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Medicina Clinica Jun 2024Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or... (Review)
Review
Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or fractionated urine metanephrines is the hormonal determination of choice for the biochemical diagnosis. Once the biochemical diagnosis is confirmed, the next step is the localization study. It is recommended to request a genetic study in all patients with pheochromocytomas since 40% of cases are hereditary. Once the diagnostic study is completed, preoperative treatment with alpha blockers should be instituted at least 7-14 days before adrenalectomy. However, in low-risk patients, the omission of presurgical treatment could be considered if the surgery is performed in centers with experience and a strict monitoring of the patient is carried out during the perioperative period. This document offers a practical guide on the diagnosis and perioperative approach in patients with pheochromocytomas.
PubMed: 38849272
DOI: 10.1016/j.medcli.2024.03.025 -
Indian Journal of Pathology &... Jun 2024The presence of distant metastasis is known to drastically reduce survival of adrenal pheochromocytoma (PH) and extra-adrenal paraganglioma (PGL). Therefore, predicting...
BACKGROUND
The presence of distant metastasis is known to drastically reduce survival of adrenal pheochromocytoma (PH) and extra-adrenal paraganglioma (PGL). Therefore, predicting malignant potential has an immense impact on prognosis. Pheochtomocytoma of adrenal gland scaled score (PASS) and the grading of adrenal pheochromocytoma and paraganglioma (GAPP) score are two histological algorithms used to predict metastatic potential, but neither has been regarded as 'gold-standard'. Both these scoring systems are yet to be validated. Here, we tried to validate the association of GAPP/PASS scores with disease outcome and strength of association between individual GAPP/PASS parameters with prognosis.
MATERIALS AND METHODS
This was a prospective study comprising 22 pheochromocytomas and eight paragangliomas. GAPP score was calculated in paraganglioma cases, and both GAPP/PASS scores were calculated for pheochromocytomas. Disease outcome was then tallied with risk stratification of the GAPP/PASS scoring system. Succinate dehydrogenase B (SDHB) immunohistochemistry was done in 15 cases to see its impact on prognosis.
RESULTS
The common PASS parameters associated with malignancy were 'high cellularity', 'tumor cell spindling' and 'extension into adipose tissue'. PASS score showed high sensitivity and negative predictive value but low specificity and positive predictive value. Similarly, GAPP score also showed high sensitivity and negative predictive value but low specificity and positive predictive value.
CONCLUSION
In our study, GAPP/PASS scores successfully segregated tumor with low malignant potential from tumor with higher risk of metastasis, although specificity of GAPP was more than PASS. We also found that addition of objective parameters like SDHB immunohistochemistry may further increase the specificity of the existing scoring system.
PubMed: 38847206
DOI: 10.4103/ijpm.ijpm_859_23 -
Handbook of Experimental Pharmacology Jun 2024β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β-AR, β-AR, β-AR are localized to the...
β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β-AR, β-AR, β-AR are localized to the human heart. Activation of β-AR and β-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of β-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of β-AR is critical in the pathogenesis of cardiac arrhythmias while activation of β-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of β-AR in cardiovascular disease, particularly arrhythmia generation. All β-blockers used therapeutically to treat cardiovascular disease block β-AR with variable blockade of β-AR depending on relative affinity for β-AR vs β-AR. Since the introduction of β-blockers into clinical practice in 1965, β-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. β-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. β-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The β-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other β-blockers and is used successfully in the treatment of heart failure. The discovery of β-AR in human heart created interest in the role of β-AR in heart failure but has not resulted in therapeutics at this stage.
PubMed: 38844580
DOI: 10.1007/164_2024_720 -
Cureus May 2024Pheochromocytomas are rare tumors that present a challenge for surgical and anesthetic management due to their ability to produce significant amounts of catecholamines....
