A case report on pheochromocytoma mimicking as fulminant myocarditis-a diagnostic challenge.

We present an exceptional case of a 53-year-old female, initially misdiagnosed with fulminant myocarditis, but later correctly diagnosed with pheochromocytoma. The presentation of the patient included a spectrum of symptoms such as headache, chest discomfort, palpitations, and dyspnea, following the intake of Domperidone. Two weeks prior to admission, the patient had experienced episodes of diarrhea and a low-grade fever. Unresolved symptoms and an unmanageable surge in blood pressure despite comprehensive fulminant myocarditis treatment prompted further investigation. The discovery of an adrenal mass via a CT scan and subsequent biochemical tests led to the confirmation of pheochromocytoma. Implementation of alpha-blockade therapy and a successful laparoscopic adrenalectomy resulted in significant clinical improvement. This case underscores the diagnostic intricacies of pheochromocytoma and highlights the need for vigilance when faced with severe, unresponsive cardiovascular symptoms.

EEG alpha reactivity on eyes opening discriminates patients with schizophrenia and schizoaffective disorder.

OBJECTIVE: Alpha activity in the electroencephalogram (EEG) is typically dominant during rest with closed eyes but suppressed by visual stimulation. Previous research has shown that alpha-blockade is less pronounced in schizophrenia patients compared to healthy individuals, but no studies have examined it in schizoaffective disorder. METHODS: A resting state EEG was used for the analysis of the alpha-reactivity between the eyes closed and the eyes opened conditions in overall (8 - 13 Hz), low (8 - 10 Hz) and high (10 - 13 Hz) alpha bands in three groups: schizophrenia patients (SC, n = 30), schizoaffective disorder (SA, n = 30), and healthy controls (HC, n = 36). All patients had their first psychotic episode and were receiving antipsychotic therapy. RESULTS: A significant decrease in alpha power was noted across all subjects from the eyes-closed to eyes-open condition, spanning all regions. Alpha reactivity over the posterior regions was lower in SC compared to HC within overall and high alpha. SA showed a trend towards reduced alpha reactivity compared to HC, especially evident over the left posterior region within the overall alpha. Alpha reactivity was more pronounced over the middle and right posterior regions of SA as compared to SC, particularly in the high alpha. Alpha reactivity in SC and SA patients was associated with various negative symptoms. CONCLUSIONS: Our findings imply distinct alterations in arousal mechanisms in SC and SA and their relation to negative symptomatology. Arousal is more preserved in SA. SIGNIFICANCE: This study is the first to compare the EEG features of arousal in SC and SA.

[Personalized treatment of pheochromocytoma]. / Personalisierte Therapie des Phäochromozytoms.

BACKGROUND: Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma. MATERIAL AND METHODS: A narrative review article based on the most recent literature is presented. RESULTS AND DISCUSSION: The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24­h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.

Different intraoperative decisions for undiagnosed paraganglioma: Two case reports.

BACKGROUND: Paragangliomas may be preoperatively misdiagnosed as non-functioning retroperitoneal tumors and are sometimes suspected only at the time of intraoperative manipulation. Without preoperative alpha blockade preparation, a hypertensive crisis during tumor manipulation and hypotension after tumor removal may result in critical consequences. Therefore, primary consideration should be given to the continuation or discontinuation of surgery on the basis of the possibility of gentle surgical manipulation and hemodynamic stabilization. We report two cases of paragangliomas detected intraoperatively. CASE SUMMARY: A 65-year-woman underwent laparoscopic small-bowel wedge resection. A hypertensive crisis occurred during manipulation of the mass, and an unrecognized catecholamine-producing paraganglioma was suspected. The surgeon and anesthesiologists believed that tumor excision could be performed with minimal manipulation of the tumor because the tumor was in a favorable location. Serious hemodynamic instability did not occur with aggressive use of vasoactive drugs. A week later, a 54-year-man underwent open resection of a 3-cm-sized retroperitoneal mass and showed the same findings during mass manipulation. For this patient, continuous manipulation of the mass seemed inevitable due to adhesion between the right adrenal gland and the mass in a narrow surgical field. The surgeon and anesthesiologists decided to cancel the surgical procedure and planned to perform a reoperation after alpha blockade therapy. Two weeks later, the tumor was uneventfully removed with small doses of vasoactive drugs. CONCLUSION: When an undiagnosed paraganglioma is suspected intraoperatively, reoperation after adequate preparation should be considered as an option to avoid fatal outcomes.

