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Acta Medica Lituanica 2023Along with the presence of the 2011 and numerous large-scale studies on the treatment of hyperprolactinemia of different origin, there are some unresolved questions,... (Review)
Review
BACKGROUND
Along with the presence of the 2011 and numerous large-scale studies on the treatment of hyperprolactinemia of different origin, there are some unresolved questions, ambiguous and sometimes contradictory points of view regarding the management of patients with prolactinomas. This overview is devoted to the analysis of the results of modern clinical studies and the approaches towards the management of hyperprolactinemia caused by prolactinoma.
MATERIALS AND METHODS
A systematic research of the literature for the appropriate keywords published mainly for the last 10 years was done; also, a reference list of each selected article was analysed. We included to our review the articles reporting controversial issues or new data on the treatment of hyperprolactinemia.
RESULTS
The review describes various problems arising during the treatment of prolactinoma. The presence of primary and secondary dopamine agonist resistance in each case requires an individual approach, and sometimes may include the use of the antineoplastic agent t . The side effects of dopamine agonists are discussed, with quite rare ones, including valvulopathy, pathological psychological conditions and cerebrospinal rhinorrhea. The controversial issue of the duration and doses of the drug used to achieve a lasting effect in the treatment of prolactinomas is considered. There are some points connected with the frequency of relapses. Thus, recurrence is correlated to the duration of treatment with dopamine agonists, prolactin levels at diagnosis, and the initial tumor size. Metformin, somatostatin analogues, selective estrogen receptor modulators, tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, epidermal growth factor receptor antagonists are investigated nowadays as potential alternative methods of drug treatment of prolactinomas.
CONCLUSION
Drug therapy with dopamine agonists makes it possible to achieve the desired results in the vast majority of patients. However, despite the proven safety of this group of medicines, the risk of side effects should still be taken into account. The therapy regimen should be determined by the clinical course of prolactinoma and the patient's response to treatment. Other options of treatment should be considered in patients intolerant to medical therapy, with contraindication or resistance to dopamine agonists, in the case of a malignant tumor. The presence of refractory to any of the applied methods of treatment and aggressive prolactinomas leads to the search for new drugs.
PubMed: 38516518
DOI: 10.15388/Amed.2023.30.2.1 -
Biomedicines Apr 2021Pituitary adenomas are tumors that arise in the anterior pituitary gland. They are the third most common cause of central nervous system (CNS) tumors among adults. Most... (Review)
Review
Pituitary adenomas are tumors that arise in the anterior pituitary gland. They are the third most common cause of central nervous system (CNS) tumors among adults. Most adenomas are benign and exert their effect via excess hormone secretion or mass effect. Clinical presentation of pituitary adenoma varies based on their size and hormone secreted. Here, we review some of the most common types of pituitary adenomas, their clinical presentation, and current diagnostic and therapeutic strategies.
PubMed: 33946142
DOI: 10.3390/biomedicines9050494 -
Journal of Experimental & Clinical... Jan 2022Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1), but its functional effects and underlying molecular mechanisms remain...
BACKGROUND
Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1), but its functional effects and underlying molecular mechanisms remain largely unexplored.
METHODS
Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1 mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1 were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA.
RESULTS
Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1 allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1 promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1 and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway.
CONCLUSIONS
Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1 mutation.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Line, Tumor; Discs Large Homolog 1 Protein; Disease Progression; Humans; Membrane Proteins; Mutation; Phosphoproteins; Pituitary Neoplasms; Prolactinoma; RNA Splicing; RNA Splicing Factors; Rats; Transfection
PubMed: 35039052
DOI: 10.1186/s13046-022-02245-0 -
Endocrine Oncology (Bristol, England) Jan 2022Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and... (Review)
Review
Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushing's disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors - obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.
PubMed: 37435457
DOI: 10.1530/EO-21-0033 -
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 -
Journal of the Endocrine Society Oct 2021Surgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain...
CONTEXT
Surgical management of prolactinomas is an important treatment for patients intolerant of dopamine agonist therapy. However, predictors of postoperative outcomes remain unclear.
OBJECT
While transsphenoidal surgical resection (TSSR) is important second-line therapy in prolactinoma patients, predictors of surgical cure and biochemical remission following TSSR remain sparse.
METHODS
A retrospective review of prolactinoma patients undergoing TSSR at the USC Pituitary Center from 1995 to 2020 was conducted. Participants were categorized as surgical cure (normalization of serum prolactin without medical treatment), surgical noncure, biochemical control (prolactin normalization with or without adjuvant therapy), and nonbiochemical control. A systematic review of the outcomes of surgically managed prolactinomas was performed.
