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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 -
Journal of Pediatric Endocrinology &... May 2024Pheochromocytomas (PHEO) are neuroendocrine tumors rarely diagnosed in children. We are reporting on the management challenges of three adolescent patients who present...
OBJECTIVES
Pheochromocytomas (PHEO) are neuroendocrine tumors rarely diagnosed in children. We are reporting on the management challenges of three adolescent patients who present with hereditary PHEO.
CASE PRESENTATION
The index patient and his male sibling presented with bilateral PHEO, while a third patient presented with a unilateral PHEO, all associated with von Hippel-Lindau (VHL) syndrome. The patients were treated with computed tomography (CT)-guided percutaneous cryoablation (CRA) of the adrenal lesions, with varying degrees of success.
CONCLUSIONS
CT-guided percutaneous CRA of hereditary PHEO has not been reported in the pediatric population and may represent a novel treatment strategy that reduces the risk of intraprocedural complications and adrenal insufficiency (AI).
PubMed: 38807486
DOI: 10.1515/jpem-2024-0033 -
Chirurgie (Heidelberg, Germany) May 2024Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline... (Review)
Review
Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, a tumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on a positive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to a lesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30 years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: a shining example for the success of translational transnational medical research for the benefit of patients.
PubMed: 38806713
DOI: 10.1007/s00104-024-02105-x -
Scientific Reports May 2024Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and...
Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and evaluate the safety and surgical outcomes of RA. The data of 122 consecutive patients who underwent RA from October 2009 to December 2022 at Korea University Anam Hospital (Seoul, Korea) were reviewed. There were no perioperative complications. Clinicopathological features and surgical outcomes were retrospectively analyzed through complete chart reviews. Noteworthy findings include the influence of sex, tumor size, and body mass index on operation time, with the female and small tumor groups exhibiting shorter operation times (P = 0.018 and P = 0.009, respectively). Pheochromocytoma was identified as a significant independent risk factor for a longer operation time in the multivariate analysis [odds ratio (OR), 3.709; 95% confidence interval (CI), 1.127-12.205; P = 0.031]. A temporal analysis revealed a decreasing trend in mean operation times across consecutive groups, reflecting a learning curve associated with RA adoption. RA is a safe and effective operative technique alternative to laparoscopic adrenalectomy that has favorable surgical outcomes and enhances the convenience of the operation.
Topics: Humans; Female; Adrenalectomy; Male; Robotic Surgical Procedures; Middle Aged; Retrospective Studies; Treatment Outcome; Adult; Adrenal Gland Neoplasms; Operative Time; Aged; Pheochromocytoma; Risk Factors; Postoperative Complications; Laparoscopy
PubMed: 38806567
DOI: 10.1038/s41598-024-63105-9 -
PloS One 2024Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy,...
Evaluation of pharmacokinetics, safety, and efficacy of [211At] meta-astatobenzylguanidine ([211At] MABG) in patients with pheochromocytoma or paraganglioma (PPGL): A study protocol.
BACKGROUND
Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells.
METHODS
We are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life.
TRIALS REGISTRATION
jRCT2021220012 registered on 17 June 2022.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Adrenal Gland Neoplasms; Guanidines; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Treatment Outcome; Clinical Trials, Phase I as Topic
PubMed: 38805424
DOI: 10.1371/journal.pone.0303623 -
Annals of Surgical Oncology May 2024Many adrenal tumors are deemed radiologically indeterminate and surgically removed. Adrenal tissue, like parathyroid glands, exhibits near-infrared autofluorescence...
BACKGROUND
Many adrenal tumors are deemed radiologically indeterminate and surgically removed. Adrenal tissue, like parathyroid glands, exhibits near-infrared autofluorescence (NIRAF) properties. This study was designed to investigate the potential of NIRAF to differentiate benign versus malignant adrenal tumors.
METHODS
Patients undergoing adrenalectomy between October 2021 and May 2023 were prospectively studied. Adrenalectomy specimens were inspected with NIRAF imaging. Specimen autofluorescence (AF) characteristics were recorded. Comparisons were made between different tumor types and a logistic regression model was constructed to differentiate benign versus malignant tumors. A receiver operating characteristic curve was used to identify an optimal AF threshold differentiating benign versus malignant tumors.
RESULTS
A total of 108 adrenal specimens were examined: adrenocortical adenomas/other benign lesions (n = 72), pheochromocytomas (n = 18), adrenocortical neoplasms of uncertain behavior (n = 4), and malignant tumors (n = 14). A significant difference in normalized AF intensity was identified when comparing adrenocortical adenomas (3.08 times background) with pheochromocytomas (1.95, p = 0.001) and malignant tumors (1.11, p < 0.0001). The Area Under the Curve differentiating benign vs malignant tumors was 0.87, with an optimal normalized AF threshold at 1.93.
CONCLUSIONS
Different adrenal pathologies exhibit diverse AF properties. These findings suggest a potential intraoperative utility of NIRAF in predicting benign versus malignant nature for radiologically indeterminate adrenal tumors.
PubMed: 38802716
DOI: 10.1245/s10434-024-15430-6 -
Journal of the Endocrine Society May 2024
PubMed: 38799768
DOI: 10.1210/jendso/bvae092