-
BMC Medical Genomics Apr 2023Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner...
BACKGROUND
Wolfram syndrome type 1 gene (WFS1), which encodes a transmembrane structural protein (wolframin), is essential for several biological processes, including proper inner ear function. Unlike the recessively inherited Wolfram syndrome, WFS1 heterozygous variants cause DFNA6/14/38 and wolfram-like syndrome, characterized by autosomal dominant nonsyndromic hearing loss, optic atrophy, and diabetes mellitus. Here, we identified two WFS1 heterozygous variants in three DFNA6/14/38 families using exome sequencing. We reveal the pathogenicity of the WFS1 variants based on three-dimensional (3D) modeling and structural analysis. Furthermore, we present cochlear implantation (CI) outcomes in WFS1-associated DFNA6/14/38 and suggest a genotype-phenotype correlation based on our results and a systematic review.
METHODS
We performed molecular genetic test and evaluated clinical phenotypes of three WFS1-associated DFNA6/14/38 families. A putative WFS1-NCS1 interaction model was generated, and the impacts of WFS1 variants on stability were predicted by comparing intramolecular interactions. A total of 62 WFS1 variants associated with DFNA6/14/38 were included in a systematic review.
RESULTS
One variant is a known mutational hotspot variant in the endoplasmic reticulum (ER)-luminal domain WFS1(NM_006005.3) (c.2051 C > T:p.Ala684Val), and the other is a novel frameshift variant in transmembrane domain 6 (c.1544_1545insA:p.Phe515LeufsTer28). The two variants were pathogenic, based on the ACMG/AMP guidelines. Three-dimensional modeling and structural analysis show that non-polar, hydrophobic substitution of Ala684 (p.Ala684Val) destabilizes the alpha helix and contributes to the loss of WFS1-NCS1 interaction. Also, the p.Phe515LeufsTer28 variant truncates transmembrane domain 7-9 and the ER-luminal domain, possibly impairing membrane localization and C-terminal signal transduction. The systematic review demonstrates favorable outcomes of CI. Remarkably, p.Ala684Val in WFS1 is associated with early-onset severe-to-profound deafness, revealing a strong candidate variant for CI.
CONCLUSIONS
We expanded the genotypic spectrum of WFS1 heterozygous variants underlying DFNA6/14/38 and revealed the pathogenicity of mutant WFS1, providing a theoretical basis for WFS1-NCS1 interactions. We presented a range of phenotypic traits for WFS1 heterozygous variants and demonstrated favorable functional CI outcomes, proposing p.Ala684Val a strong potential marker for CI candidates.
Topics: Humans; Wolfram Syndrome; Cochlear Implants; Cochlear Implantation; Pedigree; Hearing Loss; Deafness
PubMed: 37041640
DOI: 10.1186/s12920-023-01506-x -
Journal of Endocrinological... Oct 2021Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an...
PURPOSE
Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions.
METHODS
A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases-non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)-were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint.
RESULTS
All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome.
CONCLUSION
Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.
Topics: Animals; Humans; Pituitary Neoplasms; Prolactinoma; Salivary Gland Neoplasms; Salivary Glands; Sella Turcica
PubMed: 33939106
DOI: 10.1007/s40618-021-01577-6 -
BMC Neurology Feb 2022Transsphenoidal surgery is the preferred first-line therapy for most pituitary adenoma(PA), and the conventional strategy of treatment is intracapsular resection(IR).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Transsphenoidal surgery is the preferred first-line therapy for most pituitary adenoma(PA), and the conventional strategy of treatment is intracapsular resection(IR). The protocol of extracapsular resection(ER), which considers the pseudocapsule as the PA boundary for surgical removal, has also been introduced gradually. In this study, the clinical efficacies and complications were explored and compared between these two procedures.
METHODS
A systematic literature review was performed in the PubMed, EMBASE, Web of Science and Cochrane databases. Articles comparing between IR and ER were included.
