Materiały źródłowe

• #1 Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7326683/

  Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. The incidence of PCC and PGL ranges between 2 and 8 per million, with a prevalence between 1:2500 and 1:6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatric patients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between 2-4.5% in the pediatric age group. 10-49% of these tumors is detected incidentally in imaging techniques performed for other reasons. However, 4-8% of adrenal incidentalomas are PCCs. Of these neuroendocrine tumors, 80-85% are PCCs and 15-20% are PGLs. […] The annual incidence in the USA is approximately 500-1600 cases per year, which is lower than the prevalence of PPGL (0.05-0.1%) detected in the autopsy series incidentally. PPGL peaks between the 3rd and 5th decades of life, and approximately 20% of cases is pediatric patients.

• #2 Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings [Med Bull Sisli Etfal Hosp]

  https://sislietfaltip.org/jvi.aspx?un=SETB-18794&volume=

  Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. The incidence of PCC and PGL ranges between 2 and 8 per million, with a prevalence between 1: 2500 and 1: 6500. It peaks between the 3rd and 5th decades of life, and approximately 20% of cases are pediatric patients. The prevalence among patients with hypertension in outpatient clinic ranges between 0.1-0.6% in adults and between 2-4.5% in the pediatric age group. 10-49% of these tumors are detected incidentally in imaging techniques performed for other reasons. However, 4-8% of adrenal incidentalomas are PCCs. Of these neuroendocrine tumors, 80-85% are PCCs and 15-20% are PGLs. Up to 40% of patients with PCC and PGL have disease-specific germline mutations and the situation is hereditary. Of 60% of the remaining sporadic patients, at least 1/3 have somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditary cases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. Although most of the PCC and PGL are benign, metastatic disease may develop in 15-17%. Metastatic disease is reported between 2-25% in PCCs and 2.4-60% in PGLs. The TNM staging system of the American Joint Committee on Cancer (AJCC) was developed to predict the prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.

• #3 Pheochromocytoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/124059-overview

  Pheochromocytomas are rare, reportedly occurring in 0.050.2% of hypertensive individuals. This accounts for only a portion of cases, however, as patients may be completely asymptomatic. A retrospective study from the Mayo Clinic revealed that in 50% of cases of pheochromocytoma, the diagnosis was made at autopsy. Approximately 10% of pheochromocytomas are discovered incidentally. […] […] A Dutch study, by Berends et al, found an increase in the age-standardized incidence rate (ASR) of pheochromocytomas and sympathetic paragangliomas in the Netherlands between 1995 and 2015. The investigators reported that the ASR between 1995 and 1999 was 0.29 per 100,000 person-years, compared with 0.46 per 100,000 person-years between 2011 and 2015. The ASRs for sympathetic paragangliomas rose between these same two periods from 0.08 to 0.11 per 100,000 person-years. There was also a trend during this 20-year period towards patients being older and tumor size smaller at diagnosis. The investigators suggested that clinical practice changes, along with greater use of imaging and biochemical studies, were at least partially responsible for the incidence increases. […]

• #4 Pheochromocytoma – Wikipedia

  https://en.wikipedia.org/wiki/Pheochromocytoma

  Current hypotheses for why the incidence of pheochromocytoma is growing in the Dutch population point to the advent of modern imaging evaluation and the ability to detect these tumors prior to death. While each of the above studies reported varying incidence and prevalence values, all have indicated that the average age at initial diagnosis is between the third to fifth decade of life. When younger patients are diagnosed with a pheochromocytoma, there should be a high suspicion for hereditary disease, as genetic anticipation (earlier disease onset with each generation) is associated with some mutations.

• #4 Pheochromocytoma – Wikipedia

  https://en.wikipedia.org/wiki/Pheochromocytoma

  According to the North American Neuroendocrine Tumor Society, the prevalence of pheochromocytoma is between 1:2,500 and 1:6,500, meaning that for every 2,500-6,500 people, there is (on average) one person with pheochromocytoma. In the United States, this equates to an annual incidence (new cases per year) of 500 to 1,600 cases. However, approximations in the early 2000s reported that upwards of 50% of pheochromocytoma diagnoses are at autopsy; therefore, the above estimations may be lower than expected. […] Outside of the United States, several countries have documented their own epidemiological studies and compared them to what is known in North America. In the first national, epidemiological population-based study in Asia utilizing Korean National Health Insurance Service data, the prevalence of a pheochromocytoma was reported at 2.13 per 100,000 persons with an incidence of 0.18 per 100,000 person-years. This is lower than the occurrence reported from Rochester, Minnesota (0.8 per 100,000 person-years), in a study conducted from 1950 to 1979.

