Inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1: a case report.

BACKGROUND: Inflammatory rhabdomyoblastic tumors are relatively recently recognized soft tissue tumors with a low malignant potential. Here, we present a case of concurrent inflammatory rhabdomyoblastic tumor (IRMT), adrenal pheochromocytoma, and pulmonary hamartoma in a patient with neurofibromatosis type 1 (NF1). To our knowledge, this is the first time that this constellation of tumors has been described in the literature. CASE PRESENTATION: A female patient in her late 20s with known NF1 was diagnosed with an inflammatory rhabdomyoblastic tumor, pheochromocytoma, and pulmonary hamartoma in a short succession. IRMT was found to harbor a near-haploid genome and displayed a typical immunohistochemical profile as well as a focal aberrant p53 expression pattern. CONCLUSIONS: This case report strengthens the theory that defects in the tumor suppressor NF1 play a central role in the pathogenesis of inflammatory rhabdomyoblastic tumors and that IRMT may be part of the spectrum of neurofibromatosis type 1 related tumors.

[A rare case of recurrent myocarditis revealing pheochromocytoma]. / Un rare cas de myocardite récurrente révélant un phéochromocytome.

Pheochromocytoma is a rare neuroendocrine tumor characterized by overproduction of catecholamines. The overproduction of catecholamines leads to cardiac remodeling which manifests in several forms ranging from Takotsubo to dilated cardiomyopathy. Studies suggest that pheochromocytoma-induced cardiomyopathy can take various forms depending on the duration of catecholamine exposure. Myocarditis is a fairly rare presentation of cardiac manifestations of pheochromocytoma which are mainly dominated by Takotsubo and dilated cardiomyopathies. We report a rare case of recurrent myocarditis in a young 37-year-old patient revealing the diagnosis of adrenal pheochromocytoma. Through this case and through a review of the literature we will take stock of the epidemiology of cardiac involvement in pheochromocytoma, mainly cardiomyopathies, and we will take stock of the value of diagnosis and early management in improving the prognosis of patients.

Validation and Evaluation of 5 Scoring Systems for Predicting Metastatic Risk in Pheochromocytoma and Paraganglioma.

Currently, 5 scoring systems have been proposed in the literature for predicting metastatic risk in pheochromocytoma and paraganglioma (PPGL): Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP), Composite Pheochromocytoma/paraganglioma Prognostic Score (COPPS), Age, Size, Extra-adrenal location, Secretion type (ASES) score, and Size, Genetic, Age, and PASS (SGAP) model. To validate and evaluate these 5 scoring systems, we conducted a retrospective review of cases diagnosed as PPGL at the Department of Pathology, West China Hospital of Sichuan University, between January 2012 and December 2019. A total of 185 PPGL cases were included, comprising 35 cases with metastasis and 150 cases remained metastasis-free for over 8 years after surgery. The criteria of the 5 scoring systems were used for scoring and risk classification. The predictive performance of the 5 scoring systems was validated, compared, and evaluated using concordance index (C-index) and decision curve analysis (DCA). The C-indices for PASS, GAPP, and SGAP were 0.600, 0.547, and 0.547, respectively, indicating low discriminative ability. In contrast, COPPS and ASES had C-indices of 0.740 and 0.706, respectively, indicating better discriminative performance. DCA also showed that the predictive capability of COPPS was superior to that of ASES, with both outperformed PASS, while PASS had better predictive ability than GAPP and SGAP. Our analysis indicated that pathology-based scoring systems cannot accurately predict metastatic risk of PPGL. Establishing a precise prediction system requires integrating clinical, pathologic, and molecular information, using a scientific methodology for predictive factor selection and weight assessment.

A rare case of pheochromocytoma in a pregnant woman presenting with chest pain: extraordinary management.

BACKGROUND: Pheochromocytoma is rare in pregnant women. It presents as diverse symptoms, including hypertension and sweating. The symptoms of pregnant women with pheochromocytoma and comorbid hypertension often mimic the clinical manifestations of preeclampsia, and these women are often misdiagnosed with preeclampsia. CASE PRESENTATION: In this case, a pregnant woman presented with chest pain as the primary symptom, and a diagnosis of pheochromocytoma was considered after ruling out myocardial ischemia and aortic dissection with the relevant diagnostic tools. This patient then underwent successful surgical resection using a nontraditional management approach, which resulted in a positive clinical outcome. CONCLUSIONS: It is essential to consider pheochromocytoma as a potential cause of chest pain and myocardial infarction-like electrocardiographic changes in pregnant women, even if they do not have a history of hypertension.

