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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 -
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 -
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 -
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 -
Neurosurgical Review Sep 2023Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no... (Review)
Review
Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no systematic review is available. To provide a systematic and critical literature review and up-to-date description of the training models or simulators dedicated to endoscopic transsphenoidal surgery. A search was performed on PubMed and Scopus databases for articles published until February 2023; Google was also searched to document commercially available. For each model, the following features were recorded: training performed, tumor/arachnoid reproduction, assessment and validation, and cost. Of the 1199 retrieved articles, 101 were included in the final analysis. The described models can be subdivided into 5 major categories: (1) enhanced cadaveric heads; (2) animal models; (3) training artificial solutions, with increasing complexity (from "box-trainers" to multi-material, ct-based models); (4) training simulators, based on virtual or augmented reality; (5) Pre-operative planning models and simulators. Each available training model has specific advantages and limitations. Costs are high for cadaver-based solutions and vary significantly for the other solutions. Cheaper solutions seem useful only for the first stages of training. Most models do not provide a simulation of the sellar tumor, and a realistic simulation of the suprasellar arachnoid. Most artificial models do not provide a realistic and cost-efficient simulation of the most delicate and relatively common phase of surgery, i.e., tumor removal with arachnoid preservation; current research should optimize this to train future neurosurgical generations efficiently and safely.
Topics: Humans; Animals; Endoscopy; Cadaver; Computer Simulation; Databases, Factual; Skull Base Neoplasms
PubMed: 37725193
DOI: 10.1007/s10143-023-02149-3 -
Pathology, Research and Practice Sep 2023Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers.... (Review)
Review
BACKGROUND
Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers. Mir-151a-5p is believed to be one of these miRNAs with diverse roles. We have conducted this systematic review to clarify the role of mir-151a-5p in formation of various cancers.
METHODS AND MATERIALS
We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNAcentral databases up to November 2022. A total of 23 articles were qualified and included in the present systematic review. This review is registered on JBI at https://jbi.global/systematic-review-register. Expression levels, diagnostic and prognostic values, biological processes, and targeted downstream genes are included.
RESULTS
Assembled data indicate the expression levels of mir-151a-5p vary from down- to up-regulated based on the type of the cancer. Its functional role depends on the genetic profile of cancerous tissue. Results mostly point to the oncogenic role of this miRNA in Pituitary adenomas, Acute Myeloid Leukemia (AML), Endometrial, Lung, Barrett's carcinogenesis, Colorectal, Myelodysplastic syndromes, Hepatocellular carcinoma and Breast cancers, as its inhibited targets seem to be controlling several signaling pathways, cell adhesion, and cell cycle. At the same time, tumor-suppressing role has also been observed only in Malignant Pleural Mesothelioma, Central Nerve System (CNS) lymphoma, Chronic Myeloid and Acute Lymphocytic Leukemia. Two types of cancers, prostate and colon, show contradictory results as there are studies supporting both up- and down-regulation in these cancers. Pituitary adenomas, Barrett's carcinogenesis and CNS lymphomas are top cancers diagnosed with mir-151-5p. However, prognostic feature is only applicable to Lung adenocarcinoma.
DISCUSSION
Based on the present findings and further studies in the future, mir-151a-5p may be used as diagnostic and prognostic biomarkers or even a therapeutic target in cancer studies.
DATA AVAILABILITY STATEMENT
The articles used in this study can be found with the defined search phrase in mentioned databases. A list of selected articles will be available on reasonable requests.
Topics: Male; Humans; Pituitary Neoplasms; MicroRNAs; Carcinogenesis; Cell Transformation, Neoplastic; Genes, Tumor Suppressor; Gene Expression Regulation, Neoplastic
PubMed: 37562284
DOI: 10.1016/j.prp.2023.154576 -
Acta Neurochirurgica Sep 2023Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although there is an increasing body of evidence showing gender differences in various medical domains as well as presentation and biology of pituitary adenoma (PA), gender differences regarding outcome of patients who underwent transsphenoidal resection of PA are poorly understood. The aim of this study was to identify gender differences in PA surgery.
METHODS
The PubMed/MEDLINE database was searched up to April 2023 to identify eligible articles. Quality appraisal and extraction were performed in duplicate.
RESULTS
A total of 40 studies including 4989 patients were included in this systematic review and meta-analysis. Our analysis showed odds ratio of postoperative biochemical remission in males vs. females of 0.83 (95% CI 0.59-1.15, P = 0.26), odds ratio of gross total resection in male vs. female patients of 0.68 (95% CI 0.34-1.39, P = 0.30), odds ratio of postoperative diabetes insipidus in male vs. female patients of 0.40 (95% CI 0.26-0.64, P < 0.0001), and a mean difference of preoperative level of prolactin in male vs. female patients of 11.62 (95% CI - 119.04-142.27, P = 0.86).
CONCLUSIONS
There was a significantly higher rate of postoperative DI in female patients after endoscopic or microscopic transsphenoidal PA surgery, and although there was some data in isolated studies suggesting influence of gender on postoperative biochemical remission, rate of GTR, and preoperative prolactin levels, these findings could not be confirmed in this meta-analysis and demonstrated no statistically significant effect. Further research is needed and future studies concerning PA surgery should report their data by gender or sexual hormones and ideally further assess their impact on PA surgery.