• #5 Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study – PubMed

  https://pubmed.ncbi.nlm.nih.gov/33112261/

  Objective: Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data. […] A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60-79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). […] The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

• #6 Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study. | EBSCOhost

  https://openurl.ebsco.com/contentitem/doi:10.1530%2FEJE-20-0628?sid=ebsco:plink:crawler&id=ebsco:doi:10.1530%2FEJE-20-0628

  Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study. […] Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. […] The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. […] A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. […] The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. […] The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60-79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). […] The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

• #7 Pheochromocytoma epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Pheochromocytoma_epidemiology_and_demographics

  The incidence of pheochromocytoma ranges 0.2-0.8 per 100,000 persons. The median age at diagnosis is 24.9 years in familial cases and 43.9 years in sporadic cases. Both men and women are affected equally by pheochromocytoma. […] In the USA, the incidence of pheochromocytoma ranges from 0.2-0.8 per 100,000 persons. […] Annually reported cases range from 500 to 1600 in the United States. […] Autopsy studies have discovered a higher number of cases than the actual prevalence rates. Ten percent of pheochromocytomas cases are discovered by chance. […] In the USA, the prevalence of pheochromocytoma ranges from 0.2-0.8 per 100,000 persons. […] The prevalence of pheochromocytoma in patients with hypertension in general outpatient clinics is about 0.1%. […] The prevalence of pheochromocytoma is approximately 1.7% in children with hypertension.

• #8 Pheochromocytoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988683-overview

  Pheochromocytomas are rare, reportedly occurring in 0.050.2% of hypertensive individuals. This accounts for only a portion of cases, however, as patients may be completely asymptomatic. A retrospective study from the Mayo Clinic revealed that in 50% of cases of pheochromocytoma, the diagnosis was made at autopsy. Approximately 10% of pheochromocytomas are discovered incidentally. […] […] A Dutch study, by Berends et al, found an increase in the age-standardized incidence rate (ASR) of pheochromocytomas and sympathetic paragangliomas in the Netherlands between 1995 and 2015. The investigators reported that the ASR between 1995 and 1999 was 0.29 per 100,000 person-years, compared with 0.46 per 100,000 person-years between 2011 and 2015. The ASRs for sympathetic paragangliomas rose between these same two periods from 0.08 to 0.11 per 100,000 person-years. There was also a trend during this 20-year period towards patients being older and tumor size smaller at diagnosis. The investigators suggested that clinical practice changes, along with greater use of imaging and biochemical studies, were at least partially responsible for the incidence increases. […]

• #9 Epidemiology and Prognosis of Pheochromocytoma/Paraganglioma in Korea: A Nationwide Study Based on the National Health Insurance Service

  https://www.e-enm.org/journal/view.php?doi=10.3803/enm.2020.35.1.157

  Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors originating from chromaffin cells. This study aimed to investigate the epidemiology and prognosis of PPGLs in Korea using nationwide data. The overall prevalence of PPGLs was 2.13 per 100,000 persons, and the overall age-standardized incidence rate was 0.18 per 100,000 person-years. Malignant PPGLs accounted for 17.7% (185 of 1,048) of cases, and 94 subjects exhibited metastasis at the time of diagnosis. The 5-year survival rates for non-metastatic and metastatic PPGLs at diagnosis were 97% and 84%, respectively. This was the first nationwide population-based epidemiological study of PPGLs to be conducted in Asia, using NHIS data from Korea. The mean age at diagnosis was 47.6 years in Korean PPGL patients, which is similar to or lower than that in previous studies. The present study demonstrated a high incidence of metastatic PPGLs in all study subjects (17.8%), which is similar to the rates reported in previous studies (8% to 20%). Collectively, the prevalence and annual incidence rates of PPGLs in Korea are 0.18 and 2.13 per 100,000 persons, respectively. Metastatic PPGLs accounted for 17.7% of all PPGLs, including 9.0% with metastasis at the time of diagnosis. This epidemiological study may pave the way for further research on PPGLs.

• #10 Pheochromocytoma – Endocrinology Advisor

  https://www.endocrinologyadvisor.com/ddi/pheochromocytoma/

  Pheochromocytomas and paragangliomas are rare, with an estimated incidence of 2 to 8 diagnoses per every 1 million people each year. However, the actual incidence is unknown, as many people with the tumors are never diagnosed. About 0.05 to 0.2% of hypertensive patients have a pheochromocytoma. […] The incidence is equal for both genders, and diagnosis is typically made between the ages of 30 and 50 years; however, pheochromocytoma due to genetic predispositions, which account for approximately 35% of cases, may present at an earlier age. […] Most pheochromocytomas and paragangliomas are benign, with 10% of pheochromocytomas and 25% of paragangliomas being malignant. […] The causes of pheochromocytomas are largely unknown, with most cases occurring sporadically. However, approximately 35% of cases are caused by genetic mutations that are inherited in an autosomal dominant pattern.

