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Pituitary Feb 2016Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for... (Review)
Review
INTRODUCTION
Prolactinomas are the most common functional pituitary adenomas. Current classification systems rely on phenotypic elements and have few molecular markers for complementary classification. Treatment protocols for prolactinomas are also devoid of molecular targets, leaving those refractory to standard treatments without many options.
METHODS
A systematic literature review was performed utilizing the PRISMA guidelines. We aimed to summarize prior research exploring gene and protein expression in prolactinomas in order to highlight molecular variations associated with tumor development, growth, and prolactin secretion. A PubMed search of select MeSH terms was performed to identify all studies reporting gene and protein expression findings in prolactinomas from 1990 to 2014.
RESULTS
1392 abstracts were screened and 51 manuscripts were included in the analysis, yielding 54 upregulated and 95 downregulated genes measured by various direct and indirect analytical methods. Of the many genes identified, three upregulated (HMGA2, HST, SNAP25), and three downregulated (UGT2B7, Let7, miR-493) genes were selected for further analysis based on our subjective identification of strong potential targets.
CONCLUSIONS
Many significant genes have been identified and validated in prolactinomas and most have not been fully analyzed for therapeutic and diagnostic potential. These genes could become candidate molecular targets for biomarker development and precision drug targeting as well as catalyze deeper research efforts utilizing next generation profiling/sequencing techniques, particularly genome scale expression and epigenomic analyses.
Topics: Gene Expression Regulation, Neoplastic; Humans; Pituitary Neoplasms; Prolactinoma
PubMed: 26238304
DOI: 10.1007/s11102-015-0674-1 -
Pituitary Oct 2015Pituitary adenomas give rise to physical and psychological symptoms, which may persist after biochemical cure. Growing attention has been paid to quality of life (QoL)... (Review)
Review
PURPOSE
Pituitary adenomas give rise to physical and psychological symptoms, which may persist after biochemical cure. Growing attention has been paid to quality of life (QoL) in these patients. We aimed to systematically analyze QoL assessment methods and QoL outcome in these patients.
METHODS
We conducted a systematic literature search up to January 2014 in PubMed, Web of Knowledge, PsycInfo and EMBASE.
RESULTS
102 papers assessing QoL in patients with a pituitary adenoma were included. In clinical (original) studies in which QoL was the primary outcome parameter (n = 54), 19 studies combined a generic questionnaire with a disease-specific questionnaire. QoL was found to be impaired in patients with active disease relative to controls, and generally improved during biochemical cure. However, no normalization occurred, with patients with remitted Cushing's disease demonstrating the smallest improvement. Somatic factors (e.g., hypopituitarism, sleep characteristics), psychological factors (illness perceptions) and health care environment (rural vs. urban) were identified as influencing factors. Intervention studies (predominantly evaluating medical interventions) have been found to improve QoL.
CONCLUSIONS
The growing number of studies assessing QoL generally described the negative impact of pituitary adenomas. QoL research in this patient group could be further elaborated by the development of disease-specific questionnaires for prolactinoma and non-functioning adenoma, consequent use of generic and disease-specific questionnaires and using a long-term (longitudinal) follow-up. Surgical and pharmacological interventions improve but not normalize QoL. We postulate that there might be margin for further improvement of QoL, for instance by using psychosocial interventions, in addition to optimal medical treatment.
Topics: Adenoma; Cost of Illness; Humans; Pituitary Neoplasms; Prognosis; Quality of Life; Risk Factors; Surveys and Questionnaires
PubMed: 25605584
DOI: 10.1007/s11102-015-0636-7 -
Pituitary Oct 2015Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and the accurate recurrence rate associated with cabergoline withdrawal remains uncertain.
OBJECTIVE
To assess the current recurrence rate of hyperprolactinemia and possible favorable factors associated with cabergoline withdrawal in prolactinoma patients.
METHOD
The databases of PubMed, EMBASE, and Web of Science were searched up to May 2014 to identify studies containing data of recurrent hyperprolactinemia in prolactinoma patients after cabergoline withdrawal. Meta-analysis, including sensitivity analysis, meta-regression analysis, and subgroup analysis were performed.