Pheochromocytomas are rare tumors that present a challenge for surgical and anesthetic management due to their ability to produce significant amounts of catecholamines. This case report highlights the successful management of a 49-year-old woman simultaneously diagnosed with neurofibromatosis type 1, pheochromocytoma, and breast cancer. A key decision by the multidisciplinary team involving endocrinology, general surgery, senology, intensive care, and anesthesiology was to prioritize breast cancer surgery over pheochromocytoma resection. This decision considered the potential for improved prognosis and the need to minimize chemotherapy dosage. The case emphasizes the importance of thorough perioperative preparation, including assessing end-organ damage and optimizing medical therapy. Intraoperative management effectively navigated periods prone to catecholamine release, and postoperative care was closely monitored. This case demonstrates that with meticulous planning, a multidisciplinary approach, and a precise anesthetic strategy, safe anesthesia is achievable for patients with pheochromocytoma undergoing major elective surgeries other than pheochromocytoma resection, adding valuable knowledge to a scarcely documented clinical area.
PubMed: 38841026
DOI: 10.7759/cureus.59751 -
Journal of Endocrinological... Jun 2024There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which...
BACKGROUND
There are few studies on the efficacy of temozolomide (TMZ) in the treatment of Metastatic pheochromocytoma / paraganglioma (MPP) patients. And it remains unclear which MPP patients may benefit from TMZ treatment.
METHODS
This was a prospective study. MPP patients were enrolled. Patients were treated with TMZ until disease progression or intolerable toxicities. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). Secondary endpoints included biochemical response rate progression-free survival (PFS) and safety. We compared the difference between effective and ineffective groups, to explore which patients are more suitable for TMZ treatment.
RESULTS
62 patients with MPP were enrolled and tumor response were evaluated in 54 patients. The DCR was 83% (35/42), and the ORR was 24% (10/41) among the progressive patients. PFS was 25.2 ± 3.1 months. The most common adverse event was nausea (41/55). We found that 92.9% (13/14) of patients with MGMT methylation greater than 7% respond to treatment. For the patients with MGMT methylation less than 7%, Ki-67 index could be used to guide the use of TMZ in these patients. Among the patients with Ki-67 index less than 5%, 66% (8/12) patients showed respond to treatment, and only 33% (4/12) patients with Ki-67 index more than 5% showed respond to TMZ.
CONCLUSIONS
This study indicated that TMZ is a potential choice for the treatment of MPP with the high ability on disease control and well tolerability. We recommended to MGMT methylation analysis test and Ki-67 index to guide TMZ application.
PubMed: 38837102
DOI: 10.1007/s40618-024-02398-z -
Frontiers in Oncology 2024Pheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than...
BACKGROUND
Pheochromocytoma is one of the most hereditary human tumors with at least 20 susceptible genes undergoing germline and somatic mutations, and other mutations less than 1% -2%. In recent years, other rare mutations have gradually been discovered to be possibly related to the pathogenesis and metastasis of pheochromocytoma. Most patients with pheochromocytoma experience common symptoms like headaches, palpitations, and sweating, while some may have less common symptoms. The diversity of symptoms, genetic mutations, and limited treatment options make management challenging.
CASE PRESENTATION
A 53-year-old woman was hospitalized after experiencing episodic epigastric pain for one month. A mass was found in her right adrenal gland and she underwent robot-assisted laparoscopic surgery, revealing a pheochromocytoma. At the 16-month follow-up, multiple metastatic lesions consistent with metastatic pheochromocytoma were found. A germline mutation in the dihydrolipoamide succinyltransferase (DLST) gene (c.330 + 14A>G) was detected, and despite trying chemotherapy and adjuvant therapy, the patient had a limited response with an overall survival of 27 months.
CONCLUSIONS
DLST mutation is one of the rare pheochromocytoma-related mutated genes, and genetic sequencing is crucial for effective clinical management.