• #11 Pheochromocytoma – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/pheochromocytoma/

  Most common tumor of the adrenal medulla in adults. Present in up to 1% of all hypertensive patients. […] Epidemiological data refers to the US, unless otherwise specified.

• #12 Pheochromocytoma epidemiology and demographics – wikidoc

  https://www.wikidoc.org/index.php/Pheochromocytoma_epidemiology_and_demographics

  About 5% of patients with incidentally discovered adrenal masses on imaging actually have pheochromocytoma. […] The prevalence of pheochromocytoma in individuals carrying a germline mutation in pheochromocytoma susceptibility genes may be around 50%. […] The incidence of pheochromocytoma ranges from 0.2-0.8 per 100,000 persons with a perioperative case-fatality rate/mortality rate of about 2.4%. […] Metastatic PPGLs were associated with a 2.40-fold higher risk of mortality than non-metastatic PPGLs. […] Patients of all age groups may develop pheochromocytoma. Approximately 10% occur in children. […] The median age at diagnosis is 40 years. […] The average age at diagnosis is 24.9 years in hereditary cases and 43.9 years in sporadic cases. […] Hereditary tumors present at a younger age than sporadic. […] There is no racial predilection to pheochromocytoma. […] Pheochromocytoma affects men and women equally. […] Pheochromocytoma is a rare disease that tends to affect all populations equally.

• #13 Pheochromocytoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/124059-overview

  Pheochromocytomas occur in people of all races, although they are diagnosed less frequently in the black population. Pheochromocytomas may occur in persons of any age, but the peak incidence is from the third to the fifth decades of life. Approximately 10% occur in children. Fifty percent of pheochromocytomas in children are solitary intra-adrenal lesions, 25% are present bilaterally, and 25% are extra-adrenal. […] A study by Iglesias et al looking at 106 patients with pheochromocytoma found that those diagnosed with the sporadic form of the disease tended to be significantly older than those with familial pheochromocytoma (54.5 years vs 40.8 years, respectively).

• #14 Phaeochromocytoma (Investigations and Treatment)

  https://patient.info/doctor/phaeochromocytoma-pro

  Phaeochromocytomas are rare tumours, with an annual incidence of 2 to 9.1 per 1 million adults and may correspond up to 60% of all adrenal incidentalomas (epinephromas). […] The majority are benign but up to 25% may be malignant. […] Males and females are affected equally. […] Phaeochromocytomas can appear in any age, however, more commonly in the 3rd to 5th decade of life. […] Hereditary disease is more likely to present in younger patients. […] In children presenting with apparently sporadic phaeochromocytomas, up to 70% of cases are due to hereditary disease. […] Phaeochromocytomas are responsible for 0.20.6 of both systolic and diastolic hypertensions and rarely in isolated cases of systolic hypertension. […] However, about 50% of phaeochromocytomas are diagnosed only at autopsy because many of these tumours remain clinically silent during life.

• #15 Pheochromocytoma and Paraganglioma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq

  Pheochromocytomas and extra-adrenal paragangliomas are rare tumors arising from neural crest tissue that develops into sympathetic and parasympathetic paraganglia throughout the body. […] The incidence of pheochromocytoma is 2 to 8 per million persons per year. Pheochromocytoma is present in 0.1% to 1% of patients with hypertension, and it is present in approximately 5% of patients with incidentally discovered adrenal masses. The peak incidence occurs in the third to fifth decades of life. The average age at diagnosis is 24.9 years in hereditary cases and 43.9 years in sporadic cases. The incidence is equal between men and women. […] Of all pheochromocytomas and extra-adrenal paragangliomas, 35% occur in patients with a hereditary cancer syndrome. […] It has been proposed that all patients diagnosed with a pheochromocytoma or paraganglioma should consider genetic testing because the incidence of a hereditary syndrome in apparently sporadic cases is as high as 25%.

• #15 Pheochromocytoma and Paraganglioma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/pheochromocytoma/hp/pheochromocytoma-treatment-pdq

  Long-term follow-up is essential for all patients with pheochromocytoma or extra-adrenal paraganglioma, even when initial pathology demonstrates no findings that are concerning for malignancy. […] After resection of a solitary sporadic pheochromocytoma, patients should undergo baseline postoperative biochemical testing followed by annual lifelong biochemical testing. […] Patients with a hereditary pheochromocytoma/paraganglioma syndrome who have undergone resection require lifelong annual biochemical screening in addition to routine screening for other component tumors of their specific syndrome.

