Pheochromocytoma and paraganglioma genetic testing: Psychological impact.

OBJECTIVE: Genetic testing is recommended for all pheochromocytoma/paraganglioma tumor-affected patients and, if positive, for their relatives, who are at risk of developing tumors. This study aims to assess the previously unexamined psychological impact of genetic testing and identify factors associated with this impact. METHOD: A nationwide sample of 103 individuals carrying succinate dehydrogenase mutations answered the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire plus two measures of general well-being (the SF-36 Health Survey and the Hospital Anxiety and Depression scale). Sociodemographic, clinical, and personality characteristics (the 5 personality factors and locus of control) were also assessed. Data were analyzed with bivariate and GLM univariate analyses. RESULTS: Genetic testing-related mean scores were 6.12 for Distress, 11.58 for Uncertainty, 10.61 for Positive experiences, and almost 30% of the sample displayed high MICRA global suffering. Tumor-affected participants whose neoplasia was identified through presymptomatic screening felt that the genetic test has made it easier to cope with their disease. Significant aspects associated with genetic-testing-related Distress and Uncertainty included higher levels of Neuroticism and Agreeableness. An interaction between having the neoplasia and having children was also associated with higher levels of Distress. Education and Conscientiousness were associated with Positive experiences. Affected mutation carriers presented lower global quality of life and higher anxiety and depression levels than healthy mutation carriers. CONCLUSIONS: Genetic testing's impact depends on individual characteristics. The identified characteristics can inform clinical practice regarding who might benefit from special care in genetic counseling. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Psychometric Properties of the MICRA Questionnaire in Portuguese Individuals Carrying SDHx Mutations.

This study aims to present the translation and cultural adaptation, as well as the psychometric characteristics of the Portuguese version of the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire in individuals with SDHx mutations. The questionnaire was translated and culturally adapted in accordance with the process recommended by the World Health Organization. As per suggestion of the authors of the original instrument, a joint, universal European and Brazilian Portuguese version of the MICRA was created. Ninety-six (asymptomatic or affected) patients with SDHx mutations nationwide completed the adapted version of the MICRA in Portugal. Analyses consisted of confirmatory factor analysis, reliability estimation (alphas), and correlations with two other distress and quality of life instruments. The Portuguese adaptation of the MICRA was understandable to patients from various socioeconomic backgrounds. All items and factor structure of the original version were retained, yielding a good model fit. The MICRA's three subscales and total score showed good internal consistency, and the correlations found between the Portuguese version of the MICRA and the other instruments assessing similar constructs further supported its validity. The adapted version of the MICRA showed good psychometric properties with a representative population of SDHx mutation carriers. This instrument can now be used to study the multidimensional impact of taking a genetic test for these mutations. It can also be used in future studies with other Portuguese populations of patients submitted to genetic tests for cancer risk assessment.

Trends of genetic screening in patients with pheochromocytoma and paraganglioma: 15-year experience in a high-volume tertiary referral center.

BACKGROUND AND OBJECTIVES: Genetic testing for pheochromocytoma and paraganglioma allows for early detection of hereditary syndromes and enables close follow-up of high-risk patient. We investigated the trends in genetic testing among patients at a high-volume referral center and evaluated the prevalence of pheochromocytomas and paragangliomas. METHODS: We reviewed the charts of 129 patients who underwent adrenalectomy for pheochromocytoma and paraganglioma between January 2000 and July 2015. To evaluate for trends in genetic testing, patients were divided by year of diagnosis: 2000-2005 (group 1, n = 35), 2006-2010 (group 2, n = 44), and 2011-2015 (group 3, n = 50). RESULTS: Among 129 patients the mean age was 47 years and 56% were women. Groups 2 and 3 were more frequently referred for genetic consultation than group 1, 73%, and 94% versus 26% (P < 0.001). A total of 67% followed up on the referral. The prevalence of genetic mutation was 50% (21/42 tested). The percentage with a genetic syndrome was 23%, 28%, and 22% respectively for groups 1, 2, and 3. CONCLUSIONS: Referral for genetic counseling significantly increased in the past 15 years. However, only two-thirds of patients followed up with genetic counselors and, therefore, clinicians can do more to improve the adherence rate for genetic counseling.

Cases of remission of psychosis following resection of pheochromocytoma or paraganglioma.

