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Frontiers in Endocrinology 2022Adrenal hemorrhage is a rare, usually life-threating complication. The most common neoplasm resulting in spontaneous adrenal bleeding is pheochromocytoma and it accounts...
BACKGROUND
Adrenal hemorrhage is a rare, usually life-threating complication. The most common neoplasm resulting in spontaneous adrenal bleeding is pheochromocytoma and it accounts for nearly 50% of cases. Currently, the recommendations for the diagnosis and management of patients with adrenal bleeding due to pheochromocytoma are unavailable.
MATERIALS AND METHODS
We performed a database search for all pheochromocytoma patients, diagnosed and treated from 2005 to 2021 in tertiary endocrinology center. 206 patients were identified, 183 with complete data were included in the analysis. We investigated clinicopathological characteristics, treatment and outcomes of hemorrhagic pheochromocytoma cases and characterize our approach to perioperative diagnosis and medical management. Finally our experiences and data from previously published articles concerning adrenal hemorrhage were analyzed to propose a diagnostic and therapeutic algorithm for hemorrhagic pheochromocytomas.
RESULTS
In the whole group, seven patients (4 men and 3 women) with adrenal bleeding were found, (3.8%). Median patient's age was 49 years (range: 36-78 years). The most common manifestation of adrenal bleeding was acute abdominal pain (5/7). Two patients developed shock. Hormonal assessment was performed in five patients, based on 24-hour urinary fractionated metanephrines with urinary 3-methoxytyramine. Normetanephrine was elevated in all patients, metanephrine and 3-methoxytyramine - in four cases (4/5). Most patients (6/7) had symptoms suggesting pheochromocytoma before hemorrhage - most commonly paroxysmal hypertension (4/7). One patient died, before the diagnosis of adrenal bleeding was made. Diagnostic imaging performed in six out of seven patients revealed adrenal tumor, with median largest diameter equal to 7.4 cm (range: 5-11 cm). Five patients had elective surgery, in one case an urgent surgery was performed. In all cases the diagnosis of pheochromocytoma was confirmed in postoperative histopathology or in autopsy. The perioperative survival rate was 85.7%.
CONCLUSIONS
Diagnosis of pheochromocytoma should be always considered in patients with adrenal bleeding, especially with accompanying abdominal pain, hemodynamic shock and previous history of pheochromocytoma-associated symptoms. Lack of proper diagnosis of pheochromocytoma before surgery is associated with an additional perioperative risk. To improve the decision making in this life-threatening clinical situation, based on our results and literature data, we proposed a diagnostic and treatment algorithm.
Topics: Abdominal Pain; Adrenal Gland Neoplasms; Adult; Aged; Algorithms; Female; Hemorrhage; Humans; Male; Middle Aged; Pheochromocytoma
PubMed: 35992110
DOI: 10.3389/fendo.2022.908967 -
Cancer Genetics 2012Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors... (Review)
Review
Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors that are associated with high morbidity and mortality due to mass effect and high circulating catecholamines. Although most PCCs and PGLs are thought to be sporadic, over one third are associated with 10 known susceptibility genes. Mutations in three genes causing well characterized tumor syndromes are associated with an increased risk of developing PCCs and PGLs, including VHL (von Hippel-Lindau disease), NF1 (Neurofibromatosis Type 1), and RET (Multiple Endocrine Neoplasia Type 2). Mutations in any of the succinate dehydrogenase (SDH) complex subunit genes (SDHA, SDHB, SDHC, SDHD) can lead to PCCs and PGLs with variable penetrance, as can mutations in the subunit cofactor, SDHAF2. Recently, two additional genes have been identified, TMEM127 and MAX. Although these tumors are rare in the general population, occurring in two to eight per million people, they are more commonly associated with an inherited mutation than any other cancer type. This review summarizes the known germline and somatic mutations leading to the development of PCC and PGL, as well as biochemical profiling for PCCs/PGLs and screening of mutation carriers.
