently, adequate control of hyperprolactinemia should be pursued in order to reduce the risk of obesity and its metabolic complications in men with prolactinoma.
Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Cabergoline; Cross-Sectional Studies; Dopamine Agonists; Ergolines; Humans; Male; Prolactinoma
PubMed: 19169054
DOI: 10.1007/BF03345636 -
Neuroradiology Jul 2015Clinical presentations of prolactinomas are quite different between genders. In comparison with women's prolactinoma, those in men showed predominance of large tumors...
INTRODUCTION
Clinical presentations of prolactinomas are quite different between genders. In comparison with women's prolactinoma, those in men showed predominance of large tumors with high prolactin (PRL) levels. This preponderance could be attributed to a greater proliferative potential of the tumors. Differences in magnetic resonance imaging (MRI) signal at diagnosis have not been yet clearly evaluated.
METHODS
We conduct a retrospective study comparing MRI signal intensity (SI) on T2-weighted images (T2-WI) between 41 men and 41 women to investigate whether or not men prolactinoma present specific features.
RESULTS
In addition to the size of the adenoma and PRL levels (P < 0001), prolactinomas in men also exhibit differences from those in women in signal on T2-WI on MRI (P < 0001). Women's prolactinomas are mostly of high SI on T2-WI while men's prolactinomas exhibit a more heterogeneous pattern of SI on T2-WI. Prolactinomas presenting with low SI on T2-WI are almost exclusively encountered in men.
CONCLUSIONS
Presence of T2-WI hypointensities in pituitary adenoma can be predictive of a different subtype of prolactinoma almost encountered in men and possibly translate the presence of spherical amyloid deposits, in agreement with the literature.
Topics: Adult; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Plaque, Amyloid; Prolactin; Prolactinoma; Radiography; Retrospective Studies; Sex Factors
PubMed: 25845810
DOI: 10.1007/s00234-015-1519-3 -
Endocrine Sep 2014Hyperprolactinemia, frequently caused by a prolactinoma, is an important cause of infertility among young women. Dopamine agonists (DA) are the treatment of choice.... (Review)
Review
Hyperprolactinemia, frequently caused by a prolactinoma, is an important cause of infertility among young women. Dopamine agonists (DA) are the treatment of choice. Although cabergoline (CAB) is currently considered the gold standard DA, bromocriptine (BRC) remains the drug of choice for women desiring pregnancy, as it was proven to be safe in more than 6,000 pregnancies. The purpose of this review is to perform a critical evaluation of CAB safety in pregnancy, as it is used by most patients harboring prolactinomas. Although the number of CAB-induced pregnancies (about 800) is still reduced as compared with those under BRC treatment, data in the literature do not point to increase risk of preterm delivery or fetal malformations, comparing to pregnancies induced by BRC and those in the general population. Moreover, CAB use throughout pregnancy was reported in about ten cases, without evidence of any harm to fetal development. Therefore, even though BRC still remains the recommended DA drug for pregnancy induction or use during pregnancy in women with prolactinomas, increasing evidences point to the safety of CAB for this purpose.
Topics: Animals; Antineoplastic Agents; Cabergoline; Ergolines; Female; Fetal Development; Humans; Hyperprolactinemia; Infertility, Female; Pituitary Neoplasms; Pregnancy; Prolactinoma
PubMed: 24985062
DOI: 10.1007/s12020-014-0334-7 -
Zhonghua Yi Xue Za Zhi Feb 2012To explore the relationship between the prolactinoma-related microRNAs (miRNA) and the development, growth and hormone secretion of prolactinoma.
OBJECTIVE
To explore the relationship between the prolactinoma-related microRNAs (miRNA) and the development, growth and hormone secretion of prolactinoma.
METHODS
The technique of Solexa sequencing was employed to analyze the differential expressions of prolactinoma and normal anterior pituitary gland samples. And the stem-loop real-time polymerase chain reaction (PCR) was utilized for confirmation.
RESULTS
According to the differentially expressed profiles of miRNAs, 4 miRNAs were down-regulated (miR-130a, miR-199b-3p, miR-200b, miR-125b, P < 0.05) and 6 miRNAs up-regulated (miR-342-3p, miR-432, miR-23b, miR-493, miR-493(*), miR-664(*), P < 0.05). The expression levels of miR-493(*) and miR-432 had a significant positive correlation with the serum level of prolactin (r = 0.47, P < 0.05; r = 0.528, P < 0.01) while miR-342-3p a significantly positive correlation with the invasiveness (r = 0.402, P < 0.05).
CONCLUSION
miRNAs are differentially expressed between normal anterior pituitary gland and prolactinomas, between invasive and localized prolactinomas and among different hormone secretion levels. It suggests that miRNAs may be involved in the physiological process of development, growth and hormone secretion of prolactinoma.