RESULTS
When the patients who received cabergoline withdrawal were pooled, it was found that the hyperprolactinemia recurrence rate was 65% by a random effects meta-analysis [95% confidence interval 55-74%]. In a random effects meta-regression adjusting for optimal withdrawal strategies, CAB dose reduced to the lowest level before withdrawal was associated with treatment success (p = 0.006), whereas CAB treatment longer than 2 years showed no trend of effect (p = 0.587). Patients who received the lowest CAB dose and presented a significant reduction in tumor size before withdrawal were more likely to achieve the best success (p < 0.001).
CONCLUSIONS
Our meta-analysis shows that hyperprolactinemia recurs after cabergoline withdrawal in a majority of patients. The probability of success favors patients who have achieved normoprolactinemia and considerable reduction in tumor size by low dose of cabergoline treatment. In addition, our study further suggests that a beneficial strategy is associated with tapering CAB dose before withdrawal but not with CAB treatment duration longer than 2 years.
Topics: Biomarkers, Tumor; Cabergoline; Dopamine Agonists; Drug Administration Schedule; Ergolines; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma; Recurrence; Time Factors; Treatment Outcome; Tumor Burden
PubMed: 25500765
DOI: 10.1007/s11102-014-0617-2 -
The Lancet. Diabetes & Endocrinology Nov 2015Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to... (Review)
Review
Present recommendations by the US Food and Drug Administration advise that patients with prolactinoma treated with cabergoline should have an annual echocardiogram to screen for valvular heart disease. Here, we present new clinical data and a systematic review of the scientific literature showing that the prevalence of cabergoline-associated valvulopathy is very low. We prospectively assessed 40 patients with prolactinoma taking cabergoline. Cardiovascular examination before echocardiography detected an audible systolic murmur in 10% of cases (all were functional murmurs), and no clinically significant valvular lesion was shown on echocardiogram in the 90% of patients without a murmur. Our systematic review identified 21 studies that assessed the presence of valvular abnormalities in patients with prolactinoma treated with cabergoline. Including our new clinical data, only two (0·11%) of 1811 patients were confirmed to have cabergoline-associated valvulopathy (three [0·17%] if possible cases were included). The probability of clinically significant valvular heart disease is low in the absence of a murmur. On the basis of these findings, we challenge the present recommendations to do routine echocardiography in all patients taking cabergoline for prolactinoma every 12 months. We propose that such patients should be screened by a clinical cardiovascular examination and that echocardiogram should be reserved for those patients with an audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those who maintain cabergoline treatment after the age of 50 years.
Topics: Adult; Antineoplastic Agents; Cabergoline; Dopamine Agonists; Echocardiography; Ergolines; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactinoma
PubMed: 25466526
DOI: 10.1016/S2213-8587(14)70212-8 -
Endocrine Practice : Official Journal... Jan 2014Since the 1980s, it has been discussed whether the preoperative treatment of prolactinomas with dopamine agonists (DAs) is beneficial or detrimental regarding... (Review)
Review
OBJECTIVE
Since the 1980s, it has been discussed whether the preoperative treatment of prolactinomas with dopamine agonists (DAs) is beneficial or detrimental regarding postoperative residue or recurrence. Many neurosurgeons have emphasized the difficulties caused by fibrosis during the ablation of such prolactinomas.
METHODS
From February to December 2012, the authors searched electronic databases and book chapters published from 1991 to 2012; a total of 3,771 articles and 37 book chapters were searched. Ten articles that explicitly addressed this issue were identified.
RESULTS
Five articles reported that preoperative treatment did not affect postoperative status. One article described a positive influence of preoperative treatment with DAs (P < .01), and 3 articles found a negative influence (P = .040, P = .02, no significance value reported). One article described histopathological evidence of tumor fibrosis that was found intraoperatively after preoperative DA treatment.