Endocrine Fever.

Fever is usually thought to be of an infectious or inflammatory etiology. In this brief communication, we explore the multifaceted connections between fever and endocrine dysfunction. Impaired resistance to infection often leads to fever in conditions like diabetes and Cushing's syndrome. Additionally, several endocrine disorders, including hyperthyroidism, subacute thyroiditis, carcinoid syndrome, and pheochromocytoma, can manifest as fever. Furthermore, fever can be an adverse effect of various endocrine treatments, such as bisphosphonates and antithyroid drugs. We refer to these scenarios as 'endocrine fever.' Increased awareness of these clinical associations can aid in prompt diagnosis and management of these conditions.

[A rare cause of hypercorticism: ACTH-secreting pheochromocytoma (a case report)]. / Une cause rare d'hypercorticisme: un phéochromocytome sécrétant l'ACTH (à propos d'un cas).

Ectopic ACTH-secreting pheochromocytoma is a very rare cause of Cushing´s syndrome, posing diagnostic and therapeutic challenges. We here report the case of a female patient with suspected severe Cushing´s syndrome associated with melanoderma, arterial hypertension resistant to triple therapy and unbalanced diabetes treated with insulin therapy. Biologically, urinary ethoxylated, 24-hour urinary free cortisol and ACTH were very high. Imaging showed a 3.5 cm left adrenal mass. The patient underwent left adrenalectomy after medical preparation, with good clinico-biological outcome. Anatomopathological examination confirmed the diagnosis of pheochromocytoma. This case study highlights the importance of measuring methoxylated derivatives in any patient with ACTH-dependent Cushing´s syndrome associated with an adrenal mass. The aim is to ensure early treatment and avoid life-threatening complications.

[Clinical features of patients with metastatic pheochromocytoma/paraganglioma].

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.

Patient-reported burden associated with pheochromocytoma/paraganglioma diagnosis.

Pheochromocytoma and paragangliomas (PPGLs) originate from the chromaffin cells of the adrenal medulla or neural crest progenitors outside the adrenal gland, respectively. The estimated annual incidence of PPGL is between 2.0 and 8.0/million adults. Minimal data exist on the impact of PPGL from the patient's perspective. Therefore, a survey was adapted from a previously published study on gastroenteropancreatic neuroendocrine tumors to explore the voice of patients with PPGL and learn ways to improve clinical care while understanding the current gaps to direct future research. A self-reported online survey was available to patients with PPGL and those with genetic predisposition even without PPGL from June to July 2022. Survey questions captured sociodemographic and clinical characteristics, the diagnostic workup, treatment and monitoring, quality and access to care, and financial impact. Here, we report the most relevant findings on patient experience of disease burden following diagnosis. A total of 270 people responded, the majority of whom were from the USA (79%), Caucasian (88%), and female (81%). The results of this survey highlight the burden of disease on a patient's daily life, resulting in moderate to severe financial distress, increased travel time to specialized facilities resulting in loss of work and wages, and significant delays in care. Respondents reported being unheard and unacknowledged. With a median time to diagnosis just over 2 years, the physical, mental, and emotional toll are substantial. Increasing access to PPGL specialists and centers could lead to faster diagnoses and better management, which may reduce the burden on both patients and healthcare centers.

