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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 -
Cureus Apr 2024Pheochromocytomas (PCCs) and paragangliomas (PGLs) represent tumors arising from chromaffin cells of the adrenal medulla and extra-adrenal sympathetic paraganglia,...
Pheochromocytomas (PCCs) and paragangliomas (PGLs) represent tumors arising from chromaffin cells of the adrenal medulla and extra-adrenal sympathetic paraganglia, respectively. PCCs commonly produce one or more catecholamines (epinephrine, norepinephrine, and dopamine), but rarely are they biochemically silent. PGLs on the other hand, generally do not produce catecholamines. They have the highest heritability of all adrenal tumors and are known to be associated with genetic mutations. Patients with hereditary tumors typically present at a younger age and with multifocal disease when compared to sporadic disease. Specific genetic mutations have been well established with hereditary syndromes involving PCC/PGLs. Further research has aimed to identify other mutations and delineate specific phenotypes associated with these mutations. A 34-year-old woman presented for evaluation following a laparoscopic appendectomy that identified a 4-cm well-differentiated neuroendocrine tumor on final pathology. Further work-up included a repeat CT scan followed by a Dotatate PET CT scan which revealed a large (7.3 x 5.8 cm) periaortic mass related to the left adrenal gland. Functional adrenal work-up was negative and her Chromogranin A level was 679 ng/mL. She did report intermittent chest tightness and palpitations but was otherwise asymptomatic. The patient subsequently underwent an exploratory laparotomy with left adrenalectomy and adjacent tumor resection as well as completion of right hemicolectomy with ileocolonic anastomosis. Surgical pathology revealed two distinct masses consistent with multifocal PCC. No residual tumor was found in the colectomy specimen and 24 lymph nodes were negative. She had an uneventful recovery and genetic testing showed a variant of uncertain significance for the POLE and VHL genes. She has received genetic counseling and will be enrolled in an appropriate surveillance protocol.
PubMed: 38813302
DOI: 10.7759/cureus.59295 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal...
This study investigated the protective effect of ginsenoside Rg_1(GRg_1) on oxygen and glucose deprivation/reoxygenation(OGD/R)-injured rat adrenal pheochromocytoma(PC12) cells and whether the underlying mechanism was related to the regulation of inositol-requiring enzyme 1(IRE1)-c-Jun N-terminal kinase(JNK)-C/EBP homologous protein(CHOP) signaling pathway. An OGD/R model was established in PC12 cells, and PC12 cells were randomly classified into control, model, OGD/R+GRg_1(0.1, 1, 10 μmol·L~(-1)), OGD/R+GRg_1+rapamycin(autophagy agonist), OGD/R+GRg_1+3-methyladenine(3-MA,autophagy inhibitor), OGD/R+GRg_1+tunicamycin(endoplasmic reticulum stress agonist), OGD/R+GRg_1+4-phenylbutyric acid(4-PBA, endoplasmic reticulum stress inhibitor), and OGD/R+GRg_1+3,5-dibromosalicylaldehyde(DBSA, IRE1 inhibitor) groups. Except the control group, the other groups were subjected to OGD/R treatment, i.e., oxygen and glucose deprivation for 6 h followed by reoxygenation for 6 h. Cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide(MTT) assay. Apoptosis was detected by Hoechst 33342 staining, and the fluorescence intensity of autophagosomes by the monodansylcadaverine(MDC) assay. Western blot was employed to determine the expression of autophagy-related proteins(Beclin1, LC3-Ⅱ, and p62) and the pathway-related proteins [IRE1, p-IRE1, JNK, p-JNK, glucose-regulated protein 78(GRP78), and CHOP]. The results showed that GRg_1 dose-dependently increased the viability of PC12 cells and down-regulated the expression of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, compared with the model group. Furthermore, GRg_1 decreased the apoptosis rate and MDC fluorescence intensity and up-regulated the expression of p62 protein. Compared with the OGD/R+GRg_1(10 μmol·L~(-1)) group, OGD/R+GRg_1+rapamycin and OGD/R+GRg_1+tunicamycin groups showed increased apoptosis rate and MDC fluorescence intensity, up-regulated protein levels of Beclin1, LC3-Ⅱ, p-IRE1, p-JNK, GRP78, and CHOP, decreased relative cell survival rate, and down-regulated protein level of p62. The 3-MA, 4-PBA, and DBSA groups exerted the opposite effects. Taken together, GRg_1 may ameliorate OGD/R-induced PC12 cell injury by inhibiting autophagy via the IRE1-JNK-CHOP pathway.
Topics: Animals; Rats; PC12 Cells; Transcription Factor CHOP; Glucose; Ginsenosides; Protein Serine-Threonine Kinases; Apoptosis; Signal Transduction; Autophagy; Endoribonucleases; JNK Mitogen-Activated Protein Kinases; Oxygen; Endoplasmic Reticulum Stress; Multienzyme Complexes
PubMed: 38812175
DOI: 10.19540/j.cnki.cjcmm.20231128.405 -
Sisli Etfal Hastanesi Tip Bulteni 2024The purpose of our study was to investigate the role of different magnetic resonance imaging (MRI) parameters in the characterization of adrenal masses.
