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Endocrine Connections Oct 2019Recent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to...
OBJECTIVES
Recent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to systematically assess the effect of reducing prolactin with dopamine agonist on established cardiovascular risk factors in patients with prolactinomas.
DESIGN
Bibliographical search was done until February 2019 searching the following databases: PubMed, EMBASE, WHO and LILAC. Eligible studies had to include participants with verified prolactinomas where metabolic variables were assessed before and after at least 2 weeks treatment with dopamine agonists.
METHODS
Baseline data and outcomes were independently collected by two investigators. The study was registered with PROSPERO (registration number CRD42016046525).
RESULTS
Fourteen observational studies enrolling 387 participants were included. The pooled standardized mean difference of the primary outcome revealed a reduction of BMI and weight of -0.21 (95% CI -0.37 to -0.05; P = 0.01; I2 = 71%), after treatment. Subgroup analysis suggested that the reduction of weight was primarily driven by studies with high prolactin levels at baseline (P = 0.04). Secondary outcomes suggested a small decrease in waist circumference, a small-to-moderate decrease in triglycerides, fasting glucose levels, HOMA-IR, HbA1c and hsCRP, and a moderate decrease in LDL, total cholesterol and insulin.
CONCLUSION
This systematic review suggests a reduction of weight as well as an improved lipid profile and glucose tolerance after treatment with dopamine agonist in patients with prolactinomas. These data are based on low-quality evidence.
PubMed: 31518995
DOI: 10.1530/EC-19-0286 -
Frontiers in Endocrinology 2018This meta-analysis aims to evaluate the long-term efficacy of medication treatment vs. surgery treatment in patients with prolactinomas. An electronic literature...
This meta-analysis aims to evaluate the long-term efficacy of medication treatment vs. surgery treatment in patients with prolactinomas. An electronic literature search was performed using MEDLINE, EMBASE and Web of Science databases for studies dated before July in 2018. Patients with prolactinomas received primary dopamine agonists (DAs) treatment or primary surgical interventions were included in this study. A systematic review and meta-analysis were performed in pertinent studies meeting eligible criteria. The clinical outcome was measured by the long-term remission rate of prolactin (PRL) in each cohort. The pooled data was analyzed according to a random effect model. Thirteen publications with total 809 patients were included in the final meta-analysis. In the overall patients with prolactinomas, long-term remission rate was achieved in 88% patients treated with surgeries and in 52% patients treated with DAs ( = 0.001). The long-term remission rates in surgery cohort were also significantly higher than medication cohort in both microprolactinomas and macroprolactinomas (91 vs. 60%, = 0.002; 77 vs. 43%, = 0.003). Patients with prolactinomas, especially microprolactinomas, can consider transsphenoidal surgery as an alternative first-line treatment strategy. After receiving primary surgical intervention, administration of DAs should be considered based on the postoperative PRL level to achieve the best long-term remission rate.
PubMed: 30410470
DOI: 10.3389/fendo.2018.00636 -
Clinical Endocrinology Dec 2018Cancers are a leading cause of death worldwide, and transgender individuals are no exception. The effects of gender-affirming hormone therapy (GAHT) on sex...
BACKGROUND
Cancers are a leading cause of death worldwide, and transgender individuals are no exception. The effects of gender-affirming hormone therapy (GAHT) on sex hormone-dependent tumours are unclear. Therefore, this review seeks to determine whether tumour risk in transgender individuals differs from the general population, to guide clinical screening recommendations.
METHODS
We performed a systematic review based on the PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining tumour incidence, prevalence or cancer-related mortality in transgender individuals. All English peer-reviewed publications were included if histological type and temporal relation to GAHT were reported. Case reports were included if there were ≥2 cases of the same histological type.
RESULTS
The search strategy identified 307 studies. Excluding those that did not meet inclusion criteria, 43 studies (7 cohort studies, 2 cross-sectional studies and 34 case reports) were reviewed. Retrospective cohort studies suggest no increase in risk of tumour development in transgender individuals receiving GAHT compared to the general population. Notably, the mean ages of cohorts were young and were treated with GAHT for insufficient durations to assess tumour risk. Case reports raise potential associations between high-dose oestradiol and anti-androgen therapy with prolactinoma and meningioma, respectively.
CONCLUSIONS
Further longitudinal studies are required to assess the risk of GAHT and hormone-dependent tumour development. Until further evidence is available, tumour screening should be based on guidelines for the general population and the presence of organs in transgender individuals rather than gender identity or hormonal therapy status.
Topics: Estradiol; Humans; Neoplasms, Hormone-Dependent; Testosterone; Transgender Persons
PubMed: 30107028
DOI: 10.1111/cen.13835 -
Metabolic Brain Disease Jun 2018The aim of this study is to compare the efficacy of bromocriptine (BRC) versus cabergoline (CAB) in patients with giant prolactinomas. We searched MEDLINE, EMBASE,...
