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Annals of Medicine and Surgery (2012) May 2024Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare autosomal dominant neoplastic syndrome resulting from RET gene mutations, marked by medullary thyroid carcinoma...
INTRODUCTION AND IMPORTANCE
Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare autosomal dominant neoplastic syndrome resulting from RET gene mutations, marked by medullary thyroid carcinoma (MTC) and increased risk of other endocrine tumors. MEN2 includes subtypes MEN2A, MEN2B, and familial MTC. Prophylactic thyroidectomy is recommended for MEN2A due to high MTC risk.
CASE PRESENTATION
A 38-year-old woman with a family history of thyroid cancer presented with headaches, sweating, and palpable breast mass. Exam revealed skin lesions. Lab abnormalities and imaging indicated a large adrenal mass and thyroid nodules. Inconclusive biopsies led to left adrenalectomy, confirming pheochromocytoma. Subsequent total thyroidectomy revealed MTC.
CLINICAL DISCUSSION
This case represents rare MEN2B presentation, featuring MTC, pheochromocytoma, mucosal neuromas, and marfanoid habitus. Genetic testing for RET mutations is crucial with a positive family history. MEN2A individuals undergo prophylactic thyroidectomy due to high MTC risk. Although rare, pheochromocytoma can be an initial MEN2 manifestation, indicated by paroxysmal symptoms. Surgical resection is the treatment.
CONCLUSIONS
The patient's successful adrenalectomy followed by total thyroidectomy confirmed MTC. Thorough evaluation, including inconclusive initial findings, emphasizes imaging, and biopsies. Early detection and appropriate management optimize MEN2 outcomes.
PubMed: 38694328
DOI: 10.1097/MS9.0000000000001867 -
BMC Urology Apr 2024To introduce the surgical technique and our team's extensive experience with tunnel method in laparoscopic adrenalectomy.
BACKGROUND
To introduce the surgical technique and our team's extensive experience with tunnel method in laparoscopic adrenalectomy.
METHODS
From July 2019 to June 2022, we independently designed and conducted 83 cases of " Tunnel Method Laparoscopic Adrenalectomy," a prospective study. There were 45 male and 38 female patients, ages ranged from 25 to 73 years(mean: 44.6 years).The cases included 59 adrenal cortical adenomas, 9 pheochromocytomas, 6 cysts, 4 myelolipomas, 1 ganglioneuroma, and 4 cases of adrenal cortical hyperplasia. In terms of anatomical location, there were 39 cases on the left side, 42 on the right side, and 2 bilateral cases. Tumor diameters ranged from 0.6 to 5.9 cm(mean: 2.9 cm). Utilizing ultrasound monitoring, percutaneous puncture was made either directly to the target organ or its vicinity, and the puncture path was manually marked. Then, under the direct view of a single-port single-channel laparoscope, the path to the target organ in the retroperitoneum or its vicinity was further delineated and separated. This approach allowed for the insertion of the laparoscope and surgical instruments through the affected adrenal gland, thereby separating the surface of the target organ to create sufficient operational space for the adrenalectomy.
RESULTS
All 83 surgeries were successfully completed. A breakdown of the surgical approach reveals that 51 surgeries were done using one puncture hole, 25 with two puncture holes, and 7 with three puncture holes. The operation time ranged from 31 to 105 min (mean: 47 min), with a blood loss of 10 to 220mL (mean: 40 mL). Notably, there were no conversions to open surgery and no intraoperative complications. Postoperative follow-up ranged from 6 to 28 months, during which after re-examination using ultrasound, CT, and other imaging methods, there were no recurrences or other complications detected.
CONCLUSIONS
The completion of the tunnel method laparoscopic adrenalectomy represents a breakthrough, transitioning from the traditional step-by-step separation of retroperitoneal tissues to reach the target organ in conventional retroperitoneoscopic surgery. This method directly accesses the target organ, substantially reducing the damage and complications associated with tissue separation in retroperitoneoscopic surgery, As a result, it provides a new option for minimally invasive surgery of retroperitoneal organs and introduces innovative concepts to retroperitoneoscopic surgery.
Topics: Humans; Adrenalectomy; Female; Male; Middle Aged; Prospective Studies; Laparoscopy; Adult; Aged; Retroperitoneal Space; Adrenal Gland Neoplasms
PubMed: 38689249
DOI: 10.1186/s12894-024-01484-x -
ELife Apr 2024Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can...
Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin-coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation.
Topics: Proto-Oncogene Proteins c-ret; Humans; Membrane Proteins; Cell Membrane; Signal Transduction; Protein Transport; Cell Transformation, Neoplastic; Cell Proliferation; Adrenal Gland Neoplasms
PubMed: 38687678
DOI: 10.7554/eLife.89100 -
Frontiers in Endocrinology 2024For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been...
For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the gene. I-metaiodobenzylguanidine scintigraphy was negative and Ga-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.
Topics: Humans; Male; Adult; Paraganglioma; Radiofrequency Ablation; Abdominal Neoplasms; Retroperitoneal Neoplasms
PubMed: 38686210
DOI: 10.3389/fendo.2024.1346052 -
Oxford Medical Case Reports Apr 2024A pheochromocytoma is a tumor that typically originates within the chromaffin cells of the adrenal glands, resulting in excessive production of catecholamines. Cystic...
