BACKGROUND: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap.
METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP).
RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery.
CONCLUSIONS: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

We presented the clinical case of neurofibromatosis type 1 (NF-1) associated with pheochromocytoma (PHEO) in a man under 40 years old without family history. The diagnosis of NF-1 was established based on 4 signs of the disease (multiple café au lait macules, scoliotic changes in posture, the presence of multiple neurofibromas, Lisch nodules). The diagnosis of PHEO was determined by a significant increase of free metanephrin/normethanephrin levels in daily urine, a malignant CT phenotype of the right adrenal tumor, and confirmed by pathomorphological study. Genetic tests revealed a new mutation in one of the alleles of NF1 gene, a deletion of a 566 bp gene fragment, including exon 19 with a size of 73 bp. This mutation leads to splicing of exons 18 and 20, frameshift, and termination of protein synthesis. A study of the level of transcription of the genes associated with PHEO (RET, TMEM127, MAX, FGFR, MET, MERTK, BRAF, NGFR, Pi3, AKT, MTOR, KRAS, MAPK) was conducted, a statistically significant decrease in the level of transcription of the KRAS and BRAF genes and increase in the level of transcription of the TMEM127 gene in comparison with control samples have been detected. This case demonstrates the need for timely recognition of NF-1 for further appropriate patient\'s follow up and show the effectiveness of a multidisciplinary approach to the diagnosis and treatment of NF-1-associated catecholamine-secreting tumors.

This case report highlights a 47-year-old woman with an adrenal incidentaloma and a history of polysubstance abuse, finally diagnosed with pheochromocytoma. Characterized by episodic hypertension, headaches, and palpitations, pheochromocytoma is a rare condition with potential complications like uncontrolled hypertension and heart failure. Remarkably, during her 28-day hospitalization, continuous monitoring revealed no instances of tachycardia or arrhythmias despite multiple symptomatic episodes. This finding aligns with reports that while 50-70% of symptomatic pheochromocytoma patients experience palpitations, only about 20% exhibit detectable tachycardia or arrhythmias. This discrepancy suggests varied individual cardiovascular responses to catecholamine surges, possibly due to differences in catecholamine inactivation rates and receptor sensitivity. This case underscores the complexity of pheochromocytoma symptoms and highlights the need for personalized diagnostic and management strategies. Furthermore, it points to a significant gap in understanding the correlation between palpitations and arrhythmia in pheochromocytoma, indicating a critical area for future research.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with diverse clinical presentations. Alterations in energy expenditure state are commonly observed in patients with PPGL. However, the reported prevalence of hypermetabolism varies significantly and the underlying mechanisms and implications of this presentation have not been well elucidated. This review discusses and analyzes the factors that contribute to energy consumption. Elevated catecholamine levels in patients can significantly affect substance and energy metabolism. Additionally, changes in the activation of brown adipose tissue (BAT), inflammation, and the inherent energy demands of the tumor can contribute to increased resting energy expenditure (REE) and other energy metabolism indicators. The PPGL biomarker, chromogranin A (CgA), and its fragments also influence energy metabolism. Chronic hypermetabolic states may be detrimental to these patients, with surgical tumor removal remaining the primary therapeutic intervention. The high energy expenditure of PPGL has not received the attention it deserves, and an accurate assessment of energy metabolism is the cornerstone for an adequate understanding and treatment of the disease.

BACKGROUND: Carriers of germline pathogenic variants (PV) in succinate dehydrogenase type B (SDHB) are at increased risk of developing pheochromocytomas and paragangliomas (PPGL). Understanding their outcomes can guide recommendations for risk assessment and early detection.
OBJECTIVE: We performed a systematic review and meta-analysis of the following outcomes in SDHB PV carriers: age-specific risk of developing tumors, metastatic progression, second primary tumor development, and mortality.
METHODS: Pubmed, MEDLINE and EMBASE were searched. Sixteen studies met the inclusion criteria and were sorted into four outcome categories: age-specific penetrance, metastatic disease, risk of second tumour and mortality. We assessed heterogeneity and performed a meta-analysis across studies using a random effects model with the DerSimonian and Laird method.
RESULTS: Penetrance of PPGL for non-proband/non-index SDHB PV carriers by age 20 was 4% (95% CI, 3%-6%), 11% (95% CI, 8%-15%) by age 40, 24% (95% CI, 19%-31%) by age 60 and 35% (95% CI, 25%-47%) by age 80. The overall risk of metastatic disease for non-proband/non-index carriers with PPGL was 9% (95% CI, 5-16%) per lifetime. In all affected cases (combining both proband/index and non-proband/non-index carriers with tumors), the risk of a second tumor was 24% (95% CI, 18-31%) and all cause 5-year mortality was 18% (95% CI 6-40%).
CONCLUSIONS: Penetrance for PPGL in SDHB PV carriers increases linearly with age. Affected carriers are at risk of developing and dying from metastatic disease, or of developing second tumors. Lifelong surveillance is appropriate.