RESULTS
There were 7 studies containing 1768 cases in accordance with the inclusion criteria. Although the meta-analysis showed no significant difference in complete resection, a sensitivity analysis revealed that ER was more conducive to total PA resection than IR. Moreover, we found a significant difference in favor of ER regarding biochemical remission. Furthermore, there was no significant difference in the incidence rate of certain complications, such as hormone deficiency, diabetes insipidus, intraoperative cerebrospinal fluid(CSF) and postoperative CSF leakage. However, a sensitivity analysis suggested that IR decreased the risk of intraoperative CSF leakage.
CONCLUSIONS
This meta-analysis unveiled that ER contributed to biochemical remission. To some extent, our results also showed that ER played a positive role in complete resection, but that IR reduced the incidence of intraoperative CSF leakage. However, the available evidence needs to be further authenticated using well-designed prospective, multicenter, randomized controlled clinical trials.
Topics: Adenoma; Cerebrospinal Fluid Leak; Humans; Multicenter Studies as Topic; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 35151259
DOI: 10.1186/s12883-022-02574-9 -
Clinical Neurology and Neurosurgery Nov 2015Chordoid gliomas (CG) are rare neoplasms which frequently arise within the third ventricle. Surgery remains the mainstay treatment for CG. The present study... (Review)
Review
OBJECTIVE
Chordoid gliomas (CG) are rare neoplasms which frequently arise within the third ventricle. Surgery remains the mainstay treatment for CG. The present study comprehensively reviews all reported cases of CG within the literature in order to identify risk factors for surgical complications and tumor recurrence.
METHODS
A comprehensive search on MEDLINE (OVID and PubMed), Scopus, Embase, and Web of Science was conducted following PRISMA guidelines to identify all reported cases of CG.
RESULTS
A total of 81 patients met the study criteria which comprised of 33 males and 48 females. Median age at diagnosis was 48 years with a range from 5 to 72 years, and mean tumor size was 3.1cm. Biopsy, subtotal resection (STR), and gross total resection (GTR) were achieved in 8, 34, and 33 patients, respectively, with six cases not reporting extent of resection (EOR). Thirteen patients underwent adjuvant radiotherapy. Postoperative complications were noted in 30 cases (37%), with new onset diabetes insipidus being the most common. Postoperative morbidity was not associated with age, tumor size, or extent of resection. A trans-lamina terminalis approach demonstrated a strong trend towards decreased overall rates of postoperative morbidity compared to other approaches (p=0.051). GTR was associated with improved progression-free survival (PFS; p=0.028), while adjuvant radiotherapy, age, tumor size and proliferative index were not predictive of patient outcomes.
CONCLUSION
GTR should be the primary goal for the management of CG, as it is associated with improved rates of tumor control without an increased rate of postoperative complications. Surgical approach was a stronger predictor of complication rates than extent of resection. Morbidity remains high, and future studies to further elaborate on factors predictive of postoperative complications are critical.
Topics: Cerebral Ventricle Neoplasms; Disease-Free Survival; Female; Glioma; Humans; Male; Neoplasm Recurrence, Local; Neurosurgical Procedures; Prognosis; Third Ventricle
PubMed: 26342205
DOI: 10.1016/j.clineuro.2015.08.011 -
Cureus May 2020Cerebral vasospasm is a rare life-threatening complication of transsphenoidal surgery (TSS). We report our experience with two cases of symptomatic vasospasm after... (Review)
Review
Cerebral vasospasm is a rare life-threatening complication of transsphenoidal surgery (TSS). We report our experience with two cases of symptomatic vasospasm after endoscopic TSS, alongside a systematic review of published cases. Two patients who underwent endoscopic TSS for resection of a tuberculum sella meningioma (case 1) and pituitary adenoma (case 2) developed symptomatic vasospasm. Clinical variables, including demographics, histopathology, the extent of subarachnoid hemorrhage (SAH), diabetes insipidus (DI), day of vasospasm, vasospasm symptoms, vessels involved, management, and clinical outcome, were retrospectively extracted. We subsequently reviewed published cases of symptomatic post-TSS vasospasm. Including our two cases, we identified 34 reported cases of TSS complicated by symptomatic vasospasm. Female patients accounted for 20 (58.8%) of 34 cases. The average age was 48.1 ± 12.9 years. The majority of patients exhibited postoperative SAH (70.6%). The average delay to vasospasm presentation was 8.5 ± 3.6 days. The majority of patients exhibited vasospasm in multiple vessels, typically involving the anterior circulation. Hemodynamic augmentation with hemodilution, hypertension, and hypervolemia was the most common treatment. Death occurred in six (17.6%) of 34 patients. Common deficits included residual extremity weakness (17.6%), pituitary insufficiency (8.8%), and cognitive deficits (8.8%). Symptomatic vasospasm is a rare, potentially fatal complication of TSS. The most consistent risk factor is SAH. Early diagnosis requires a high index of suspicion when confronted with intractable DI, acute mental status change, or focal deficits in the days after TSS. Morbidity and death are significant risks in patients with this complication.
