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Frontiers in Veterinary Science 2023Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia,...
Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs ( = 19) and normal adrenal medullas (NAMs; = 10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs. Of these, 232 had a log fold change of >3 or < -3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (), Dopamine Receptor D2 (), and Secreted Frizzled Related Protein 2 (). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores ( = 0.035) and shorter survival times ( = 0.04) than group 2. Increased expression of 1 of the differentially expressed genes between group 1 and 2, pleiotrophin (), appeared to correlate with a more aggressive tumor phenotype. This study has shed light on the transcriptomic profile of canine PPGL, yielding new insights into the pathogenesis of these tumors in dogs, and revealed potential novel targets for therapy. In addition, we identified 2 transcriptionally distinct groups of PPGLs that had significantly different survival times.
PubMed: 37691636
DOI: 10.3389/fvets.2023.1155804 -
The Journal of Clinical Endocrinology... Dec 2023Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear.
CONTEXT
Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear.
OBJECTIVE
We aimed to assess the proportion and clinical, biochemical, radiological, genetic, histopathological, and follow-up characteristics of incidental pheochromocytomas.
METHODS
A retrospective review was conducted of patients with pheochromocytoma seen between January 2010 and October 2022 at a large UK tertiary care center. The diagnosis was confirmed histologically or by the combined presence of increased plasma and/or urinary metanephrines (MN), indeterminate adrenal mass on cross-sectional imaging, and metaiodobenzylguanidine avidity.
RESULTS
We identified 167 patients with pheochromocytoma; 144 (86.2%) underwent adrenalectomy, for 23 (13.8%) surgery was either awaited, deemed unsuitable due to frailty or other metastatic malignancy, or declined by the patients. Excluding pheochromocytomas diagnosed via screening genetically predisposed individuals (N = 20), 37 of 132 (28.0%) presented with adrenergic symptoms and/or uncontrolled hypertension, while 91 of 132 (69.0%) patients presented with an incidentally detected adrenal mass. Incidentally detected patients were older (median age 62 years) than those detected due to clinical suspicion (aged 42 years) or after genetic screening (aged 33 years) (all P < .05). Incidentally detected pheochromocytomas were smaller (median 42 mm) than tumors detected due to adrenergic symptoms/uncontrolled hypertension (60 mm), but larger than tumors identified by genetic screening (30 mm) (all P < .05). Increased MN excretion showed a similar pattern (symptomatic/uncontrolled hypertension > incidental > genetic screening) (all P < .05). Hereditary predisposition was detected in 20.4% of patients (incidental, 15.3%; symptomatic/uncontrolled hypertension, 42.9%).
CONCLUSION
The majority of pheochromocytomas are diagnosed incidentally and have distinct clinical, radiological, biochemical, and genetic features. Their detection at older age but smaller size may point to a different underlying tumor biology.
Topics: Humans; Middle Aged; Adrenal Gland Neoplasms; Pheochromocytoma; Hypertension; Adrenergic Agents; Genetic Predisposition to Disease
PubMed: 37417693
DOI: 10.1210/clinem/dgad401 -
Diagnostics (Basel, Switzerland) Sep 2023Phaeochromocytomas (PC) and sympathetic paragangliomas (PGL) are potentially malignant tumours arising from the adrenal medulla (PC) or elsewhere in the sympathetic... (Review)
Review
Phaeochromocytomas (PC) and sympathetic paragangliomas (PGL) are potentially malignant tumours arising from the adrenal medulla (PC) or elsewhere in the sympathetic nervous system (PGL). These tumours usually secrete catecholamines and are associated with significant morbidity and mortality, so accurate and timely diagnosis is essential. The initial diagnosis of phaeochromocytoma/paraganglioma (PPGL) is often dependent on biochemical testing. There is a range of pre-analytical, analytical and post-analytical factors influencing the analytical and diagnostic performance of biochemical tests for PPGL. Pre-analytical factors include patient preparation, sample handling and choice of test. Analytical factors include choice of methodology and the potential for analytical interference from medications and other compounds. Important factors in the post-analytical phase include provision of appropriate reference ranges, an understanding of the potential effects of various medications on metanephrine concentrations in urine and plasma and a consideration of PPGL prevalence in the patient population being tested. This article reviews these pre-analytical, analytical and post-analytical factors that must be understood in order to provide effective laboratory services for biochemical testing in the diagnosis of PPGL.
PubMed: 37761307
DOI: 10.3390/diagnostics13182940 -
Cancers Sep 2023In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment.... (Review)
Review
In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.
PubMed: 37760633
DOI: 10.3390/cancers15184666 -
Exploration of Targeted Anti-tumor... 2024Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex () genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors.
PubMed: 38745767
DOI: 10.37349/etat.2024.00222 -
World Journal of Surgical Oncology Sep 2023To compare the surgical effects of lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) for pheochromocytoma of different sizes.