BACKGROUND: Paragangliomas of the urinary tract are exceptionally uncommon, and sporadic case reports of primary paraganglioma of the prostate have been reported in the literature.
METHODS: Systematic research in PubMed/Medline and Scopus databases concerning primary prostatic paraganglioma was performed by two independent investigators.
RESULTS: This analysis included 25 adult males, with a mean age of 49.8 ± 22.4 years. 32% of included patients had a history of hypertension. Problems during urination (52%), blood loss (44%), either as hematuria or hemospermia, and catecholamine-related symptoms (36%) comprised the most frequently reported clinical manifestations. Digital rectal examination found a palpable nodule in 36% of patients, while prostatic specific antigen (PSA) was normal in all tested patients. Abdominal ultrasound (44%), computed tomography (44%) and magnetic resonance imaging (28%) helped to identify the primary lesion. 24-hour urine epinephrine, norepinephrine and vanillylmandelic acid (VMA) levels were elevated in 90%, 80% and 90% of included patients. Open surgical excision of the mass was performed in 40%, transurethral resection in 8%, open radical prostatectomy in 24%, transurethral resection of the prostate in 16% and robot-assisted radical prostatectomy in 4% of included patients.
CONCLUSIONS: Due to atypical clinical manifestation and scarcity of prostatic paraganglioma, urologists should be aware of this extremely rare entity.

BACKGROUND: Pheochromocytomas are rare catecholamine-secreting tumors with a high potential for recurrence post-surgery, necessitating prolonged follow-up. This case highlights the diagnostic and therapeutic challenges in managing recurrent pheochromocytoma.
METHODS: A 25-year-old female, with a history of left pheochromocytoma treated with adrenalectomy a decade earlier, presented with a right adrenal mass. Despite controlled hypertension, elevated urine metanephrines suggested recurrence. Imaging showed a right adrenal mass and suspicious left paraaortic lymph nodes, confirming the diagnosis of recurrent malignant pheochromocytoma in the left adrenal bed and right adrenal gland, with metastasis to the paraaortic lymph nodes. The patient underwent right adrenalectomy coupled with cytoreductive surgery (CRS) in the form of excision of left-sided adrenal bed recurrence and left paraaortic lymph node dissection, intraoperative radiation therapy (IORT), and hyperthermic intraperitoneal chemotherapy (HIPEC). On follow-up six years later, the patient remains free from recurrence.
CONCLUSIONS: This case illustrates the importance of continued surveillance in pheochromocytoma patients, even those with a low-risk profile. The recurrence in this case, despite a smaller initial tumor size and no genetic predispositions, underscores the unpredictable nature of pheochromocytomas. The successful management with CRS, IORT, and HIPEC emphasizes the need for a personalized and multifaceted treatment approach.
CONCLUSIONS: Pheochromocytoma patients, including those initially considered low risk, require long-term monitoring due to the risk of recurrence. The utilization of CRS, IORT, and HIPEC in this case was pivotal in managing the recurrent and metastatic malignant disease effectively, demonstrating the significance of a comprehensive, multidisciplinary treatment strategy in such complex cases.