CONCLUSIONS
This systematic review did not identify any strong evidence that preoperative treatment of prolactinomas with DAs is harmful or beneficial. Therefore, further studies are needed.
Topics: Adolescent; Adult; Dopamine Agonists; Humans; Middle Aged; Postoperative Period; Preoperative Period; Prolactinoma
PubMed: 24013992
DOI: 10.4158/EP13165.RA -
CNS & Neurological Disorders Drug... Dec 2012Many researches that discourse the treatment of prolactinomas with dopamine agonists (DA) provide data about pituitary tumor apoplexy of some prolactinomas. Therefore,... (Review)
Review
Many researches that discourse the treatment of prolactinomas with dopamine agonists (DA) provide data about pituitary tumor apoplexy of some prolactinomas. Therefore, DA are listed as risk factors for apoplexy of prolactinomas. The authors wish to explore the percentage (frequency) of pituitary tumor apoplexy during the treatment of prolactinomas with DA. From June 2011 to February 2012, we sought electronic databases and found 2169 articles and 71 book chapters relevant to DA. Only seven articles have been included into systematic review and from 4 articles we extracted numerical data that showed percentage of pituitary tumor apoplexy. One hundred and fifty-seven patients treated with DA were included in four studies. Results showed the following percentage of apoplexy during the treatment of prolactinomas with DA (apoplexy/therapy ratio): 1/84(1,19%), 13/29(44,83%), 1/15(6,67%) and 1/29(3,45%). One result stands out from the other (13/29-44,83%) because of retrospective search for pituitary hemorrhage by MRI imaging of sellar region and some of the patients were without clinical signs of apoplexy. Median and mean age of included patients was usually over 30 years. Pituitary tumor apoplexy appeared more frequently in macroprolactinomas than in microprolactinomas and also within a year and a half since the beginning of treatment with DA. Conclusively, clinically manifested pituitary tumor apoplexy appears in relatively small percentage of prolactinomas treated with DA. We were also concluded that apoplexy appears asymptomatic and because of that and because of more frequently appearing in macroprolactinomas, there are recommendations for performing MRI imaging of sellar region more often in patients with macroprolactinomas than in patients with microprolactinomas who are treated with DA.
Topics: Animals; Clinical Trials as Topic; Dopamine Agonists; Humans; Pituitary Apoplexy; Pituitary Neoplasms; Prolactinoma; Time Factors; Treatment Outcome
PubMed: 23244423
DOI: 10.2174/1871527311211080011 -
Current Opinion in Endocrinology,... Aug 2011Despite the widespread use of dopamine agonists for patients with prolactinomas and symptomatic idiopathic hyperprolactinemia for many decades, the optimal treatment... (Review)
Review
PURPOSE OF REVIEW
Despite the widespread use of dopamine agonists for patients with prolactinomas and symptomatic idiopathic hyperprolactinemia for many decades, the optimal treatment strategy and duration of treatment is still not evident. This review highlights the effects of dopamine agonist withdrawal in patients with idiopathic hyperprolactinemia and prolactinomas in detail, including the factors influencing the success of treatment outcome.
RECENT FINDINGS
It appeared that a subgroup of patients with a high likelihood of achieving remission could be identified on clinical criteria, which were incorporated in the Pituitary Society 2006 consensus guidelines. A recent systematic review and meta-analysis, however, demonstrated that the pooled proportion of patients with persisting normoprolactinemia after dopamine agonist withdrawal was only 21%, with a higher treatment success in idiopathic hyperprolactinemia (32%), compared with both microprolactinomas (21%) and macroprolactinomas (16%). In a random effects meta-regression, longer treatment duration was associated with treatment success. The probability of treatment success was highest when cabergoline was used for at least 2 years. Recommendations have now been adjusted accordingly in the 2011 Endocrine Society Practical guideline.
SUMMARY
Hyperprolactinemia will recur after dopamine agonist withdrawal in a considerable proportion of patients, but not all dopamine agonists have comparable efficacy. The optimal withdrawal strategy still needs to be determined in further studies.
