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Zhonghua Wai Ke Za Zhi [Chinese Journal... Jun 2024The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular...
The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the gene.
PubMed: 38937132
DOI: 10.3760/cma.j.cn112139-20240102-00002 -
Cancers Jun 2024Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor...
Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.
PubMed: 38927897
DOI: 10.3390/cancers16122191 -
Biomedicines Jun 2024Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study...
BACKGROUND
Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases.
METHODS
A retrospective analysis of 136 patients in a tertiary hospital (1984-2021). Epidemiological, clinical, and histological variables were analysed.
STATISTICS
SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. < 0.05 was considered statistically significant.
RESULTS
64.71% of the cases ( = 88) presented a genetic mutation (familial cases). Additionally, 32.39% ( = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89-0.97)), blood pressure-related symptoms (OR = 0.22 (0.06-0.89)), bilaterality (OR = 15.49 (3.76-63.84)), and size (OR = 0.70 (0.54-0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24-144.34)).
CONCLUSIONS
Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.
PubMed: 38927559
DOI: 10.3390/biomedicines12061352 -
BMC Cardiovascular Disorders Jun 2024Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of...
BACKGROUND
Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL).
MATERIALS AND METHODS
In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT.
RESULTS
The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P < 0.001). Among 365 patients with complete echocardiography data, left ventricular mass index (86.58 ± 26.70 vs. 75.80 ± 17.26, P < 0.001) and relative wall thickness (0.43 ± 0. 08 vs. 0.41 ± 0.06, P = 0.012) were significantly higher in patients with PPGL and a history of HT. The proportions with left ventricular hypertrophy (LVH) (19.40% vs. 8.25%, P = 0.011) and LVR (53.73% vs. 39.18%, P = 0.014) were also higher when there was a history of HT. After adjusting for age, gender, body mass index, alcohol consumption, smoking status, diabetes, stroke, creatinine level, tumor location, and tumor size, a history of HT was significantly correlated with LVH (odds ratio 2.71, 95% confidence interval 1.18-6.19; P = 0.018) and LVR (odds ratio 1.83, 95% confidence interval 1.11-3.03; P = 0.018).
CONCLUSION
HT is common in patients with PPGL (70.74% in this cohort). PPGL without a history of HT is more likely to be found incidentally (59.43% in our cohort). HT is associated with LVR in PPGL patients with complete echocardiography data. These patients should be observed carefully for cardiac damage, especially those with a history of HT.
Topics: Humans; Pheochromocytoma; Male; Female; Middle Aged; Adrenal Gland Neoplasms; Adult; Ventricular Remodeling; Paraganglioma; Hypertension; Prevalence; Retrospective Studies; Ventricular Function, Left; Risk Factors; Risk Assessment; Aged; Blood Pressure
PubMed: 38926862
DOI: 10.1186/s12872-024-03936-6 -
JCEM Case Reports Jun 2024Pheochromocytomas predominantly produce catecholamines, and rarely also produce ACTH, causing Cushing syndrome (CS). Cyclic CS, an uncommon presentation of...
Pheochromocytomas predominantly produce catecholamines, and rarely also produce ACTH, causing Cushing syndrome (CS). Cyclic CS, an uncommon presentation of hypercortisolism, poses a diagnostic challenge. We report a 71-year-old woman who developed cyclic ectopic ACTH secretion from a pheochromocytoma. Previous evaluations showed intermittent elevations in cortisol and ACTH levels, normal pituitary magnetic resonance imaging, and an adrenal nodule. On admission, she was hypertensive and had cushingoid features. Bilateral inferior petrosal sinus sampling with desmopressin stimulation and an 8-mg dexamethasone suppression test suggested ectopic ACTH secretion, but ACTH increased during the peripheral desmopressin stimulation test. Plasma normetanephrines were about 2-fold above the upper reference limit. F-fluoro-dopa and Gallium-DOTATATE positron emission tomography/computed tomography scans, computed tomography, and magnetic resonance imaging identified an adrenal mass. After doxazosin adrenoceptor blockade, she underwent right adrenalectomy; histopathology and immunohistochemistry confirmed an ACTH-secreting pheochromocytoma. Postoperative blood pressure normalized and serum cortisol and plasma ACTH levels were suppressed, requiring physiologic hydrocortisone replacement. This case underscores the importance of considering pheochromocytoma in ACTH-dependent hypercortisolism with elevated metanephrines and an adrenal mass. Timely diagnosis and treatment can reduce morbidity and improve quality of life.
PubMed: 38915761
DOI: 10.1210/jcemcr/luae094 -
JCEM Case Reports Jun 2024Pheochromocytomas (PCCs) and/or paragangliomas (PGLs) are a challenge to diagnose during pregnancy because of elusive signs and testing difficulties. We report a...
Pheochromocytomas (PCCs) and/or paragangliomas (PGLs) are a challenge to diagnose during pregnancy because of elusive signs and testing difficulties. We report a 25-year-old woman with no pertinent medical history who presented to the hospital with hypertension, vision loss, and weakness and was initially diagnosed with preeclampsia. Imaging showed hemangioblastomas in the medulla and thoracic spine, pancreatic cysts, and a renal cyst. The endocrinology service was consulted for possible PCCs associated with von Hippel-Lindau disease (VHL). Serum and urine normetanephrine levels were elevated despite the lack of overt PCCs/PGLs seen on magnetic resonance imaging and magnetic resonance angiography. The patient was medically managed with doxazosin and then labetalol. Despite successful resection of the hemangioblastoma in the medulla, the patient suffered respiratory distress requiring tracheostomy and venous-venous extracorporeal membrane oxygenation (V-V ECMO) and fetal demise. After 3 months, the patient was discharged to rehabilitation. Follow-up genetics were heterozygous for VHL and Lynch syndrome. DOTATATE positron emission tomography/computed tomography scan showed a small hepatic focus of a maximum standard uptake value of 12.1. Altogether, this case illustrates the importance of prompt diagnosis and proper management of PCCs/PGLs during pregnancy and incorporating genetic information during surveillance to lower morbidity and mortality.