The aim of this study is to compare the efficacy of bromocriptine (BRC) versus cabergoline (CAB) in patients with giant prolactinomas. We searched MEDLINE, EMBASE, CENTRAL and Clinical Trials.gov for studies dated before March 1st, 2016, that used BRC or CAB for the treatment of patients with giant prolactinomas. Specific eligibility criteria were set to identify articles and cases. The selected articles were reviewed, and the data were extracted for analysis. The compared outcomes included tumor shrinkage, tumor response, normalization of prolactin (PRL) level, and visual field defect (VFD) improvement. Gender differences were also considered. Differences between the groups were assessed using Student's t test and the chi-square test. Two hundred and forty-five records were identified, and 10 articles and 104 cases met the inclusion criteria. Based on our analysis, CAB is significantly better than BRC in normalizing PRL levels in patients, especially males, with giant prolactinomas (69.4% versus 31.7%, p = 0.01). However, there was no significant difference between the two drugs in terms of tumor shrinkage, tumor response and VFD improvement (p > 0.05) in male or female patients. CAB exhibits significantly better efficacy than BRC in the normalization of PRL levels in male patients with giant prolactinomas. Regarding tumor reduction and VFD improvement, both drugs are comparably effective for patients of both genders. This quantitative and systematic review provides preliminary evidence in favor of CAB as a medical therapy for treating giant prolactinomas in male patients, especially those with extremely high PRL levels.
Topics: Adult; Bromocriptine; Cabergoline; Female; Humans; Hydranencephaly; Kidney Diseases; Male; Middle Aged; Prolactin; Prolactinoma; Sex Distribution; Treatment Outcome
PubMed: 29546691
DOI: 10.1007/s11011-018-0217-3 -
Neurosurgery Oct 2018Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk...
BACKGROUND
Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology.
OBJECTIVE
To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence.
METHODS
A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth.
RESULTS
Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression.
CONCLUSION
Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.
Topics: Adenoma; Adult; Aged; Female; Humans; Middle Aged; Pituitary Neoplasms; Prognosis
PubMed: 29165661
DOI: 10.1093/neuros/nyx541 -
Endocrine Jan 2018Dopamine agonists (DAs) are recommended as first-line treatment for patients with hyperprolactinemia. Generally, it is accepted that patients with hyperprolactinemia do... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Dopamine agonists (DAs) are recommended as first-line treatment for patients with hyperprolactinemia. Generally, it is accepted that patients with hyperprolactinemia do not need lifelong medication, but the optimal timing for DA withdrawal has not been determined. The aim of this systematic review and meta-analysis is to assess the impact of DA withdrawal on the clinical outcomes of patients with hyperprolactinemia, and to explore possible factors affecting successful DA withdrawal.
METHODS
The databases of PubMed, Cochrane and EMBASE were searched up to May 2016.
RESULTS
The proportion of patients with persisting normoprolactinemia after DA withdrawal reached 36.6% in a random effects model (95% CI, 29.4-44.2%; I-squared: 82.5%). Data of stratified analysis showed that the success rate of drug withdrawal was high in patients using cabergoline (CAB) as the only treatment (41.2%; 95% CI 32.3-50.4%) and those using CAB over 24 months (48.7%; 95% CI 38.9-58.5%), especially in patients with idiopathic hyperprolactinemia (73.2%; 95% CI 55.6-87.7%). In addition, patients who received a low maintenance dose of CAB, and had a significant reduction in tumor size (over 50%) before withdrawal, were more likely to achieve success (51.5 and 49.4%, respectively).
CONCLUSION
The success rate of DA withdrawal has increased in recent years. Further, the success rate of CAB withdrawal was higher than that of bromocriptine, especially in patients with a duration of treatment longer than 24 months. Conclusively, the probability of success was higher in patients who received low-dose CAB maintenance treatment and those who achieved a significant reduction in tumor size before withdrawal.
Topics: Dopamine Agonists; Drug Administration Schedule; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Time Factors; Withholding Treatment
PubMed: 29043560
DOI: 10.1007/s12020-017-1444-9 -
Cancers Aug 2017Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by... (Review)
Review
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959-2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3-14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5-9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas.
PubMed: 28786923
DOI: 10.3390/cancers9080103 -
Hormones (Athens, Greece) Apr 2017Pituitary tumors represent 10-15% of all intracranial tumors; of these, prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to dopamine... (Review)
Review
Pituitary tumors represent 10-15% of all intracranial tumors; of these, prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to dopamine agonists (DA) as first-line therapy. However, treatment resistance remains a concern. Temozolomide (TMZ) is an oral alkylating agent that has shown promise in treating aggressive pituitary adenomas and carcinomas that are resistant to other therapies. To date, no control trials have been undertaken and only single case reports of pituitary tumors treated with TMZ have been published. A systematic literature search was conducted for studies reporting the use of TMZ for the treatment of prolactinomas that were resistant to standard therapy. In total, 42 reported cases were identified and included in our analysis: 23 cases of prolactin-secreting adenomas and 19 of prolactin-secreting carcinomas. Prior to TMZ administration, patients had exhibited tumor progression and had previously undergone various treatments including surgery, radiotherapy, and drug therapy. Tumor shrinkage was reported in 76% of patients. Reduced prolactin levels were observed in 75% of patients, while normalization of prolactin was reported in 8%. TMZ failure occurred in 20.6% of cases. Most patients exhibited no serious adverse effects. In conclusion, TMZ has potential for the treatment of highly aggressive and resistant prolactin-secreting adenomas and carcinomas, as demonstrated by tumor shrinkage or complete response and normalization of hormone hypersecretion, and exhibits good tolerability and few side effects.