Feocromocitoma y paraganglioma en un hospital pediátrico de Argentina. Serie de casos / Pheochromocytoma and paraganglioma at a children's hospital in Argentina. A case series

El feocromocitoma y el paraganglioma son tumores neuroendocrinos secretores de catecolaminas. Los feocromocitomas se originan en la médula suprarrenal, mientras que los paragangliomas son extraadrenales. Se describe una serie de casos de niños con diagnóstico anatomopatológico de feocromocitoma o paraganglioma que consultaron en un hospital pediátrico de alta complejidad de Argentina. Se incluyeron 21 pacientes, 14 varones, con una mediana de edad de 11,4 años; 8 casos con feocromocitoma y 13 casos con paraganglioma. Se presentaron con hipertensión arterial 14/21. La mayoría de los paragangliomas tuvieron localización paraaórtica (9/13). Debido a que representan una causa potencialmente curable de hipertensión arterial, la sospecha clínica es muy importante. El diagnóstico temprano y la instauración de un tratamiento antihipertensivo adecuado, que permita afrontar la cirugía con normotensión arterial, aseguran la curación en la mayoría de los casos si la resección tumoral es completa.

Pheochromocytomas and paragangliomas are neuroendocrine tumors producing catecholamines. Pheochromocytomas occur in the adrenal medulla, while paragangliomas are those that occur outside the adrenal gland. Here we describe a case series of children with a pathological diagnosis of pheochromocytoma or paraganglioma who consulted at a tertiary care children's hospital in Argentina. A total of 21 patients (14 males) were included; their median age was 11.4 years; 8 children had pheochromocytoma and 13, paraganglioma. Arterial hypertension was observed in 14/21. Most paragangliomas were para-aortic (9/13). Since they are a potentially curable cause of hypertension, clinical suspicion is very important. An early diagnosis and the initiation of an adequate antihypertensive treatment, which allows the patient to undergo surgery with normal blood pressure, ensure a cure in most cases if tumor resection is complete.

A multidisciplinary approach of a patient with pheochromocytoma presenting as recurrent acute fulminant myocarditis: A rare case report and comprehensive review of literature.

Fulminant myocarditis (FM) is a rare illness characterized by abrupt and severe widespread cardiac inflammation, which frequently results in mortality due to cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Pheochromocytoma is an uncommon and difficult-to-diagnose cause of FM, and it is associated with a significant risk of recurrent acute myocarditis. There is, however, little information on reoccurring acute FM. Herein, we report a rare case of recurrent acute FM due to pheochromocytoma. We present the case of a 22-year-old woman who was admitted to our hospital three days previously with acute dyspnea. Five months prior, the patient was diagnosed with post-acute myocarditis, and a massive tumor on the right adrenal gland was discovered, which lead to pheochromocytoma diagnosis. In this present admission, following the exclusion of infection, autoimmune, and metabolic derangements, pheochromocytoma was presumed to be the reason for the recurrence and more severe acute FM during the current hospitalization. The patient responded favorably to high-dose steroids combined with heart failure therapy regimens. To detect recurrent acute myocarditis related to pheochromocytoma, a multidisciplinary approach was used, including several laboratory biomarkers and imaging findings. Following pheochromocytoma removal and biopsy, the patient recovered satisfactorily. Our findings may provide beneficial contributions to the literature as pheochromocytoma is an uncommon but important cause of recurrent acute myocarditis. A multidisciplinary approach is essential in identifying acute FM and determining the underlying causes of this malady.

Pediatric malignant pheochromocytoma with atypical presentation as vision changes, lung metastasis, and recurrence: a case report.

BACKGROUND: This case report documents a case of malignant pheochromocytoma manifested as vision changes with lung metastasis and recurrence. CASE PRESENTATION: A 10-year-old Han Chinese girl presented with vision changes and was eventually diagnosed with pheochromocytoma by contrast-enhanced computed tomography, urine vanillylmandelic acid. After medication for hypertension and surgery, clinical symptoms disappeared. Malignant pheochromocytoma with lung metastasis was confirmed histologically using the Pheochromocytoma of the Adrenal Gland Scaled Score scoring system and genetically with succinate dehydrogenase complex iron sulfur subunit B mutation, and 3 months later, unplanned surgery was performed because of the high risks and signs of recurrence. She is asymptomatic as of the writing of this case report. Our patient's case highlights the importance of considering a diagnosis of malignant pheochromocytoma, and long-term follow-up for possible recurrence. CONCLUSION: Although there are well-recognized classic clinical manifestations associated with pheochromocytoma, atypical presentation, such as vision changes in children, should be considered. In addition, malignant pheochromocytoma children with a high Pheochromocytoma of the Adrenal Gland Scaled Score and succinate dehydrogenase complex iron sulfur subunit B mutation require a long-term follow-up or even unplanned surgery because of the higher risk of recurrence.

