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Drugs Jun 1996A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently... (Review)
Review
A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently in women than in men and may differ in size, invasive growth and secretory activity. At presentation, macroadenomas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taking a single sample on 3 separate days or 3 sequential samples (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200 micrograms/L are commonly considered diagnostic for the presence of a prolactinoma; however, prolactinoma cannot be excluded in the presence of lower levels, and prolactin levels > 100 micrograms/L are present in some patients with idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed to differentiate idiopathic from tumorous hyperprolactinaemia. Although they could be used for group discrimination, these tests cannot be used for individual patients. To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a dopamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be observed. After hyperprolactinaemia is confirmed, imaging with computerised tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choice in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a reduction or normalisation of prolactin levels is usually observed, together with the disappearance or improvement of clinical symptoms. The sensitivity to bromocriptine is variable and patients may need different dose of the drug. Bromocriptine is also able to shrink the tumour in most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including prolactin levels and CT or MRI studies, is therefore emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however, a single evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse effects (nausea, vomiting, postural hypotension) may be initially present, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patients are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prolactinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlargement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine should be stopped as soon as pregnancy is confirmed, but re
Topics: Bromocriptine; Dopamine Agonists; Humans; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 8736617
DOI: 10.2165/00003495-199651060-00004 -
Neuroendocrinology 2022Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors in the clinic. The preferred...
INTRODUCTION
Prolactinomas, also called lactotroph adenomas, are the most encountered type of hormone-secreting pituitary neuroendocrine tumors in the clinic. The preferred first-line therapy is a medical treatment with dopamine agonists (DAs), mainly cabergoline, to reduce serum prolactin levels, tumor volume, and mass effect. However, in some cases, patients have displayed DA resistance with aggressive tumor behavior or are faced with recurrence after drug withdrawal. Also, currently used therapeutics have notorious side effects and impair the life quality of the patients.
METHODS
Since the amalgamation of clinical and laboratory data besides tumor histopathogenesis and transcriptional regulatory features of the tumor emerges to exhibit essential roles in the behavior and progression of prolactinomas; in this work, we integrated mRNA- and microRNA (miRNA)-level transcriptome data that exploit disease-specific signatures in addition to biological and pharmacological data to elucidate a rational prioritization of pathways and drugs in prolactinoma.
RESULTS
We identified 8 drug candidates through drug repurposing based on mRNA-miRNA-level data integration and evaluated their potential through in vitro assays in the MMQ cell line. Seven repurposed drugs including 5-fluorocytosine, nortriptyline, neratinib, puromycin, taxifolin, vorinostat, and zileuton were proposed as potential drug candidates for the treatment of prolactinoma. We further hypothesized possible mechanisms of drug action on MMQ cell viability through analyzing the PI3K/Akt signaling pathway and cell cycle arrest via flow cytometry and Western blotting.
DISCUSSION
We presented the transcriptomic landscape of prolactinoma through miRNA and mRNA-level data integration and proposed repurposed drug candidates based on this integration. We validated our findings through testing cell viability, cell cycle phases, and PI3K/Akt protein expressions. Effects of the drugs on cell cycle phases and inhibition of the PI3K/Akt pathway by all drugs gave us promising output for further studies using these drugs in the treatment of prolactinoma. This is the first study that reports miRNA-mediated repurposed drugs for prolactinoma treatment via in vitro experiments.
Topics: Drug Repositioning; Humans; MicroRNAs; Prolactinoma; RNA, Messenger; Transcriptome
PubMed: 33706313
DOI: 10.1159/000515801 -
Journal of Endocrinological... Aug 2023Prolactinomas are one of the most common pituitary neuroendocrine tumors (PitNETs), accounting for approximately 50% of all pituitary tumors. Dopamine agonists are the...
PURPOSE
Prolactinomas are one of the most common pituitary neuroendocrine tumors (PitNETs), accounting for approximately 50% of all pituitary tumors. Dopamine agonists are the main treatment for prolactinoma, but a small number of patients are still resistant to pharmacotherapy. Recent discoveries have revealed that ferroptosis is involved in regulating tumor drug resistance. However, the role of ferroptosis in prolactinoma has not been reported. In this study, we aimed to explore the mechanism of a circRNA in ferroptosis in prolactinoma.
