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Reviews in Endocrine & Metabolic... Feb 2023Diagnosis of pheochromocytoma or paraganglioma (PPGL) in pregnancy has been associated historically with high rates of materno-fetal morbidity and mortality. Recent... (Review)
Review
Diagnosis of pheochromocytoma or paraganglioma (PPGL) in pregnancy has been associated historically with high rates of materno-fetal morbidity and mortality. Recent evidence suggests outcomes are improved by recognition of PPGL before or during pregnancy and appropriate medical management with alpha-blockade. Whether antepartum surgery (before the third trimester) is required remains controversial and open to case-based merits. Women with PPGL in pregnancy are more commonly delivered by Caesarean section, although vaginal delivery appears to be safe in selected cases. At least some PPGLs express the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) which may explain their dramatic manifestation in pregnancy. PPGLs in pregnancy are often associated with heritable syndromes, and genetic counselling and testing should be offered routinely in this setting. Since optimal outcomes are only achieved by early recognition of PPGL in (or ideally before) pregnancy, it is incumbent for clinicians to be aware of this diagnosis in a pregnant woman with hypertension occurring before 20 weeks' gestation, and acute and/or refractory hypertension particularly if paroxysmal and accompanied by sweating, palpitations and/or headaches. All women with a past history of PPGL and/or heritable PPGL syndrome should be carefully assessed for the presence of residual or recurrent disease before considering pregnancy.
Topics: Pregnancy; Humans; Female; Pheochromocytoma; Cesarean Section; Paraganglioma; Adrenal Gland Neoplasms; Hypertension
PubMed: 36637675
DOI: 10.1007/s11154-022-09773-2 -
Endocrine Oncology (Bristol, England) Jan 2022Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors arising from the adrenal medulla and extra-adrenal ganglia, respectively. Approximately 15-25% of PCC/PGL can become metastatic. Up to 30-40% of patients with PCC/PGL have a germline pathogenic variant in a known susceptibility gene for PCC/PGL; therefore, all patients with PCC/PGL should undergo clinical genetic testing. Most of the susceptibility genes are associated with variable penetrance for PCC/PGL and are associated with different syndromes, which include susceptibility for other tumors and conditions. The objective of this review is to provide an overview of the germline susceptibility genes for PCC/PGL, the associated clinical syndromes, and recommended surveillance.
PubMed: 37435466
DOI: 10.1530/EO-22-0044 -
Therapeutic Advances in Endocrinology... 2023This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40-60% of... (Review)
Review
This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40-60% of tumors are linked to a known mutation. Tumor DNA should be sampled first. Next-generation sequencing is the best and most cost-effective choice and also helps with the expansion of current knowledge. Recent advancements have also led to the increased incorporation of regulatory RNA, metabolome markers, and the NETest in PPGL workup. PPGL presentation is highly volatile and nonspecific due to its multifactorial etiology. Symptoms mainly derive from catecholamine (CMN) excess or mass effect, primarily affecting the cardiovascular system. However, paroxysmal nature, hypertension, and the classic triad are no longer perceived as telltale signs. Identifying high-risk subjects and diagnosing patients at the correct time by using appropriate personalized methods are essential. Free plasma/urine catecholamine metabolites must be first-line examinations using liquid chromatography with tandem mass spectrometry as the gold standard analytical method. Reference intervals should be personalized according to demographics and comorbidity. The same applies to result interpretation. Threefold increase from the upper limit is highly suggestive of PPGL. Computed tomography (CT) is preferred for pheochromocytoma due to better cost-effectiveness and spatial resolution. Unenhanced attenuation of >10HU in non-contrast CT is indicative. The choice of extra-adrenal tumor imaging is based on location. Functional imaging with positron emission tomography/computed tomography and radionuclide administration improves diagnostic accuracy, especially in extra-adrenal/malignant or familial cases. Surgery is the mainstay treatment when feasible. Preoperative α-adrenergic blockade reduces surgical morbidity. Aggressive metastatic PPGL benefits from systemic chemotherapy, while milder cases can be managed with radionuclides. Short-term postoperative follow-up evaluates the adequacy of resection. Long-term follow-up assesses the risk of recurrence or metastasis. Asymptomatic carriers and their families can benefit from surveillance, with intervals depending on the specific gene mutation. Trials primarily focusing on targeted therapy and radionuclides are currently active. A multidisciplinary approach, correct timing, and personalization are key for successful PPGL management.
