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Problemy Endokrinologii Oct 2023Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and... (Review)
Review
Currently, all pheochromocytoma/paraganglioma (PPGLs) are considered malignant due to metastatic potential. Consequently, PPGLs are divided into «metastatic» and «non-metastatic». Metastatic PPGLs can be with synchronous metastasis (metastases appear simultaneously with the identified primary tumor) or metachronous (metastases develop after removal of the primary tumor). The term metastatic PPGLs is not used in the presence of tumor invasion into surrounding organs and tissues, without the presence of distant metastases of lymphogenic or hematogenic origin. It is generally believed that about 10% of pheochromocytomas and about 40% of sympathetic paragangliomas have metastatic potential. On average, the prevalence of PPGLs with the presence of metastases is 15-20%. Risk factors for metastatic PPGLs are widely discussed in the literature, the most significant of which are groups of clinical, morphological and genetic characteristics. The review presents a discussion of such risk factors for metastatic PPGLs as age, localization and type of hormonal secretion of the tumor, the size and growth pattern of the adrenal lesion, the presence of necrosis and invasion into the vessels, the tumor capsule surrounding adipose tissue, high cellular and mitotic activity, Ki-67 index, expression of chromogranin B and S100 protein, the presence of genetic mutations of three main clusters (pseudohypoxia, kinase signaling and Wnt signaling).Over the past two decades, a number of authors have proposed various predictor factors and scales for assessing a probability of metastatic PPGLs. The review contains detailed description and comparison of sensitivity and specificity of such predictor scales as PASS, GAPP, M-GAPP, ASES and COPPS.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Risk Factors; Paraganglioma; Neoplasm Metastasis
PubMed: 38796759
DOI: 10.14341/probl13331 -
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 -
Endocrinology and Metabolism Clinics of... Dec 2019Hypertension is a common clinical complication in pregnancy, representing possible short-term and long-term risks of complications for both mothers and babies. Even if... (Review)
Review
Hypertension is a common clinical complication in pregnancy, representing possible short-term and long-term risks of complications for both mothers and babies. Even if in a majority of cases hypertension is essential, possible secondary causes, which can be related to endocrine disorders, must be detected and correctly managed. This review focuses on the evaluation and the management of primary hyperaldosteronism, Cushing syndrome, and pheochromocytoma in pregnancy.
Topics: Adrenal Gland Neoplasms; Cushing Syndrome; Female; Humans; Hyperaldosteronism; Hypertension; Pheochromocytoma; Pregnancy; Pregnancy Complications
PubMed: 31655779
DOI: 10.1016/j.ecl.2019.08.011 -
Frontiers in Endocrinology 2021Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This... (Review)
Review
Neuroendocrine tumors overexpress somatostatin receptors, which serve as important and unique therapeutic targets for well-differentiated advanced disease. This overexpression is a well-established finding in gastroenteropancreatic neuroendocrine tumors which has guided new medical therapies in the administration of somatostatin analogs, both "cold", particularly octreotide and lanreotide, and "hot" analogs, chelated to radiolabeled isotopes. The binding of these analogs to somatostatin receptors effectively suppresses excess hormone secretion and tumor cell proliferation, leading to stabilization, and in some cases, tumor shrinkage. Radioisotope-labeled somatostatin analogs are utilized for both tumor localization and peptide radionuclide therapy, with Ga-DOTATATE and Lu-DOTATATE respectively. Benign and malignant pheochromocytomas and paragangliomas also overexpress somatostatin receptors, irrespective of embryological origin. The pattern of somatostatin receptor overexpression is more prominent in gene mutation, which is more aggressive than other subgroups of this disease. While the Food and Drug Administration has approved the use of Ga-DOTATATE as a radiopharmaceutical for somatostatin receptor imaging, the use of its radiotherapeutic counterpart still needs approval beyond gastroenteropancreatic neuroendocrine tumors. Thus, patients with pheochromocytoma and paraganglioma, especially those with inoperable or metastatic diseases, depend on the clinical trials of somatostatin analogs. The review summarizes the advances in the utilization of somatostatin receptor for diagnostic and therapeutic approaches in the neuroendocrine tumor subset of pheochromocytoma and paraganglioma; we hope to provide a positive perspective in using these receptors as targets for treatment in this rare condition.