PubMed: 38835385
DOI: 10.3389/fonc.2024.1394552 -
Blood Pressure Dec 2024Von Hippel-Lindau disease (e.g. VHL) is an autosomal dominant multi-organ cancer syndrome caused by a mutation in the tumour suppressor gene. In this study, we...
Discovering a novel genetic variant in 11 family members who had isolated pheochromocytoma linked to von Hippel-Lindau (VHL) syndrome, aligning with the type 2c phenotype.
INTRODUCTION
Von Hippel-Lindau disease (e.g. VHL) is an autosomal dominant multi-organ cancer syndrome caused by a mutation in the tumour suppressor gene. In this study, we introduce a novel genetic variant found in 11 family members diagnosed initially with isolated Pheochromocytoma. Subsequent findings revealed its association with VHL syndrome and corresponds to the Type 2 C phenotype.
METHODS
The gene was amplified through the utilisation of the polymerase chain reaction (PCR). PCR fragments were sequenced using bidirectional Sanger sequencing, using BigDye™ Terminator v3.1 Cycle Sequencing Kit, running on the 3500 genetic analyser. Results were assembled and analysed Using Software SeqA and chromas pro.
RESULTS
A heterozygous in-frame duplication of three nucleotides, specifically ATG, c.377_379dup; p.Asp126dup in exon 2, was identified in all the patients tested within the pedigree.
CONCLUSION
In this study, we disclose the identification of a novel genetic variant in a Jordanian family, affecting eleven family members with pheochromocytoma associated with VHL disease. This finding underscores the importance of screening family members and contemplating genetic testing for individuals newly diagnosed with pheochromocytoma and could enhance our comprehension of the potential adverse consequences associated with VHL germline mutations.
Topics: Humans; Pheochromocytoma; von Hippel-Lindau Disease; Female; Male; Pedigree; Von Hippel-Lindau Tumor Suppressor Protein; Adult; Phenotype; Adrenal Gland Neoplasms; Middle Aged; Genetic Variation
PubMed: 38824681
DOI: 10.1080/08037051.2024.2355268 -
World Journal of Clinical Cases May 2024Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the proto-oncogene is the only gene implicated in MEN2A...
BACKGROUND
Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.
CASE SUMMARY
Herein, we present proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the proto-oncogene was conducted. The mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the mutation, and the corresponding treatments administered based on test results and associated clinical guidelines.
CONCLUSION
Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.
PubMed: 38817239
DOI: 10.12998/wjcc.v12.i15.2627 -
World Journal of Clinical Cases May 2024Paraganglioma (PGL) located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location, lack of specific symptoms in the early...
BACKGROUND
Paraganglioma (PGL) located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location, lack of specific symptoms in the early stages, and absence of distinctive manifestations on imaging.
CASE SUMMARY
A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination. She did not have a history of smoking, alcohol consumption, or other harmful habits, no surgical procedures or infectious diseases, and had a 4-year history of hypertension. Upon admission, she did not exhibit fever, vomiting, or abdominal distension. Physical examination indicated mild percussion pain in the left upper abdomen, with no palpable enlargement of the liver or spleen. Laboratory tests and tumor markers showed no significant abnormalities. Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm × 4.5 cm, with inhomogeneous enhancement in the arterial phase, closely associated with the lesser curvature of the stomach and the pancreas. The patient underwent laparoscopic resection of the retroperitoneal mass, which was successfully removed without tumor rupture. A 12-month postoperative follow-up period showed good recovery.
CONCLUSION
This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL, resulting in a good recovery observed at the 12-month follow-up. Interestingly, the patient also experienced unexpected cure of hypertensive disease.
PubMed: 38817224
DOI: 10.12998/wjcc.v12.i15.2672 -
Annales D'endocrinologie May 2024Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of...
CONTEXT
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date.
PURPOSE
To describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001-2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS).
METHOD
The activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared.
RESULTS
In total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX.
CONCLUSION
Our experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.
PubMed: 38815921
DOI: 10.1016/j.ando.2024.05.024