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Gland Surgery Feb 2020Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that secrete excess catecholamines leading to secondary hypertension and cardiovascular... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that secrete excess catecholamines leading to secondary hypertension and cardiovascular morbidity. Once biochemical testing with either 24-hour urinary fractioned metanephrines or plasma free metanephrines confirms the diagnosis, patients are optimized with adequate hydration to maintain their intravascular volume and the appropriate antihypertensive medications are initiated for optimal blood pressure control. Genetic testing and imaging is performed to determine the extent of adrenalectomy and the optimal surgical approach. Surgical approaches include transabdominal or retroperitoneal minimally invasive approaches, and transabdominal open approaches. Factors that influence the surgical approach include germline genetic test results, the size of the tumor, body mass index, surgeon experience, and the likelihood of malignancy. The extent of adrenalectomy is based on germline genetic findings. Patients with syndromes such as von Hippel Lindau (VHL) or multiple endocrine neoplasia 2 (MEN 2) benefit from cortical-sparing adrenalectomy to avoid chronic steroid replacement and the risk of Addisonian crisis. Postoperative management includes hemodynamic monitoring and assessment for signs of hypoglycemia. Outcomes after surgery show improved blood pressure control in most patients and normalization of blood pressure in about a third of patients. Long-term follow-up is required for all patients to assess for recurrence.
PubMed: 32206597
DOI: 10.21037/gs.2019.10.20 -
Genes Sep 2023The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4)...
UNLABELLED
The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET).
METHODS
Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the and genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors.
RESULTS
A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for (Group B). No patient was positive for . In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria.
CONCLUSION
These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.
Topics: Humans; Adult; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pituitary Neoplasms; Genetic Testing; Gastrointestinal Tract
PubMed: 37761922
DOI: 10.3390/genes14091782 -
European Journal of Case Reports in... 2020Pheochromocytoma, papillary thyroid carcinoma and hyperparathyroidism have rarely been reported together. Whether this association is coincidental or results from an...
UNLABELLED
Pheochromocytoma, papillary thyroid carcinoma and hyperparathyroidism have rarely been reported together. Whether this association is coincidental or results from an unknown genetic predisposition is difficult to ascertain. We present the case of a patient who was diagnosed with pheochromocytoma, bilateral papillary thyroid carcinoma and parathyroid hyperplasia with primary hyperparathyroidism. A genetic mutation was hypothesized as the connection between these lesions. Previously described mutations were explored.
LEARNING POINTS
Parathyroid hyperplasia, primary hyperparathyroidism and papillary thyroid carcinoma individually are common conditions, but association with each other, although possibly incidental, should trigger genetic testing.Further research is needed to reliably explain the relationship between primary hyperparathyroidism and non-medullary thyroid cancer.
PubMed: 33194854
DOI: 10.12890/2020_001818 -
International Journal of Molecular... Apr 2021Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1-2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine... (Review)
Review
Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1-2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). pNETs affect 30-80% of MEN1 patients, manifesting prevalently as multiple microadenomas. pNETs in patients with MEN1 are particularly difficult to treat due to differences in their growth potential, their multiplicity, the frequent requirement of extensive surgery, the high rate of post-operative recurrences, and the concomitant development of other tumors. MEN1 syndrome is caused by germinal heterozygote inactivating mutation of the gene, encoding the menin tumor suppressor protein. MEN1-related pNETs develop following the complete loss of function of wild-type menin. Menin is a key regulator of endocrine cell plasticity and its loss in these cells is sufficient for tumor initiation. Somatic biallelic loss of wild-type menin in the neuroendocrine pancreas presumably alters the epigenetic control of gene expression, mediated by histone modifications and DNA hypermethylation, as a driver of MEN1-associated pNET tumorigenesis. In this light, epigenetic-based therapies aimed to correct the altered DNA methylation, and/or histone modifications might be a possible therapeutic strategy for MEN1 pNETs, for whom standard treatments fail.
Topics: Animals; Epigenesis, Genetic; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Signal Transduction
PubMed: 33919851
DOI: 10.3390/ijms22084041 -
Hormones (Athens, Greece) Mar 2024Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH)... (Review)
Review
Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
Topics: Infant, Newborn; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Adenoma; Fibroma; Hyperparathyroidism; Jaw Neoplasms
PubMed: 38038882
DOI: 10.1007/s42000-023-00508-9 -
Visceral Medicine Feb 2020Some gender-related differences have been reported in multiple endocrine neoplasia type 1 (MEN1), although not all reports are conclusive. This systematic review with... (Review)
Review
BACKGROUND
Some gender-related differences have been reported in multiple endocrine neoplasia type 1 (MEN1), although not all reports are conclusive. This systematic review with analysis of the own MEN1 cohort evaluates gender differences and potential consequences for screening.
METHODS
A systematic review of the literature between 1990 and 2019 with the search terms "MEN1" or "multiple endocrine neoplasia type 1" and "gender" or "sex" was performed. In addition, the prospectively collected data of a genetically confirmed MEN1 cohort of the Philipps University Marburg were retrospectively analyzed.