The author previously proposed that schizophrenia has similar cytokine expression compared to melanoma, a neural crest cell tumor. One possible tumor model of schizophrenia includes anti-NMDA receptor encephalitis, a paraneoplastic syndrome. While examining the possible relationship of neural crest cell tumors to schizophrenia, the author found several case reports of psychosis resulting from pheochromocytomas and paragangliomas, types of neural crest cell tumors that secrete catecholamines. In most cases, surgical resection of the tumors resulted in remission of psychotic symptoms, and some remissions were associated with reduced levels of peripheral catecholamine levels. These reports suggest, first, that the differential diagnosis of psychosis with autonomic instability should include these tumors. Second, the cases raise a theoretical question as to how these tumors might cause psychosis. On one hand, the elevated peripheral catecholamines caused by these tumors generally agree with aspects of the dopamine hypothesis of schizophrenia although the mechanism of how peripheral dopamine would cause psychosis is unknown. On the other hand, these tumors could possibly secrete an unidentified antibody to a receptor similar to what is observed in anti-NMDA receptor encephalitis.

Avoiding and nonexpressing: coping styles of patients with paragangliomas.

CONTEXT: Paraganglioma (PGL) patients and succinate dehydrogenase (SDH) gene mutation carriers at risk for PGLs have a decreased quality of life (QoL). QoL may be affected by the strategy an individual uses when dealing with a stressful situation, ie, specific coping styles. Understanding the various approaches to coping may allow the development of targeted interventions to improve patient QoL. OBJECTIVE: The objective of the study was to assess coping styles in PGL patients and SDH mutation carriers. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a tertiary referral center. PATIENTS AND METHODS: Coping styles were assessed using the Utrecht Coping List. The results from the study cohort were compared with a control group and data derived from the literature. Potential differences in coping styles between the various SDH mutation carriers and PGL patients without an SDH mutation were explored. RESULTS: Of the 174 patients who responded, 122 were SDHD, 25 SDHB, and 2 SDHC mutation carriers. An additional 25 patients lacked an SDH mutation. They recruited 100 peers as controls. Compared with the general population, the study cohort was more avoidant of problems (P < .001) and reported less expression of emotion (P < .01). Compared with patients with other conditions, they sought more social support (P < .001). There were no significant differences in coping styles between the various categories of mutation carriers or PGL patients lacking a mutation. CONCLUSIONS: Coping styles of PGL patients and SDH mutation carriers differ from those of control and reference groups and include an avoidant coping style and a lack of emotional expression.

Quality of life is decreased in patients with paragangliomas.

CONTEXT: Germline mutations in succinate dehydrogenase (SDH) genes predispose carriers for developing paragangliomas, and studies on their quality of life (QoL) are scarce. OBJECTIVES: The objectives of this study were to assess QoL in patients with paragangliomas (PGL), to evaluate long-term QoL, and to explore potential differences in QoL between SDH mutation carriers and paraganglioma patients without an SDH mutation. DESIGN: Cross-sectional, case-control study. SETTING: Tertiary referral center. SUBJECTS: ONE HUNDRED AND SEVENTY FOUR PARAGANGLIOMA PATIENTS WERE INCLUDED: 25 SDHB, two SDHC, and 122 SDHD mutation carriers and 25 patients without an SDH mutation. They provided 100 peers as control persons. Furthermore, patients were compared with age-adjusted reference populations. MAIN OUTCOME MEASURES: QOL WAS ASSESSED USING THREE VALIDATED HEALTH-RELATED QOL QUESTIONNAIRES: the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Index 20, and the Short Form 36. RESULTS: Patients reported a significantly impaired QoL compared with their own controls, mainly on fatigue and physical condition subscales. Compared with age-adjusted literature values, patients had significantly impaired scores on physical, psychological, and social subscales. A decreased QoL was mainly related to paraganglioma-associated complaints. There was no difference in QoL between the various SDH mutation carriers or paraganglioma patients without an SDH mutation. QoL in asymptomatic mutation carriers, i.e. without manifest disease, did not differ from QoL of the general population. Long-term results in 41 patients showed no alteration in QoL besides a reduced level of activity. CONCLUSION: QoL is decreased in paraganglioma patients but stable when measured over time.

Neurological manifestations of phaeochromocytomas and secretory paragangliomas: a reappraisal.