Clinical diagnosis of pheochromocytoma and paraganglioma-induced secondary hypertension through UPLC-MS/MS analysis of plasma catecholamines and their metabolites.

This study aimed to elucidate the clinical diagnostic value of plasma catecholamines and their metabolites for pheochromocytoma and paraganglioma (PPGL)-induced secondary hypertension using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS). The study population included 155 patients with PPGL that were divided into the PPGL with hypertension (n = 79) and a PPGL without hypertension (n = 76) groups, and 90 healthy volunteers and 90 patients with primary hypertension as the control groups. UPLC-MS/MS was performed to detect plasma levels of catecholamines and their metabolites, including dopamine, vanillylmandelic acid (VMA), norepinephrine, metanephrine, and normetanephrine. Receiver operating characteristic curves were generated to analyze the diagnostic value of the plasma levels of catecholamines and their metabolites in PPGL-induced secondary hypertension. Patients in the primary hypertension and PPGL without hypertension groups had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal group (all p < .05). On the other hand, patients in the PPGL with hypertension group had higher levels of dopamine, VMA, norepinephrine, metanephrine, and normetanephrine than patients in the normal, primary hypertension, and PPGL without hypertension groups (all p < .05). Collectively, our findings showed that dopamine, VMA, norepinephrine, metanephrine, and normetanephrine are all effective biomarkers for the diagnosis of PPGL and PPGL-induced secondary hypertension.

Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

BACKGROUND: Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. CONTENT: This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. SUMMARY: Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

Chromogranin A as a diagnostic marker of pheochromocytoma and paraganglioma: A systematic review and meta-analysis.

OBJECTIVES: This work aims to assess the diagnostic value of chromogranin A (CgA) in the laboratory diagnosis of neuroendocrine tumors classified as pheochromocytoma and paraganglioma (PPGL). METHODS: A comprehensive search was performed in PubMed, Embase, the Cochrane Library, and Web of Science databases to obtain relevant studies reporting the diagnostic accuracy of CgA in patients with PPGL. The search involved studies written in English between the time of library inception and May 1, 2023. We computed the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Additionally, the receiver operating characteristic curve and area under the curve (AUC) were determined. The heterogeneity was assessed using the Chi-square test and the I2 test. The subgroup analyses were performed to investigate the origins of heterogeneity. Stata 15.1 statistical software was used in all data analyses. RESULTS: This meta-analysis included 13 studies involving 1470 patients. CgA had a pooled diagnostic sensitivity of 0.86 (95% CI 0.81-0.91), a specificity of 0.90 (95% CI 0.81-0.95), and a DOR of 57 (95% CI 23-142). CgA had an AUC of 0.93. The studies did not reveal any threshold effect (r = -0.165; p > 0.05). The subgroup analyses revealed that the control group category and the detection method caused the overall heterogeneity. CONCLUSIONS: Our study suggests that CgA is a helpful PPGL biomarker. However, relying solely on CgA for diagnosis is not advisable. A comprehensive approach is essential for accurate diagnosis. Future large-scale research is needed to refine CgA's clinical application.

[Headache and hypertension as a form of presentation of pheochromocytoma and simulating a post-COVID-19 syndrome]. / Cefalea e hipertensión como forma de presentación de un feocromocitoma y simulando un síndrome post-COVID-19.

Post-COVID-19 syndrome is a set of symptoms and signs that persist for more than 12 weeks after COVID-19 infection and currently lacks a standardised clinical definition. Only one case has been reported in which a pheochromocytoma was mistaken for post-COVID-19 syndrome. The symptomatology of this syndrome is variable and ranges from headache and fatigue to persistent dyspnoea and neurocognitive disturbances. In addition, SARS-CoV-2 can affect the autonomic nervous system, contributing to symptoms resembling those of pheochromocytoma. The importance and need to discern between COVID-19-related symptoms and other conditions is emphasised, as the specificity of the clinical manifestations of post-COVID-19 syndrome is very low and can be confused with other vital pathologies. A case is presented in which a pheochromocytoma was mistaken for post-COVID-19 syndrome in a patient with no medical history.