PubMed: 32566415
DOI: 10.7759/cureus.8171 -
PloS One 2015Patients with pituitary adenomas usually receive "stress dose" steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with pituitary adenomas usually receive "stress dose" steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.
METHODS
We searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.
FINDINGS
There are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60-270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.
Topics: Adolescent; Adrenal Insufficiency; Adult; Aged; Aged, 80 and over; Female; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Male; Middle Aged; Perioperative Period; Pituitary Neoplasms; Young Adult
PubMed: 25775019
DOI: 10.1371/journal.pone.0119621 -
Orphanet Journal of Rare Diseases Jun 2023Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting...
BACKGROUND
Pituitary abscess (PA) is a rare condition and not well understood. We aimed to describe a case and perform a comprehensive systematic review to explore presenting symptoms, radiological findings, endocrine abnormalities and mortality.
AIM
To identify presenting symptoms, radiological findings, endocrinological abnormalities and predictors of mortality for PA.
METHODS
We systematically reviewed the literature to identify all case reports of PA. Data regarding presentation, mortality, radiological findings, endocrinological abnormalities and treatment was extracted.
RESULTS
We identified 488 patients from 218 articles meeting the inclusion criteria. Mortality was 5.1%, with days to presentation (OR 1.0005, 95% CI 1.0001-1.0008, p < 0.01) being the only identified independent predictor of mortality. Mortality rates have decreased over time, with cases published prior to 2000 having higher mortality rates (OR 6.92, 95% CI 2.80-17.90, p < 0.001). The most common symptom was headache (76.2%), followed by visual field defects (47.3%). Classical signs of infection were only present in 43%. The most common imaging feature on magnetic resonance imaging (MRI) was high T2 and low T1 signal of the pituitary gland with peripheral contrast enhancement. Over half (54.8%) were culture negative, with the most common bacterial organism being staphylococcus aureus (7.8%) and fungal organism being aspergillus (8.8%). The most common endocrine abnormality was hypopituitarism (41.1%), followed by diabetes insipidus (24.8%). Whilst symptoms resolved in most patients, persistent endocrine abnormalities were present in over half of patients (61.0%).
CONCLUSION
PA is associated with significant mortality, with delayed presentation increasing risk of mortality. Ongoing endocrinological abnormalities are common. Given the non-specific clinical presentation, the appearance of high T2, low T1 and peripheral contrast enhancement of the pituitary on MRI should prompt consideration of this rare disease.
Topics: Humans; Abscess; Pituitary Diseases; Hypopituitarism; Pituitary Neoplasms; Magnetic Resonance Imaging
PubMed: 37365629
DOI: 10.1186/s13023-023-02788-1 -
European Archives of... Apr 2024Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Clinical presentations encompass respiratory, feeding issues, nasopharyngeal mass, meningitis, CSF leakage, craniofacial anomalies, and endocrine problems. Surgery is the primary treatment, transitioning from frontal craniotomy to endoscopic methods, offering improved outcomes. Yet, more studies are needed. A comprehensive review on trans-sellar trans-sphenoidal encephalocele (TSTSE) is missing. Our study aims to fill this gap, offering a comprehensive perspective for physicians.
