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Frontiers in Endocrinology 2023The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.
METHODS
We searched for articles that evaluated ketoconazole use in Cushing's disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.
RESULTS
After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.
CONCLUSION
Ketoconazole can be considered a safe and efficacious option for Cushing's disease treatment after pituitary surgery.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).
Topics: Humans; Ketoconazole; Pituitary ACTH Hypersecretion; Cushing Syndrome; Hydrocortisone; Prospective Studies; Retrospective Studies
PubMed: 37223017
DOI: 10.3389/fendo.2023.1145775 -
Pituitary Aug 2023Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical... (Review)
Review
OBJECTIVE
Diagnostic delay is high in acromegaly and leads to increased morbidity and mortality. The aim of this study is to systematically assess the most prevalent clinical signs, symptoms and comorbidities of acromegaly at time of diagnosis.
DESIGN
A literature search (in PubMed, Embase and Web of Science) was performed on November 18, 2021, in collaboration with a medical information specialist.
METHODS
Prevalence data on (presenting) clinical signs, symptoms and comorbidities at time of diagnosis were extracted and synthesized as weighted mean prevalence. The risk of bias was assessed for each included study using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data.
RESULTS
Risk of bias and heterogeneity was high in the 124 included articles. Clinical signs and symptoms with the highest weighted mean prevalence were: acral enlargement (90%), facial features (65%), oral changes (62%), headache (59%), fatigue/tiredness (53%; including daytime sleepiness: 48%), hyperhidrosis (47%), snoring (46%), skin changes (including oily skin: 37% and thicker skin: 35%), weight gain (36%) and arthralgia (34%). Concerning comorbidities, acromegaly patients more frequently had hypertension, left ventricle hypertrophy, dia/systolic dysfunction, cardiac arrhythmias, (pre)diabetes, dyslipidemia and intestinal polyps- and malignancy than age- and sex matched controls. Noteworthy, cardiovascular comorbidity was lower in more recent studies. Features that most often led to diagnosis of acromegaly were typical physical changes (acral enlargement, facial changes and prognatism), local tumor effects (headache and visual defect), diabetes, thyroid cancer and menstrual disorders.
CONCLUSION
Acromegaly manifests itself with typical physical changes but also leads to a wide variety of common comorbidities, emphasizing that recognition of a combination of these features is key to establishing the diagnosis.
Topics: Humans; Acromegaly; Prevalence; Delayed Diagnosis; Comorbidity; Headache; Hypertension; Diabetes Mellitus
PubMed: 37210433
DOI: 10.1007/s11102-023-01322-7 -
Brain Sciences Mar 2023DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate... (Review)
Review
DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were "DNA methylation", "suicide", "epigenetics", "HPA axis" and "suicide behavior". This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.
PubMed: 37190549
DOI: 10.3390/brainsci13040584 -
Frontiers in Oncology 2023Extra-axial brain tumors are extra-cerebral tumors and are usually benign. The choice of treatment for extra-axial tumors is often dependent on the growth of the tumor,...
Extra-axial brain tumors are extra-cerebral tumors and are usually benign. The choice of treatment for extra-axial tumors is often dependent on the growth of the tumor, and imaging plays a significant role in monitoring growth and clinical decision-making. This motivates the investigation of imaging biomarkers for these tumors that may be incorporated into clinical workflows to inform treatment decisions. The databases from Pubmed, Web of Science, Embase, and Medline were searched from 1 January 2000 to 7 March 2022, to systematically identify relevant publications in this area. All studies that used an imaging tool and found an association with a growth-related factor, including molecular markers, grade, survival, growth/progression, recurrence, and treatment outcomes, were included in this review. We included 42 studies, comprising 22 studies (50%) of patients with meningioma; 17 studies (38.6%) of patients with pituitary tumors; three studies (6.8%) of patients with vestibular schwannomas; and two studies (4.5%) of patients with solitary fibrous tumors. The included studies were explicitly and narratively analyzed according to tumor type and imaging tool. The risk of bias and concerns regarding applicability were assessed using QUADAS-2. Most studies (41/44) used statistics-based analysis methods, and a small number of studies (3/44) used machine learning. Our review highlights an opportunity for future work to focus on machine learning-based deep feature identification as biomarkers, combining various feature classes such as size, shape, and intensity. PROSPERO, CRD42022306922.
PubMed: 37182138
DOI: 10.3389/fonc.2023.1131013 -
BMC Neurology Apr 2023Pituitary dysfunction (PD) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). The prevalence of PD varies widely at a global level and no recent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pituitary dysfunction (PD) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). The prevalence of PD varies widely at a global level and no recent meta-analysis is available. Therefore, the aim of our systematic review and meta-analysis was to summarize the updated estimates of worldwide prevalence of PD after aSAH.
METHODS
Scopus, Embase, Web of Science, and PubMed databases were used to comprehensively search the appropriate literature and a random-effects meta-analysis on the results of the available studies was performed. The heterogeneity in the prevalence estimates was evaluated by subgroup analysis in terms of types of PD, and acute and chronic phases of aSAH. The onset of PD within 6 months after aSAH was considered as acute, while that after 6 months was considered as chronic.
