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The Surgical Clinics of North America Aug 2024Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors.... (Review)
Review
Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors. Traditionally, there are 2 types of MEN that have unique clinical associations: MEN 1 (parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary tumors) and MEN 2 (medullary thyroid carcinoma and pheochromocytoma), which is further classified into MEN 2A (adds parathyroid adenomas) and 2B (adds ganglioneuromas and marfanoid habitus). Many of the endocrine tumors are resected surgically, and the pre, intra, and postoperative management strategies used must take into account the high recurrence rates asscioated with MEN tumors.
Topics: Humans; Multiple Endocrine Neoplasia
PubMed: 38944508
DOI: 10.1016/j.suc.2024.02.016 -
The Surgical Clinics of North America Aug 2024Pheochromocytomas and paragangliomas are distinctive neuroendocrine tumors which frequently produce excess catecholamines with resultant cardiovascular morbidity. These... (Review)
Review
Pheochromocytomas and paragangliomas are distinctive neuroendocrine tumors which frequently produce excess catecholamines with resultant cardiovascular morbidity. These tumors have a strong genetic component, with up to 40% linked to hereditary pathogenic variants; therefore, germline genetic testing is recommended for all patients. Surgical resection offers the only potential cure in the case of localized disease. Given the potential for catecholaminergic crises, appropriate perioperative management is crucial, and all patients should undergo alpha-adrenergic blockade before resection. Therapeutic options for metastatic disease are limited and include surgical debulking, radiopharmaceutical therapies, and conventional chemotherapy.
Topics: Humans; Pheochromocytoma; Adrenal Gland Neoplasms; Paraganglioma; Adrenalectomy
PubMed: 38944505
DOI: 10.1016/j.suc.2024.02.014 -
The Surgical Clinics of North America Aug 2024Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal... (Review)
Review
Adrenal incidentalomas have increased due to advanced and more sensitive imaging modalities, their increased utilization, and the aging population. Most adrenal incidentalomas are nonfunctional and benign, but a subset of patients has functional and/or malignant tumors. The evaluation of patients with an adrenal incidentaloma involves addressing 2 clinical questions: (1) Is the tumor functional? (2) Is the tumor malignant? A careful history and physical examination focused on signs and symptoms of adrenal functional tumors, biochemical testing, and imaging features are the cornerstone in the evaluation of patients with an adrenal incidentaloma.
Topics: Humans; Adrenal Gland Neoplasms; Incidental Findings; Diagnosis, Differential; Tomography, X-Ray Computed
PubMed: 38944503
DOI: 10.1016/j.suc.2024.02.012 -
Journal of Forensic and Legal Medicine Jun 2024Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and...
Pheochromocytoma is a neuroendocrine tumor that secretes catecholamines; excessive catecholamine secretion can lead to pheochromocytoma crisis (PCC), a rare and life-threatening condition. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, was previously used for obesity treatment but is now banned due to its cardiovascular side effects. Although fatalities related to PCC and adverse events associated with sibutramine have been frequently reported individually, there is no documented literature addressing PCC-induced by sibutramine. Here we report a rare case of fatal sibutramine-induced PCC in a previously asymptomatic young female with undiagnosed pheochromocytoma. The 25-year-old patient took a weight-loss pill containing sibutramine for the first time and subsequently experienced nausea, vomiting, chest tightness, and other symptoms. She went to hospital about 6 hours after taking the pill but died approximately 4 hours later despite the resuscitation efforts. An autopsy revealed a pheochromocytoma in the right adrenal gland. The cause of death was attributed to sibutramine-induced PCC. To our knowledge, this is the first report to document the occurrence of sibutramine-induced PCC.
PubMed: 38941912
DOI: 10.1016/j.jflm.2024.102711 -
The Journal of Clinical Endocrinology... Jun 2024Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive,...
Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis. Consequent "primary stress system disorders" were popularly accepted, with phenotypes based on conditions such as Cushing syndrome, pheochromocytoma, and adrenal insufficiency. Cardiometabolic and major depressive disorders are candidates for hypercortisolemic etiology, contrasting the "hypocortisolemic symptom triad" of stress sensitivity, chronic fatigue, and pain. However, acceptance of chronic stress etiology requires cause-and-effect associations, and practical utility such as therapeutics altering stress system function. Inherent predispositions to stress system perturbations may be relevant. Glucocorticoid receptor (GR) variants have been associated with metabolic/neuropsychological states. The SERPINA6 gene encoding corticosteroid-binding globulin (CBG), was the sole genetic factor in a single-nucleotide variation-genome-wide association study linkage study of morning plasma cortisol, a risk factor for cardiovascular disease, with alterations in tissue-specific GR-related gene expression. Studies showed genetically predicted high cortisol concentrations are associated with hypertension and anxiety, and low CBG concentrations/binding affinity, with the hypocortisolemic triad. Acquired CBG deficiency in septic shock results in 3-fold higher mortality when hydrocortisone administration produces equivocal results, consistent with CBG's role in spatiotemporal cortisol delivery. We propose some stress system disorders result from constitutional stress system variants rather than stressors themselves. Altered CBG:cortisol buffering may influence interstitial cortisol ultradian surges leading to pathological tissue effects, an example of stress system variants contributing to stress-related disorders.
PubMed: 38941154
DOI: 10.1210/clinem/dgae412 -
Annals of Agricultural and... Jun 2024Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid...
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare autosomal dominant hereditary cancer syndrome which is characterized by the appearance of medullary thyroid carcinoma (MTC), pheochromocytoma, parathyroid adenomas, ganglioneuromas of the digestive tract, and musculoskeletal abnormalities. The case is presented of a 31-year-old male patient with numerous polyps in the colon described as ganglioneuromas which are ectodermal neoplasms emerging from a proliferation of ganglionic cells of the sympathetic nervous system. The results show elevated levels of normetanephrine, which is an endogenous catecholamine metabolite, and has high diagnostic sensitivity as well as specificity in pheochromocytoma detection. The patient underwent partial thyreoidectomy due to a nodular goiter. He was admitted to the Department of Gastroenterology to lead a diagnostic pathway towards MEN 2B.
Topics: Humans; Male; Adult; Multiple Endocrine Neoplasia Type 2b; Ganglioneuroma
PubMed: 38940117
DOI: 10.26444/aaem/171736 -
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