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Journal of Psychiatric Practice May 2024Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin...
OBJECTIVE
Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin pathway, making them the first-line treatment for prolactinomas. However, the main side effect of DA treatment, hyperdopaminergia, is an explicit etiology for psychiatric side effects. Psychiatric conditions are often treated with dopamine antagonists, which can induce hyperprolactinemia. This presents a challenge for patients with both a prolactinoma and a preexisting psychiatric condition, as treatment of one condition could worsen the other. This review seeks to identify an adequate therapeutic regimen for patients with coexisting prolactinomas and psychiatric symptoms.
METHODS
This review examined PubMed citations from 1960 to 2023 published in English and involving human subjects. Case reports, case series, and cohort studies involving patients with concomitant prolactinomas and psychiatric symptoms, as validated by brain imaging, serologic prolactin levels, and medical history or chart reports of psychiatric symptoms, were included.
RESULTS
Thematic analysis included 23 reports involving 42 participants; 27 of the 42 patients experienced a significant reduction in prolactin levels and psychiatric symptoms (64%). Treatment of those 42 patients included discontinuing or altering antipsychotic/dopamine antagonist therapy or discontinuing DA therapy to reduce psychiatric symptoms, with surgery or radiation postpharmacotherapy as a last-line strategy. However, in some cases (reported in Tables 2 to 4), either psychiatric or prolactin-related symptoms recurred despite adjustment.
CONCLUSIONS
Clinicians may find it beneficial to prioritize specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) over others (risperidone, thioridazine, thiothixene, and remoxipride). Discontinuing DA medication at least periodically until the patient's condition improves may also be advisable. If these 2 initial approaches do not yield a significant improvement in symptom management, surgery or radiation therapy may be considered. As patients may respond differently to these therapies, our study still recommends a patient-centered approach.
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Mental Disorders; Dopamine Agonists; Antipsychotic Agents; Dopamine Antagonists
PubMed: 38819244
DOI: 10.1097/PRA.0000000000000783 -
Polish Archives of Internal Medicine May 2024
PubMed: 38809213
DOI: 10.20452/pamw.16767 -
Endocrine May 2024Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to...
OBJECTIVE
Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls.
METHODS
Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36).
RESULTS
Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05).
CONCLUSIONS
Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation.
CLINICAL TRIAL REGISTRATION
This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829).
PubMed: 38801597
DOI: 10.1007/s12020-024-03880-7 -
European Journal of Endocrinology Jun 2024Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune...
OBJECTIVE
Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells.
DESIGN AND METHODS
Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.
RESULTS
Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples.
CONCLUSIONS
Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG.
Topics: Humans; Cabergoline; Prolactinoma; Male; Female; Pituitary Neoplasms; Adult; Middle Aged; Fibrosis; Prolactin; Dopamine Agonists; CD8-Positive T-Lymphocytes; Stromal Cells; Young Adult; Tumor Microenvironment
PubMed: 38781434
DOI: 10.1093/ejendo/lvae055 -
Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.Journal of Biochemical and Molecular... Jun 2024We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor...
We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.
Topics: MicroRNAs; Curcumin; Humans; Autophagy; Prolactinoma; Cell Line, Tumor; Up-Regulation; Male; TOR Serine-Threonine Kinases; Female; Pituitary Neoplasms; Adult; Proto-Oncogene Proteins c-akt; Antineoplastic Agents; Signal Transduction; Cell Proliferation; Middle Aged; Rats
PubMed: 38764151
DOI: 10.1002/jbt.23734 -
Journal of Neuro-oncology Jun 2024Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very... (Review)
Review
CONTEXT
Functioning pituitary adenomas (FPAs) include most frequently prolactinomas, somatotroph or corticotroph adenomas, while thyrotroph and gonadotroph adenomas are very rare. Despite their benign histological nature (aggressive tumors are rare and malignant ones exceptional), FPAs could cause significant morbidity and increased mortality due to complications associated with hormonal excess syndromes and/or mass effect leading to compression of adjacent structures. This mini review will focus on the increasing role of medical therapy in the multimodal treatment, which also includes transsphenoidal surgery (TSS) and radiotherapy.
EVIDENCE SYNTHESIS
Most patients with prolactinomas are treated only with medications, but surgery could be considered for some patients in a specialized pituitary center, if higher chances of cure. Dopamine agonists, especially cabergoline, are efficient in reducing tumor size and normalizing prolactin. TSS is the first-line treatment for all other FPAs, but most patients require complex adjuvant treatment, including a combination of therapeutic approaches. Medical therapy is the cornerstone of treatment in all patients after unsuccessful surgery or when surgery cannot be offered and includes somatostatin receptor ligands and dopamine agonists (almost all FPAs), growth hormone receptor antagonists (acromegaly), adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers (Cushing's disease). Novel medical treatments, especially for acromegaly and Cushing's disease are under research.
