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Journal of the American Veterinary... Apr 2019
Topics: Animals; Female; Prolactinoma; Sheep; Sheep Diseases
PubMed: 30888268
DOI: 10.2460/javma.254.7.819 -
Brain Research Nov 2018Prolactinomas are the most common functional pituitary adenomas. While dopamine agonists are a primary method of therapeutic treatment, the rate of resistance to these...
Prolactinomas are the most common functional pituitary adenomas. While dopamine agonists are a primary method of therapeutic treatment, the rate of resistance to these drugs continues to increase each year. During previous long-term clinical investigations, we found that partial resistant prolactinomas exhibited significantly more fibrosis than did sensitive adenomas, suggesting a role of fibrosis in their drug resistance. Furthermore, resistant adenomas with extensive fibrosis mainly express type I and type III collagens. Since TGF-β1 is the key factor in the initiation and development of tissue fibrosis, including in the pituitary, in this study, we aimed to determine whether TGF-β1 mediated fibrosis in prolactinomas and whether fibrosis was related to prolactinoma drug resistance. Using immunochemistry and western blotting, we found that the TGF-β1/Smad3 signaling pathway-related proteins were elevated in resistant prolactinoma specimens with high degrees of fibrosis compared to levels in sensitive samples, suggesting that this pathway may play a role in prolactinoma fibrosis. In vitro, TGF-β1 stimulation promoted collagen expression in normal HS27 fibroblasts. Furthermore, the sensitivity of rat prolactinoma MMQ cells to bromocriptine decreased when they were co-cultured with HS27 cells treated with TGF-β1. The TGF-β1/Smad3 signaling-specific inhibitor SB431542 counteracted these effects, indicating that TGF-β1/Smad3-mediated fibrosis was involved in the drug-resistant mechanisms of prolactinomas. These results indicate that SB431542 may serve as a promising novel treatment for preventing fibrosis and further improving the drug resistance of prolactinomas.
Topics: Adult; Benzamides; Cell Line; Dioxoles; Dopamine Agonists; Drug Resistance; Female; Fibroblasts; Fibrosis; Humans; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Smad3 Protein; Transforming Growth Factor beta1
PubMed: 30055965
DOI: 10.1016/j.brainres.2018.07.024 -
The New England Journal of Medicine Mar 2004
Topics: Antineoplastic Agents; Cabergoline; Ergolines; Follow-Up Studies; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Recurrence; Withholding Treatment
PubMed: 15002121
DOI: No ID Found -
Archives of Medical Research Dec 2023Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly... (Review)
Review
Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly cabergoline, is considered the primary therapy for these patients. Prolactin normalization is achieved in 80-90% of prolactinomas treated with cabergoline. Patients resistant to the standard dose can escalate the dose of cabergoline up to the maximum tolerated dose. The expression of dopamine (D2) receptors and dopamine affinity is decreased in aggressive and resistant prolactinomas. Patients with aggressive and DA-resistant adenomas or with rare PRL-secreting carcinomas can be treated off-label with temozolomide (TMZ), a DNA alkylating agent. TMZ is effective in 40-50% of treated lactotroph tumors showing at least a partial response. However, patients tend to escape from the effect of TMZ after a limited time of response. Other therapeutic options include aromatase inhibitors, the somatostatin receptor ligand pasireotide, peptide receptor radionuclide therapy (PRRT), immune-checkpoint inhibitors, tyrosine-kinase inhibitors, or everolimus, the mammalian target of rapamycin inhibitor. These experimental treatments were effective in some patients carrying refractory prolactinomas showing usually partial tumor control. However, the number of treated patients with any of these new therapeutic options is very limited and treatment results are inconsistent, thus additional experience with more patients is required.
Topics: Humans; Prolactinoma; Dopamine Agonists; Cabergoline; Dopamine; Pituitary Neoplasms; Temozolomide; Prolactin
PubMed: 37689507
DOI: 10.1016/j.arcmed.2023.102883 -
International Journal of Molecular... Oct 2021Prolactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some... (Review)
Review
Prolactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some clinical, radiological and pathology features have been associated with a poor prognostic. Therefore, it can be considered as a group of heterogeneous tumours. The aim of this paper is to give an overview of the molecular pathways involved in the behaviour of prolactinoma in order to improve our approach and gain deeper insight into the better understanding of tumour development and its management. This is essential for identifying patients harbouring aggressive prolactinoma and to establish personalised therapeutics options.
Topics: Animals; Antineoplastic Agents; Dopamine Agonists; Humans; Pituitary Neoplasms; Prolactinoma; Signal Transduction
PubMed: 34681905
DOI: 10.3390/ijms222011247 -
Clinical Rheumatology Jul 2006The lactogenic hormone prolactin is produced in part by cells of the immune system and serves as an upregulator of immune function. Hyperprolactinemia is common in...