• #16 Pheochromocytoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/988683-overview

  Pheochromocytomas occur in people of all races, although they are diagnosed less frequently in the black population. Pheochromocytomas may occur in persons of any age, but the peak incidence is from the third to the fifth decades of life. Approximately 10% occur in children. Fifty percent of pheochromocytomas in children are solitary intra-adrenal lesions, 25% are present bilaterally, and 25% are extra-adrenal. […] […] A study by Iglesias et al looking at 106 patients with pheochromocytoma found that those diagnosed with the sporadic form of the disease tended to be significantly older than those with familial pheochromocytoma (54.5 years vs 40.8 years, respectively).

• #17 Pheochromocytoma: New Updates and Breakthroughs 2024

  https://oncodaily.com/oncolibrary/cancer-types/73253

  Pheochromocytoma is a rare condition, with an estimated incidence of 0.66 cases per 100,000 people per year. The prevalence of pheochromocytoma and paraganglioma has been reported to be around 64.4 per million inhabitants. The incidence of these tumors has increased over time, likely due to improved diagnostic techniques and increased use of imaging studies, which often detect these tumors incidentally. […] These tumors can occur at any age but are most commonly diagnosed in individuals between 30 and 50 years old. They affect both men and women equally, although some studies suggest a slight female predilection with a female-to-male ratio of 1.4:1. The tumors are often part of hereditary syndromes, with about 25-35% of cases being linked to genetic mutations. […] Long-term follow-up studies indicate that the risk of recurrence is significant, even for tumors that appear benign at diagnosis. Patients with hereditary tumors have a higher risk of recurrence compared to those with sporadic tumors. Therefore, lifelong follow-up is recommended for all patients diagnosed with pheochromocytoma.

• #18 Clinical presentation and diagnosis of pheochromocytoma – UpToDate

  https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-pheochromocytoma

  Catecholamine-secreting tumors are rare neoplasms, probably occurring in less than 0.2 percent of patients with hypertension. It is estimated that the annual incidence of pheochromocytoma is approximately 0.8 per 100,000 person-years. However, this is likely to be an underestimate as 50 percent of pheochromocytomas were diagnosed at autopsy in one series. Although pheochromocytomas may occur at any age, they are most common in the fourth to fifth decade and are equally common in males and females. […] Most catecholamine-secreting tumors are sporadic. However, approximately 40 percent of patients have the disease as part of a familial disorder; in these patients, the catecholamine-secreting tumors are more likely to be bilateral adrenal pheochromocytomas or paragangliomas. […] Hereditary catecholamine-secreting tumors typically present at a younger age than sporadic neoplasms. Sporadic pheochromocytoma is usually diagnosed on the basis of symptoms or an incidental discovery on computed imaging, whereas syndromic pheochromocytoma is frequently diagnosed earlier in the course of disease because of biochemical surveillance or genetic testing.

• #19 The epidemiology of pheochromocytoma: increasing incidence and changing clinical presentation. A population-based retrospective study 1977–2015 | ECE2017 | 19th European Congress of Endocrinology | Endocrine Abstracts

  https://www.endocrine-abstracts.org/ea/0049/ea0049oc1.4

  Pheochromocytoma is a rare disease but frequently poses a diagnostic dilemma due to the unspecific symptoms and its potentially life-threatening nature. […] There is a perception of an increase in the incidence of pheochromocytomas in recent years, but no data on time trends exist. […] A significant increasing trend (P0.001) was observed in incidence rates from 2.06 (CI95% 1.682.49) per million person-years 19772006 to 4.65 (CI95% 3.725.82) 20072015. […] The incidence of pheochromocytoma has increased significantly in recent years, presumably due to increased use of imaging studies. […] Therefore, these incidentaloma patients appear to represent a new group of pheochromocytomas not previously diagnosed.

• #20 Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7326683/

  Up to 40% of patients with PPGL have disease-specific germline mutations and the situation is hereditary. Of the 60% of the remaining sporadic patients, at least 1/3 has a somatic mutation in predisposing genes. 8% of the sporadic cases, 20-75% of the hereditary cases, 5% of the bilateral, adrenal cases, and 33% of the extra-adrenal cases at first presentation are metastatic. […] Although most of the PCC and PGL are benign, the metastatic disease may develop in 15-17%. Metastatic disease is reported between 2-25% in PCCs and 2.4-60% in PGLs. The TNM staging system of the American Joint Committee on Cancer (AJCC) was developed to predict the prognosis, based on the specific anatomical features of the primary tumor and the occurrence of metastasis.

