Prevalence Of Pheochromocytoma Research Articles

Genetic Alterations and Clinical Features in Brazilian Patients With Pheochromocytomas and Paragangliomas

Abstract Pheochromocytomas and paragangliomas are tumors derived from chromaffin cells which result from mutations of at least six different genes as autosomal dominant disorders. We evaluated the existence of correlations between genetic alterations and clinical data in 16 patients with pheochromocytomas and/or paragangliomas. From 2007 to 2019, 13 patients with pheochromocytoma [3 men, medium age 39 years (14–61)] and 3 with paraganglioma [1 men, medium age 33 years (22–35)] were evaluated regarding the presence of genetic mutations and possible correlations between the latter and some clinical features. Besides the mutations, tumor size, symptoms and signs present by the time of the diagnosis were studied. Four patients had pathogenic mutations (SDHB deletion encompassing the promoter and exon 1, C98Y in the SDHB gene, N78S in the VHL gene, and C634R in the RET gene) and one subject had a V90M variant in the TMEM127 gene. Two patients did not present mutations and nine had nonpathogenic mutations. Regarding the presence of clinical features before treatment, there was a predominance of arterial hypertension (75.0%), while the prevalence of tachycardia, abdominal pain and headaches was respectively 12.5%, 12.5% and 6.25%. There was no significant difference between the age of patients with pathogenic mutations and that of the other patients (31.2 vs. 38.6 years, p= 0.3952). Moreover, there were no differences regarding the prevalence of pheochromocytoma (p= 0.2143) or clinical features (p: hypertension= 0.6346, tachycardia= 0.4583, abdominal pain= 0.5417, headaches= 0.6875), or tumor dimensions (p= 0.4578) when the two groups were compared. However, the prevalence of paragangliomas was higher in patients with pathogenic mutations (p= 0.0179). In patients with pheochromocytoma and paraganglioma, the absence of correlations between pathogenic mutations and clinical features increases the importance of the genetic studies in the determination of treatment and prognosis of these tumors. Furthermore, subjects with germline mutations associated with pheochromocytoma and paraganglioma should undergo lifelong clinical, biochemical and imaging surveillance and their families should receive genetic counseling.

Detection of severe hypertension in a patient with neurofibromatosis type 1 during anesthesia induction: a case report

BackgroundNeurofibromatosis type 1 has a higher prevalence of pheochromocytoma and paraganglioma than the general population: 1.0–5.7% versus 0.2–0.6%. Currently, there are no generally accepted guidelines for screening for pheochromocytoma and paragangliomas in asymptomatic patients with neurofibromatosis type 1.Case presentationSevere hypertension developed during anesthesia induction in our patient, a 44-year-old Chinese man with neurofibromatosis type 1. We screened for catecholamine level after glioma resection, and the patient was diagnosed with combined pheochromocytoma and paraganglioma.ConclusionsA delay in diagnosis or lack of a diagnosis in pheochromocytoma and paraganglioma may increase the perioperative morbidity and mortality risk due to excess catecholamine secretion. Therefore, routine pheochromocytoma and paraganglioma screening preoperatively in patients with neurofibromatosis type 1 is very important.

FEOCROMOCITOMA E NEUROFIBROMATOSE 1

Introdução: Feocromocitomas são tumores originários de células cromafins do sistema simpato-adrenal. As suas manifestações clínicas são múltiplas e diversificadas, função do perfil secretório variável de múltiplos compostos, incluindo catecolaminas, neuropéptidos e outros compostos vasoactivos. A Neurofibromatose 1 (D de von Recklinghausen), a mais prevalente das variantes das neurofibromatoses, é genodermatose transmitida segundo padrão mendeliano autossómico dominante. O diagnóstico de NF1 assenta em critérios diagnósticos, entre os quais as alterações cutâneas, oculares e esqueléticas são as mais relevantes, embora múltiplas neoplasias envolvendo diversos orgãos e sistemas não possam ser esquecidas ou sub-valorizadas já que é bem conhecido que o produto genético do gene alterado da NF1 – a neurofibromina – é uma proteina de supressão tumoral. Feocromocitomas ocorrem em menos de 1% dos doentes com NF1; por outro lado, apenas 5% dos casos reportados de feocromocitoma estão associados com a NF I. No entanto, entre doentes hipertensos com NF1, a prevalência de feocromocitoma pode atingir os 50%.Caso clínico: É relatado caso de eurocaucasiana de 27 A de idade, com diagnóstico de NF1 com história de 4 meses de cólicas abdominais, hiperhidrose generalizada, dispneia e hipertensão arterial paroxística. As catecolaminas e metanefrinas urinárias estavam aumentadas e a exploração topográfica levada a cabo (RMN e I-MIBG) permitiram detectar uma massa na glândula suprarrenal direita, a qual, após adrenalectomia confirmou o diagnóstico de feocromocitoma. Conclusão: O caso apresentado enfatiza a necessidade de uma abordagem multissistémica, multidisciplinar a doentes com NF1, tendo em conta as manifestações sistémicas associadas, na base de um prognóstico por vezes fechado da doença.

