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Endocrine-related Cancer Dec 2022Prolactinomas have harmful effects on human health. Bromocriptine is the only commercially available drug in China, but about 25% of prolactinoma patients do not respond...
Prolactinomas have harmful effects on human health. Bromocriptine is the only commercially available drug in China, but about 25% of prolactinoma patients do not respond to it in clinic, its pathogenesis remains unknown. Thus, its pathogenesis needs to be determined to develop new therapeutic methods for prolactinomas. The expression of ERβ, TLR4, and prolactin (PRL) in the pituitary gland of C57BL/6 mice and human prolactinoma specimen was examined by immunofluorescence or immunohistochemistry. The role of TLR4 in prolactinoma was determined using estradiol-induced models of C57BL/6 wild-type and TLR4-/- mice. MMQ cells were treated with estradiol, fulvestrant, and lipopolysaccharide (LPS) or transfected with TLR4 siRNA to study the expression of ERβ, TLR4, and PRL in these cells. Furthermore, the interaction between ERβ and TLR4 was investigated by immunoprecipitation analysis. The expression of PRL and TLR4 was co-located and increased in the pituitary gland of mice and human prolactinoma specimen compared to that in the control specimen. Meanwhile, TLR4 knockout or treatment with the TLR4 inhibitor TAK242 not only significantly inhibited tumor overgrowth but also decreased the expression of PRL in estradiol-treated mice through p38 MAPK pathway regulation. However, MMQ treated with estradiol and LPS enhanced PRL expression than treated with estradiol or LPS alone. Finally, ERβ or TLR4 inhibition prevented the estradiol-induced PRL increase by regulating the TLR4/p38 MAPK pathway in vitro. Estradiol promoted prolactinoma development by activating the TLR4/p38 MAPK pathway through ERβ, and TLR4 is a potential therapeutic target for prolactinoma treatment.
Topics: Animals; Humans; Mice; Estradiol; Estrogen Receptor beta; Estrogens; Lipopolysaccharides; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Pituitary Neoplasms; Prolactin; Prolactinoma; Toll-Like Receptor 4
PubMed: 36219868
DOI: 10.1530/ERC-22-0168 -
Archives of Medical Research Dec 2023The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent...
BACKGROUND
The increased prevalence of Impulse Control Disorders (ICDs) in dopamine agonist (DA) treated patients with Parkinson's disease is well described. Despite the frequent use of DAs in the management of pituitary tumors, the relationship between DAs and prevalence of ICDs in patients with pituitary tumours is unclear.
AIMS
To establish the prevalence of ICDs in patients with prolactinoma or acromegaly and determine whether prevalence differs in those on DAs to those treated without.
METHODS
Systematic review of the literature (registered a priori) reporting prevalence of ICDs in patients with prolactinoma or acromegaly (conducted June 2023). A narrative synthesis describing prevalence of ICDs according to assessment method was performed. Prevalence comparisons between patients with prolactinoma or acromegaly treated with DAs, to patients treated without, were summarised.
RESULTS
Studies were largely retrospective, observational and heterogenous, with few patients with prolactinoma and acromegaly treated without DA. Prevalence of ICDs varied between 0-60% in patients with prolactinoma, and from 5-23% in studies with at least five patients with acromegaly. In most studies comparing DA exposed to non-DA exposed cases, DA use was not associated with ICDs.
CONCLUSIONS
Reported prevalence of ICDs in patients with prolactinoma and acromegaly varies considerably. Given ICDs were reported to be highly prevalent in some studies, clinicians should be mindful of these potentially serious disorders. ICD screening tools validated for use in patients with pituitary tumors combined with prospective studies including appropriate controls, are necessary to accurately establish prevalence of ICDs and true impact of DAs in their development.
Topics: Humans; Dopamine Agonists; Pituitary Neoplasms; Prolactinoma; Acromegaly; Retrospective Studies; Prospective Studies; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 37985276
DOI: 10.1016/j.arcmed.2023.102910 -
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 -
Osteoporosis International : a Journal... Jul 2022Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this...
PURPOSE
Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this study is to evaluate bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in prolactinoma patients.
