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Medicina 2024Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are...
INTRODUCTION
Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant inherited disease with an estimated prevalence of 2-10:100 000. The main locations of tumors are parathyroid glands (HPT), gastroenteropancreatic tract (GEPT), and anterior pituitary gland (PT). The aim of our investigation was to describe the phenotype and genotype of Argentinian patients with MEN1.
METHODS
A total of 68 index patients diagnosed with at least two of the three main tumors or one tumor and a relative with MEN1, and 84 first-degree relatives were studied. We sequenced the coding region (exons 2-10); the promoter, exon 1; and the flanking intronic regions of the MEN1 gene, following the Sanger method. We used MLPA in index patients without mutation.
RESULTS
Prevalence of tumors: HPT 87.5%, GEPT 49% (p< 0.001). No statistical differences in the prevalence of HPT vs. PT (68%). Prevalence of pathogenic variants: 90% in familial cases and 51% in sporadic cases. Of the different 36 pathogenic variants, 13 (36.2%) were frameshift micro-rearrangement, 8 (22.2%) were missense, 9 (25%) were nonsense, 3 (8.3%) were mutations in splicing sites, 2 (5.5%) were large deletions and, 1 in-frame micro-rearrangement. We found 7 novel pathogenic variants. Thirty-nine percent (n = 33) of first-degree relatives of 23 families were found to be mutation carriers.
CONCLUSION
The phenotype and genotype of Argentinian patients was similar to other MEN1 populations. A high frequency of PT and the identification of seven novel mutations are underscored.
Topics: Humans; Argentina; Male; Multiple Endocrine Neoplasia Type 1; Phenotype; Female; Adult; Genotype; Middle Aged; Adolescent; Young Adult; Child; Aged; Mutation; Child, Preschool; Parathyroid Neoplasms; Proto-Oncogene Proteins
PubMed: 38907957
DOI: No ID Found -
Cell Death & Disease Jun 2024Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high...
Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.
Topics: Humans; Craniopharyngioma; Tumor Microenvironment; Pituitary Neoplasms; Tumor-Associated Macrophages; Male; Female; Keratins; Transcriptome; Gene Expression Regulation, Neoplastic; Adult; Middle Aged; Multiomics
PubMed: 38906852
DOI: 10.1038/s41419-024-06840-1 -
BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4 -
World Journal of Clinical Cases Jun 2024As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many...
BACKGROUND
As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes.
CASE SUMMARY
Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved.
CONCLUSION
Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.
PubMed: 38899290
DOI: 10.12998/wjcc.v12.i16.2813 -
Frontiers in Endocrinology 2024Post-operative CSF leak is the major source of morbidity following transsphenoidal approaches (TSA) and expanded endonasal approaches (EEA) to lesions of the sella...
AIMS
Post-operative CSF leak is the major source of morbidity following transsphenoidal approaches (TSA) and expanded endonasal approaches (EEA) to lesions of the sella turcica and the ventral skull base. There are conflicting reports in the literature as to whether obesity (BMI ≥30) is a risk factor for this complication. We aimed to evaluate data collected as part of prospective multi-centre cohort study to address this question.
METHODS
The CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) study database was reviewed and patients were divided into obese and non-obese cohorts. Data on patient demographics, underlying pathology, intra-operative findings and skull base repair techniques were analysed.
RESULTS
TSA were performed on 726 patients, of whom 210 were obese and 516 were non-obese. The rate of post-operative CSF leak in the obese cohort was 11/210 (5%), compared to 17/516 (3%) in the non-obese cohort, which was not statistically significant (χ 1.520, p=0.217). EEA were performed on 140 patients, of whom 28 were obese and 112 were non-obese. The rate of post-operative CSF leak in the obese cohort was 2/28 (7%), which was identical to the rate observed in the non-obese cohort 8/112 (7%) Fisher's Exact Test, p=1.000). These results persisted following adjustment for inter-institutional variation and baseline risk of post-operative CSF leak.