METHODS
This review adhered to the PRISMA guideline. Eligible studies focused on human subjects, specifically trans-sellar encephaloceles, and provided comprehensive treatment details. English language articles published up to April 11th, 2023, were considered. Two trained researchers conducted article screening using consistent criteria. Data extraction covered various aspects, including clinical presentation, surgical methods, and outcomes, with results presented descriptively in two tables. Due to the rarity of this congenital anomaly, meta-analysis and publication bias assessment were not feasible. Data extraction was independently conducted by two reviewers, with subsequent cross-verification.
RESULTS
A total of 36 patients were identified from 14 studies, the most frequently observed clinical presentation was dyspnea (41.67%) and the most frequently observed accompanying anomaly was cleft lip/palate (55.56%). CT and MRI were adopted in nearly all the cases, and trans-nasal approach was the most often used surgical approach (57.14%) with the 'soft material combination' the most commonly used method for cranial base repairment (35.71%). A total of two deaths occurred and diabetes insipidus was the most common perioperative complication which occurred in six surgery patients (21.43%).
CONCLUSION
TSTSE predominantly affects males and presents with dyspnea, visual deficits, pituitary insufficiency, and cranial base-related symptoms. Early diagnosis is critical, with advanced imaging playing a key role. Endocrine assessment is vital for hormone management. Surgery offers symptom relief but entails risks, including reported fatalities and complications. The choice between surgery and conservative management requires careful deliberation. The trans-nasal approach is favored for its reduced trauma, yet further research is necessary to validate this preference.
Topics: Male; Humans; Encephalocele; Cleft Lip; Cleft Palate; Prognosis; Dyspnea
PubMed: 38189965
DOI: 10.1007/s00405-023-08355-5 -
Frontiers in Endocrinology 2021Xanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its...
PURPOSE
Xanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed.
METHODS
Here, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed.
RESULTS
The mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68.
CONCLUSION
Diagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.
Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Child; Female; Follicle Stimulating Hormone; Human Growth Hormone; Humans; Hypophysitis; Insulin-Like Growth Factor I; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Thyrotropin; Xanthomatosis; Young Adult
PubMed: 34659121
DOI: 10.3389/fendo.2021.735655 -
PloS One 2016Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Over the past several decades, the endoscopic endonasal transsphenoidal approach (EETA) has gradually become a preferred option of pituitary adenomas surgery because of its minimal invasiveness and high efficiency. However, some EETA operations were performed through one nostril (mononostril), while other EETA operations were performed through both nostrils (binostril). Therefore, we conducted this study to compare the pros and cons of these two methods in an attempted to confirm which method is more effective.
METHODS
We executed a systematic literature search of PubMed, the Cochrane Library, and the Web of Science and Medline (1992-2015). The language is limited to English and all studies should meet the inclusion criteria. Comparisons were made for postoperative outcomes, complications, and other relevant parameters between the mononostril and the binostril group. Statistical analyses of categorical variables were undertaken by the use of Stata 12.0 and SPASS 19.0.
RESULTS
Thirty studies, involving 4805 patients, were included. The two groups had similar results in GTR rate (included GTR rate of macroadenomas), hormonal remission rate, improvement in visual function, postoperative CSF leak, permanent diabetes insipidus, meningitis, and sinusitis. The binostril group had less temporary diabetes insipidus (2.9% vs. 5.3%, p = 0.022), less anterior pituitary insufficiency (2.3% vs. 6.4%, p = 0.000) and few hospitalization days (3.2 days vs. 4.4 days, p<0.05) than the mononostril group. However, the mononostril group had less rate of epistaxis (0.4% vs. 1.5%, p = 0.008) than the binostril group. For invasive macroadenomas, the binostril group seem to demonstrate a tendency towards better outcomes though there was no subgroup analysis between the two groups.
CONCLUSION
The binostril approach had less temporary diabetes insipidus, anterior pituitary insufficiency, and a shorter length of hospital stay, although they demonstrated a higher rate of epistaxis than the mononstril group. Additionally, the binostril group seemed to suggest a tendency towards better outcomes for invasive macroadenomas.
Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Child; Endoscopy; Female; Humans; Male; Middle Aged; Neurosurgical Procedures; Nose; Pituitary Neoplasms; Treatment Outcome; Young Adult
PubMed: 27124276
DOI: 10.1371/journal.pone.0153397