-
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