METHODS
The expression of circOMA1 in prolactinoma tissues was examined by quantitative reverse transcription PCR (qRT-PCR). The biological function of circOMA1 was evaluated in vitro and in vivo. To explore the role of ferroptosis in prolactinoma, we used qRT-PCR and western blotting. Glutamate-cysteine ligase, modifier subunit (GCLM) was predicted to be a direct target gene of miR-145-5p by bioinformatics analysis, which was confirmed by luciferase reporter assays.
RESULTS
circOMA1 was overexpressed in drug-resistant prolactinoma tissues compared with sensitive prolactinoma samples. We further found that circOMA1 promoted MMQ cells growth in vivo and in vitro. In addition, GCLM was directly targeted by miR-145-5p and indirectly regulated by circOMA1. Importantly, circOMA1 induced ferroptosis resistance through the increased expression of Nrf2, GPX4, and xCT, and circOMA1 attenuated CAB-induced ferroptosis in MMQ cells in vivo and in vitro.
CONCLUSION
The present study demonstrates that circOMA1 attenuates CAB efficacy through ferroptosis resistance and may be a new therapeutic target for the individualized treatment of DA-resistant prolactinoma patients.
Topics: Humans; Prolactinoma; Cabergoline; Ferroptosis; Pituitary Neoplasms; Dopamine Agonists; MicroRNAs
PubMed: 36853491
DOI: 10.1007/s40618-023-02010-w -
Endocrinology and Metabolism Clinics of... Mar 2015Identifying the correct cause of hyperprolactinemia is crucial for treatment. Prolactinoma is the most common pathologic cause of hyperprolactinemia. Dopamine agonists... (Review)
Review
Identifying the correct cause of hyperprolactinemia is crucial for treatment. Prolactinoma is the most common pathologic cause of hyperprolactinemia. Dopamine agonists are efficacious in about 80% to 90% of patients with prolactinoma, leading to reduction of serum prolactin levels and tumor dimensions. Neurosurgery, mainly by the transsphenoidal route, is indicated in cases of intolerant and resistant dopamine agonists. Radiotherapy is rarely used because of its side effects and low efficacy. The alkylating agent temozolomide showed efficacy for treatment of aggressive and resistant prolactinomas. Other approaches, such as thyrosine kinase inhibitors, are currently being tested and could be an additional tool for these troublesome tumors.
Topics: Humans; Hyperprolactinemia; Infertility; Pituitary Neoplasms; Prolactinoma
PubMed: 25732643
DOI: 10.1016/j.ecl.2014.11.003 -
Neuroendocrinology 2019Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in... (Review)
Review
Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. Most macroprolactinomas measure between 10 and 40 mm. Giant prolactinomas, measuring >40 mm, are rare, accounting for only 1-5% of all prolactinomas. Although generally benign, giant prolactinomas are aggressive and invasive, extending into the suprasellar region and also involving the cavernous sinuses. The optic chiasm is frequently involved, which leads to visual damage, and patients occasionally suffer from ophthalmoplegia. Long-term (usually lifetime) therapy with high-dose dopamine agonists (cabergoline or bromocriptine), together with pituitary surgery in some cases and radiotherapy if required, can achieve biochemical remission, tumor control, and clinical improvement in most patients.
Topics: Female; Humans; Male; Pituitary Neoplasms; Prolactinoma
PubMed: 30404098
DOI: 10.1159/000495184 -
Clinical Endocrinology Mar 2021To report the clinical presentation, management and outcomes of young patients with prolactinomas (<20 years) and conduct a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To report the clinical presentation, management and outcomes of young patients with prolactinomas (<20 years) and conduct a systematic review and meta-analysis.