Fulminant myocarditis (FM) is a rare illness characterized by abrupt and severe widespread cardiac inflammation, which frequently results in mortality due to cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Pheochromocytoma is an uncommon and difficult-to-diagnose cause of FM, and it is associated with a significant risk of recurrent acute myocarditis. There is, however, little information on reoccurring acute FM. Herein, we report a rare case of recurrent acute FM due to pheochromocytoma. We present the case of a 22-year-old woman who was admitted to our hospital three days previously with acute dyspnea. Five months prior, the patient was diagnosed with post-acute myocarditis, and a massive tumor on the right adrenal gland was discovered, which lead to pheochromocytoma diagnosis. In this present admission, following the exclusion of infection, autoimmune, and metabolic derangements, pheochromocytoma was presumed to be the reason for the recurrence and more severe acute FM during the current hospitalization. The patient responded favorably to high-dose steroids combined with heart failure therapy regimens. To detect recurrent acute myocarditis related to pheochromocytoma, a multidisciplinary approach was used, including several laboratory biomarkers and imaging findings. Following pheochromocytoma removal and biopsy, the patient recovered satisfactorily. Our findings may provide beneficial contributions to the literature as pheochromocytoma is an uncommon but important cause of recurrent acute myocarditis. A multidisciplinary approach is essential in identifying acute FM and determining the underlying causes of this malady.

To compare the clinical efficacy and safety of robot-assisted adrenalectomy (RA) and laparoscopic adrenalectomy (LA) for pheochromocytoma (PHEO). We conducted a comprehensive search of PubMed, the Cochrane Library, and Embase databases for studies comparing RA and LA treatment for PHEO, covering the period from database inception to January 1, 2024. Two researchers will independently screen literature and extract data, followed by meta-analysis using Review Manager 5.3 software. Six studies with 658 patients were included in the analysis. There were no significant differences in operation time [MD = -8.03, 95% CI (-25.68,9.62), P > 0.05], transfusion rate [OR = 1.10, 95% CI (0.55, 2.19) , P > 0.05], conversion rate [OR = 0.31, 95% CI (0.08, 1.12), P > 0.05], complication rate [OR = 0.93, 95% CI (0.52, 1.70), P > 0.05], Intraoperative max SBP [MD = -4.08, 95% CI (-10.13,1.97), P > 0.05], Intraoperative min SBP [MD = -2.71, 95% CI (-9.60,4.18), P > 0.05] among patients undergoing RA and LA. However, compared with patients who underwent LA, patients who underwent RA had less estimated blood loss [MD = -37.72, 95% CI (-64.11,-11.33), P < 0.05], a shorter length of hospital stay [MD = -0.43, 95% CI (-0.65,-0.21) P < 0.05]. RA has higher advantages in some aspects compared to LA. RA is a feasible, safe, and comparable treatment option for PHEO.

We present a first case report of an IL-6-producing pheochromocytoma associated with von Hippel Lindau (vHL) disease. Pheochromocytomas are rare tumors that produce catecholamines, leading to various symptoms. In this case, a 28-year-old woman with a family history of vHL disease presented with a prolonged fever. Laboratory examinations revealed elevated C-reactive protein levels, and notably, a significantly increased serum IL-6 level. Imaging studies confirmed bilateral adrenal tumors with increased uptake on fluorodeoxyglucose-positron emission tomography and 123I-metaiodobenzylguanidine scintigraphy in the right adrenal gland. Despite partial relief with nonsteroidal anti-inflammatory drugs and alpha-blockers, her fever persisted until prednisolone administration, which promoted a complete resolution. A histopathological analysis following a right laparoscopic adrenalectomy revealed a typical pheochromocytoma. We conducted further analyses, including an enzyme-linked immunosorbent assay (ELISA), a quantitative real-time polymerase chain reaction (PCR) test, and immunoblot assays from the resected tumor tissues. We compared the current case with other cases of pheochromocytoma that presented neither elevated serum IL-6 nor high fever. Using ELISA, we found that this patient exhibited more IL-6 secretion than that seen in other cases. Additionally, quantitative real-time PCR and immunoblot found that both the phosphorylated signal transducer and activator of transcription 3 (STAT3) messenger RNA (mRNA) and protein expression levels exceeded those of the other cases. Thus, we surmised that IL-6 was produced directly from the tumor tissue and IL-6 expression was potentiated through the IL-6/STAT3 signaling pathway. Our findings contribute to the understanding of IL-6-producing pheochromocytomas and their distinct clinical characteristics.