Comparative Analysis of FSE T2 Weighted, Chemical Shift and Dynamic Contrast-Enhanced MR Imaging in the Characterization of Adrenal Masses Based on Qualitative and Quantitative Parameters.
OBJECTIVES
The purpose of our study was to investigate the role of different magnetic resonance imaging (MRI) parameters in the characterization of adrenal masses.
METHODS
A total of 150 patients who presented with 186 adrenal tumors were retrospectively evaluated in this study. Final patient cohort consisted of 17 pheochromocytomas, 3 adrenocortical carcinomas, 24 metastases, 31 lipid-poor adenomas and 111 lipid-rich adenomas. We carried out a visual assessment on FSE (Fast spin echo)T2 weighted images and also calculated T2 signal intensity ratio of all adrenal masses and also performed a qualitative assessment on chemical shift imaging (CSI) together with quantitative calculation using Adrenal to spleen signal intensity (si) ratio and Adrenal si index formulas. On dynamic contrast-enhanced sequences, visual assessment based on enhancement patterns on late-arterial phase images was performed and also mean signal intensity measurements were carried out. All examinations were interpreted by two abdominal radiologists in consensus who were blinded to the clinical and pathological findings. Statistical analysis was performed.
RESULTS
On FSE T2 weighted imaging, isointense to liver and slightly hyperintense than liver was found higher in benign cases, however, in malignant cases moderately and strikingly hyperintense than liver was higher than in benign cases (p=0.001, p<0.01). There was a statistically significant difference between the T2 signal intensity ratio values of adrenal tumor groups (p=0.001, p<0.01). In lipid-rich and lipid-poor adenoma groups, T2 signal intensity ratio values was significantly lower than in pheochromocytoma and metastasis cases. In malignant group, T2 signal intensity ratio values were found statistically significantly higher than in the benign group (p=0.001, p<0.01). There was a statistically significant difference between CSI visual assessment of adrenal tumor groups (p=0.001, p<0.01). Although moderate and significant signal intensity loss was usually detected in lipid-rich adenoma group, never detected in other tumor groups. There was also a statistically significant difference between benign and malignant adrenal tumor groups (p=0.001, p<0.01). In the malignant group, Adrenal to spleen si ratio values were found significantly higher whereas, Adrenal si index values were significantly lower compared to benign tumors (p=0.001, p<0.01). Based on malignancy, there was a statistically significant difference between adrenal tumor groups (p=0.001, p<0.01). Although capillary blush and homogenous type enhancement were more common in benign cases than in malignant ones, peripheral-patchy and strikingly capillary blush type enhancement was more frequent in malignant tumors. Based on malignancy, mean arterial signal intensity values of malignant tumors were statistically higher than benign tumors (p=0.001; p<0.01).
CONCLUSION
Dynamic contrast-enhanced MRI protocol including CSI aids in the characterization of indeterminate adrenal masses. Herein, the combined use of qualitative and quantitative parameters enables more tumors to be recognized that otherwise would be indeterminate.
PubMed: 38808044
DOI: 10.14744/SEMB.2023.02328 -
Oncology Letters Jul 2024Pheochromocytoma is a tumor of the sympathetic nervous system, characterized by atypical symptoms and signs. Pheochromocytoma metastases can be found in various tissues...
Pheochromocytoma is a tumor of the sympathetic nervous system, characterized by atypical symptoms and signs. Pheochromocytoma metastases can be found in various tissues and organs. However, synchronous metastasis at the initial diagnosis of pheochromocytoma is rare. The present study described a case with synchronous liver metastasis at the initial diagnosis of adrenal pheochromocytoma based on imaging findings. A 41-year-old woman presented with liver pain and fatigue for 1 month. Physical examination showed increased blood pressure and heart rate with sinus tachycardia. Laboratory examination revealed normal levels of liver tumor markers and increased levels of serum or urine epinephrine and norepinephrine. CT examination revealed a large cystic solid mass in the right lobe of the liver and right adrenal gland, and the solid part of the mass was enhanced after enhancement. The pathological diagnosis was pheochromocytoma of the right adrenal gland with liver metastasis. The patient underwent right hepatectomy and right adrenal tumor resection. During the postoperative follow-up, the patient's blood pressure and catecholamine levels were within the normal range. Three years after surgery, the CT examination revealed multiple liver metastases. Chemotherapy was administered to the patient. A year later, re-examination revealed an increase and enlargement of the metastases, and the mass of the right adrenal gland remained similar to the previous one. After 6 months of follow-up, the patient succumbed to recurrence and metastasis. Preoperative diagnosis of metastatic pheochromocytoma is challenging. This case mainly emphasizes that imaging findings can help the clinical diagnosis of metastatic pheochromocytoma.
PubMed: 38807675
DOI: 10.3892/ol.2024.14462