Ectopic pheochromocytomas in the third trimester: A case report and literature review.

INTRODUCTION: To investigate the clinical features, pregnancy care, timing, and approaches of pregnancy termination as well as the perinatal management of pregnant women with ectopic pheochromocytomas (EPCC) (paragangliomas, PGL). METHODS: We report the diagnosis and treatment of a pregnant women with EPCC which was confirmed in the third trimester in our hospital. Literature in relation to EPCC during pregnancy both in and outside China was searched for data analysis such as maternal clinical features and maternal and fetal prognosis. RESULTS: A total of 20 papers including 21 cases (plus ours) were retrieved. The average age of pregnant patients was 28 years old (from 21 to 37). Two patients presented no hypertension. Nineteen had hypertension in various extent with the accompany of headache (11 cases, 57.9%), palpitations (8 cases, 42.1%), sweating (6 cases, 31.6%), nausea (6 cases), abdominal pain (2 cases), etc. The tumor was found in the chest in 3 patients, in the upper abdomen in 1 patient, in the middle abdomen in 10 patients, between the lower abdomen and pelvic cavity in 3 patients and in the pelvic cavity in 3 patients. Five patients had a surgical removal of the tumor before delivery, 3 during cesarean section and 10 after giving birth. CONCLUSION: EPCC (PGL) during pregnancy is a rare extra-adrenal tumor, whose manifestations are often confused with those of pregnancy-induced hypertension. It is extremely hard to diagnosis the disease before surgery. Patients still have an opportunity of undergoing spontaneous delivery if their tumors have been removed before labor. However, for patients whose pheochromocytomas is localized before labor, it is better to terminate their pregnancy via cesarean section in a proper time according to their obstetric conditions, while under the supervision of multidisciplinary specialists. The preparations of both α and ß adrenergic receptor blocker treatment that is normally carried out before PGL removal surgery are unnecessary to be overemphasized before the cesarean section.

Rare and aggressive metastatic pheochromocytoma recurrence in a patient with MEN 2A syndrome.

An adult male in his early 30s diagnosed with multiple endocrine neoplasia type 2A syndrome, confirmed through genetic testing, presented as bilateral pheochromocytoma in a metachronous fashion, primary hyperparathyroidism and medullary thyroid carcinoma. Left and right adrenalectomy was done 9 years and 3 years ago, respectively. He was also subjected to total thyroidectomy with neck dissection and left inferior parathyroidectomy. During surveillance monitoring, 24-hour total urine metanephrines were elevated 13.977 mg (Normal value 0-1 mg) 1 year after right adrenalectomy. Adrenal CT scan demonstrated a 2.1 cm ovoid focus in the right suprarenal region, and functional imaging (131I meta-iodobenzylguanidine (MIBG scan) showed an avid uptake on the right frontal bone. Excision of the right adrenal bed and the right frontal bone tumour was performed, and metastatic pheochromocytoma was confirmed histologically. The patient achieved clinical and biochemical remission postoperatively and is currently receiving steroid and thyroxine replacement.

Triad of cluster-like headaches, hypertension and hypercoagulability a pointer to pheochromocytoma.

We report the case of a middle-aged hypertensive woman presenting to the neurology department with short-lasting episodic headaches for 4 years. She was initially diagnosed and treated with cluster headaches for one year. Following this, she presented with right lower limb arterial claudication. Arterial Doppler of lower limbs showed thrombosis of the bilateral common femoral arteries. Further computed tomography (CT) angiogram of the lower limbs confirmed extensive arterial thrombosis in bilateral lower limbs. The CT angiogram incidentally detected a left adrenal lesion. She had elevated urinary vanillylmandelic Acid and 24-hour metanephrines suggesting the presence of a pheochromocytoma. She was initially medically managed and later underwent left open adrenalectomy. Histopathology examination of the sections proved pheochromocytoma. Postsurgery, the patient's symptoms improved remarkably. This case highlights the importance of diagnosing pheochromocytoma when you encounter a patient with refractory short-lasting headaches, hypertension and hypercoagulability.