Topics: Antineoplastic Agents, Alkylating; Carcinoma; Dacarbazine; Humans; Pituitary Neoplasms; Prolactinoma; Temozolomide
PubMed: 28742502
DOI: 10.14310/horm.2002.1729 -
Medicine Jun 2016The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix... (Meta-Analysis)
Meta-Analysis Review
Matrix metalloproteinase-9 and -2 and tissue inhibitor of matrix metalloproteinase-2 in invasive pituitary adenomas: A systematic review and meta-analysis of case-control trials.
The extracellular matrix is important for tumor invasion and metastasis. Normal function of the extracellular matrix depends on the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The objective of this meta-analysis was to assess the relationship between expression of MMP-9, MMP-2, and TIMP-2 and invasion of pituitary adenomas.We searched Pubmed, Embase, and the Chinese Biomedical Database up to October 2015. RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark) was used for statistical analysis. We calculated the standardized mean difference (SMD) for data expressed as mean ± standard deviation because of the difference in the detection method.Twenty-four studies (1320 patients) were included. MMP-9 expression was higher in the patients with invasive pituitary adenomas (IPAs) than patients with noninvasive pituitary adenomas (NIPAs) with detection methods of IHC [odds ratio (OR) = 5.48, 95% confidence interval (CI) = 2.61-11.50, P < 0.00001), and reverse transcriptase-polymerase chain reaction (SMD = 2.28, 95% CI = 0.91-3.64, P = 0.001). MMP-2 expression was also increased in patients with IPAs at the protein level (OR = 3.58, 95% CI = 1.63-7.87, P = 0.001), and RNA level (SMD = 3.91, 95% CI = 1.52-6.29, P = 0.001). Meta-analysis showed that there was no difference in TIMP-2 expression between invasive and NIPAs at the protein level (OR = 0.38, 95% CI = 0.06-2.26, P = 0.29). MMP-9 expression in prolactinomas and nonfunctioning pituitary adenomas was also no difference (OR = 1.03, 95% CI = 0.48-2.20, P = 0.95).The results indicated that MMP-9 and -2 may be correlated with invasiveness of pituitary adenomas, although their relationship with functional status of pituitary adenomas is still not clear. TIMP-2 expression in IPAs needs to be investigated further.
Topics: Biomarkers, Tumor; Case-Control Studies; Clinical Trials as Topic; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Pituitary Neoplasms; Tissue Inhibitor of Metalloproteinase-2
PubMed: 27310993
DOI: 10.1097/MD.0000000000003904 -
Neuro Endocrinology Letters 2015Hyperprolactinemia is associated with bone fragility. Traditionally attributed to prolactin-induced hypogonadism, recent studies have identified increased fracture rates... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Hyperprolactinemia is associated with bone fragility. Traditionally attributed to prolactin-induced hypogonadism, recent studies have identified increased fracture rates independent of gonadal function.
METHODS
We performed a systematic review to identify studies assessing fracture risk in patients with untreated hyperprolactinemia compared to those on dopamine agonists. MEDLINE, EMBASE, Cochrane, Web of Science and BIOSIS Previews databases were searched from inception to December 2013 for studies of hyperprolactinemia with fractures as an outcome. Two authors independently performed title and abstract searches, full-text searches, data abstraction, and quality assessment. A summary odds ratio (OR) was calculated using a random effects model.
RESULTS
Of the 197 articles identified, 2 met inclusion criteria. Both cross-sectional studies examined cabergoline use (or non-use) in patients with prolactin-secreting adenomas, with vertebral fractures as the primary outcome. For women, vertebral fractures were identified in 46% of untreated patients, vs. 20% of patients on cabergoline (OR: 0.29, 95% CI: 0.10-0.78). For men, the results were 67% in untreated, vs. 26% in cabergoline treated patients (OR: 0.18, CI: 0.03-0.94), with no difference between gonadal and hypogonadal men (p=0.8). Combining studies gave a summary odds ratio of 0.25 (CI: 0.11-0.59), I2=0%.
CONCLUSIONS
In the limited studies available, fracture prevalence was increased in patients with untreated hyperprolactinemia compared to those on treatment, independent of gonadal function. Further studies are needed to clarify if post-menopausal women, or high-risk men, with no other indication for treatment, should be on dopamine agonists to decrease fracture risk.
Topics: Cabergoline; Dopamine Agonists; Ergolines; Female; Humans; Hyperprolactinemia; Hypogonadism; Male; Odds Ratio; Osteoporotic Fractures; Pituitary Neoplasms; Prevalence; Prolactinoma; Sex Factors; Spinal Fractures
PubMed: 26921574
DOI: No ID Found