PATIENTS AND DESIGN
Clinical, biochemical and radiological data (1996-2018) were collected from our centre. A systematic review and meta-analysis of published literature (1994-2019) on prolactinoma (age <20 years) were conducted. Both random and fixed effects meta-analysis were used to pool outcomes across studies. RESULTS 1 CASE SERIES: Twenty-two patients (14 females) were identified; median age at diagnosis 15.7 years (range 13-19); 12 patients (6 females) had a macroprolactinoma. Seven patients (macroprolactinoma-6) had associated pituitary hormone deficiencies at presentation. Five patients (4 males) underwent surgical resection due to poor response to cabergoline or apoplexy. Patients undergoing surgery had larger tumours (p < .02) and higher serum prolactin concentration (p < .005). All patients with macroprolactinoma >20 mm required surgical intervention. RESULTS 2 SYSTEMATIC REVIEW AND META-ANALYSIS: We selected 11 studies according to strict inclusion criteria describing 275 patients. Macroprolactinoma was more common in girls (78.7% [95% CI 70.5-85.9]) than boys and was more frequent than microprolactinoma (56.6% [95% CI 48.4-64.5]). In males, only 6/57 (10.5%) of tumours were microprolactinoma as compared to 102/198 (51.5%) microprolactinoma in females (risk difference -0.460; [95% CI -0.563 to -0.357]; p < .001). Surgery was first-line therapy in 18.9% patients, with another 15.4% requiring it as a second line (overall 31.3%).
CONCLUSIONS
Macroprolactinoma, particularly if >20 mm, usually requires multimodal therapy including surgical intervention. While overall prolactinomas in <20 years age group are more common in females, the proportion of macroprolactinoma vs microprolactinoma is greater in males, particularly for large invasive tumours. Microprolactinoma is a rare diagnosis in adolescent males.
Topics: Adolescent; Adult; Age Factors; Cabergoline; Dopamine Agonists; Female; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Young Adult
PubMed: 33340135
DOI: 10.1111/cen.14394 -
Neurosurgical Review May 2023Initial treatment for prolactinoma is usually conservative with dopamine agonists. However, the duration of treatment is often lifelong and can be associated with...
Initial treatment for prolactinoma is usually conservative with dopamine agonists. However, the duration of treatment is often lifelong and can be associated with significant side effects. Surgical outcomes are usually favorable and treatment complications low, raising the question whether surgical therapy should be included earlier in the treatment of prolactinoma. The aim of this study was to analyze the outcome of surgical resection of prolactinomas at our institution, to compare it with other published surgical and conservative series and to discuss the role of surgery in modern prolactinoma therapy. The authors reviewed a database of single-center consecutively operated prolactinoma cases and analyzed the extent of resection (EOR), endocrinological and neurological outcomes, and complications. Thirty patients were analyzed. Mean patient age was 37.2 ± 15.5 years (range 16-76) and consisted of 17 (56.7%) females and 13 (43.3%) males. Twenty-one patients (70%) failed medical therapy, the main reasons being intolerable side effects in 11 cases (52.4%) and insufficient response in 10 cases (47.6%). Nine patients (30%) received no medical treatment prior to surgery, of which five (55.6%) were operated because of pituitary apoplexy, two (22.2%) because of acute visual deterioration and two (22.2%) refused medical treatment and opted for surgery as first-line treatment. Of the 30 operated tumors, 56.7% (n = 17) were microadenomas, 30% (n = 9) were macroadenomas (≥ 10 mm), and 13.3% (n = 4) were giant adenomas (≥ 40 mm). GTR was achieved in 75% (n = 21) of cases. The overall remission rate was 63.3%. MRI showed a residual tumor in seven patients (25%), typically with invasive growth. Postoperative CSF leaks did not occur. Mean follow-up was 34.9 ± 60.3 months (range 0-246 months). Endocrine remission was defined as a morning fasting basal PRL level of 22.3 < ng/mL and measured at the last available follow-up. Postoperative Prolactine levels were missing in three patients. Our analysis describes a highly selected sample with a disproportionate number of larger, invasive tumors and emergency cases. Nevertheless, the results are satisfactory and comparable with other published series. The consistently good results of transphenoidal surgery, especially for microprolactinomas, have led to a greater acceptance of surgery in the treatment of prolactinomas in recent years. The timing of surgery in each individual case must be determined by a multidisciplinary team to ensure the best possible outcome.
Topics: Male; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Prolactinoma; Pituitary Neoplasms; Treatment Outcome; Adenoma; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 37249700
DOI: 10.1007/s10143-023-02033-0 -
Cephalalgia : An International Journal... Jun 2014The aim of this article is to investigate the phenotype and etiology of prolactinoma-associated headache as well as present and discuss the plausible pain-relieving...
