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European Journal of Endocrinology Jul 2023Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are...
European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.
Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma, or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the Grading of Recommendations Assessment, Development and Evaluation system and updated systematic reviews on 4 predefined clinical questions crucial for the management of incidentalomas: (1) How to assess risk of malignancy?; (2) How to define and manage mild autonomous cortisol secretion?; (3) Who should have surgical treatment and how should it be performed?; and (4) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: (1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with Hounsfield unit (HU) ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. (2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/L [≤1.8 µg/dL]). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/L (>1.8 µg/dL) harbor increased risk of morbidity and mortality. For this condition, we propose the term "mild autonomous cortisol secretion" (MACS). (3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (eg, hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. (4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. (5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health, and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. (6) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of nonoperated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest 10 important research questions for the future.
Topics: Aged; Humans; Adrenal Gland Neoplasms; Dexamethasone; Diabetes Mellitus, Type 2; Hydrocortisone
PubMed: 37318239
DOI: 10.1093/ejendo/lvad066 -
Endocrine Regulations Jul 2019Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of... (Review)
Review
Pheochromocytomas are rare tumors originating in the adrenal medulla. They may be sporadic or in the context of a hereditary syndrome. A considerable number of pheochromocytomas carry germline or somatic gene mutations, which are inherited in the autosomal dominant way. All patients should undergo genetic testing. Symptoms are due to catecholamines over production or to a mass effect. Diagnosis is confirmed by raised plasma or urine metanephrines or normetanephrines. Radiology assists in the tumor location and any local invasion or metastasis. All the patients should have preoperative preparation with α-blockers and/or other medications to control hypertension, arrhythmia, and volume expansion. Surgery is the definitive treatment. Follow up should be life-long.
Topics: Adrenal Gland Neoplasms; Adult; Child; Female; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans; Male; Pheochromocytoma; Pregnancy
PubMed: 31517632
DOI: 10.2478/enr-2019-0020 -
The Journal of Clinical Endocrinology... Apr 2021Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas... (Review)
Review
CONTEXT
Pheochromocytomas and paragangliomas (PPGLs) are believed to harbor malignant potential; about 10% to 15% of pheochromocytomas and up to 50% of abdominal paragangliomas will exhibit metastatic behavior.
EVIDENCE ACQUISITION
Extensive searches in the PubMed database with various combinations of the key words pheochromocytoma, paraganglioma, metastatic, malignant, diagnosis, pathology, genetic, and treatment were the basis for the present review.
DATA SYNTHESIS
To pinpoint metastatic potential in PPGLs is difficult, but nevertheless crucial for the individual patient to receive tailor-made follow-up and adjuvant treatment following primary surgery. A combination of histological workup and molecular predictive markers can possibly aid the clinicians in this aspect. Most patients with PPGLs have localized disease and may be cured by surgery. Plasma metanephrines are the main biochemical tests. Genetic testing is important, both for counseling and prognostic estimation. Apart from computed tomography and magnetic resonance imaging, molecular imaging using 68Ga-DOTATOC/DOTATATE should be performed. 123I-MIBG scintigraphy may be performed to determine whether 131I-MIBG therapy is a possible option. As first-line treatment in patients with metastatic disease, 177Lu-DOTATATE or 131I-MIBG is recommended, depending on which shows best expression. In patients with very low proliferative activity, watch-and-wait or primary treatment with long-acting somatostatin analogues may be considered. As second-line treatment, or first-line in patients with high proliferative rate, chemotherapy with temozolomide or cyclophosphamide + vincristine + dacarbazine is the therapy of choice. Other therapies, including sunitinib, cabozantinib, everolimus, and PD-1/PDL-1 inhibitors, have shown modest effect.
CONCLUSIONS
Metastatic PPGLs need individualized management and should always be discussed in specialized and interdisciplinary tumor boards. Further studies and newer treatment modalities are urgently needed.
Topics: Abdominal Neoplasms; Adrenal Gland Neoplasms; Animals; Humans; Paraganglioma; Pheochromocytoma
PubMed: 33462603
DOI: 10.1210/clinem/dgaa982 -
European Journal of Case Reports in... 2023Pseudopheochromocytoma is a pathological condition presenting with paroxysmal hypertension with normal or moderate elevation in catecholamines and metanephrine levels,...