METHODS
31 prolactinoma patients and 62 age- and sex-matched healthy controls in our center were included, and HR-pQCT was used to evaluate their bone microarchitecture at the radius and tibia. Z-scores for bone microarchitecture parameters were calculated based on previously published reference.
RESULTS
After adjusting for height and weight, prolactinoma patients had lower trabecular (- 0.011 mm, p = 0.005) and cortical thickness (- 0.116 mm, p = 0.008) and cortical area (- 6.0 mm2, p = 0.013) at radius, as well as lower trabecular (- 0.014 mm, p = 0.008) and cortical (- 0.122 mm, p = 0.022) thickness at tibia compared with the controls. Patients with higher prolactin level had more severe bone microarchitecture impairments. After adjusting for prolactin level and age, male patients had lower trabecular volumetric BMD (vBMD), trabecular number, trabecular thickness, and cortical porosity at radius, as well as lower trabecular vBMD, trabecular bone volume fraction, trabecular number, and cortical area, and higher trabecular separation at tibia compared with female patients. Z-score for radius vBMD was correlated with Z-score for areal BMD (aBMD) at lumbar and femoral neck, while Z-score for tibia vBMD was correlated with Z-score for lumbar aBMD, and some patients with vBMD Z-score below - 2.0 had aBMD Z-score within normal range.
CONCLUSION
Peripheral bone microarchitecture was impaired in prolactinoma patients, especially in patients with higher prolactin level. We compared the bone microarchitecture of prolactinoma patients and healthy controls by high-resolution peripheral quantitative computed tomography (HR-pQCT), and found that many bone microarchitecture parameters were impaired among prolactinoma patients. Such impairment was more prominent among patients with higher prolactin level.
Topics: Absorptiometry, Photon; Bone Density; Female; Femur Neck; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Radius; Tibia
PubMed: 35190851
DOI: 10.1007/s00198-021-06289-4 -
Pituitary Feb 2021Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma....
Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma. AIP-associated tumours are most commonly growth hormone (GH) producing. In our cohort of 175 AIP mutation positive patients representing 93 kindreds, 139 (79%) have GH excess, 19 have prolactinoma (17 familial and 2 sporadic cases) and out of the 17 clinically non-functioning tumours 4 were subsequently operated and found to be GH or GH & prolactin immunopositive adenoma. Here we report a family with an AIP variant, in which multiple family members are affected by prolactinoma, but none with GH excess. To our knowledge this is the first reported family with an AIP pathogenic variant to be affected solely by prolactinoma. These data suggest that prolactinoma families represent a small subset of AIP mutation positive kindreds, and similar to young-onset sporadic prolactinomas, AIP screening would be indicated.
Topics: Adenoma; Adult; Female; Genetic Testing; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Middle Aged; Mutation; Pedigree; Pituitary Neoplasms; Prolactinoma
PubMed: 33010004
DOI: 10.1007/s11102-020-01085-5 -
Cancers Feb 2024Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is...
Several subtypes of pituitary neuroendocrine tumors (PitNETs), such as acromegaly and Cushing's disease, can result in hypertension. However, whether prolactinoma is associated with this complication remains unknown. Moreover, the effect of treatment with surgery or drugs on blood pressure (BP) is unknown. Herein, a retrospective study reviewed 162 patients with prolactinoma who underwent transsphenoidal surgery between January 2005 and December 2022. BP measurements were performed 1 day before and 5 days after surgery. Accordingly, patients' medical characteristics were recorded. In addition, in situ rat and xenograft nude-mice prolactinoma models have been used to mimic prolactinoma. In vivo BP and serum prolactin (PRL) levels were measured after cabergoline (CAB) administration in both rats and mice. Our data suggest that surgery can effectively decrease BP in prolactinoma patients with or without hypertension. The BP-lowering effect was significantly associated with several variables, including age, sex, disease duration, tumor size, invasion, dopamine agonists (DAs)-resistance, recurrence, and preoperative PRL levels. Moreover, in situ and xenograft prolactinomas induced BP elevation, which was alleviated by CAB treatment without and with a statistical difference in rats and mice, respectively. Thus, surgery or CAB can decrease BP in prolactinoma, indicating that pre- and postoperative BP management becomes essential.