Topics: Adult; Female; Gene Expression Profiling; Humans; Male; MicroRNAs; Middle Aged; Oligonucleotide Array Sequence Analysis; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Young Adult
PubMed: 22490835
DOI: No ID Found -
Endocrinology and Metabolism Clinics of... Mar 2008Any process interfering with dopamine synthesis, its transport to the pituitary gland, or its action at the level of lactotroph dopamine receptors can cause... (Review)
Review
Any process interfering with dopamine synthesis, its transport to the pituitary gland, or its action at the level of lactotroph dopamine receptors can cause hyperprolactinemia. As described in this article, considering the complexity of prolactin regulation, many factors could cause hyperprolactinemia, and hyperprolactinemia can have clinical effects not only on the reproductive axis. Once any drug effects are excluded, prolactinomas are the most common cause of hyperprolactinemia. The most frequent symptom is hypogonadism in both genders. Medical and surgical therapies generally have excellent results, and most prolactinomas are well controlled or even cured in some cases.
Topics: Bromocriptine; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma
PubMed: 18226731
DOI: 10.1016/j.ecl.2007.10.013 -
European Journal of Endocrinology Dec 2023Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on...
BACKGROUND
Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma.
OBJECTIVE
We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas.
MATERIALS AND METHODS
A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients.
RESULTS
About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas.
CONCLUSIONS
We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.
Topics: Male; Humans; Female; Adult; Prolactinoma; Cohort Studies; Retrospective Studies; Genetic Testing; Pituitary Neoplasms; Germ-Line Mutation
PubMed: 37956455
DOI: 10.1093/ejendo/lvad148 -
Pituitary Feb 2020Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia.... (Review)
Review
Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia. However, it remains to be established the best timing to withdraw DAs and in which patients this should be attempted. Studies in the 1980s, mainly using bromocriptine, started to defy the concept that DAs should be regarded as a lifelong therapy considering that sustained normoprolactinemia was attained in a small subset of patients after drug withdrawal. The introduction of the more effective agent cabergoline led to an increase in the percentages of remission. The most recent meta-analysis on the topic stated than remission rates after withdrawal can range from 15% in macroprolactinoma patients treated with bromocriptine to 41% in those with microprolactinomas previously treated with cabergoline. When more stringent criteria were applied before attempting withdrawal, sustained remission ensued in more than 50% of the individuals. Treatment duration for more than 24 months, the achievement of normoprolactinemia, marked reduction (≥ 50%) in tumoral size and DAs tapering till a low maintenance dose (e.g. cabergoline 0.5 mg/week) have been the most consistently identified predictors of success. In addition, a growing amount of evidence suggests that the post-pregnancy/breastfeeding period and menopause are reasonable timings to re-access the need for continuing DAs therapy. Considering that the achievement of sustained normoprolactinemia is still far from being universal after the withdrawal, even in highly selected cohorts, future larger prospective studies should continue to address this issue.
Topics: Cabergoline; Dopamine Agonists; Female; Humans; Male; Prolactinoma
PubMed: 31556013
DOI: 10.1007/s11102-019-00989-1 -
Pituitary 2005In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of... (Review)
Review
In recent years the demonstration that human pituitary adenomas are monoclonal in origin provides further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. However, with the exception of one RAS mutation identified in a single unusually aggressive prolactinoma resistant to dopaminergic inhibition that resulted to be lethal, no mutational changes have been so far detected in prolactinomas. In the absence of genetic changes, modifications in the level of expression of oncogenes or tumor suppressor genes have been detected in these tumors, although it is unknown whether these changes have a causative role or are a secondary event. Indeed, our knowledge on the molecular events involved in lactotroph proliferation is even more limited in comparison to the other tumor types, since these tumors are very infrequently surgically removed and therefore available for molecular biology studies. In this respect, it is worth noting that the molecular and biological abnormalities so far described in prolactinomas mainly concern aggressive and atypical tumors and likely do not apply to the typical prolactinomas, that are characterized by good response to medical treatment and a very low growth rate.
Topics: Cell Cycle; Cell Proliferation; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Growth Substances; Humans; Mutation; Pituitary Neoplasms; Prolactinoma; Proto-Oncogenes
PubMed: 16411063
DOI: 10.1007/s11102-005-5080-7 -
Nigerian Journal of Clinical Practice 2016Prolactinomas are the most common pituitary tumors but rarely seen in adolescent males. There is no indication for surgery both in micro- and macro-adenomas unless an...
Prolactinomas are the most common pituitary tumors but rarely seen in adolescent males. There is no indication for surgery both in micro- and macro-adenomas unless an urgent treatment is necessary. First line treatment is always medical with dopamine agonists. In this report, we presented a patient with pubertal arrest and giant prolactinoma that disappeared in a short time with cabergoline treatment.
Topics: Antineoplastic Agents; Cabergoline; Dopamine Agonists; Ergolines; Humans; Male; Pituitary Neoplasms; Prolactinoma; Puberty, Delayed; Young Adult
PubMed: 27538562
DOI: 10.4103/1119-3077.188693