BACKGROUND
To compare the surgical effects of lateral transperitoneal approach (LTA) and posterior retroperitoneal approach (PRA) for pheochromocytoma of different sizes.
METHODS
Data on patients with pheochromocytoma from 2014 to 2023 were collected from our hospital. According to different surgical approaches and tumor size, all patients were divided into four groups: tumor size < 6 cm for LTA and PRA and tumor size ≥ 6 cm for LTA and PRA. We compared these two surgical methods for pheochromocytoma of different sizes.
RESULTS
A total of 118 patients with pheochromocytoma underwent successful laparoscopic surgery, including PRA group (n = 80) and LTA group (n = 38). In tumor size < 6 cm, the outcomes were no significant difference in LTA and PRA. In tumor size ≥ 6 cm, there was a significant difference in operation time (214.7 ± 18.9 vs. 154.3 ± 8.2, P = 0.007) and intraoperative blood loss (616.4 ± 181.3 vs. 201.4 ± 45.8, P = 0.037) between LTA and PRA.
CONCLUSION
LTA and PRA were performed safely with similar operative outcomes in patients with pheochromocytoma size < 6 cm. While both LTA and PRA were executed with a commendable safety profile and comparable operative results in patients afflicted by pheochromocytomas < 6 cm, the PRA technique distinctly showcased advantages when addressing large-scale pheochromocytomas (≥ 6 cm). Notably, this manifested in reduced operative time, diminished intraoperative blood loss, decreased hospitalization expenses, and a paucity of procedural complications.
Topics: Humans; Pheochromocytoma; Blood Loss, Surgical; Retrospective Studies; Adrenal Gland Neoplasms; Hospitalization
PubMed: 37697366
DOI: 10.1186/s12957-023-03164-w -
Frontiers in Endocrinology 2023Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients... (Review)
Review
Targeted radionuclide therapy plays an increasingly important role in managing endocrine-related tumors and significantly advances the therapeutic landscape for patients with these diseases. With increasing FDA-approved therapies and advances in the field, come an increased knowledge of the potential for long-term toxicities associated with these therapies and the field must develop new strategies to increase potency and efficacy while individualizing the selection of patients to those most likely to respond to treatment. Novel agents and modalities of therapy are also being explored. This review will discuss the current landscape and describe the avenues for growth in the field currently being explored.
Topics: Humans; Endocrine Gland Neoplasms; Radioisotopes
PubMed: 38053729
DOI: 10.3389/fendo.2023.1187870 -
Frontiers in Endocrinology 2023Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose... (Review)
Review
Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose metabolism disorders at variable degrees and requiring immediate treatment, until patients are ready to undergo surgery. This review focuses on the management of diabetes mellitus in endocrine disorders related to an excess of counterregulatory hormones. Currently, the landscape of approved agents for treatment of diabetes is dynamic and is mainly patient-centred and not glycaemia-centred. In addition, personalized medicine is more and more required to provide a precise approach to the patient's disease. For this reason, we aimed to define a practical therapeutic algorithm for management of diabetes mellitus in patients with glucagonoma, pheochromocytoma, Cushing's syndrome and acromegaly, based on our practical experience and on the physiopathology of the specific endocrine disease taken into account. This document is addressed to all specialists who approach patients with diabetes mellitus secondary to endocrine disorders characterized by an excess of counterregulatory hormones, in order to take better care of these patients. Care and control of diabetes mellitus should be one of the primary goals in patients with an excess of counterregulatory hormones requiring immediate and aggressive treatment.
Topics: Humans; Cushing Syndrome; Acromegaly; Neuroendocrine Tumors; Diabetes Mellitus; Hormones
PubMed: 37842314
DOI: 10.3389/fendo.2023.1248985 -
Molecules (Basel, Switzerland) Aug 2023() is widely distributed in Northeast China. In addition to medicines, it has also been used to prepare food, wine, tobacco, cosmetics, perfume, and functional foods....
() is widely distributed in Northeast China. In addition to medicines, it has also been used to prepare food, wine, tobacco, cosmetics, perfume, and functional foods. Other studies have investigated the neuroprotective effects of extract. As the therapeutic basis, the active constituents should be further evaluated. In this paper, six new compounds (-) were isolated, including five iridoids (Xiecaoiridoidside A-E) and one bisepoxylignan (Xiecaolignanside A), as well as six known compounds (-). The neuroprotective effects of - were also investigated with amyloid protein - (Aβ)-induced injury to rat pheochromocytoma (PC12) cells. As a result, iridoids and and lignans , , and could markedly maintain the cells' viability by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assay.
Topics: Rats; Animals; Lignans; Amyloid beta-Peptides; Neuroprotective Agents; Valerian; Iridoids; Plant Roots
PubMed: 37570763
DOI: 10.3390/molecules28155793