• #21 CME Activity: Hereditary Pheochromocytoma and Paraganglioma: Strategies for Screening and Surveillance – Pheo Para Alliance

  https://pheopara.org/2021/09/cme-activity-hereditary-pheochromocytoma-and-paraganglioma-strategies-for-screening-and-surveillance

  Pheochromocytomas are catecholamine-secreting neuroendocrine tumors. […] A key feature is that up to 40% are hereditary, and in children, that number is even higher, with up to 80% being hereditary. […] All patients who develop pheochromocytoma and or paraganglioma should be offered genetic testing since up to 40% have a hereditary susceptibility gene, pathogenic variant, or mutation. […] Through discussions with a patient who is SDHB positive, we hope to provide clinicians with information on hereditary paraganglioma-pheochromocytoma syndrome, the significance of mutations and associated tumor risks, surveillance recommendations and best practices on how to manage patients with the germline mutations who are MIBG avid/not avid.

• #22 Pheochromocytoma and paraganglioma: germline genetics and hereditary syndromes in: Endocrine Oncology Volume 2 Issue 1 (2022)

  https://eo.bioscientifica.com/view/journals/eo/2/1/EO-22-0044.xml

  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. […] About 30-40% of the PCC/PGL cases are associated with a germline PV in a known susceptibility gene, so it is important that patients with PCC/PGL be offered clinical genetic testing. Providers must be aware of the high rate of hereditary PCC/PGL and make the referral for all patients to have genetic counseling and possible testing. […] Knowledge of the germline genetics of PCC/PGL has significantly expanded over the past 20 years. It is now known that about 30-40% of patients with PCC/PGL and 80% of children with PCC/PGL carry a germline PV in one of over 12 well-defined susceptibility genes. Therefore, it is recommended that all patients who are diagnosed with PCC/PGL undergo clinical genetic testing.

• #23 International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-024-01024-5

  The reported prevalence of metastatic PPGL in children and adolescents presenting with PPGL varies between studies (2.4-85.7%) owing to potential referral bias and lack of long-term follow-up. […] In children with confirmed hereditary PPGL, lifelong follow-up is essential to screen for both recurrent metastatic disease and synchronous tumours or syndrome-related pathologies. […] The risk of metastatic disease is lower in patients with sporadic PPGL than in patients with pathogenic variants in the cluster 1 genes (such as SDHx), but in one large multicentre study, the rate of recurrence in adult patients with sporadic PPGL was 14.7%. […] The prevalence of hereditary PPGL is notably higher in paediatric populations (~80%) than in adult populations (~50%), and genetic testing can inform tailored surveillance and management strategies.

• #23 International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents | Nature Reviews Endocrinology

  https://www.nature.com/articles/s41574-024-01024-5

  Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. […] The management of PPGL in childhood is complicated by the high incidence of multifocality and/or recurrence and metastatic disease, together with the limited evidence base and paucity of international guidance and the lack of clinical trials. […] The higher incidence of hereditary PPGL in children requires multidisciplinary care and lifelong follow-up, with surveillance tailored to the specific gene variant or clinical phenotype. […] Early diagnosis and therapeutic intervention are expected to reduce morbidity and mortality. Therefore, family-based identification of children with disease-causing variants followed by enrolment into surveillance programmes is likely to improve the detection of the initial tumours at a time and size that allows resection, and is likely to minimize, if not avoid, metastatic progression.

• #24 SciELO Brazil – Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, and surveillance Pheochromocytoma and paraganglioma: implications of germline mutation investigation for treatment, screening, a

  https://www.scielo.br/j/aem/a/8DPHFNYfHpj3X5Y48n3KhDC/

  PGL/PCC are more commonly associated with a germline mutation than any other cancer type, therefore, all individuals with these types of tumors should undergo genetic risk evaluation. […] Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical and imaging surveillance and their families should undergo genetic counseling. […] Genetic testing should be considered in all patients with these tumors because at least 30~40% of all patients with PGL/PCC have pathogenic germline mutations, and up to 50% of metastatic PGL/PCC may be associated with SDHB mutations. […] Individuals with germline mutations associated with PGL/PCC should undergo lifelong clinical, biochemical, and imaging surveillance. […] Surveillance should include three facets. Firstly, annual careful history and physical examination, including blood pressure monitoring, should be performed. Secondly, at-risk individuals should be subjected to annual biochemical screening of catecholamine metabolites, known as free metanephrines, in plasma and/or fractionated metanephrines in 24-hour urine samples. Thirdly, regular imaging studies should be performed; MRI may be the preferable imaging modality to limit radiation exposure. […] It is critical that all medical personnel interacting with these patients can recognize signs of inherited cancer predisposition syndromes, because the presence of germline mutations has important implications for treatment, screening, and the surveillance of patients and their family members.