PubMed: 38911362
DOI: 10.1210/jcemcr/luae097 -
Biochimica Et Biophysica Acta. Reviews... Jun 2024Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable... (Review)
Review
Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable tumors. Massive sequencing combined with careful patient selection has so far identified more than twenty susceptibility genes, leading to an over-detection of variants of unknown significance (VUS) that require precise molecular markers to determine their pathogenic role. Moreover, some PPGL patients remain undiagnosed, possibly due to mutations in regulatory regions of already known genes or mutations in undiscovered genes. Accurate classification of VUS and identification of new genes require well-defined clinical and molecular markers that allow effective genetic diagnosis of most PPGLs.
PubMed: 38908536
DOI: 10.1016/j.bbcan.2024.189141 -
Talanta Jun 2024Abnormal amount of dopamine (DA) in human body is closely relate to various diseases, such as Parkinson's disease, pheochromocytoma. Real-time monitoring DA is crucial...
Abnormal amount of dopamine (DA) in human body is closely relate to various diseases, such as Parkinson's disease, pheochromocytoma. Real-time monitoring DA is crucial for disease warning, diagnosis and treatment. Currently, most methods rely on invasive blood testing for detecting DA, which is only completed with the aid of the medical staffs in hospitals. Herein, a non-invasive fluorescence visual strategy is developed for the real-time monitoring DA, based on luminescent nanoparticles and modified mesoporous zeolite imidazole framework (ZIF-8-NH) dodecahedrons. During the reaction process, DA is enriched through the spatial configuration of ZIF-8-NH and hydrogen bonding effect. The luminescence of Cr-doped zinc gallate (ZnGaO:Cr, ZGC) is inhibited by the photo-induced electron transfer (PET) mechanism to realize sensitively detecting DA. The intelligent sensing platform based on the designed fluorescence probe and color recognition system is structured for real-time detection of DA in urine. Furthermore, a skin-fitting hydrogel patch is prepared by combining a fluorescent probe with chitosan, which enables sensitive and accurate detection of DA in sweat without the complex sample pretreatment. The non-invasive fluorescence detection method provides an effective strategy for quantitatively monitoring DA in human fluids.
PubMed: 38905963
DOI: 10.1016/j.talanta.2024.126356 -
Surgical Case Reports Jun 2024Tumors arising from catecholamine-producing chromophil cells in paraganglia are termed paragangliomas (PGLs), which biologically resemble pheochromocytomas (PCCs) that...
BACKGROUND
Tumors arising from catecholamine-producing chromophil cells in paraganglia are termed paragangliomas (PGLs), which biologically resemble pheochromocytomas (PCCs) that arise from the adrenal glands. Spontaneous rupture of a PGL is rare and can be fatal. Although elective surgery for ruptured PCCs after transcatheter arterial embolization (TAE) has been shown to provide good outcomes, the efficacy of TAE pretreatment for ruptured PGL remains unknown.
CASE PRESENTATION
A 65-year-old female with hypertension and tachycardia was diagnosed with a 3-cm PGL located behind the inferior vena cava. The patient was scheduled to undergo an elective surgery with antihypertensive therapy. However, she presented with a chief complaint of abdominal pain and was diagnosed with intratumoral hemorrhage. Urgent TAE was performed that successfully achieved hemorrhage control. After TAE, serum levels of both epinephrine and norepinephrine were within the normal range. Abdominal computed tomography revealed resolving retroperitoneal hematoma. Elective open surgery was performed without significant intraoperative bleeding or fluctuations in blood pressure.
CONCLUSION
We report a case of successful preoperative TAE for functional PGL to control intraoperative blood pressure fluctuations and bleeding. Preoperative TAE could be a useful procedure for the surgical preparation of functional PGL, including unruptured cases.
PubMed: 38904868
DOI: 10.1186/s40792-024-01907-9 -
Frontiers in Surgery 2024Solitary fibrous tumor (SFT) is a rare mesenchymal tumor, probably of fibroblastic origin, mainly in the extremities and pleura. Primary SFT of the adrenal gland is...
Solitary fibrous tumor (SFT) is a rare mesenchymal tumor, probably of fibroblastic origin, mainly in the extremities and pleura. Primary SFT of the adrenal gland is clinically more rare. Here, we report the case of a 47-year-old woman who detected a left adrenal mass on physical examination, without any symptoms, and no laboratory abnormalities. A computed tomography (CT) examination of the adrenal gland suggested a round-like soft tissue density shadow in the left adrenal area. An unenhanced scan showed uneven density of the mass, with a scattered circular-like cystic low-density shadow inside, and an enhanced scan showed obvious uneven enhancement. We considered it to be adrenal pheochromocytoma. Ultimately, the patient was treated with laparoscopic left adrenalectomy. A pathological examination suggested an adrenal SFT. We reviewed previous case reports of adrenal SFTs and summarized the clinical characteristics of adrenal SFT combined with the relevant literature. For adrenal tumors with uneven low-density shadow and uneven CT enhancement features, we should consider the differential diagnosis of adrenal SFT.
PubMed: 38903862
DOI: 10.3389/fsurg.2024.1363807