RESULTS
Review of the literature identified five retrospective case series with original data of 1,057 MEN1 patients. One series suggested a higher frequency of pancreatic neuroendocrine neoplasms (NEN), especially gastrinomas, in men (61 vs. 54%) and a higher frequency of pituitary tumors in women (47 vs. 30%), but others did not. Only thymic NEN occurred predominantly in men throughout all studies. Women with MEN1 were found to have an increased risk of breast cancer. In the own series consisting of 116 MEN1 patients (male = 58, female = 58), thymic lesions were also more frequently detected in male patients (male = 5, female = 1). No gender difference was found with regard to the other manifestations.
CONCLUSION
Regarding the typical MEN1 tumor manifestations, gender-adapted diagnostic and therapeutic approaches cannot be recommended. Female MEN1 patients should be encouraged to participate in breast cancer screening programs.
PubMed: 32110650
DOI: 10.1159/000505498 -
Problemy Endokrinologii Nov 2023This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The... (Review)
Review
This review article contains a summary of modern aspects of preoperative preparation, surgical treatment, and follow-up of patients with adrenal pheochromocytomas. The main component of preoperative preparation is the use of alpha-blockers. The need to prescribe them to all patients is increasingly disputed, especially for patients without severe hypertension. An increasing number of publications demonstrate positive results of treatment without the use of alpha-blockers, advocating an individual approach and the use of the drug according to certain indications. Minimally invasive endoscopic techniques of adrenalectomy have become widespread in surgical treatment. They are represented by laparoscopic and retroperitonescopic technic, including using their single-port modifications. The earliest possible intersection of the central vein in the past was considered the most important aspect of adrenalectomy for pheochromocytoma, currently, due to the development of surgical techniques and anesthesiological manuals, this has ceased to be a mandatory rule of successful surgery. Despite the significant influence of the intersection of this vessel on intraoperative hemodynamics, surgical tactics with its later intersection have their own justifications and do not lead to a deterioration in treatment results. The standard volume of surgical intervention for pheochromocytomas is total adrenalectomy, however, in the presence of hereditary syndromes, such as multiple endocrine neoplasia type 2 syndrome, neurofibomatosis type 1, von Hippel-Lindau syndrome, it is possible to perform cortical-sparing adrenalectomy.
Topics: Humans; Pheochromocytoma; von Hippel-Lindau Disease; Adrenal Gland Neoplasms; Multiple Endocrine Neoplasia Type 2a; Adrenalectomy; Syndrome
PubMed: 37968950
DOI: 10.14341/probl13283 -
Endocrine Mar 2021Pituitary tumours are usually benign and relatively common intracranial tumours, with under- and overexpression of pituitary hormones and local mass effects causing... (Review)
Review
BACKGROUND
Pituitary tumours are usually benign and relatively common intracranial tumours, with under- and overexpression of pituitary hormones and local mass effects causing considerable morbidity and increased mortality. While most pituitary tumours are sporadic, around 5% of the cases arise in a familial setting, either isolated [familial isolated pituitary adenoma, related to AIP or X-linked acrogigantism], or in a syndromic disorder, such as multiple endocrine neoplasia type 1 or 4, Carney complex, McCune-Albright syndrome, phaeochromocytoma/paraganglioma with pituitary adenoma, DICER1 syndrome, Lynch syndrome, and USP8-related syndrome. Genetically determined pituitary tumours usually present at younger age and show aggressive behaviour, and are often resistant to different treatment modalities.
SUBJECT
In this practical summary, we take a practical approach: which genetic syndromes should be considered in case of different presentation, such as tumour type, family history, age of onset and additional clinical features of the patient.
CONCLUSION
The identification of the causative mutation allows genetic and clinical screening of relatives at risk, resulting in earlier diagnosis, a better therapeutic response and ultimately to better long-term outcomes.
Topics: Adenoma; DEAD-box RNA Helicases; Endopeptidases; Endosomal Sorting Complexes Required for Transport; Growth Hormone-Secreting Pituitary Adenoma; Humans; Multiple Endocrine Neoplasia Type 1; Pituitary Gland; Pituitary Neoplasms; Ribonuclease III; Ubiquitin Thiolesterase
PubMed: 33543431
DOI: 10.1007/s12020-021-02633-0 -
TouchREVIEWS in Endocrinology Nov 2022Pancreatic neuroendocrine tumours (pNETs) are a major manifestation of multiple endocrine neoplasia type 1 (MEN1), and the most significant cause of morbidity and...
Pancreatic neuroendocrine tumours (pNETs) are a major manifestation of multiple endocrine neoplasia type 1 (MEN1), and the most significant cause of morbidity and mortality in this disorder. There is some evidence that the early use of somatostatin analogues can retard progression, especially of small non-functioning tumours, but there are no other prophylactic therapies for patients, and the treatment of metastatic disease is similar to that for sporadic pNETs. A recent study has shown that in cell line and animal models, mutations lead to an upregulation of the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in increasing precursor metabolites for the synthesis of pyrimidines. In these studies, blockade of this pathway by various means, including the DHODH inhibitor leflunomide, attenuates cell growth and tumour progression, suggesting a critical dependence on DHODH specifically in -mutated tissue. Preliminary clinical studies in three patients with MEN1 and pNETs have indicated some therapeutic potential of this drug, which has previously been used for some years in patients with rheumatoid arthritis. It is suggested that further clinical trials of this re-purposed drug are indicated to evaluate its potential for the treatment of patients with MEN1 and pNETS. This article describes the clinical problem of MEN1 and pNETs, and reviews the recent publication reporting on these initial results.
PubMed: 36694894
DOI: 10.17925/EE.2022.18.2.86