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Open Life Sciences 2024The pheochromocytoma is an uncommon endocrine neoplasm that originates from chromaffin cells and causes significant cardiovascular effects through the intermittent or...
The pheochromocytoma is an uncommon endocrine neoplasm that originates from chromaffin cells and causes significant cardiovascular effects through the intermittent or sustained release of catecholamines. In this report, we present a rare case of myocardial infarction (MI) induced by pheochromocytoma. A 53-year-old female presented to the emergency department with a history of intermittent palpitations, back pain, and sweating for over 10 years, which had worsened over the past 2 days. The patient's cardiac enzymes and troponin levels were significantly elevated, and the electrocardiogram (ECG) showed ST-segment elevation, leading to an initial diagnosis of acute myocardial infarction. Echocardiography revealed apical ballooning, indicative of stress cardiomyopathy. Emergency coronary angiography revealed no significant stenosis, and the patient's blood pressure was fluctuating. Computerized tomography (CT) scan of the adrenal gland revealed a bilateral adrenal mass, with the left adrenal mass being larger in size after contrast-enhanced CT scan. The patient's left adrenal gland was successfully removed through laparoscopic adrenalectomy, and histopathology results confirmed the presence of adrenal pheochromocytoma. Follow-up for 3 months after discharge showed the patient had no symptoms and good prognosis. The abnormal findings on echocardiography and ECG resolved. Prompt diagnosis and management of pheochromocytoma are crucial for a favorable prognosis.
PubMed: 38465332
DOI: 10.1515/biol-2022-0830 -
The Journal of Clinical Endocrinology... Nov 2023Somatic EPAS1 variants account for 5% to 8% of all pheochromocytoma and paragangliomas (PPGL) but are detected in over 90% of PPGL in patients with congenital cyanotic...
CONTEXT
Somatic EPAS1 variants account for 5% to 8% of all pheochromocytoma and paragangliomas (PPGL) but are detected in over 90% of PPGL in patients with congenital cyanotic heart disease, where hypoxemia may select for EPAS1 gain-of-function variants. Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with chronic hypoxia and there are isolated reports of PPGL in patients with SCD, but a genetic link between the conditions has yet to be established.
OBJECTIVE
To determine the phenotype and EPAS1 variant status of patients with PPGL and SCD.
METHODS
Records of 128 patients with PPGL under follow-up at our center from January 2017 to December 2022 were screened for SCD diagnosis. For identified patients, clinical data and biological specimens were obtained, including tumor, adjacent non-tumor tissue and peripheral blood. Sanger sequencing of exons 9 and 12 of EPAS1, followed by amplicon next-generation sequencing of identified variants was performed on all samples.
RESULTS
Four patients with both PPGL and SCD were identified. Median age at PPGL diagnosis was 28 years. Three tumors were abdominal paragangliomas and 1 was a pheochromocytoma. No germline pathogenic variants in PPGL-susceptibility genes were identified in the cohort. Genetic testing of tumor tissue detected unique EPAS1 variants in all 4 patients. Variants were not detected in the germline, and 1 variant was detected in lymph node tissue of a patient with metastatic disease.
CONCLUSION
We propose that somatic EPAS1 variants may be acquired through exposure to chronic hypoxia in SCD and drive PPGL development. Future work is needed to further characterize this association.
Topics: Adult; Humans; Adrenal Gland Neoplasms; Anemia, Sickle Cell; Germ-Line Mutation; Hypoxia; Paraganglioma; Pheochromocytoma
PubMed: 37285480
DOI: 10.1210/clinem/dgad311 -
TouchREVIEWS in Endocrinology Nov 2023Hypertension affects about 1.28 billion adults globally, and significantly increases the risk of chronic morbidity and mortality among sufferers. About 15% of these... (Review)
Review
Hypertension affects about 1.28 billion adults globally, and significantly increases the risk of chronic morbidity and mortality among sufferers. About 15% of these individuals have secondary hypertension, the majority of whom have dysfunction of one or more endocrine systems as the cause of hypertension. Although adrenal disorders are often identified as the cause of endocrine hypertension, extra-adrenal disease and pituitary disorders also can cause the disease. Timely diagnosis is of paramount importance, because of the potential for a surgical cure or optimal disease control with pharmacotherapy to prevent hypertensive complications. Even with its relatively high prevalence compared with many other chronic illnesses, the diagnosis of endocrine hypertension is often delayed or never made because of poor awareness about the disease among physicians. This review attempts to provide an overview of the disease, with some practical aspects of diagnosis and management of a few of the important disorders causing endocrine hypertension.
PubMed: 38187076
DOI: 10.17925/EE.2023.19.2.11 -
Frontiers in Endocrinology 2023
Topics: Humans; Adrenal Gland Neoplasms; Pheochromocytoma; Endocrinology
PubMed: 37810878
DOI: 10.3389/fendo.2023.1291582 -
Medicinski Glasnik : Official... Aug 2023Aim To determine the most common indications for measuring metanephrine and normetanephrine in plasma by gender and age and to compare the concentrations of metanephrine...