Topics: Adrenal Gland Neoplasms; Animals; Comprehension; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Multiple Endocrine Neoplasia; Paraganglioma; Pheochromocytoma; Syndrome; von Hippel-Lindau Disease
PubMed: 22429592
DOI: 10.1016/j.cancergen.2012.01.009 -
Reviews in Cardiovascular Medicine Dec 2021Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism,... (Review)
Review
Although many endocrine diseases can be associated with acquired cardiomyopathy and heart failure, conditions except hypothyroidism, hyperthyroidism, phaeochromocytoma-paraganglioma (PPGL), and primary hyperaldosteronism are rare. PPGL is a rare catecholamine-secreting neuroendocrine tumour arising from the adrenal gland in 80-85% or extra-adrenal chromaffin cells of the autonomic neural ganglia in the remainder. The annual incidence of PPGL is 3-8 cases per million per year in the general population. Catecholamine-induced cardiomyopathy (CICMP) has got a prevalence of 8-11% among patients with PPGL. Hypertension, either sustained or episodic, is present in the vast majority (95%) of PPGL patients. However, among patients with CICMP, hypertension is present only in 65% of cases and the classical triad of paroxysmal headache, sweating, and palpitation is present only in 4%. Based on the cardiac remodelling in response to endogenous catecholamine excess, PPGL patients might present with one of the three CICMPs, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or Takotsubo cardiomyopathy (TCM). Regardless of the subtypes, all CICMPs have many features in common - a dramatic clinical presentation, reversible cardiomyopathy, similar repolarisation electrocardiography changes, mild-moderate cardiac biomarker elevation, and normal coronary arteries on coronary angiography. CICMP should be suspected in patients with non-ischaemic, non-valvular forms of cardiomyopathy, even in those without definite features of catecholamine excess. PPGL associated TCM should be suspected in all acute coronary syndrome (ACS) patients exhibiting pronounced blood pressure variability with no culprit lesions on coronary angiography. This article will provide a review of the various CICMPs, their pathophysiology, clinical features, and the management options.
Topics: Adrenal Gland Neoplasms; Cardiomyopathies; Catecholamines; Endocrinologists; Humans; Pheochromocytoma
PubMed: 34957765
DOI: 10.31083/j.rcm2204130 -
Endocrine Pathology Jun 2021Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although... (Review)
Review
Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although few pathologists outside of endocrine tertiary centers will ever diagnose such a lesion, the tumors are well known through the medical community-possible due to a combination of the sheer rarity, their often-spectacular presentation due to excess catecholamine secretion as well as their unrivaled coupling to constitutional susceptibility gene mutations and hereditary syndromes. All PPGLs are thought to harbor malignant potential, and therefore pose several challenges to the practicing pathologist. Specifically, a responsible diagnostician should recognize both the capacity and limitations of histological, immunohistochemical, and molecular algorithms to pinpoint high risk for future metastatic disease. This focused review aims to provide the surgical pathologist with a condensed update regarding the current strategies available in order to deliver an accurate prognostication of these enigmatic lesions.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Humans; Immunohistochemistry; Paraganglioma; Pathology, Molecular; Pheochromocytoma
PubMed: 33768452
DOI: 10.1007/s12022-021-09675-0 -
Current Opinion in Endocrinology,... Jun 2022Many publications review perioperative management of pheochromocytomas/paragangliomas (PPGLs); however, a large population, including 10-20% of metastatic PPGL patients,... (Review)
Review
PURPOSE OF REVIEW
Many publications review perioperative management of pheochromocytomas/paragangliomas (PPGLs); however, a large population, including 10-20% of metastatic PPGL patients, have inoperable disease. This has necessitated the development of noninvasive treatments (e.g., radio/chemotherapy), which, in affording disease-modification, have led to an ever-growing population of surviving patients with inoperable PPGL. These patients experience debilitating symptoms arising from discomforts related to the masses themselves (e.g., pain from osseous metastasis) and symptoms from tumoral catecholamine production and release. Unfortunately, management of these conditions is not yet well-defined. Adding further insult-to-injury, these noninvasive treatments can trigger catecholamine release, worsening catecholamine-induced symptoms. Herein, we detail these ailments and their management, especially while patients receive these noninvasive treatments.
RECENT FINDINGS
Improved diagnostic evaluations have allowed for earlier detection of PPGL, prolonging survival in patients with inoperable PPGLs. Accordingly, noninvasive treatment strategies have rapidly evolved alongside state-of- the-art theranostics and genetic testing, which inform ongoing management and therapeutic response.
SUMMARY
While treatments afford improved survival, there must be a corresponding attention to quality-of-life. This is ensured by employing supportive management, which mitigates debilitating symptoms. This is best accomplished with a multidisciplinary approach and familiarity with genetic and biochemical determinants which guide patient education and management.
Topics: Adrenal Gland Neoplasms; Catecholamines; Genetic Testing; Humans; Paraganglioma; Pheochromocytoma
PubMed: 35621181
DOI: 10.1097/MED.0000000000000724 -
The International Journal of... May 2021Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest... (Review)
Review
Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours. So far, over 20 causative genes have been identified, of which the most frequent and strongest indicator for malignancies are mutations in succinate dehydrogenase subunit B. No curative therapy is available for patients with metastases resulting in poor prognosis. Therapy development has been hindered by lack of suitable model systems. The succinate dehydrogenase complex is located in the inner membrane of the mitochondria and plays a crucial role in the oxidative phosphorylation chain and the tricarboxylic acid-cycle. Succinate dehydrogenase deficiency results in accumulation of the oncometabolite succinate inducing hypoxia inducible factor stabilization, deoxyribonucleic acid and histone methylation inhibition, and impaired production of adenosine triphosphate. It remains unknown which combination of pathways and/or triggers are decisive for metastases development. In this review, the role of mitochondria in malignant succinate dehydrogenase subunit B-associated phaeochromocytomas and paragangliomas and implications for mitochondria as therapeutic target are discussed.