PubMed: 37916027
DOI: 10.1177/20420188231207544 -
Translational Cancer Research Nov 2019Neuroendocrine tumors derived from the adrenal medulla and the adrenal gland are called pheochromocytoma (PHEO) and paraganglioma (PGL), respectively. PGLs are... (Review)
Review
Neuroendocrine tumors derived from the adrenal medulla and the adrenal gland are called pheochromocytoma (PHEO) and paraganglioma (PGL), respectively. PGLs are neuroepithelial cell clusters associated with sympathetic or parasympathetic nerves, and are scattered throughout the body. According to the World Health Organization, the presence of distant metastases indicates malignant PGL. Most PGLs are benign, but their high secretion of catecholamines in the blood is associated with high blood pressure, cardiovascular disease, and death. Further research on PGL is required to provide a theoretical basis for clinical diagnosis and treatment. This article reviews the genetics, clinical manifestations, benign and malignant forms, current major diagnostic methods, and progress in the treatment of PGL.
PubMed: 35117020
DOI: 10.21037/tcr.2019.10.11 -
The Journal of Clinical Endocrinology... Aug 2023Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess. (Meta-Analysis)
Meta-Analysis
CONTEXT
Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess.
OBJECTIVE
To increase knowledge about AMH by reviewing the reported cases of this disorder.
DESIGN
Systematic review and meta-analysis of the genotype/phenotype relationship in all reported cases of AMH.
SETTING
Literature review and analysis.
PATIENTS OR OTHER PARTICIPANTS
All cases of AMH published to date.
MAIN OUTCOME MEASURE(S)
Characteristics of AMH cases and genotype-phenotype relationships.
RESULTS
A total of 66 patients, median age of 48 years, were identified from 29 reports. More than one-half were male (n = 39, 59%). The majority had unilateral (73%, n = 48) disease; 71% (n = 47) were sporadic and 23% (n = 15) were associated with the MEN2. Most (91%, n = 60) displayed signs and symptoms of excess catecholamine secretion, particularly hypertension. Elevated catecholamine concentrations (86%, n = 57) and adrenal abnormalities on imaging were common (80%, n = 53). More than one-half (58%, n = 38) had concurrent tumors: pheochromocytoma (42%, n = 16/38); medullary thyroid cancer (24%, n = 9/38); and adrenocortical adenoma (29%, n = 11/38). Most (88%, n = 58) underwent adrenalectomy with 45/58 achieving symptom resolution. Adrenalectomy was less common in patients under 40 years and those with bilateral disease (both P < .05).
CONCLUSION
AMH may be sporadic or associated with MEN2, most have catecholamine excess and imaging abnormalities. Unilateral involvement is more common. Most reported patients have been treated with adrenalectomy, which is usually curative with regard to catecholamine hypersecretion.
Topics: Male; Humans; Female; Hyperplasia; Adrenal Gland Neoplasms; Pheochromocytoma; Adrenal Medulla; Adrenalectomy; Catecholamines
PubMed: 36896586
DOI: 10.1210/clinem/dgad121 -
Autopsy & Case Reports 2021Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas...
Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas may develop a gangliocytic component with ganglion cells (Gangliocytic paragangliomas). Nearly 25%of cauda equina paragangliomas are gangliocytic paragangliomas. Here, we describe the case of a 35-year-old male who presented with weakness of both lower limbs over the last two months. Radiological findings were suggestive of myxopapillary ependymoma. However, the histopathological examination revealed a tumor with cells arranged in sheets, papillae, lobules, and around vessels forming pseudo rosettes. Ganglion cells were seen in small groups and, also singly. Tumor cells were immunopositive for chromogranin, synaptophysin, and S-100. Ganglion cells were immunopositive for synaptophysin, NSE, and NFP. A final histological diagnosis of Gangliocytic paraganglioma (WHO grade I) was made. To date, only nine gangliocytic paraganglioma cases have been previously reported, and to the best of our knowledge, this is the largest gangliocytic paraganglioma.
PubMed: 34307231
DOI: 10.4322/acr.2021.277 -
Indian Journal of Endocrinology and... 2015Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging... (Review)
Review
Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations.
PubMed: 25593821
DOI: 10.4103/2230-8210.146859 -
Tumour Biology : the Journal of the... Apr 2016Pheochromocytoma (PCC) is a catecholamine-producing and neuroendocrine tumor, which originates from chromaffin cells in adrenal medulla or at extra-adrenal sites. The... (Review)
Review
Pheochromocytoma (PCC) is a catecholamine-producing and neuroendocrine tumor, which originates from chromaffin cells in adrenal medulla or at extra-adrenal sites. The clinical symptoms of PCC patients were including paroxysmal hypertension and cardiovascular crises. Despite the identification of many molecular-level basics involved in these pathogenesis processes, the 5-year survival of advanced stage PCC is <40 %. The 5-year survival of advanced stage PCC is <40 %. microRNAs (miRNAs) are a class of single-strand, highly conserved, small, non-coding RNAs which inhibit gene expression by binding to the target messenger RNA (mRNA) 3'UTR to induce translational repression or their degradation. Increasing data have shown that the deregulated expression of miRNAs has been implicated in the diagnosis and treatment of tumors including PCC. In this review, we summarized the expressions and roles of miRNAs in PCC and comment on the potential role of miRNAs in improving diagnosis, prognosis, and treatment of PCC.
Topics: Adrenal Gland Neoplasms; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Pheochromocytoma; Prognosis; Survival Analysis
PubMed: 26462836
DOI: 10.1007/s13277-015-4199-z -
Cell and Tissue Research May 2018Adrenal catecholamine (CAT) secretion is a general physiological response of animals to environmental stressors such as hypoxia. This represents an important adaptive... (Review)
Review
Adrenal catecholamine (CAT) secretion is a general physiological response of animals to environmental stressors such as hypoxia. This represents an important adaptive mechanism to maintain homeostasis and protect vital organs such as the brain. In adult mammals, CAT secretory responses are triggered by activation of the sympathetic nervous system that supplies cholinergic innervation of adrenomedullary chromaffin cells (AMC) via the splanchnic nerve. In the neonate, the splanchnic innervation of AMC is immature or absent, yet hypoxia stimulates a non-neurogenic CAT secretion that is critical for adaptation to extra-uterine life. This non-neurogenic, hypoxia-sensing mechanism in AMC is gradually lost or suppressed postnatally along a time course that parallels the development of splanchnic innervation. Moreover, denervation of adult AMC results in a gradual return of the direct hypoxia-sensing mechanism. The signaling pathways by which neonatal AMC sense acute hypoxia leading to non-neurogenic CAT secretion and the mechanisms that underlie the re-acquisition of hypoxia-sensing properties by denervated adult AMC, are beginning to be understood. This review will focus on current views concerning the mechanisms responsible for direct acute hypoxia sensing and CAT secretion in perinatal AMC and how they are regulated by innervation during postnatal development. It will also briefly discuss plasticity mechanisms likely to contribute to CAT secretion during exposures to chronic and intermittent hypoxia.
Topics: Animals; Catecholamines; Cell Plasticity; Chromaffin Cells; Humans; Hypoxia; Ion Channels; Reactive Oxygen Species
PubMed: 29052004
DOI: 10.1007/s00441-017-2703-z