OBJECTIVE: To determine the frequency and range of neurological manifestations of phaeochromocytomas and secretory paragangliomas. METHODS: A retrospective review of case notes of patients admitted to Auckland Hospital from 1985 to 2011 with a discharge diagnosis of phaeochromocytoma or secretory paraganglioma. RESULTS: Ninety-three patients were admitted with a phaeochromocytoma or secretory paraganglioma. Sixty-eight patients (73%) had neurological symptoms, but only 15 patients (16%) received a neurological consultation. Neurological manifestations occurred in three main clinical contexts. First, paroxysmal symptoms occurred in 66 of 93 patients (71%). Neurological symptoms were common features of these attacks and included headache (47 patients), anxiety (24 patients), tremulousness (15 patients) and dizziness (12 patients). The headaches typically had an explosive onset. Delay in diagnosis was common. Second, 28 patients (30%) had an acute crisis, which was associated with neurological symptoms in 11 (39%) of the episodes: headache (10 patients); seizures (five patients); strokes (three patients); delirium (three patients) and subarachnoid haemorrhage (one patient). Third, five of six patients with a head and neck secretory paraganglioma had neurological symptoms related to infiltration of the middle ear or compression of cranial nerves. Reversible cerebral vasoconstriction syndrome (RCVS) was documented in three patients. CONCLUSIONS: Neurological manifestations of phaeochromocytomas and secretory paragangliomas were common, and these tumours can present with various neurological manifestations. The paroxysmal symptoms can be incorrectly attributed to other headache syndromes, panic attacks or cerebral vasculitis. RCVS may play a role in the pathogenesis of the neurological symptoms associated with acute crises and paroxysmal attacks.

Presymptomatic genetic testing in minors at risk of paraganglioma and pheochromocytoma: our experience of oncogenetic multidisciplinary consultation.

The aim of the work was to define quality criteria for presymptomatic genetic testing in minors at risk of paraganglioma/pheochromocytoma. A 3-step multidisciplinary procedure was developed: 1) preparatory consultations for parents, providing decision support and advice concerning the way of informing the children; 2) consultation with the minor and blood sampling; and 3) announcement of the result of the genetic test to the minor and his/her parents. Twenty-three minors (mean age=9.22) were tested. The result was positive in 16 cases (presence of the familial mutation) and negative in 7. The 23 procedures were classified according to emotional reactions at the announcement of the result: calm (18/23) or tense (5/23). In parallel, 4 criteria for a good testing procedure was defined: 1) both parents agreeing to have their child tested when they felt ready; 2) parents being given advice concerning the way to inform their child; 3) the most appropriate time for testing being discussed for each child; and 4) avoidance of testing during medical examination periods for the carrier parent. The frequencies of the above criteria were as follows: 1 (17/23); 2 (19/23); 3 (17/23); and 4 (17/23). The overall quality of the testing procedure, calculated as the sum of the four criteria, differed significantly between calm and tense announcements (p<0.01). This study highlights the important role of careful preparation with the parents in emotional acceptance of the result of testing. The 4 criteria identified should be evaluated in further prospective studies.

Reduced quality of life in patients with head-and-neck paragangliomas.

OBJECTIVE: The objective of this study was to assess the quality of life (QoL) in patients with head-and-neck paragangliomas ('glomus tumors'). DESIGN: We conducted a case-control study. METHODS: We assessed QoL in 82 patients with head-and-neck paragangliomas using four validated health-related questionnaires: Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index (MFI-20), Short Form-36 (SF-36), and Nottingham Health Profile (NHP). Patient outcomes were compared with controls provided by the patients and with a large age- and sex-adjusted control group. RESULTS: The QoL scores in the paraganglioma patients were significantly reduced in 12 out of the 21 subscales compared with own controls, and in 18 out of the 21 subscales compared with age- and sex-adjusted values derived from the previous studies. In the MFI-20 questionnaire, patients reported more general fatigue, physical fatigue, mental fatigue, and a reduction in activity and motivation. The scores in the NHP showed a difference in energy, emotional reaction, and social isolation. General health perception, pain, and physical functioning were reported to be worse in the paraganglioma patients on the SF-36 scale. Although anxiety and depression did not reveal any significant differences between patients and their own controls, an increased score on both anxiety and depression was seen when compared with the extended control group. Especially, dysphonia contributes to a reduced QoL. CONCLUSION: QoL is considerably reduced in patients with head-and-neck paragangliomas.

A novel mutation in the SDHD gene responsible for familial paraganglioma. Medical and psychological implications.

Familial paragangliomas/pheochromocytomas are dominantly inherited disorders characterized by the development of highly vascularized tumors of the head and neck, derived from non-chromaffin cells of the extra-adrenal paraganglia, and tumors with endocrine activity, derived from chromaffin cells, usually located in the adrenal medulla and pre- and para-vertebral thoracoabdominal regions. Germline inactivating heterozygous mutations in one of the genes encoding for succinate dehydrogenase subunits B, C or D (SDHB, SDHC or SDHD) are responsible for hereditary paragangliomas (PGLs), accounting for nearly 70% of familial cases. Particularly in the SDHD gene, different types of mutations have been found, nevertheless, alterations other than point mutations and deletion leading to missense/nonsense/splicing mutations are extremely rare. Here we report a family with multiple cases of PGL which co-segregates with a novel SDHD gene mutation predictable to give rise to an abnormal gene product (CybS). The identification of the molecular event responsible for PGL in our family made genetic counseling particularly useful for younger first degree relatives at risk to develop this late-onset disease.