A Case of Pheochromocytoma Associated with Diabetic Ketoacidosis and Infective Endocarditis

Pheochromocytoma is a rare neuroendocrine tumor that is usually derived from adrenal medulla or chromaffin cells along with sympathetic ganglia. In Western countries, the prevalence of pheochromocytoma is estimated to be between 1:6,500 and 1:2,500, compared with an incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, pheochromocytoma should always be considered for differential diagnoses because previous studies have shown that this condition can be cured in approximately 90% of cases. However, an untreated tumor is likely to be fatal due to catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias or metastatic disease. Symptoms that result primarily from excess circulating catecholamines and hypertension include severe headaches, generalized inappropriate sweating and palpitations (with tachycardia or occasionally bradycardia). Pheochromocytoma, however, has highly variable and heterogeneous clinical manifestations, including fever, general weakness and dyspepsia, and can be observed in patients who are suffering from infectious diseases. Several of such case reports have been presented, but most of these included infectious patients with high blood pressure and severe fluctuations. In this study, we presented the case of a 53-year-old male who showed normal blood pressure, but had a sustained fever. He was diagnosed with diabetic ketoacidosis, infective endocarditis and asymptomatic adrenal incidentaloma. Despite treatment with antibiotics and valve replacement, the fever persisted. After the patient underwent evaluation for the fever, adrenal incidentaloma was identified as pheochromocytoma. After removal of the abdominal mass, his fever improved. (J Korean Diabetes 2013;14:156-161)

Maladies surrénaliennes infracliniques : cas du phéochromocytome silencieux et de la maladie d’Addison infra-clinique

The silent pheochromocytoma, a hidden form of pheochromocytoma, exposes the patient to an increased risk of mortality if the diagnosis is not etablished on time. Biological diagnosis of pheochromocytoma can be difficult. Catecholamine secretion is dependent on tumor size and a large number of physiological, pharmacological, lifestyle modifications and sampling conditions influence the measurement of urinary and plasma metanephrines. The prevalence of pheochromocytoma is 2% among adrenal incidentaloma smaller than 3cm (2/3 of tumors). Recent studies suggest the almost zero risk of pheochromocytoma among these tumors if they are hypodense (<10 housfield units) on adrenal tomography. Addison's disease is a pathology affecting about 1 in 8000. Immunopathology is still unknown, but some elements advocated the hypothesis of a predominant cell-mediated immunity in particular Interferon-gamma production by CD4 T lymphocytes in the presence of an epitope from the 21-hydroxylase, as well as IgG1 subtype produced by activated B lymphocytes, autoantibodies do appear to be a simple marker of the disease. Subclinical Addison's disease is defined by the presence of anti-21-hydroxylase autoantibodies, without clinical symptoms. It evolves faster to the clinical phase in young subjects, male, having high levels of autoantibodies and with an initially impaired adrenal function. Dosage of ACTH, plasma renin active, and basal cortisol and after Synacthen allow to discriminate the subjects with low or high risk of evolution and establish an appropriate monitoring.

Cyclic Rapid Fluctuation of Hypertension and Hypotension in Pheochromocytoma

Cyclic Rapid Fluctuation of Hypertension and Hypotension in Pheochromocytoma

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype. German Medullary Thyroid Carcinoma Study Group

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation.

Mutations of the ret protooncogene in German multiple endocrine neoplasia families: relation between genotype and phenotype. German Medullary Thyroid Carcinoma Study Group.

It has been suggested that not only the position but also the nature of the mutations of the ret protooncogene strongly correlate with the clinical manifestation of the multiple endocrine neoplasm type 2 (MEN 2) syndrome. In particular, individuals with a Cys634-Arg substitution should have a greater risk of developing parathyroid disease. We, therefore, analyzed 94 unrelated families from Germany with inherited medullary thyroid carcinoma (MTC) for mutation of the ret protooncogene. In all but 1 of 59 families with MEN 2A, germline mutations in the extracellular domain of the ret protein were found. Some 81% of the MEN 2A mutations affected codon 634. Phenotype-genotype correlations suggested that the prevalence of pheochromocytoma and hyperparathyroidism is significantly higher in families with codon 634 mutations, but there was no correlation with the nature of the mutation. In all but 1 of 27 familial MTC (FMTC) families, mutations were detected in 1 of 4 cysteines in the extracellular domain of the ret protooncogene. Half of the FMTC mutations affected codon 634. Mutations outside of codon 634 occurred more often in FMTC families than in MEN 2A families. In all but 1 of 8 MEN 2B patients, de novo mutations in codon 918 were found. These data confirm the preferential localization of MEN 2-associated mutations and the correlation between disease phenotype and the position of the ret mutation, but there was no correlation between the occurrence of hyperparathyroidism or pheochromocytoma and the nature of the mutation.

Prevalence of pheochromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term follow-up.

Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant condition in which virtually all affected kindred members have medullary thyroid carcinoma (MTC). However, the penetrance of pheochromocytoma and hyperparathyroidism in affected kindred members is variable, and the true prevalence of these neoplasms is unclear from previous studies. Members of MEN 2A kindreds with more than 10 years of follow-up screening for MTC, pheochromocytoma, or hyperparathyroidism were studied. The diagnosis of pheochromocytoma was based on histologic examination and hyperparathyroidism on both parathyroid hyperplasia plus preoperative elevation of serum calcium levels. Eighty-six patients operated on for MTC from 12 different MEN 2A kindreds were studied, with a mean follow-up of 12.9 years of screening for pheochromocytoma (79 patients) and 15.0 years for hyperparathyroidism (78 patients). Pheochromocytomas developed in 42% of patients with MTC, with a range of 6% to 100% in different kindreds. The prevalence of hyperparathyroidism was 35%, ranging from 0% to 53% between kindreds. The average age at diagnosis of MTC, pheochromocytoma, and hyperparathyroidism was 29, 37, and 36 years, respectively. We conclude that the penetrance of pheochromocytoma and hyperparathyroidism is variable in different kindreds with MEN 2A but that the overall prevalence of pheochromocytoma approximates 40% and that of hyperparathyroidism 35%.