AIM
The aim of this article is to investigate the phenotype and etiology of prolactinoma-associated headache as well as present and discuss the plausible pain-relieving effect of dopamine agonist treatment.
METHODS
In this case-based audit we included 11 patients with prolactinomas and one patient with idiopathic hyperprolactinemia presenting with headache that subsequently improved or resolved after dopamine agonist treatment.
RESULTS
A significant ipsilateral location of tumor mass and reported headache symptoms was observed (p = 0.018). After dopamine agonist treatment seven out of 12 patients became pain free within 2.5 months; after one year of treatment 11 out of 12 reported headache improvement or resolution. Average tumor volume reduction after treatment was 47 ± 22% during 9.5 ± 8.4 months of follow-up. There was no significant association between headache relief and tumor shrinkage (p = 0.43) or normalization of serum prolactin (p = 1.00), respectively.
CONCLUSIONS
1) The significant association between lateralization of tumor and headache suggests a mechanical origin of the headache, 2) headache responded to dopamine agonist treatment in most patients, and 3) our observations encourage future prospective controlled trials to investigate the role of hyperprolactinemia in the pathogenesis of headache as well as the therapeutic effects of dopamine agonists.
Topics: Adult; Aminoquinolines; Cabergoline; Case-Control Studies; Dopamine Agonists; Ergolines; Female; Headache; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma; Recurrence; Substance Withdrawal Syndrome
PubMed: 24351278
DOI: 10.1177/0333102413515343 -
Acta Endocrinologica Sep 1991We studied the influence of pregnancy on the serum prolactin levels after surgery in 35 patients with prolactinomas. Eighteen out of 22 patients with postoperative... (Review)
Review
We studied the influence of pregnancy on the serum prolactin levels after surgery in 35 patients with prolactinomas. Eighteen out of 22 patients with postoperative normalization of the prolactin level were able to achieve repeated spontaneous pregnancies and endocrine cure by surgery alone, but the other 4 had recurrent hyperprolactinemia. Thirteen patients with persistent hyperprolactinemia after surgery achieved one pregnancy with or without bromocriptine treatment, but did not achieve a second one owing to an increase in the prolactin level after delivery. None of the patients with postoperative hyperprolactinemia showed spontaneous normalization of the prolactin level or restoration of menstruation after delivery. In these 13 patients, the mean increase from the postoperative to the post-delivery prolactin level was less for the patients with bromocriptine-induced pregnancy than for those with spontaneous pregnancy. It is concluded that pregnancy did not adversely affect the serum prolactin level in the patients with a normal postoperative level.
Topics: Adult; Bromocriptine; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Pituitary Gland; Postpartum Period; Pregnancy; Pregnancy Complications; Prolactin; Prolactinoma; Radioimmunoassay; Remission, Spontaneous; Retrospective Studies
PubMed: 1950339
DOI: 10.1530/acta.0.1250259 -
Acta Otorrinolaringologica Espanola Mar 1998Large prolactin-secreting tumors are rare and their endocrinological and surgical management may be complex. We report the case of a patient with a prolonged history of... (Review)
Review
Large prolactin-secreting tumors are rare and their endocrinological and surgical management may be complex. We report the case of a patient with a prolonged history of unilateral tinnitus and sensation of a stopped-up ear who had a very large, invasive and aggressive tumor of the sphenoidal region with bone destruction, invasion of structures in every direction from the sellar region and extracranial extension to the ethmoid and nasopharynx. Serum prolactin level at the time of diagnosis was 16,860 ng/ml (normal: 3-17 ng/ml). Medical treatment with bromocriptine reduced the prolactin level to 31 ng/ml and reduced the size of the tumor, although less than expected. The literature is reviewed and the rarity of such large, invasive prolactinomas is highlighted, as well as the absence of symptoms and signs suggesting the presence of such a large tumor of the skull base.
Topics: Adult; Bromocriptine; Hormone Antagonists; Humans; Magnetic Resonance Imaging; Male; Neoplasm Invasiveness; Neoplasms, Second Primary; Pituitary Neoplasms; Prolactinoma; Skull Base Neoplasms
PubMed: 9650316
DOI: No ID Found