A pheochromocytoma is a tumor that typically originates within the chromaffin cells of the adrenal glands, resulting in excessive production of catecholamines. Cystic forms are exceptional and pose a diagnostic challenge, especially those that are non-secreting. The most prevalent symptom associated with this condition is arterial hypertension, which can be either persistent or, more commonly, intermittent. The Ménard triad, comprising headaches, excessive sweating, and palpitations, may accompany episodes of hypertension. The presence of elevated levels of methoxylated derivatives serves to confirm the diagnosis of an adrenal pheochromocytoma. We report the case of a woman who presented with arterial hypertension associated with the Ménard triad, along with elevated methoxylated derivative levels. Imaging modalities revealed a predominantly cystic left retroperitoneal mass. The diagnosis of a cystic pheochromocytoma was established and confirmed through histological examination of the surgical specimen after adrenalectomy.
PubMed: 38680774
DOI: 10.1093/omcr/omae033 -
Medicina (Kaunas, Lithuania) Apr 2024Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension...
Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension and sweating, but could also be accompanied by symptoms involving multiple organs. Surgery is the gold standard treatment for both PGLs and pheochromocytomas (PHEOs). We used a computerized endocrine surgery registry to record the demographic and clinical data of 153 patients who underwent surgery for PPGL between 2010 and 2023 at our hospital. Thirteen patients (8.43%) with paragangliomas underwent surgery at our institute. Five patients presented symptomatic syndrome. Preoperative investigations included enhanced abdominal CT (nine patients) and enhanced MRI (seven patients). In cases of suspicious mass, we performed 131I-MIBG scans (two patients) or 68GA-DOTATOC PET-CT scans (11 patients). Laparoscopic approach was used in four cases (30.7%) and abdominal laparotomy in the other nine (69.3%). Biochemical tests were performed on all patients. In this retrospective study, we discuss the multidisciplinary management in our institute of this rare disease, from its challenging diagnosis to the surgical strategy for PGLs. Laparoscopic surgery is the gold standard, but a tailored approach should be adopted for each patient.
Topics: Humans; Female; Male; Middle Aged; Adult; Retrospective Studies; Paraganglioma; Aged; Positron Emission Tomography Computed Tomography; Abdominal Neoplasms; Tomography, X-Ray Computed
PubMed: 38674250
DOI: 10.3390/medicina60040604 -
Journal of Clinical Medicine Apr 2024Neurocristopathies (NCPs) encompass a spectrum of disorders arising from issues during the formation and migration of neural crest cells (NCCs). NCCs undergo... (Review)
Review
Neurocristopathies (NCPs) encompass a spectrum of disorders arising from issues during the formation and migration of neural crest cells (NCCs). NCCs undergo epithelial-mesenchymal transition (EMT) and upon key developmental gene deregulation, fetuses and neonates are prone to exhibit diverse manifestations depending on the affected area. These conditions are generally rare and often have a genetic basis, with many following Mendelian inheritance patterns, thus making them perfect candidates for precision medicine. Examples include cranial NCPs, like Goldenhar syndrome and Axenfeld-Rieger syndrome; cardiac-vagal NCPs, such as DiGeorge syndrome; truncal NCPs, like congenital central hypoventilation syndrome and Waardenburg syndrome; and enteric NCPs, such as Hirschsprung disease. Additionally, NCCs' migratory and differentiating nature makes their derivatives prone to tumors, with various cancer types categorized based on their NCC origin. Representative examples include schwannomas and pheochromocytomas. This review summarizes current knowledge of diseases arising from defects in NCCs' specification and highlights the potential of precision medicine to remedy a clinical phenotype by targeting the genotype, particularly important given that those affected are primarily infants and young children.
PubMed: 38673496
DOI: 10.3390/jcm13082223 -
Medicine Apr 2024Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly... (Review)
Review
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.
Topics: Humans; Energy Metabolism; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Catecholamines; Adipose Tissue, Brown; Chromogranin A
PubMed: 38669419
DOI: 10.1097/MD.0000000000037916 -
Toxics Apr 2024Biochar materials have garnered attention as potential catalysts for peroxymonosulfate (PMS) activation due to their cost-effectiveness, notable specific surface area,...
Biochar materials have garnered attention as potential catalysts for peroxymonosulfate (PMS) activation due to their cost-effectiveness, notable specific surface area, and advantageous structural properties. In this study, a suite of plantain-derived biochar (MBB-400, MBB-600, and MBB-800), possessing a well-defined pore structure and a substantial number of uniformly distributed active sites (oxygen vacancy, OVs), was synthesized through a facile calcination process at varying temperatures (400, 600, and 800 °C). These materials were designed for the activation of PMS in the degradation of sulfamethoxazole (SMX). Experimental investigations revealed that OVs not only functioned as enriched sites for pollutants, enhancing the opportunities for free radicals (OH/SO) and surface-bound radicals (SBRs) to attack pollutants, but also served as channels for intramolecular charge transfer leaps. This role contributed to a reduction in interfacial charge transfer resistance, expediting electron transfer rates with PMS, thereby accelerating the decomposition of pollutants. Capitalizing on these merits, the MBB-800/PMS system displayed a 61-fold enhancement in the conversion rate for SMX degradation compared to inactivated MBB/PMS system. Furthermore, the MBB-800 exhibited less cytotoxicity towards rat pheochromocytoma (PC12) cells. Hence, the straightforward calcination synthesis of MBB-800 emerges as a promising biochar catalyst with vast potential for sustainable and efficient wastewater treatment and environmental remediation.
PubMed: 38668506
DOI: 10.3390/toxics12040283