Aim To determine the most common indications for measuring metanephrine and normetanephrine in plasma by gender and age and to compare the concentrations of metanephrine and normetanephrine by indication, gender and age. Methods The study was conducted on 224 patients whose plasma metanephrine and normetanephrine concentrations were measured at the Clinical Institute for Laboratory Diagnostics at the University Hospital Centre Osijek for one year, until 1st January 2020. Results The most frequent indications for biochemical testing were adrenal incidentaloma, 138 (6.6 %), and symptoms of pheochromocytoma, 41 (18.3%). Metanephrine concentration was lower in females (p=0.009). No significant correlation was found between age and metanephrine concentration, while age and normetanephrine concentration were positively correlated (p=0.01). Of the 224 patients, only one patient was diagnosed with pheochromocytoma, whose indication for measurement of metanephrine and normetanephrine was adrenal incidentaloma. Conclusion Adrenal incidentalomas and symptoms suggestive of pheochromocytoma are very common in the general population, while the incidence of pheochromocytoma is extremely low. Clear guidelines for the referral of patients for biochemical testing are needed to avoid unnecessary costs and to identify the correct diagnosis promptly.
PubMed: 37300464
DOI: 10.17392/1588-23 -
Cancers Aug 2023Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC... (Review)
Review
Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.
PubMed: 37568824
DOI: 10.3390/cancers15154009 -
BioRxiv : the Preprint Server For... Jan 2024Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we...
UNLABELLED
Cancer immunotherapies have produced remarkable results in B-cell malignancies; however, optimal cell surface targets for many solid cancers remain elusive. Here, we present an integrative proteomic, transcriptomic, and epigenomic analysis of tumor specimens along with normal tissues to identify biologically relevant cell surface proteins that can serve as immunotherapeutic targets for neuroblastoma, an often-fatal childhood cancer of the developing nervous system. We apply this approach to human-derived cell lines (N=9) and cell/patient-derived xenograft (N=12) models of neuroblastoma. Plasma membrane-enriched mass spectrometry identified 1,461 cell surface proteins in cell lines and 1,401 in xenograft models, respectively. Additional proteogenomic analyses revealed 60 high-confidence candidate immunotherapeutic targets and we prioritized Delta-like canonical notch ligand 1 (DLK1) for further study. High expression of DLK1 directly correlated with the presence of a super-enhancer spanning the DLK1 locus. Robust cell surface expression of DLK1 was validated by immunofluorescence, flow cytometry, and immunohistochemistry. Short hairpin RNA mediated silencing of DLK1 in neuroblastoma cells resulted in increased cellular differentiation. ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), showed potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Moreover, DLK1 is highly expressed in several adult cancer types, including adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PCPG), hepatoblastoma, and small cell lung cancer (SCLC), suggesting potential clinical benefit beyond neuroblastoma. Taken together, our study demonstrates the utility of comprehensive cancer surfaceome characterization and credentials DLK1 as an immunotherapeutic target.
HIGHLIGHTS
Plasma membrane enriched proteomics defines surfaceome of neuroblastomaMulti-omic data integration prioritizes DLK1 as a candidate immunotherapeutic target in neuroblastoma and other cancersDLK1 expression is driven by a super-enhancer silencing in neuroblastoma cells results in cellular differentiation ADCT-701, a DLK1-targeting antibody-drug conjugate, shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma preclinical models.
PubMed: 38106022
DOI: 10.1101/2023.12.06.570390 -
Endocrine-related Cancer Jan 2024Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a... (Observational Study)
Observational Study
Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.
Topics: Humans; Pheochromocytoma; Normetanephrine; Antidepressive Agents, Tricyclic; Selective Serotonin Reuptake Inhibitors; Metanephrine; Paraganglioma; Norepinephrine; Adrenal Gland Neoplasms
PubMed: 37955319
DOI: 10.1530/ERC-23-0063 -
Biomedicines Jul 2023We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases...
We delved into the expression of amine oxidase family proteins and their potential significance in adrenal gland neoplasm. Tissue microarrays were prepared for 132 cases of adrenal cortical neoplasm (ACN) consisting of 115 cases of adrenal cortical adenoma (ACA), 17 cases of adrenal cortical carcinoma (ACC), and 163 cases of pheochromocytoma (PCC). Immunohistochemical stainings for MAOA, MAOB, LOX, and AOC3 were performed to evaluate the H-scores and compare them with clinicopathological parameters. The H-scores of MAOA (T; = 0.005) and MAOB (T; = 0.006) in tumor cells (T) were high in ACN, whereas LOX (T, S; < 0.001) in tumor and stromal cells (S) and AOC3 (T; < 0.001) were higher in PCC. In stromal cells, MAOA (S; < 0.001) and AOC3 (S; = 0.010) were more expressed in ACA than in ACC. MAOB (S) in PCC showed higher H-scores when the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score was 3 or higher ( = 0.027). In the univariate analysis, low MAOA expression in stromal cells of ACN was associated with shorter overall survival ( = 0.008). In conclusion, monoamine oxidase proteins revealed differences in expression between ACN and PCC and also between benign and malignant cells.
PubMed: 37509535
DOI: 10.3390/biomedicines11071896