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Journal of Neurotrauma Nov 2023Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last... (Review)
Review
Traumatic brain injury (TBI) is the leading cause of death and disability in children. Many clinical practice guidelines (CPGs) have addressed pediatric TBI in the last decade but significant variability in the use of these guidelines persists. Here, we systematically review CPGs recommendations for pediatric moderate-to-severe TBI, evaluate the quality of CPGs, synthesize the quality of evidence and strength of included recommendations, and identify knowledge gaps. A systematic search was conducted in MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Web sites of organizations publishing recommendations on pediatric injury care. We included CPGs developed in high-income countries from January 2012 to May 2023, with at least one recommendation targeting pediatric (≤ 19 years old) moderate-to-severe TBI populations. The quality of included clinical practice guidelines was assessed using the AGREE II tool. We synthesized evidence on recommendations using a matrix based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We identified 15 CPGs of which 9 were rated moderate to high quality using AGREE II. We identified 90 recommendations, of which 40 (45%) were evidence based. Eleven of these were based on moderate to high quality evidence and were graded as moderate or strong by at least one guideline. These included transfer, imaging, intracranial pressure control, and discharge advice. We identified gaps in evidence-based recommendations for red blood cell transfusion, plasma and platelet transfusion, thromboprophylaxis, surgical antimicrobial prophylaxis, early diagnosis of hypopituitarism, and mental health mangement. Many up-to-date CPGs are available, but there is a paucity of evidence to support recommendations, highlighting the urgent need for robust clinical research in this vulnerable population. Our results may be used by clinicians to identify recommendations based on the highest level of evidence, by healthcare administrators to inform guideline implementation in clinical settings, by researchers to identify areas where robust evidence is needed, and by guideline writing groups to inform the updating of existing guidelines or the development of new ones.
Topics: Adult; Child; Humans; Young Adult; Anticoagulants; Brain Injuries, Traumatic; Erythrocyte Transfusion; Hypopituitarism; Venous Thromboembolism; Practice Guidelines as Topic
PubMed: 37341019
DOI: 10.1089/neu.2023.0149 -
The Lancet. Diabetes & Endocrinology Aug 2023Cyclic Cushing's syndrome is a subentity of Cushing's syndrome in which phases of biochemical hypercortisolism (peaks) are followed by spontaneous periods of... (Review)
Review
Cyclic Cushing's syndrome is a subentity of Cushing's syndrome in which phases of biochemical hypercortisolism (peaks) are followed by spontaneous periods of physiological or even hypocortisolaemic cortisol secretion (troughs). To identify common features of cyclic Cushing's syndrome, we systematically reviewed single case reports and case series in MEDLINE from database inception to Oct 10, 2022, and identified 707 articles, of which 149 articles were assessed for eligibility and 118 articles (covering 212 cases) were included in the analysis. Pituitary tumours accounted for 67% of cases of cyclic Cushing's syndrome (n=143), ectopic tumours for 17% (n=36), and adrenal tumours for 11% (n=23). Occult tumours accounted for 2% of cases (n=4), and 3% of cases were unclassified (n=6). We compared the clinical symptoms and comorbidities of patients with cyclic Cushing's syndrome with those of patients with non-cyclic Cushing's syndrome and observed no major difference. In adrenocorticotropic hormone (ACTH)-dependent cyclic Cushing's syndrome, bilateral inferior petrosal sinus sampling had a positive (ie, true pituitary) and negative (ie, true ectopic) predictive value of 100% when performed during periods of hypercortisolism, versus a positive predictive value of 73% and a negative predictive value of 86% when performed, irrespective of cortisolaemic status. Overall, 6% of patients (n=12) with cyclic Cushing's syndrome had unnecessary surgery due to misclassification. Remission rates were significantly lower and the time to remission significantly longer in patients with cyclic Cushing's syndrome compared with patients with non-cyclic Cushing's syndrome (p<0·001). Variations in biochemical test results due to unpredictable cycle duration and frequency might cause diagnostic challenges resulting in misdiagnoses and missed diagnoses.
Topics: Humans; Cushing Syndrome; Adrenocorticotropic Hormone; Petrosal Sinus Sampling; Pituitary Neoplasms; Predictive Value of Tests; Diagnosis, Differential
PubMed: 37429301
DOI: 10.1016/S2213-8587(23)00150-X -
Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Pituitary May 2024This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland. (Review)
Review
PURPOSE
This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland.
METHOD
PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease.
RESULTS
Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination.
CONCLUSION
Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts.
PubMed: 38761322
DOI: 10.1007/s11102-024-01402-2 -
Pituitary Oct 2023Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
PURPOSE
Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
METHODS
We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas.
RESULTS
Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14).
CONCLUSION
Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.
Topics: Humans; Pituitary Neoplasms; Neoplasm Recurrence, Local; Adenoma; ACTH-Secreting Pituitary Adenoma; Pituitary Gland
PubMed: 37523025
DOI: 10.1007/s11102-023-01341-4 -
International Journal of Molecular... Oct 2023Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine... (Review)
Review
Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.