CONCLUSIONS
An enlarged panel of effective drugs available with increased knowledge of predictive factors for response and/or adverse effects will enhance the possibility to offer a more individualized treatment. This would not only improve disease control and prognosis, but also quality of life.
Topics: Humans; Pituitary Neoplasms; Adenoma; Combined Modality Therapy; Clinical Trials as Topic
PubMed: 38760632
DOI: 10.1007/s11060-024-04670-x -
Neuroendocrinology May 2024Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predict the biological behaviour, aggressiveness, and response to immune checkpoint inhibitors in... (Review)
Review
BACKGROUND
Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predict the biological behaviour, aggressiveness, and response to immune checkpoint inhibitors in different cancers. We reviewed the published data on PD-L1 expression in pituitary tumours from the perspective of its biological role and prognostic usefulness.
SUMMARY
A literature review focused on PD-L1 expression in pituitary tumours was performed. Six immunohistochemistry-based studies which assessed PD-L1 positivity in pituitary tumours were included, encompassing 704 patients. The cohort consisted of 384 (54.5%) nonfunctioning tumours and 320 (43.5%) functioning pituitary tumours. PD-L1 expression was positive in 248 cases (35.2%). PD-L1 positivity rate was higher in functioning than in nonfunctioning tumours (46.3% vs. 26.0%; p < 0.001) but also higher in growth hormone-secreting tumours (56.7%) and prolactinomas (53.6%) than in thyrotroph (33.3%) or corticotroph tumours (20.6%). While proliferative pituitary tumours showed higher rate of PD-L1 positivity than non-proliferative tumours (p < 0.001), no association with invasion or recurrence was found.
KEY MESSAGES
PD-L1 is expressed in a substantial number of pituitary tumours, predominantly in the functioning ones. PD-L1 positivity rates were significantly higher in proliferative pituitary tumours in comparison to non-proliferative tumours, but no differences were found concerning invasive or recurrent pituitary tumours. More studies following homogeneous and standardised methodologies are needed to fully elucidate the role and usefulness of PD-L1 expression in pituitary tumours.
PubMed: 38754394
DOI: 10.1159/000539345 -
Journal of Neurological Surgery Reports Apr 2024Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom...
Prolactinomas are a common intracranial neoplasm and constitute most pituitary tumors. Although patients can present with variable hormone dysregulation and symptom severity, the use of dopamine agonists remains a first-line treatment. While bromocriptine has been found to increase tumor fibrosis, the effect of cabergoline on collagen deposition has been disputed. The aim of this article is to understand the influence of cabergoline on tumor fibrosis prior to resection. Four male patients who underwent prolactinoma resection were included in this report. The average age was 39.8 years (range: 26-52 years). Pre-treatment prolactin levels ranged from 957.8 to 16,487.4 ng/mL. Three patients received cabergoline for at least 1 month prior to surgery (treatment range: 1-6 months). One patient had surgery without prior cabergoline use. Pathology reports confirmed each tumor to be of lactotroph origin. For each sample, Masson's trichrome staining was performed and the percentage of sample fibrosis was quantified using an artificial intelligence imaging software. Among those who received preoperative cabergoline, the extent of tumor fibrosis was in the range of 50 to 70%. In contrast, specimen fibrosis was approximately 15% without cabergoline use. This report demonstrates that a short duration of preoperative cabergoline can cause significant prolactinoma fibrosis. Understanding the effect of cabergoline on tumor consistency prior to surgery is essential as increased fibrosis can lead to more difficult tumor removal, reduce the extent of resection, and increase surgical complications. Considering these effects, further studies regarding the use of surgery prior to cabergoline for prolactinoma management are warranted.
PubMed: 38751869
DOI: 10.1055/s-0044-1786740 -
Surgical Neurology International 2024Giant prolactinomas are rare; among them, the amyloidogenic variant, prolactinomas with extensive spherical amyloid deposits, are rare, with only 30 cases reported with...
BACKGROUND
Giant prolactinomas are rare; among them, the amyloidogenic variant, prolactinomas with extensive spherical amyloid deposits, are rare, with only 30 cases reported with recommendations of surgical management contrary to the routine prolactinoma's medical management.
CASE DESCRIPTION
We report here a case of giant amyloidogenic prolactinoma in a 32-year-old male patient who had a very atypical presentation in terms of clinical, radiological, and pathological features and responded to dopamine agonist therapy like a normal prolactinoma.
CONCLUSION
Amyloidogenic giant prolactinomas are rare. Contrary to usual belief, even they remain medically responsive; however, more literature is required to decide their ideal management.
PubMed: 38741982
DOI: 10.25259/SNI_150_2024