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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 -
Journal of Neurological Surgery. Part... Dec 2023Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We...
Stereotactic Radiosurgery Outcomes in Medically and Surgically Failed or Nonsurgical Candidates with Medically Failed Prolactinomas: A Systematic Review and Meta-Analysis.
Prolactinomas are treated with dopamine agonists (DAs) as first-line therapy and transsphenoidal surgery as an alternative approach for medically failed tumors. We sought to summarize the efficacy of stereotactic radiosurgery (SRS) in the medically and surgically failed prolactinomas as well as in nonsurgical candidates with medically failed prolactinomas by systematic review and meta-analysis. A literature search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. A total of 11 articles (total = 709) met inclusion criteria. Thirty-three percent of patients were able to achieve endocrine remission at a mean follow-up of 54.2 ± 42.2 months with no association between stopping DA and endocrine remission. Sixty-two percent of patients were able to achieve endocrine control with DA therapy and 34% of patients were able to decrease the dose of DA dose when compared with pre-SRS DA dose at the end of the follow-up period. However, 54% of patients required DA at the end of the follow-up to control hyperprolactinemia. Ninety percent of patients were able to achieve radiologic control at the end of the follow-up in comparison to pre-SRS imagings. Furthermore, 26% of patients newly developed hypopituitarism (one or more pituitary hormones) post-SRS throughout the follow-up period. This systematic review and meta-analysis demonstrates SRS as an effective adjunct therapy in medically failed nonsurgical candidates or surgically and medically recalcitrant prolactinomas with a 33% chance of achieving endocrine remission, 62% of patients achieved hormonal control with DA and GKRS (gamma knife radio-surgery), with a 34% chance of decreasing DA dose and 90% chance of achieving radiologic control.
PubMed: 37854534
DOI: 10.1055/a-1934-9028 -
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 -
Pituitary Dec 2021In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This... (Meta-Analysis)
Meta-Analysis
PURPOSE
In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy.
METHOD
A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically.
RESULTS
10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I = 86.34%).
CONCLUSIONS
This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.
Topics: Dopamine Agonists; Humans; Pituitary Neoplasms; Prolactin; Prolactinoma; Treatment Outcome
PubMed: 34580821
DOI: 10.1007/s11102-021-01188-7 -
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 -
World Neurosurgery Oct 2021Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Prolactin-secreting tumors respond well to medical management, with a few patients requiring surgery. We conducted a systematic review and meta-analysis to study the determinants of surgical remission in these tumors.
METHODS
We searched PubMed to identify eligible studies reporting postoperative remission in patients treated with transsphenoidal surgery for prolactinoma. Primary outcomes included postoperative remission, follow-up remission, and recurrence. Postoperative and follow-up remission were defined as normoprolactinemia at <1 year and >1 year after operation, respectively. Recurrence was defined as hyperprolactinemia after initial normalization of prolactin levels. Odds ratios (ORs) were calculated, stratified by radiologic size, tumor extension, and tumor invasion, and analyzed using a random-effects model meta-analysis.
RESULTS
Thirty-five studies were included. Macroadenomas were associated with lower rates of postoperative remission (OR, 0.20; 95% confidence interval [CI], 0.16-0.24) and lower rates of remission at follow-up (OR, 0.11; 95% CI, 0.053-0.22). Postoperative remission was less likely in tumors with extrasellar or suprasellar extension (OR, 0.16; 95% CI, 0.06-0.43) and tumors with cavernous sinus invasion (OR, 0.03; 95% CI, 0.01-0.13). Female gender and absence of preoperative dopamine agonist treatment were also associated with higher remission rates. Across the included studies, there was considerable heterogeneity in each primary outcome (postoperative remission, I = 94%; follow-up remission, I = 86%; recurrence, I = 68%).
CONCLUSIONS
Transsphenoidal surgery for prolactinomas may be particularly effective in small, noninvasive, treatment-naive tumors and may provide a viable first-line alternative to dopamine agonist therapy in such patients.
Topics: Humans; Neurosurgical Procedures; Pituitary Neoplasms; Prolactinoma; Remission Induction; Treatment Outcome
PubMed: 34325023
DOI: 10.1016/j.wneu.2021.07.035 -
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 -
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 -
Cureus Feb 2023The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy.... (Review)
Review
The management of dopamine agonist (DA)-resistant prolactinomas unresponsive to second and third-line treatment is challenging and requires alternative medical therapy. The presence of estrogen receptors on pituitary tumors, and the variable behavior of pituitary tumors in the presence of estrogen, prompted investigation of the role of anti-estrogen in the treatment of DA-resistant prolactinomas. The goal of this paper is to perform a systematic review of the role of tamoxifen in the treatment of DA-resistant prolactinomas. A systematic review was conducted. Inclusion criteria were case reports, case series, and experimental studies using tamoxifen in DA-resistant prolactinomas. Exclusion criteria included review articles, DA-sensitive prolactinomas, and those that were not previously treated with DA. Data were analyzed using descriptive statistics. For continuous data, the mean was used. For dichotomous data, frequencies and percentages were used. Data on 22 patients were extracted from the seven included studies. Twenty patients (90.9%) responded positively to the use of tamoxifen with a mean reduction in prolactin levels of 57.4%. Ten patients (45.5%) showed normalization of prolactin post-tamoxifen administration. Regression of tumor size and stability of tumor growth were reported in four out of 22 cases (18.2%). Combination therapy with DA and tamoxifen increased DA sensitivity and had a clinically significant inhibitory effect on prolactin secretion. Furthermore, tamoxifen may be considered an effective adjuvant for tumor size control. Therefore, further studies are needed to draw more clinically and statistically robust conclusions.
PubMed: 36950000
DOI: 10.7759/cureus.35171 -
Pituitary Jun 2022Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies.
METHODS
PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis.
RESULTS
We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm (range, 0.01-31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6 Gy (range, 6-49), maximum dose 50 Gy (range, 25-90), and isodose line 50% (range, 9-100%). Median maximum point doses were 9 Gy (range, 0.5-25) to the pituitary stalk, 7 Gy (range, 1-38) to the optic apparatus, and 5 Gy (range, 0.4-12.3) to the optic chiasm. Pooled 5 year rates of endocrine normalization and local tumor control were 48% (95%CI 45-51%) and 97% (95%CI 95-98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45 months (range, 4-187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6-9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%).
CONCLUSION
Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18-32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance.
Topics: Adenoma; Follow-Up Studies; Hormones; Humans; Pituitary Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35349010
DOI: 10.1007/s11102-022-01219-x