RESULTS
Twenty-seven studies with 1848 patients were included in this analysis. The pooled prevalence of PD in the acute phase was 49.6% (95% CI, 32.4-66.8%), and 30.4% (95% CI, 21.4-39.4%) in the chronic phase. Among the hormonal deficiencies, growth hormone dysfunction was the most prevalent in the acute phase, being 36.0% (95% CI, 21.0-51.0%), while hypoadrenalism was the most prevalent in the chronic phase, being 21.0% (95% CI, 12.0-29.0%). Among the six World Health Organization regions, the South-East Asia Region has the highest prevalence of PD in the acute phase (81.0%, 95%CI, 77.0-86.0%, P < 0.001), while the European Region had the highest prevalence of PD in the chronic phase (33.0%, 95%CI, 24.0-43.0%, P < 0.001). Moreover, single pituitary hormonal dysfunction occurred more frequently than the multiple one, regardless of acute or chronic phase.
CONCLUSIONS
Almost half (49.6%) of the included patients with aSAH developed PD complication in the acute phase, while 30.4% of the patients developed them in the chronic phase. Although prevalence varies globally, the high healthcare burden, morbidity and mortality require greater awareness among clinicians.
Topics: Humans; Subarachnoid Hemorrhage; Prevalence
PubMed: 37081429
DOI: 10.1186/s12883-023-03201-x -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
Asian Journal of Neurosurgery Mar 2023There is considerable variation in the surgical techniques for transsphenoidal excision of pituitary tumors. Recently, an extracapsular method has been developed that... (Review)
Review
There is considerable variation in the surgical techniques for transsphenoidal excision of pituitary tumors. Recently, an extracapsular method has been developed that involves using the tumor pseudocapsule as a dissection plane to increase the extent of resection. This review assessed the outcomes of this new approach as compared with standard transsphenoidal surgery. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE/PubMed, the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch), and LILACS databases for relevant literature and checked reference lists of relevant articles. Randomized controlled trials and prospective and retrospective cohort studies comparing extracapsular and intracapsular resection of pituitary tumors were included in the review. Five cohort studies with 1,588 participants were included. Extracapsular resection was associated with a higher likelihood of complete excision (relative risk [RR] 1.31, 95% confidence interval [CI] 1.01-1.70, = 0.04) and endocrinologic remission (RR 1.26, 95% CI 1.03-1.54, = 0.02). Because there was a significant risk of bias and substantial heterogeneity, the estimates of effect may not be robust. In patients with pituitary adenomas undergoing transsphenoidal excision, extracapsular resection may be associated with higher rates of complete excision and endocrinologic remission, but the evidence is not strong. Hence, randomized controlled trials to determine the magnitude of benefit and identify an improvement in progression-free or overall survival are warranted.
PubMed: 37056896
DOI: 10.1055/s-0043-1761237 -
European Archives of... Sep 2023We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery.
METHODS
Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed.
RESULTS
The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting.
CONCLUSION
Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.
Topics: Humans; Retrospective Studies; Epistaxis; Surgical Flaps; Endoscopy; Pituitary Gland; Skull Base; Pituitary Diseases; Pituitary Neoplasms; Postoperative Complications; Treatment Outcome
PubMed: 36988686
DOI: 10.1007/s00405-023-07934-w -
Brain Sciences Mar 2023The complex nature and heterogeneity involving pituitary surgery results have increased interest in machine learning (ML) applications for prediction of outcomes over... (Review)
Review
BACKGROUND
The complex nature and heterogeneity involving pituitary surgery results have increased interest in machine learning (ML) applications for prediction of outcomes over the last decade. This study aims to systematically review the characteristics of ML models involving pituitary surgery outcome prediction and assess their reporting quality.
METHODS
We searched the PubMed, Scopus, and Web of Knowledge databases for publications on the use of ML to predict pituitary surgery outcomes. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) to assess report quality. Our search strategy was based on the terms "artificial intelligence", "machine learning", and "pituitary".
RESULTS
20 studies were included in this review. The principal models reported in each article were post-surgical endocrine outcomes ( = 10), tumor management ( = 3), and intra- and postoperative complications ( = 7). Overall, the included studies adhered to a median of 65% (IQR = 60-72%) of TRIPOD criteria, ranging from 43% to 83%. The median reported AUC was 0.84 (IQR = 0.80-0.91). The most popular algorithms were support vector machine ( = 5) and random forest ( = 5). Only two studies reported external validation and adherence to any reporting guideline. Calibration methods were not reported in 15 studies. No model achieved the phase of actual clinical applicability.
CONCLUSION
Applications of ML in the prediction of pituitary outcomes are still nascent, as evidenced by the lack of any model validated for clinical practice. Although studies have demonstrated promising results, greater transparency in model development and reporting is needed to enable their use in clinical practice. Further adherence to reporting guidelines can help increase AI's real-world utility and improve clinical practice.
PubMed: 36979305
DOI: 10.3390/brainsci13030495 -
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