Topics: Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Treatment Outcome; Withholding Treatment
PubMed: 21844709
DOI: 10.1097/MED.0b013e328347c94a -
Pituitary Sep 2011Cabergoline and bromocriptine are the most used drugs in the treatment of hyperprolactinemia, they are able to normalize the prolactin levels, restore gonadal function... (Meta-Analysis)
Meta-Analysis Review
Cabergoline and bromocriptine are the most used drugs in the treatment of hyperprolactinemia, they are able to normalize the prolactin levels, restore gonadal function and promote tumor reduction in the majority of patients. We undertake a systematic review and meta-analysis of randomized controlled trials to compare cabergoline versus bromocriptine in the treatment of patients with idiopathic hyperprolactinemia and prolactinomas. The data sources were: Embase, Pubmed, Lilacs and Cochrane Central. The outcome measures were: normalization of prolactin secretion, restoration of gonadal function, reduction of tumoral volume, quality of life and adverse drug effects. Were identified 418 references and after screening by title and abstract, we obtained complete copies of 34 articles potentially eligible for inclusion in the review. From this total, 19 were selected to be included, but fifteen of them were excluded due to the following reasons: one randomized study compared cabergoline versus placebo and other randomized study compared different doses of cabergoline; five references were cases series; four were only controlled studies; three were retrospectives series and; one was a cohort study. Therefore, four publications were included in the review and in the final analysis. The meta-analysis of normalization of serum prolactin levels and menstruation with return of ovulatory cycle showed a significant difference in favor of cabergoline group (RR 0.67 [CI 95% 0.57, 0.80]) e (RR 0.74 [CI 95% 0.67, 0.83]), respectively. The number of adverse effects was significantly higher in the bromocriptine number than in cabergoline group (RR 1.43 [CI 95% 1.03, 1.98]). The meta-analysis showed new evidence favoring the use of cabergoline in comparison with bromocriptine for the treatment of prolactinomas and idiopathic hyperprolactinemia.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Humans; Hyperprolactinemia; Randomized Controlled Trials as Topic
PubMed: 21221817
DOI: 10.1007/s11102-010-0290-z -
The Journal of Clinical Endocrinology... Jan 2010Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia. However, the optimal treatment strategy and treatment... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia. However, the optimal treatment strategy and treatment duration is not clear in all details.
OBJECTIVE
The aim of the study was to assess the effect of dopamine agonist withdrawal in patients with idiopathic hyperprolactinemia and prolactinomas.
DATA SOURCES
PubMed, the Cochrane Library, the Web of Science, and EMBASE were searched electronically. No restriction was made with respect to language.
STUDY SELECTION
Studies reporting the proportion of normoprolactinemic patients after withdrawal of dopamine agonist or studies in which this proportion could be calculated were eligible. Both observational studies and clinical trials were eligible. Nineteen studies were included in the meta-analysis, with a total of 743 patients.
DATA EXTRACTION
Data extraction was performed by two reviewers independently.
DATA SYNTHESIS
The pooled proportion of patients with persisting normoprolactinemia after dopamine agonist withdrawal was 21% in a random effects model [95% confidence interval (CI), 14-30%; I(2) 81%). Stratified analysis showed higher proportions of treatment success in idiopathic hyperprolactinemia (32%; 95% CI, 5-80%), compared with both microprolactinomas (21%; 95% CI, 10-37%), and macroprolactinomas (16%; 95% CI, 6-36%). In a random effects meta-regression adjusting for cause of hyperprolactinemia, a longer treatment duration was associated with treatment success (P = 0.015), whereas the use of cabergoline showed a trend of effect (P = 0.07).
CONCLUSIONS
This meta-analysis showed that hyperprolactinemia will recur after dopamine agonist withdrawal in a considerable proportion of patients. The probability of treatment success was highest when cabergoline was used for at least 2 yr.
Topics: Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Recurrence; Treatment Outcome; Withholding Treatment
PubMed: 19880787
DOI: 10.1210/jc.2009-1238