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Pheochromocytoma; Precision Medicine; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 33854479
DOI: 10.3389/fendo.2021.625312 -
Current Cardiology Reports Jan 2022Pseudopheochromocytoma or paroxysmal hypertension is an underrecognized condition that requires a thorough investigation of secondary causes of hypertension. In this... (Review)
Review
PURPOSE OF REVIEW
Pseudopheochromocytoma or paroxysmal hypertension is an underrecognized condition that requires a thorough investigation of secondary causes of hypertension. In this review, we aim to provide an overview of pathogenesis, clinical manifestations, biochemical evaluation, and potential therapeutic options to manage patients with pseudopheochromocytoma.
RECENT FINDINGS
The pathogenesis of this condition has not been completely elucidated but certain patients show overactivity of the sympathetic nervous system and present with elevated epinephrine and dopamine levels. Workup should include a proper evaluation of blood pressure in distinct clinical scenarios, including ambulatory blood pressure monitoring. Management should be focused on treatment of acute hypertensive episodes and prevention of paroxysms. Treatment of patients with pseudopheochromocytoma should be individualized. Psychopharmacotherapy and psychotherapeutic interventions play an important role in controlling patients' symptoms.
Topics: Adrenal Gland Neoplasms; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Humans; Hypertension; Pheochromocytoma
PubMed: 35000148
DOI: 10.1007/s11886-021-01624-x -
Expert Review of Endocrinology &... Jul 2021An adrenal incidentaloma (AI) is an adrenal neoplasm incidentally discovered during an imaging unrelated to suspected adrenal disease. The aim of the present review is... (Review)
Review
An adrenal incidentaloma (AI) is an adrenal neoplasm incidentally discovered during an imaging unrelated to suspected adrenal disease. The aim of the present review is to offer practical guidance on the multidisciplinary approach of AIs.Areas covered:The prevalence of AI is high in the aging population (up to 5-8%); however, hormonally active or malignant conditions are rare. After the discovery of an AI, it is suggested to assess in parallel if the mass is potentially malignant and functionally active. The answer to the former question is mainly based on medical history (extra-adrenal malignancies, new-onset of signs or symptoms) and imaging (conventional radiology and/or nuclear medicine). The answer to the latter question is a complete endocrine evaluation of both cortical (glucocorticoids, mineralocorticoids) and medullary (catecholamines) secretion.Expert opinion:A multidisciplinary discussion is suggested for patients with adrenal disease, after the exclusion of nonfunctioning benign cortical adenoma, in order to plan a close and tailored follow-up for the suspected malignant or functioning forms. Surgery is advised for patients with malignant disease (adrenocortical cancer) or with clinically relevant secreting neoplasm (primary aldosteronism, Cushing's syndrome, and pheochromocytoma).
Topics: Adrenal Gland Neoplasms; Aged; Cushing Syndrome; Humans; Incidental Findings; Pheochromocytoma
PubMed: 34240680
DOI: 10.1080/17446651.2021.1948327 -
Current Opinion in Oncology Jan 2021Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The... (Review)
Review
PURPOSE OF REVIEW
Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceutical modalities in patients with pheochromocytomas and paragangliomas (I-MIBG and PRRT).
RECENT FINDINGS
I-MIBG (Azedra) has received FDA approval for patients with iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas who require systemic anticancer therapy, whereas peptide receptor radionuclide therapy using radiolabelled somatostatin analogues is currently performed in compassionate use, with very promising results. No prospective head-to-head comparison between the modalities has been conducted to date.
SUMMARY
Promising results have been reported for both radiopharmaceutical agents, mostly in the setting of retrospective series. No prospective head-to-head comparison between the modalities is yet available.
Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Humans; Iodine Radioisotopes; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Receptors, Peptide
PubMed: 33093336
DOI: 10.1097/CCO.0000000000000691 -
Endocrine Regulations Jan 2023Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal...
Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal medulla or extra-adrenal paraganglionic tissues. Despite the recent advances in imaging technologies, biochemical evidence of excessive catecholamine production by the tumor is considered the most important test for the diagnosis of these tumors. The aim of the present study is to investigate the role of the catecholamine metabolites (normetanephrine and metanephrine) levels in the diagnosis of PHEO/PGLs and to evaluate if their levels correlate with the size of these tumors. Twenty-five patients were included in the study during the time period of 10 years. Their data were compared with another set of 25 patients to obtain the sensitivity and specificity of metanephrine and normetanephrine in the diagnosis of PHEO/PGLs. The tumor size was reviewed in every patient to obtain the correlation coefficient between the tumor sizes and the plasma/24-hour urinary metanephrine levels. The sensitivity and specificity rates for plasma metanephrine were 80-92% and 92-96%, respectively; while for 24-hour urinary metanephrine were 80-90% and 95-100%, respectively. We found a strong positive relationship between the tumor size and the plasma levels of normetanephrine (r=0.518, p<0.01), and metanephrine (r=0.577, p<0.01). While the relation with the 24-hour urinary concentrations of normetanephrine (r=0.384, p=0.01) and 24-h urinary meta-nephrine (r=0.138, p<0.01) was low. The determination of plasma and 24-hour urinary levels of metanephrines is a reliable test for the diagnosis of PHEO, as they are continuously produced by the tumor cells in contrast to catecholamines.
Topics: Humans; Pheochromocytoma; Metanephrine; Normetanephrine; Adrenal Gland Neoplasms; Paraganglioma
PubMed: 37715982
DOI: 10.2478/enr-2023-0022 -
Journal of Endocrinological... Dec 2022Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of... (Review)
Review
PURPOSE
Pheochromocytoma crisis is a life-threatening endocrine emergency that requires prompt diagnosis and treatment. Because of its rarity, sudden onset, and lack of internationally uniform and validated diagnostic criteria, pheochromocytoma crisis remains to be fully clarified. Therefore, we aimed to describe the clinical characteristics and outcomes of pheochromocytoma crisis through a literature review.
METHODS
We performed a systematic literature search of PubMed/MEDLINE database, Igaku-Chuo-Zasshi (Japanese database), and Google Scholar to identify case reports of pheochromocytoma crisis published until February 5, 2021. Information was extracted and analyzed from the literature that reported adequate individual patient data of pheochromocytoma crisis in English or Japanese. Cases were also termed as pheochromocytoma multisystem crisis (PMC) if patients had signs of hyperthermia, multiple organ failure, encephalopathy, and labile blood pressure.
RESULTS
In the 200 cases of pheochromocytoma crisis identified from 187 articles, the mean patient age was 43.8 ± 15.5 years. The most common symptom was headache (39.5%). The heart was the most commonly damaged organ resulting from a complication of a pheochromocytoma crisis (99.0%), followed by the lungs (44.0%) and the kidney (21.5%). PMC accounted for 19.0% of all pheochromocytoma crisis cases. After excluding 12 cases with unknown survival statuses, the mortality rate was 13.8% (26/188 cases). Multivariable logistic regression analysis revealed that nausea and vomiting were significantly associated with a higher mortality rate.
CONCLUSION
Pheochromocytoma can present with different symptomatology, affecting different organ systems. Clinicians should be aware that patients with nausea or vomiting are at a higher risk of death because of pheochromocytoma crisis.
Topics: Adult; Humans; Middle Aged; Adrenal Gland Neoplasms; Multiple Organ Failure; Nausea; Pheochromocytoma; Vomiting
PubMed: 35857218
DOI: 10.1007/s40618-022-01868-6 -
AJR. American Journal of Roentgenology Jul 2022A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. The purpose of this...
A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted values were computed to account for multiple comparisons. Hereditary pheochromocytoma ( = 32), compared with sporadic pheochromocytoma ( = 39), was associated with younger median age (38 vs 52 years, = .001) and smaller median size (24 vs 40 mm, < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI ( > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas ( = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 ( = 11) and cluster 2 ( = 21) germ-line mutations, respectively. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Diagnostic Imaging; Female; Humans; Male; Middle Aged; Necrosis; Pheochromocytoma; Retrospective Studies
PubMed: 35080458
DOI: 10.2214/AJR.21.26918