• #25 Pheochromocytoma Diagnosis & Treatment – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/ddi/pheochromocytoma/

  Pheochromocytomas and paragangliomas are rare, with an estimated incidence of 2 to 8 diagnoses per every 1 million people each year. However, the actual incidence is unknown, as many people with the tumors are never diagnosed. About 0.05 to 0.2% of hypertensive patients have a pheochromocytoma. […] The incidence is equal for both genders, and diagnosis is typically made between the ages of 30 and 50 years; however, pheochromocytoma due to genetic predispositions, which account for approximately 35% of cases, may present at an earlier age. Most pheochromocytomas and paragangliomas are benign, with 10% of pheochromocytomas and 25% of paragangliomas being malignant. […] The causes of pheochromocytomas are largely unknown, with most cases occurring sporadically. However, approximately 35% of cases are caused by genetic mutations that are inherited in an autosomal dominant pattern. Pheochromocytomas are associated with familial syndromes, such as multiple endocrine neoplasia syndromes type IIA and type IIB, Von Hippel-Lindau syndrome, and type 1 neurofibromatosis.

• #26 Prevalence of pheochromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term follow-up – University of Iowa

  https://iro.uiowa.edu/esploro/outputs/journalArticle/Prevalence-of-pheochromocytoma-and-hyperparathyroidism-in/9984051988102771

  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. […] 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. […] 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%.

• #27 Screening for Hereditary Pheochromocytoma in a Patient with Neurofibromatosis Type 1: A Case Report – touchENDOCRINOLOGY

  https://touchendocrinology.com/endocrine-oncology/journal-articles/screening-for-hereditary-pheochromocytoma-in-a-patient-with-neurofibromatosis-type-1-a-case-report/

  Pheochromocytoma (PHEO) is a rare tumour that arises from adreno-medullary chromaffin cells and secretes catecholamines. At least one-third of PHEOs are familial. The incidence of PHEO in NF1 is 0.15-7% and explains hypertension in 20-50% of these patients. Recent prospective studies suggested that PHEO prevalence in NF1 was underestimated, since they obtained a prevalence of 14.6% and 7.7%, respectively. The frequency of PHEO in VHL is 10-20%, in MEN2 is 50%, and in NF1 is 0.15-7%. The incidence in autopsy series reached 3.3-13%. Hypertension, very common in these patients, is in the majority of cases of reno-vascular aetiology as a result of chronic vascular lesions. However, PHEO can be a not so rare cause of hypertension in these patients. Retrospective studies described a prevalence of PHEO in NF1 of 0.15-7%, which increased to 20-50% if hypertension was present. In fact, persistent hypertension is seen in about 60% of patients with NF1 and PHEO. Recent studies reinforce the idea that PHEO prevalence in NF1 is underestimated and it may have atypical presentation (asymptomatic/normotensive or associated with non-specific symptoms). Patients with undiagnosed PHEO are at risk of developing encephalopathy, cerebrovascular disease, cardiac arrhythmias, congestive heart failure, acute myocardial infarction, myocarditis, cardiomyopathy, pulmonary oedema and shock. Furthermore, patients with PHEO associated with NF1 have more intraoperative hypertension variability and perioperative complications than patients with other genetic syndromes. As a preventive measure, authors highlight the important role of routine screening in the absence of hypertension or classical symptoms, particularly prior to elective surgeries, during preconception planning or early in pregnancy. The Endocrine Society recommends genetic testing for patients presenting with PHEO/paraganglioma and family history or clinical features suggesting an hereditary syndrome. In terms of follow-up, the recommendations for patients with a prior diagnosis of PHEO advocate lifelong annual biochemical surveillance. Biochemical Screening for PHEO by checking plasma or urinary metanephrines should be performed in all patients with NF1 who are hypertensive. Furthermore, systematic screening for PHEO might be considered in all patients with NF1, irrespective of their blood pressure, given the atypical presentation. Early identifications of PHEO could reduce the mortality and morbidity associated with PHEO crisis in patients with NF1; patients with NF1 can develop life threatening complications if PHEO diagnosis is missed.

• #28

  http://www.diva-portal.org/smash/record.jsf?pid=diva2:1297236

  Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.

• #29 Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance

  https://www.mdpi.com/2072-6694/14/12/2942

  At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PPGLs) may recur after the initial surgery. […] The optimal follow-up time for these tumors remains unknown. […] Guidelines recommend annual screening for recurrence in non-metastatic tumors for at least 10 years after the initial surgical resection and lifelong screening in high-risk patients. […] The recurrence rate for PPGLs is approximately 6.5–17.4%, and early detection is important to reduce morbidity and mortality caused by mass effect, catecholamine secretion, and metastatic recurrence. […] The 2014 Endocrine Society Guidelines suggest lifelong follow-up to assess for recurrence or metastatic disease. […] More recently, the European Society of Endocrinology Guidelines suggests a biochemical follow-up of at least ten years for low-risk patients and lifelong follow-up for high-risk patients.