Topics: Animals; Humans; Pituitary Neoplasms; Pituitary Gland; Neuroendocrine Tumors; Aggression; Tumor Microenvironment
PubMed: 37958702
DOI: 10.3390/ijms242115719 -
TouchREVIEWS in Endocrinology Nov 2023Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be... (Review)
Review
Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor β1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3 , neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-d esigned interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.
PubMed: 38187082
DOI: 10.17925/EE.2023.19.2.12 -
Current Psychiatry Reports Nov 2023Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia... (Review)
Review
PURPOSE OF REVIEW
Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia.
RECENT FINDINGS
We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.
Topics: Female; Humans; Male; Aged; Antipsychotic Agents; Schizophrenia; Aripiprazole; Hyperprolactinemia; Raloxifene Hydrochloride; Estrogens
PubMed: 37864676
DOI: 10.1007/s11920-023-01460-6 -
World Neurosurgery Apr 2024This study aims to evaluate the impact of surgical intervention on anxiety levels in patients with various types of pituitary adenoma (PA). (Review)
Review
OBJECTIVE
This study aims to evaluate the impact of surgical intervention on anxiety levels in patients with various types of pituitary adenoma (PA).
METHOD
A systematic review was conducted following PRISMA guidelines until October 2022, searching Embase, PubMed, Web of Sciences, and Scopus.
RESULTS
A total of 32 studies were included, encompassing 2,681 patients with the mean age of 53.33 ± 6.48 years (43.4% male). Among all subtypes, 664 diagnosed with Cushing's disease (25.8%), 612 with acromegaly (23.8%), 282 with prolactinoma (10.9%), and 969 with nonfunctional pituitary adenomas (37.6%). Pituitary insufficiency was the most common complication. Considering therapeutic modalities, 515 patients (29.8%) underwent endoscopic trans-sphenoidal surgery, while 222 (12.9%) underwent microscopic trans-sphenoidal surgery. The type of trans-sphenoidal surgery was not specified in 977 (56.6%) patients. A total of 17 studies including 1510 patients which mostly assessed anxiety using the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety Scale (SAS) were included in the meta-analysis. Preoperative evaluation using Hospital Anxiety and Depression Scale (HADS) questionnaire showed a pooled score of 8.27 (95%CI 4.54-12.01), while postoperative evaluation yielded a pooled score of 6.49 (95%CI 5.35-7.63), indicating no significant difference. Preoperative SAS assessment resulted in a pooled score of 50.43 (95%CI 37.40-63.45), with postoperative pooled score of 55.91 (95%CI 49.40-62.41), showing no significant difference.
CONCLUSIONS
Our analysis revealed no significant difference in anxiety scores pre- and postoperatively. While our findings suggest stability in anxiety levels following surgical intervention, it is imperative to recognize the limitations of the current evidence base. The observed lack of consensus may be influenced by factors such as the heterogeneous nature of the patient population, variations in the characteristics of pituitary adenomas, diverse therapeutic approaches, and potential confounding variables such as pre-existing mental health conditions and coping mechanisms. Further research is warranted to elucidate the nuanced relationship between surgical intervention for PA and anxiety outcomes, considering these complex interactions and employing rigorous methodologies to address potential sources of bias.
PubMed: 38697260
DOI: 10.1016/j.wneu.2024.04.154 -
Endocrine Dec 2023Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Data on silent corticotroph tumor (SCT) are still heterogeneous and controversial. In this study, we aimed to compare the demographic, clinicopathological manifestations, postoperative complications, and patient outcomes of SCTs with other non-functioning pituitary neuroendocrine tumor (NFT) and functioning corticotroph tumor (FCT) or so-called Cushing disease adenoma.
METHODS
We searched PubMed and Web of Science for data of interest. Odds ratio (OR), mean difference (MD), hazard ratio (HR), and their 95% confidence intervals (CI) were pooled using the random-effect model.
RESULTS
Twenty-nine studies with 985 SCTs were included in meta-analyses. In comparison to other NFTs, SCTs were more commonly associated with female gender, younger age, cavernous sinus invasion, apoplexy, and radiotherapy administration. Postoperatively, SCT patients were more likely to experience hypocortisolism, new-onset visual disturbances, and a higher risk for tumor progression than other NFTs. We did not find any significant differences between SCT type I and type II. Compared to FCTs, SCTs were more likely male, older age, and had larger tumor sizes. The prevalence of a USP8 mutation was significantly higher in FCT than in SCT.
CONCLUSION
SCT was demographically, clinicopathologically, and prognostically distinct from other NFTs and FCTs. These tumors should be considered high-risk; appropriate treatment decisions and more stringent follow-up should be tailored to improve patient outcomes.
Topics: Humans; Male; Female; Corticotrophs; Adenoma; Pituitary Neoplasms; Pituitary ACTH Hypersecretion; Prognosis; ACTH-Secreting Pituitary Adenoma
PubMed: 37462809
DOI: 10.1007/s12020-023-03449-w