CONCLUSION
CSF leak rates following TSA and EEA, in association with modern skull base repair techniques, were found to be low in both obese and non-obese patients. However, due to the low rate of post-operative CSF leak, we were unable to fully exclude a small contributory effect of obesity to the risk of this complication.
Topics: Humans; Obesity; Female; Male; Skull Base; Cerebrospinal Fluid Leak; Middle Aged; Prospective Studies; Postoperative Complications; Adult; Aged; Endoscopy; Cerebrospinal Fluid Rhinorrhea; Risk Factors; Cohort Studies; Young Adult
PubMed: 38899009
DOI: 10.3389/fendo.2024.1353494 -
Acta Neurochirurgica Jun 2024Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective...
BACKGROUND
Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas.
METHOD
We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach.
CONCLUSION
A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury.
Topics: Humans; Pituitary Neoplasms; Adenoma; Neuroendoscopy; Cavernous Sinus; Endoscopy; Neurosurgical Procedures
PubMed: 38890156
DOI: 10.1007/s00701-024-06168-x -
Operative Neurosurgery (Hagerstown, Md.) Jun 2024Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy...
Thyroid-stimulating hormone-secreting adenomas (TSH-oma) are exceptionally rare.1 The primary treatment is surgical resection with radiation and pharmacotherapy postoperatively if subtotal resection, especially with cavernous sinus invasion.2 We present the case of a 29-year-old man with TSH-oma with cavernous sinus medial wall invasion. This is the first documented case with selective resection of the cavernous sinus medial wall to achieve a complete resection and biochemical remission in TSH-oma through endoscopic endonasal approach. The patient had elevated TSH and thyroid hormones with symptoms of weight loss, palpitations, excess sweating, and decreased endurance. MRI revealed a 1.3 × 2.1 × 1.2 cm contrast-enhancing sellar mass with rightward pituitary gland displacement without evidence of cavernous sinus invasion (Knosp 2). The patient consented to procedure/publication. No institutional review board approval needed per institution. We performed standard resection of the firm sellar tumor portion and noted that there was tumor invasion into the left cavernous sinus medial wall dura. The bony opening was expanded to expose the anterior wall of the cavernous sinus, which was opened to identify the cavernous internal carotid artery and the medial wall attachments. The thickened medial wall was completely resected. We achieved a complete tumor resection, and the patient's TSH and thyroid hormone dropped to a desired threshold.3 Tumor stained for GATA3 and PIT1, characterizing the TSH-oma.4,5 Understanding cavernous sinus vascular and ligamentous anatomy allows for safe separation of invaded medial wall dura from the cavernous internal carotid artery,6 allowing for a more complete tumor resection, improving surgical cure rates, and sparing the patient from future radiation and pharmacotherapy.
PubMed: 38888332
DOI: 10.1227/ons.0000000000001240 -
Nature Reviews. Endocrinology Jun 2024Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine... (Review)
Review
Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.
PubMed: 38886617
DOI: 10.1038/s41574-024-01005-8 -
International Forum of Allergy &... Jun 2024Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study...
INTRODUCTION
Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques.
METHODS
A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test.
RESULTS
Five hundred and one patients were identified. The median tumor size was 2.1 cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3 cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p < 0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication.
CONCLUSION
The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks.
PubMed: 38884280
DOI: 10.1002/alr.23382 -
Indian Journal of Otolaryngology and... Jun 2024A skull- base defect with grade-3 cerebrospinal fluid (CSF) leak following a pituitary macroadenoma removal is rare and challenging. We provide a simple sample model of...
A skull- base defect with grade-3 cerebrospinal fluid (CSF) leak following a pituitary macroadenoma removal is rare and challenging. We provide a simple sample model of multilayer closure with naturally available hard and soft tissue components. Tamponade was provided to the reconstructed site with a simple inflated Foley's catheter bulb. There was no repair failure and cavities were well mucosalised on follow-up. Mucosal and turbinate preservation was fully achieved in this method as no turbinate flaps were raised or large raw surface exposure was there.
PubMed: 38883493
DOI: 10.1007/s12070-024-04529-7