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.

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.

Psicosis paranoide recurrente: primera manifestación de feocromocitoma / Relapsing paranoid psychosis as the first manifestation of phaeochromocytoma

Aunque de vez en cuando se ven manifestaciones psiquiátricas en los pacientes con feocromocitoma, éstas se limitan normalmente a estados de ansiedad. Otras manifestaciones menos frecuentes son la depresión y los síntomas psicóticos. En este artículo describimos a un paciente que presentó una psicosis paranoide como única manifestación de un feocromocitoma mucho antes de que éste fuera diagnosticado de dicha enfermedad. El trastorno delirante, que se trató con fármacos antipsicóticos durante dos años, desapareció tras la resección del tumor. Se podría especular que las catecolaminas podrían tener relación con el estado psicótico de este paciente y nos planteamos hasta que punto el feocromocitoma podría ser un "ejemplo natural" para explicar la fisiopatología catecolaminérgica involucrada en algunos trastornos psicóticos (AU)

Unusual clinical manifestation of pheochromocytoma in a MEN2A patient.

A case of unusual clinical manifestation of pheochromocytoma in a type 2A multiple endocrine neoplasia (MEN2A) patient is presented. A 27-year-old man affected by MEN2A syndrome, complaining of anxiety and depression, was admitted in our Division. Past medical history included a total thyroidectomy for medullary carcinoma in 1985, and left adrenalectomy for pheochromocytoma in 1994. Blood pressure was 130/ 85 mmHg without orthostatic hypotension and pulse rate was 72 beats/min. Laboratory data revealed thyroid hormones and carcinoembryonic antigen (CEA) in the normal range and high basal serum calcitonin levels (158 pg/ml). Plasma catecholamines and vanillylmandelic acid resulted in normal levels but epinephrine/norepinephrine ratio was elevated (0.65). The glucagon stimulation test showed positive clinical and biochemical response. Magnetic resonance imaging (MRI) and meta-iodobenzylguanidine (MIBG) scintiscan confirmed the presence of bilateral adrenal masses. Bilateral adrenalectomy by laparoscopic anterior approach was performed. Histology was consistent with adrenal pheochromocytomas. After surgical approach, psychiatric findings disappeared and did not recur at follow-up in spite of no medication for two years. In conclusion, bilateral pheochromocytoma is more frequent in MEN2A syndrome and probably understimated if the follow-up is not prolonged. In these cases clinical features are often aspecific and basal hormonal data may be normal in a great number of patients. Therefore long-term observation is justified in these patients. Pheochromocytoma was described as the "great mimic" for the numerous subjective manifestations. Differential diagnosis among typical features of neuropsychiatric disorders and pheochromocytoma must be considered.

Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment.

Severe, symptomatic paroxysmal hypertension always generates suspicion of a pheochromocytoma, a catecholamine-secreting tumor. However, most patients with this disorder do not have this tumor and their condition remains undiagnosed and ineffectively treated. This case series, summarizing the course of 21 such patients, suggests a cause and an effective treatment approach. All 21 patients insisted that the paroxysms were not related to stress or emotional distress, initially discouraging consideration of a link to emotions. Nevertheless, with careful psychosocial interviewing, the disorder could be attributed to emotions patients were not aware of, and, therefore, unable to report. Such emotions were related either to previous severe emotional trauma or to a general tendency to keep distressful emotions out of awareness. With treatment based on this understanding, further paroxysms were eliminated in 13 (62%) of 21 patients. Alpha- plus beta-blockade was used, combined, when necessary, with an antidepressant agent, with or without an anxiolytic agent. In 3 cases, the disorder was cured with psychotherapy alone. Because the presenting symptoms are physical rather than emotional, patients present to internists and primary care physicians rather than to psychotherapists. For this reason, more awareness of this disorder in the medical community is needed.

[Hypertensive derailment in marital crisis]. / Hypertensive Entgleisung bei Ehekrise.

A 34-year-old man was admitted because of headache with neck pain, hypertension and tachycardia. The symptoms started 10 days prior to presentation. In the past the patient was treated because of different vegetative symptoms, which were interpreted in relation to excessive private problems. Despite suggestive clinical presentation, the diagnosis phaeochromocytoma was confirmed late. Following removal of the tumor, blood pressure came into the normal range. The operation also abolished all vegetative symptoms and lead to stabilisation of the psychosocial situation.

[Unmasking pheochromocytoma by amitriptyline]. / Demaskierung eines Phäochromozytoms durch Amitriptylin.

A report is given about a 57-year-old woman with a major depression, melancholic subtype. While under amitriptyline 75 mg/day no adverse effects were observed, immediately after increasing the dosage to 150 mg/day "head spasms" with headache, profuse sweating and arterial hypertension appeared. The diagnosis of a pheochromcytoma was made and adrenalectomy was performed. This is the first case of unmasking a pheochromcytoma by amitriptyline; furthermore a connexion was found with the daily dosage of the antidepressant.

The practical use of carbon dioxide-induced anxiety in the diagnosis and care of patients with panic disorder.

The authors utilized inhalation of 35% carbon dioxide and 65% oxygen as a diagnostic tool in the evaluation of suspected panic disorder. In two inpatients admitted for a medical evaluation for pheochromocytoma and carcinoid syndrome, respectively, a positive response to the double-blind administration of CO2/O2 or room air was consistent with a diagnosis of panic disorder by psychiatric history. In two additional patients in whom denial of mental illness was a psychological impediment to proper treatment, a positive CO2/O2 challenge resulted in therapeutic benefit.