• #30 Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance

  https://www.mdpi.com/2072-6694/14/12/2942

  In sum, the optimal timing, duration, and modality of follow-up vary from study to study due to a lack of systematic studies and the rarity of the disease. […] Our study included a cohort of 309 patients with PPGLs: 177 patients (57.3%) with PHEO, 129 (41.7%) with PGL, and 3 (1.0%) with both PHEO and PGL at diagnosis. […] We identified 39 patients with recurrences: 20 PHEOs and 19 PGLs. […] The overall mean delay of recurrence was 116.6 months (14–584 months) or 9.7 years and the median was 71 months or 5.9 years. […] The majority of patients had a recurrence more than 5 years after initial resection (64.1%) and one-third of patients had a recurrence after 10 years of follow-up. […] Overall, the safest option remains a lifelong follow-up.

• #31 Page 3 – Long-term surveillance following resection of pheochromocytoma

  https://cua.org/sites/default/files/Flipbooks/Guidelines/G78_en/files/basic-html/page3.html

  Long-term surveillance following resection of pheochromocytoma is crucial. The incidence of new events the postoperative metanephrines fail to normalize, persistent disease should be strongly suspected. Further imaging testing to confirm and locate residual catecholamine-secreting tissue should be undertaken. Extra-adrenal disease, age 20 years, familial pheochromocytoma, and tumor size 150 mm appeared to correlate with an increased risk of recurrence. The incidence of new events is lower than previous estimates. Even after long and uneventful follow-up, there can be recurrent disease. This appears more common in cases of familial and extra-adrenal disease. There is no tumor size below which there is no risk of a new event nor is there any subgroup in which follow-up may be safely abandoned. We suggest monitoring for PPGL recurrence by annually measuring plasma-free metanephrines and/or 24-hour urinary fractionated metanephrines. We suggest annual follow-up for at least 10 years following complete resection to monitor for local or metastatic recurrences or new tumors. The incidence rates from individual studies were pooled in a meta-analysis. The overall rate of recurrent disease was calculated as 0.95 events/100 person-years, which equates to a five-year cumulative incidence of 4.7%. Of these new events, 22% were new tumors, 23% were local recurrences, and 55% were metastases. Familial disease was identified as a main independent risk factor of recurrent disease. The presence of extra-adrenal disease (paraganglioma) was a strong predictor, and younger age and large tumor size were weak predictors of recurrence. The risk of recurrence was 10% over the first five years of follow-up.

• #32 Page 1 – Long-term surveillance following resection of pheochromocytoma

  https://www.cua.org/sites/default/files/Flipbooks/Guidelines/G78_en/files/basic-html/page1.html

  Pheochromocytoma is a tumor of the catecholamine-producing cells of the adrenal medulla. The incidence is estimated to be 12 cases per 100,000 individuals and they make up approximately 5% of incidental adrenal masses. Following surgery, patients are at risk for tumor persistence and recurrence. Despite an overall good prognosis, the disease can recur in up to 16% of patients within 10 years following surgery. Recurrences may be local or metastatic and have been reported up to 53 years post-initial resection, making long-term follow-up essential. Extra-adrenal disease, hereditary pheochromocytomas, right-sided tumors, bilateral tumors, and larger tumors are thought to be risk factors for recurrence. Currently, there is no consensus on the proper methodology for follow-up. There have been no randomized studies addressing optimal follow-up nor prospective registries to provide higher-quality evidence for this issue. Important clinical questions remain regarding duration of follow-up and which tests should be used to detect and monitor recurrences. […] This Best Practice Report (BPR) aims to standardize clinical care regarding the long-term surveillance following surgery for pheochromocytoma, specifically with respect to the duration and monitoring methods.

• #33

  https://link.springer.com/article/10.1007/s12094-021-02622-9

  Overall, the prognosis of PPGL is heterogeneous. Goffredo et al. analyzed 508 PPGL patients from 18 US registries (time frame 1988-2009) and reported a 5-year overall survival (OS) rate of 58% for metastatic PCCs and 80% for metastatic PGLs. […] More recently, a retrospective study of 169 patients from 18 European centers (time frame 1998-2010) by Hescot et al. reported a global 5-year OS rate of 62% and a median OS of 6.7 years for mPPGL.