Topics: Humans; Male; Female; Treatment Outcome; Prolactin; Retrospective Studies; Pituitary Neoplasms; Adenoma; Hormones; Postoperative Complications
PubMed: 37555999
DOI: 10.1007/s00701-023-05726-z -
Pituitary Oct 2023Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the... (Review)
Review
PURPOSE
Giant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.
METHODS
A structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.
RESULTS
196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.
CONCLUSION
Giant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.
Topics: Female; Adult; Male; Humans; Prolactinoma; Pituitary Neoplasms; Hyperprolactinemia; Prolactin; Amenorrhea; Dopamine Agonists; Hypopituitarism; Vision Disorders; Adrenocorticotropic Hormone
PubMed: 37544978
DOI: 10.1007/s11102-023-01337-0 -
World Neurosurgery Aug 2023The primary objective of this systematic review is to evaluate the effectiveness of intraoperative ultrasound (IOUS) in improving outcomes in patients undergoing... (Review)
Review
OBJECTIVE
The primary objective of this systematic review is to evaluate the effectiveness of intraoperative ultrasound (IOUS) in improving outcomes in patients undergoing pituitary surgery.
METHODS
A systematic review was performed by searching MEDLINE (PubMed), Web of Science, Scopus, and Embase electronic bibliographic databases from conception to 2022.
RESULTS
The included studies yielded a total of 660 patients, with 488 patients undergoing IOUS. Outcome were available for 341 patients treated with IOUS and 157 patients who were treated without the IOUS application, and the remission rates following surgery were 76% and 59%, respectively. Only 2 studies reported remission rates for both groups, and meta-analysis for these studies showed significant superiority of intraoperative ultrasonography (Random effect, odds ratio 4.99, P < 0.01). Regarding extent of resection, IOUS resulted in 71% gross total resection, while absence of IOUS yielded a gross total resection rate of 44%. Among studies with available follow-up on IOUS, the recurrence rate was 3%. Pituitary dysfunction (34%), cerebrospinal fluid leak (31%), and central nervous system infection (8%) were the most common complications in the IOUS group. The mean follow-up was 19.97 months in studies reporting follow-up time.
CONCLUSIONS
The application of the IOUS is both safe and effective and could improve the outcome of pituitary surgeries. IOUS can assist surgeons in the identification of pituitary tumors and their surrounding anatomy and can help minimize the risk of complications associated with this complex surgical procedure.
Topics: Humans; Monitoring, Intraoperative; Pituitary Neoplasms; Ultrasonography
PubMed: 37164206
DOI: 10.1016/j.wneu.2023.04.126 -
Neurosurgical Focus Nov 2023Pituitary surgery is a frequent neurosurgical procedure for the management of pituitary adenomas, but little research has been done on the impact of healthcare...
OBJECTIVE
Pituitary surgery is a frequent neurosurgical procedure for the management of pituitary adenomas, but little research has been done on the impact of healthcare disparities on surgical results. Healthcare inequity/disparity in terms of race and socioeconomic status (SES), in addition to age and gender, was evaluated in this study to see if they affect the results of pituitary surgery.
METHODS
A systematic literature search was carried out utilizing the MEDLINE (PubMed), Web of Science, Scopus, and Embase electronic databases from conception to 2023. The Newcastle-Ottawa Scale was used for quality assessment of the included studies.
RESULTS
Twenty-one studies yielded a total of 381,643 patients, and removal of the studies with temporal overlap resulted in 134,832 patients with a mean ± SD age of 51.52 ± 0.41 years. Based on the available data, 46.63% of patients were male. Black patients were more likely to be recommended against surgery, while Asian or Pacific Islander patients were more likely to be recommended for surgery. Postoperative course and outcome showed mixed results, with some studies reporting higher rates of transient diabetes insipidus and stroke in racial minority populations. Private hospitals admitted more White patients, and certain racial groups had reduced access to high-volume centers. SES disparities were assessed in terms of insurance and income. Patients with government insurance or without insurance were more likely to be recommended active surveillance instead of definitive treatment. Furthermore, high SES was associated with a higher likelihood of receiving surgical treatment, better treatment outcomes, and better access to high-volume centers. In terms of age and gender disparity, older patients and females were less likely to be recommended for surgical treatment. Age and gender did not consistently impact postoperative course and treatment outcomes, with varying results across studies. No significant age and gender disparities were observed in hospital admissions and charges.
CONCLUSIONS
This study revealed the presence of disparities in pituitary adenoma surgery based on race, SES, age, and gender. These disparities highlight the need for further research and interventions to ensure equitable access to appropriate surgical treatment and improved outcomes for all patients with pituitary adenomas.
Topics: Female; Humans; Male; Middle Aged; Healthcare Disparities; Pituitary Neoplasms; Racial Groups; Socioeconomic Factors; United States; Ethnicity
PubMed: 37913542
DOI: 10.3171/2023.8.FOCUS23467