RESULTS
The 40 female and 16 male participants had an average age of 35.6 years. Prior treatment included transsphenoidal resection (6, 11%) and dopamine agonist treatment (47, 84%). The 40 macroadenomas and 15 microadenomas exhibited suprasellar extension (24, 43%) and parasellar invasion (20, 36%). Fifteen (27%) were purely intrasellar. Gross total resection was achieved in 25 patients (45%) and subtotal in 26 (46%). Surgical cure was achieved in 25 patients (46%) and biochemical control in 35 (64%). Surgical cure was more likely in smaller, noninvasive tumors, those that were fully resected, and patients with lower preoperative (< 1000 ng/mL) and immediately postoperative (< 7.6 ng/mL) prolactin levels. Ten of 26 patients (38%) undergoing adjuvant therapy achieved biochemical control, which was less likely in men and those with higher preoperative prolactin or invasive tumors.
CONCLUSION
Surgical resection of prolactinomas is a safe procedure that, when offered judiciously, can achieve symptom and/or biochemical control in a majority of patients. A variety of predictors may be useful in advising patients on likelihood of postoperative remission.
PubMed: 34466765
DOI: 10.1210/jendso/bvab074 -
Journal of Clinical Neuroscience :... Sep 2023Pituitary adenomas are the most common sellar tumors, and may cause adverse outcomes in terms of morbidity and mortality if left untreated or if diagnosis is delayed. No...
PURPOSE
Pituitary adenomas are the most common sellar tumors, and may cause adverse outcomes in terms of morbidity and mortality if left untreated or if diagnosis is delayed. No data exists on the prevalence, characteristics, and prognosis of pituitary adenomas in Thailand. The systematic registration of clinical characteristics may improve patient care and prognosis for this disease in Thailand.
METHODS
This was a retrospective study conducted in 11 academic referral centers. All patients diagnosed with pituitary adenomas during the 2011---2014 period were enrolled in the study. The information was correlated with two national databases.
RESULTS
A total of 1,283 pituitary adenoma patients were identified. The adenomas were: non-functioning 50.1%, prolactinoma 29.4%, acromegaly 14.7%, Cushing disease 3.8%, gonadotropin-producing tumor 1.0%, TSH-secreting tumor 0.6%. The mean age was 49.2±15.2 years. Sixty-three percent of patients were female. Most common complaint was visual impairment (27.7%). The average size of the tumor was 22.2±16.1 mm. Fifty-nine percent of patients underwent surgery. Median follow-up was 27.4 months (0-24 years). After treatment, 72.4% improved, and 10.4% were cured. Overall results of treatment in non-functioning adenoma, prolactinoma (medically treated), acromegaly, Cushing, TSH, gonadotropin producing adenoma were: improved/cured in 81/5.5, 86/5.7, 55.9/30, 54.2/31.2, 85.7/14.3, 69.2/15.4% respectively.
CONCLUSION
Pituitary adenomas in academic centers in Thailand were found predominantly in female in the 4th decade of life. After treatment 72.4% of patients improved and 10% had full recovery. A health promotion system aimed to improve patient and physician recognition and physician expertise may improve the prognosis of these diseases.
Topics: Humans; Female; Adult; Middle Aged; Male; Pituitary Neoplasms; Prolactinoma; Acromegaly; Retrospective Studies; Thailand; Adenoma; Thyrotropin
PubMed: 37572520
DOI: 10.1016/j.jocn.2023.07.026 -
Journal of Medical Case Reports Apr 2022Managing treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and...
BACKGROUND
Managing treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited.
CASE PRESENTATION
A 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case.
CONCLUSION
This case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.
Topics: Adolescent; Adult; Cabergoline; Female; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactin; Prolactinoma; Temozolomide; Young Adult
PubMed: 35488355
DOI: 10.1186/s13256-022-03390-y -
Turkish Journal of Ophthalmology Dec 2022To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of...
OBJECTIVES
To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia.
MATERIALS AND METHODS
Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients.
RESULTS
The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036).
CONCLUSION
Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent.
Topics: Humans; Prolactinoma; Hyperprolactinemia; Cross-Sectional Studies; Tears; Pituitary Neoplasms
PubMed: 36578179
DOI: 10.4274/tjo.galenos.2022.98752