Topics: Adrenal Gland Neoplasms; Animals; Electron Transport Complex II; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Metabolism, Inborn Errors; Mitochondria; Mitochondrial Diseases; Mutation; Paraganglioma; Pheochromocytoma; Reactive Oxygen Species; Succinate Dehydrogenase
PubMed: 33609747
DOI: 10.1016/j.biocel.2021.105949 -
Current Opinion in Endocrinology,... Jun 2015About 40% of the neuroendocrine tumors pheochromocytomas and paragangliomas (PPGLs) are caused by an inherited mutation. Diagnostic genetic screening is recommended for... (Review)
Review
PURPOSE OF REVIEW
About 40% of the neuroendocrine tumors pheochromocytomas and paragangliomas (PPGLs) are caused by an inherited mutation. Diagnostic genetic screening is recommended for patients and their families. However, the number of susceptibility genes involved is high and continues to grow, making conventional sequencing costly and burdensome. Next-generation sequencing (NGS) enables accurate, thorough, and cost-effective identification of inherited mutations. Here we review recent successes, limitations, and the future of NGS for diagnosis of pheochromocytoma and paraganglioma syndromes.
RECENT FINDINGS
NGS-based screen of genetic disorders in the clinical setting shows improved diagnostic rates over conventional tests. Both broad, whole-exome sequencing, and targeted NGS approaches have been tested for screening of PPGLs, with accurate mutation detection, higher speed, and reduced costs compared with current assays. Flexibility to expand the targeted gene set is immediate in whole-exome sequencing, and adjustable in targeted NGS, but both methods have limitations.
SUMMARY
The high degree of genetic heterogeneity and heritability of PPGLs make NGS an ideal medium for their diagnostic screening. However, improved detection of large genomic defects and underrepresented gene areas are needed before NGS can fully realize its potential as the premier option for routine genetic testing of these syndromes.
Topics: Adrenal Gland Neoplasms; High-Throughput Nucleotide Sequencing; Humans; Paraganglioma; Pheochromocytoma
PubMed: 25871962
DOI: 10.1097/MED.0000000000000150 -
The Oncologist Jul 2008Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of the excess... (Review)
Review
Pheochromocytomas are rare catecholamine-secreting tumors that arise from chromaffin tissue within the adrenal medulla and extra-adrenal sites. Because of the excess secretion of hormones, these tumors often cause debilitating symptoms and a poor quality of life. While medical management plays a significant role in the treatment of pheochromocytoma patients, surgical excision remains the only cure. Improved medical management and surgical techniques and an increased understanding of hereditary disease have improved the outcome of pheochromocytoma patients with benign disease; however, the outcome of patients with malignant disease remains poor. In this review, we discuss the presentation, diagnosis, management, and future directions in the management of this disease.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Chemotherapy, Adjuvant; Genetic Predisposition to Disease; Humans; Neoplasm Metastasis; Pheochromocytoma; Radiotherapy, Adjuvant
PubMed: 18617683
DOI: 10.1634/theoncologist.2008-0043 -
Frontiers in Endocrinology 2023Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and... (Review)
Review
Pheochromocytomas (PCC)/paragangliomas (PGL) are catecholamine (CA) -secreting neuroendocrine tumors, which are known as PPGL due to their histological and pathophysiological similarities. In addition to the typical triad of paroxysmal headache, palpitation, and sweating, PPGL may also be accompanied by symptoms and signs involving multiple organs and systems such as the cardiovascular system, digestive system, endocrine system, and nervous system. Currently, surgical resection is the first choice for PPGL. Safe and effective surgical management of complicated PPGL is the goal of clinical work. In this paper, we discuss this hot issue based on complicated PPGL cases, aiming to share our experience of the surgical management strategy of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms; Neuroendocrine Tumors; Catecholamines
PubMed: 37152961
DOI: 10.3389/fendo.2023.1129622 -
Endocrine Regulations Jan 2018Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues. Accordingly, there is an extreme need for new diagnostic marker(s) to identify tumors with malignant prospective. Th e aim of this study was to review all suggested genetic and epigenetic alterations that are remarkably different between benign and malignant PPGLs. It seems that more than two genetic mutation clusters in PPGLs and other genetic and methylation biomarkers could be targeted for malignancy discrimination in different studies.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Epigenesis, Genetic; Humans; Paraganglioma; Pheochromocytoma
PubMed: 29453919
DOI: 10.2478/enr-2018-0006