UNLABELLED
Pseudopheochromocytoma is a pathological condition presenting with paroxysmal hypertension with normal or moderate elevation in catecholamines and metanephrine levels, but no evidence of a tumoural cause. Imaging studies and I-123 metaiodobenzylguanidine scintigraphy are essential for exclusion of pheocromocytoma. We describe a case of pseudopheochromocytoma related to levodopa in a patient with paroxysmal hypertension, headache, sweating, palpitations and increased plasmatic and urinary metanephrine levels, without adrenal or extra-adrenal tumour. The beginning of the patient's clinical symptoms coincided with the initiation of the levodopa treatment and the complete resolution of the symptoms occurred after the discontinuation of levodopa.
LEARNING POINTS
Pseudopheochromocytoma and pheochromocytoma may have the same clinical and laboratorial presentation but different aetiologies.The diagnosis of pseudopheochromocytoma is based on paroxysmal hypertension with normal or increased plasma and urine levels of catecholamines or metanephrines after exclusion of a tumoural process.The pseudopheochromocytoma may be associated with levodopa, alone or in combination with other drugs that are likely to interfere with dopamine or catecholamine metabolism.
PubMed: 37304996
DOI: 10.12890/2023_003813 -
International Braz J Urol : Official... 2023Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other... (Review)
Review
Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37115176
DOI: 10.1590/S1677-5538.IBJU.2023.0038 -
Endocrinology and Metabolism Clinics of... Dec 2019Pseudopheochromocytoma manifests as severe, symptomatic paroxysmal hypertension without significant elevation in catecholamine and metanephrine levels and lack of... (Review)
Review
Pseudopheochromocytoma manifests as severe, symptomatic paroxysmal hypertension without significant elevation in catecholamine and metanephrine levels and lack of evidence of tumor in the adrenal gland. The clinical manifestations are similar but not identical to those in excess circulating catecholamines. The underlying symptomatic mechanism includes augmented cardiovascular responsiveness to catecholamines alongside heightened sympathetic nervous stimulation. The psychological characteristics are probably attributed to the component of repressed emotions related to a past traumatic episode or repressive coping style. Successful management can be achieved by strong collaboration between a hypertension specialist and a psychiatrist or psychologist with expertise in cognitive-behavioral panic management.
Topics: Adrenal Gland Neoplasms; Humans; Hypertension; Panic Disorder; Pheochromocytoma; Somatoform Disorders
PubMed: 31655774
DOI: 10.1016/j.ecl.2019.08.004 -
Endocrine Practice : Official Journal... Dec 2022Pheochromocytomas and paragangliomas continue to be defined by significant morbidity and mortality despite their several recent advances in diagnosis, localization, and... (Review)
Review
Pheochromocytomas and paragangliomas continue to be defined by significant morbidity and mortality despite their several recent advances in diagnosis, localization, and management. These adverse outcomes are largely related to mass effect as well as catecholamine-induced hypertension, tachyarrhythmias and consequent target organ damage, acute coronary syndromes, and strokes (ischemic and hemorrhagic stroke). Thus, a proper understanding of the physiology and pathophysiology of these tumors and recent advances are essential to affording optimal care. These major developments largely include a redefinition of metastatic behavior, a novel clinical categorization of these tumors into 3 genetic clusters, and an enhanced understanding of catecholamine metabolism and consequent specific biochemical phenotypes. Current advances in imaging of these tumors are shifting the paradigm from poorly specific anatomical modalities to more precise characterization of these tumors using the advent and development of functional imaging modalities. Furthermore, recent advances have revealed new molecular events in these tumors that are linked to their genetic landscape and, therefore, provide new therapeutic platforms. A few of these prospective therapies translated into new clinical trials, especially for patients with metastatic or inoperable tumors. Finally, outcomes are ever-improving as patients are cared for at centers with cumulative experience and well-established multidisciplinary tumor boards. In parallel, these centers have supported national and international collaborative efforts and worldwide clinical trials. These concerted efforts have led to improved guidelines collaboratively developed by healthcare professionals with a growing expertise in these tumors and consequently improving detection, prevention, and identification of genetic susceptibility genes in these patients.
Topics: Humans; Neoplasms
PubMed: 36150627
DOI: 10.1016/j.eprac.2022.09.003