• #34

  https://link.springer.com/article/10.1007/s12094-021-02622-9

  PPGLs are commonly diagnosed within the 4th and 6th decades, although these neoplasms can occur over a wide age range. […] At pediatric ages, extra-adrenal PGLs account for more than two-thirds of the cases, and four of five cases are associated with a hereditary form of the disease. […] The rate of metastatic disease (mPPGL) ranges from less than 1% to 79%, depending upon tumor site and size, age at diagnosis and genotype. […] Although some features included size greater than 5 cm, extra-adrenal primary tumor site, or high levels of plasma 3-metoxitiramine (3-MT) provide useful information to assess the risk of metastasis, the presence of mutations in the succinate dehydrogenase complex iron sulfur subunit B (SDHBMut) is the only universally accepted criterion associated with a high risk of distant disease, both at diagnosis or during follow-up, ranging from 20 to 70% in different patient cohorts.

• #35

  https://www.healio.com/news/endocrinology/20211122/multidisciplinary-care-key-in-updated-pheochromocytoma-paraganglioma-guideline

  Frequent monitoring is recommended for people with secreting metastatic pheochromocytomas and paragangliomas, according to the guideline. […] Surveillance imaging with anatomical cross-sectional imaging with either CT or MRI every 3 to 6 months is recommended for people with metastatic pheochromocytomas and paragangliomas in the first year of disease. […] The researchers wrote there is a lack of evidence for any therapy treating metastatic pheochromocytomas and paragangliomas, and follow-up is limited in retrospective studies. […] Multidisciplinary care at an expert center is critical for patients with metastatic pheochromocytoma and paragangliomas to receive the most up-to-date recommendations and treatments from providers who are experienced in treating this rare cancer. […] Additionally, Fishbein said more multicenter collaborative research is needed to study the biology of tumors, biomarkers for high-risk tumors and therapeutic options in metastatic pheochromocytomas and paragangliomas.

• #36 Systematic Review: Incidence of Pheochromocytoma and Paraganglioma Over 70 Years.

  https://researchspace.auckland.ac.nz/handle/2292/62389

  The annual incidence of PPGL has increased over time. Much of this increase is likely from incidental identification of tumors on imaging. However, the epidemiology of PPGL remains understudied, in particular, in associations with altitude, ethnicity, and genetics. To improve early detection and management guidelines, these gaps should be addressed.

• #37 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma in: Endocrine-Related Cancer Volume 25 Issue 8 (2018)

  https://erc.bioscientifica.com/view/journals/erc/25/8/ERC-18-0085.xml

  The incidence of pheochromocytoma and HNP based on nearly 1500 patients who were diagnosed and histopathologically confirmed between 1995 and 2015 was 0.040.21 per 100,000 person-years. The incidence increased in the latter years of this study mainly by detection of the tumors in older age and a smaller tumor size at diagnosis. […] Due to the use of genetic testing and the widespread use of computed imaging, an increasing proportion of patients with pheochromocytoma are detected before the development of symptoms. […] The germline mutations were all of the missense type and were mainly located in exons 10 (10%), 11 (85%) and 16 (5%) of RET. […] The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers.

• #38 65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma in: Endocrine-Related Cancer Volume 25 Issue 8 (2018)

  https://erc.bioscientifica.com/view/journals/erc/25/8/ERC-18-0085.xml

  Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with 35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. […] In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. […] Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.

• #39 Pheochromocytoma – National Adrenal Diseases Foundation

  https://www.nadf.us/pheochromocytoma.html

  Pheochromocytomas (PCCs) are tumors of the chromaffin cells that arise within the adrenal medulla. They belong to a group of diseases termed neuroendocrine tumors (NETs). Pheochromocytomas are related to another group of endocrine tumors called paragangliomas which occur outside the adrenal gland and originate at any level of extra-adrenal paraganglia (from the skull base to the pelvic floor). […] The diagnosis of pheochromocytoma is often delayed, impacting patients and their families. In part, these tumors can have an insidious course with non-specific symptoms, and in many cases they can be silent tumors. […] Therefore, the diagnosis and management of these uncommon tumors should be carried out in specialized centers with expertise in the management of these tumors. […] The genetic cause can dictate the behavior of these tumors to some extent; experts in the field call this genotype-phenotype correlation.

• #40 Pheochromocytoma – National Adrenal Diseases Foundation

  https://www.nadf.us/pheochromocytoma.html

  Furthermore, genetic identification provides valuable information for establishing a treatment plan and procures the rationale for appropriate guidance for follow-up surveillance. […] If children are found to carry the mutation, they will need to follow up with an expert physician and undergo periodic active surveillance for early detection of the tumors. […] The first step any patient should take is establishing care at a specialized center with physicians who have treated at least a few hundred patients with these syndromes. […] Unfortunately, in some circumstances failing to do so can result in tumor metastasis developing over the course of the years due to the absence of active surveillance by specialized centers. […] Therefore, blocking these hormones with the appropriate medications with appropriate titration and dosing is essential for good care management.

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