The lactogenic hormone prolactin is produced in part by cells of the immune system and serves as an upregulator of immune function. Hyperprolactinemia is common in patients with systemic lupus erythematosus (SLE), raising the possibility that the hormone contributes to the excessive immune response in the disease. The highest levels of circulating prolactin occur in association with prolactin-secreting tumors, but prolactinomas have only rarely been encountered in patients with SLE. We present here three patients with SLE and prolactinomas. As with the previously reported six patients, there was no consistency in the presence of findings related to prolactin excess or in the coincidence of hyperprolactinemia with flares of SLE disease activity. We speculate that this may be due to genetic differences in the response to prolactin and/or to the presence of variant prolactin isoforms detected in the clinical immunoassay that have reduced or absent biologic activity.
Topics: Adult; Child; Female; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Pituitary Neoplasms; Prolactin; Prolactinoma; Radiography
PubMed: 16404500
DOI: 10.1007/s10067-005-0117-x -
Hormones (Athens, Greece) Sep 2021Giant prolactinomas, which have extremely large sizes and high prolactin (PRL) values, are rarely seen. Although medical therapy is effective, surgical treatment is more... (Comparative Study)
Comparative Study
PURPOSE
Giant prolactinomas, which have extremely large sizes and high prolactin (PRL) values, are rarely seen. Although medical therapy is effective, surgical treatment is more frequently applied due to slightly lower response rates and compression symptoms. This study aimed to compare the medical and surgical treatment results in giant prolactinomas.
METHODS
Thirty-nine patients who were followed up in our center for giant prolactinoma were included in the study, and the response rates of the patients were evaluated after the medical and surgical treatments. The treatment responses were compared in terms of tumor volume, PRL level, visual field, and pituitary function.
RESULTS
The outcomes of the 66 treatment periods (medical n = 42; surgical n = 24) in 39 patients (mean age, 47.2 years; men, 89.7%) were evaluated. The most common presentations were hypogonadism and visual defects. The mean longest tumor diameter at diagnosis was 52.2 ± 11.8 mm, and the median PRL levels were 5000 ng/mL. PRL level normalization was achieved in 69% with medical therapy, and a curative response was obtained in only two patients with surgery. Tumor volume reduction was 67% (no cure) in the medical and 75% (13% cure) in the surgical groups (p = 0.39). Improvement of visual field was 70.8% in the medical and 84.2% in the surgical group (p = 0.12).
CONCLUSION
In our study, it was observed that medical therapy was effective and safe in patients with giant prolactinomas. The use of surgical treatment should be limited to prolactinomas with compression or post-resistance to medical treatment in serious cases.
Topics: Female; Follow-Up Studies; Humans; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome
PubMed: 34236607
DOI: 10.1007/s42000-021-00307-0 -
Neurosurgery Clinics of North America Oct 2019Prolactinomas are the most common functional pituitary adenoma. Many prolactinomas can be treated with medication, but all patients should be evaluated at a... (Review)
Review
Prolactinomas are the most common functional pituitary adenoma. Many prolactinomas can be treated with medication, but all patients should be evaluated at a neuroendocrine center including experienced neurosurgeons trained in transsphenoidal surgery. Surgery for prolactinomas is feasible and can be performed with low morbidity. Patients never previously treated with dopamine agonists should be considered for surgery if they have neurologic deficits, pituitary apoplexy, an uncertain diagnosis, or a significantly cystic prolactinoma. Patients previously treated with dopamine agonists should be considered for surgery in cases of intolerance or resistance. Recurrent and aggressive prolactinomas often require multimodal therapy.
Topics: Combined Modality Therapy; Dopamine Agonists; Humans; Pituitary Neoplasms; Prolactinoma; Stroke; Treatment Outcome; Vision Disorders
PubMed: 31471058
DOI: 10.1016/j.nec.2019.05.010 -
Expert Review of Endocrinology &... May 2019Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist... (Review)
Review
INTRODUCTION
Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist (DA) such as cabergoline, their management becomes problematic since a resistance to DA can occur and/or if the tumor displays features of aggressiveness, two conditions that are closely related.
AREAS COVERED
Epidemiology and medical treatment of prolactinomas; resistance to DA and molecular basis of DA-resistance; therapeutical alternatives in case of DA-resistant Prolactinomas and therapies in development; summarizing conclusions.
EXPERT OPINION
The management of DA-resistant prolactinomas requires a multidisciplinary approach by an expert team. Along with discussions about surgery with or without gamma knife radiosurgery, genetic screening for multiple endocrine neoplasia type 1 (MEN1) syndrome is actively discussed in a case-by-case approach. In case of surgery, a careful analysis of the tumor sample can provide information about its aggressivity potential according to recent criteria. Ultimately, temozolomide can be indicated if the tumor is rapidly growing and/or threatening for the patient.
Topics: Disease Management; Dopamine Agonists; Drug Resistance, Neoplasm; Humans; Pituitary Neoplasms; Prolactinoma; Signal Transduction; Treatment Outcome
PubMed: 30913932
DOI: 10.1080/17446651.2019.1596024 -
Endocrine May 2017
Topics: Combined Modality Therapy; Dopamine Agonists; Drug Resistance; Humans; Pituitary Neoplasms; Practice Guidelines as Topic; Prolactinoma; Tumor Burden
PubMed: 28050685
DOI: 10.1007/s12020-016-1225-x