PubMed: 38398117
DOI: 10.3390/cancers16040726 -
Trends in Endocrinology and Metabolism:... Apr 2023Pituitary hormones regulate skeletal physiology, and excess levels affect bone remodeling and alter bone microstructure. Vertebral fractures (VFs) are an early... (Review)
Review
Pituitary hormones regulate skeletal physiology, and excess levels affect bone remodeling and alter bone microstructure. Vertebral fractures (VFs) are an early phenomenon of impaired bone health in secreting pituitary adenomas. However, they are not accurately predicted by areal bone mineral density (BMD). Emerging data demonstrate that a morphometric approach is essential for evaluating bone health in this clinical setting and is considered to be the gold standard method in acromegaly. Several novel tools have been proposed as alternative or additional methods for the prediction of fractures, particularly in pituitary-driven osteopathies. This review highlights the novel potential biomarkers and diagnostic methods for bone fragility, including their pathophysiological, clinical, radiological, and therapeutic implications in acromegaly, prolactinomas, and Cushing's disease.
Topics: Humans; Pituitary Neoplasms; Bone Density; Acromegaly; Prolactinoma; Fractures, Bone
PubMed: 36869001
DOI: 10.1016/j.tem.2023.01.006 -
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 -
Endocrinology and Metabolism (Seoul,... Jun 2021Only a few studies have established the epidemiology of prolactinoma and Cushing's disease in Korea. Furthermore, the incidence of these disease are increasing than...
BACKGROUND
Only a few studies have established the epidemiology of prolactinoma and Cushing's disease in Korea. Furthermore, the incidence of these disease are increasing than before associated with the development of technologies. This study was designed to evaluate the epidemiology of prolactinoma and Cushing's disease and their survival analysis according to treatment.
METHODS
The nationwide, population-based study evaluated incidence and prevalence of prolactinoma and Cushing's disease using de-identified claims data in The Korean Health Insurance Review and Assessment Service database between 2013 and 2017. The survival analysis investigated regarding treatment over a period of 6 years. A log-rank test and Cox proportional hazard regression analysis were used.
RESULTS
The 6,056 patients with newly diagnosed prolactinoma and 584 patients with Cushing's disease were recorded between 2013 and 2017. The annual incidence of prolactinoma was 23.5 cases per million, and its prevalence was 82.5 cases per million, and 2.3 cases per million/year and 9.8 cases per million for Cushing's disease. The survival benefit was insignificant in prolactinoma according to treatment, but treatment of Cushing's disease ameliorated the survival rate significantly.
CONCLUSION
Overall, the incidence of prolactinoma and Cushing's disease was similar with those found previously, but the prevalence of two diseases were inconsistent when compared with the early studies. The present study also proposed necessity of treatment in Cushing's disease for improving the survival rate.
Topics: Humans; Incidence; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactinoma; Survival Analysis
PubMed: 34218648
DOI: 10.3803/EnM.2021.1000 -
Pituitary Dec 2022To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization.
PURPOSE
To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization.
DESIGN
Retrospective cohort study.
METHODS
Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging, and visual fields tests were obtained. Univariate and multivariate models were used to identify predictors of HH persistence.
RESULTS
Fifty-eight male patients (age 49.2 ± 12.6 years) with a median baseline prolactin of 1154 ng/mL (IQR 478-2763 ng/mL) and adenoma (maximal) diameter of 25.9 ± 14.8 mm were followed for a median of 5.6 years (IQR 3.0-10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the first year following prolactin normalization. In a multivariate logistic regression model, hypopituitarism (OR 10.1; 95% CI 1.10-101.94), visual field defect (OR 9.9; 95% CI 1.07-92.33), and low baseline testosterone levels (OR 0.5; 95% CI 0.29-0.93) were independent predictors of HH persistence.
CONCLUSION
In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone deficiency, visual field defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the first year following prolactin normalization. These findings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas.
Topics: Humans; Male; Adult; Middle Aged; Prolactinoma; Cabergoline; Prolactin; Retrospective Studies; Hypopituitarism; Testosterone; Pituitary Neoplasms; Hypogonadism
PubMed: 36036309
DOI: 10.1007/s11102-022-01259-3