Management of Patients with Treatment of Pheochromocytoma: A Critical Appraisal.

The management of pheochromocytomas has significantly evolved these last 50 years, especially with the emergence of new technologies such as laparoscopic procedures in the 1990s. A preoperative blockade using antihypertensive medications to prevent intraoperative hemodynamic instability and cardiocirculatory events is recommended by current clinical guidelines. However, these guidelines are still based on former experiences and are subject to discussion in the scientific community. The aim of this systematic review was to assess the evolution of the management of pheochromocytomas. Laparoscopic procedure is established as the standard of care in current practices. Preoperative medical preparation should be questioned because it does not significantly improve intraoperative events or the risk of postoperative complications in current clinical practice. Current clinical recommendations should be revised and upgraded to current clinical practices.

Comparison of Preoperative Alpha-blockade for Resection of Paraganglioma and Pheochromocytoma.

OBJECTIVE: Phenoxybenzamine (nonselective, noncompetitive alpha-blocker) is the preferred drug for preoperative treatment of pheochromocytoma, but doxazosin (selective, competitive alpha-blocker) may be equally effective. We compared the efficacy of doxazosin vs phenoxybenzamine. METHODS: We conducted a prospective study of patients undergoing pheochromocytoma or paraganglioma resection by randomizing pretreatment with phenoxybenzamine or doxazosin at a single tertiary referral center. The high cost of phenoxybenzamine led to high crossover to doxazosin. Randomization was halted, and a consecutive historical cohort of phenoxybenzamine patients was included for a case-control study design. The efficacy of alpha-blockade was assessed with preinduction infusion of incremental doses of phenylephrine. The primary outcomes were mortality, cardiovascular complications, and intensive care unit admission. The secondary outcomes were hemodynamic instability index (proportion of operation outside of hemodynamic goals), adequacy of blockade by the phenylephrine titration test, and drug costs. RESULTS: Twenty-four patients were prospectively enrolled (doxazosin, n = 20; phenoxybenzamine, n = 4), and 15 historical patients treated with phenoxybenzamine were added (total phenoxybenzamine, n = 19). No major cardiovascular complications occurred in either group. The phenylephrine dose-response curves showed less blood pressure rise in the phenoxybenzamine than in the doxazosin group (linear regression coefficient = 0.008 vs 0.018, P = .01), suggesting better alpha-blockade in the phenoxybenzamine group. The median hemodynamic instability index was 14% vs 13% in the phenoxybenzamine and doxazosin groups, respectively (P = .56). The median highest daily cost of phenoxybenzamine was $442.20 compared to $5.06 for doxazosin. CONCLUSION: Phenoxybenzamine may blunt intraoperative hypertension better than doxazosin, but this difference did not translate to fewer cardiovascular complications and is offset by a considerably increased cost.

Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes.

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref <1.09 nmol/L) and a tumor biopsy confirmed the diagnosis of a paraganglioma. Phenoxybenzamine and Labetalol were used in high doses ((Dibenyline®, 90 mg x 3 daily) and labetalol (Trandate®, 200 + 300 + 300 mg daily) to stabilize blood pressure. The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.

Risk factors for intraoperative complications in pheochromocytomas.

We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10-110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 µg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 µg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.

Analysis of clinical characteristics for hypertensive attack during pheochromocytoma and paraganglioma operation:a single center case report of 219 cases / 中华泌尿外科杂志

Objective To analyze the clinical characteristics for hypertensive attack during operation and clinical experience of preoperative evaluation and preparation in patients with pheochromocytoma and paraganglioma(PHEO/PGL).Methods A total 219 PHEO/PGL cases from September 2016 to September 2018 were retrospectively reviewed.It included 99 males and 120 females,aged 13 to 76 (average 47) years old.The mean diameter of tumor was 5.3 cm (1.5-18.0 cm).140 cases were unilateral PHEO,6 cases were bilateral PHEO,68 cases were PGL(jugular,mediaphragm,heart,retroperitoneum,pelvic and bladder) and 5 cases were PHEO combined with PGL.Preoperative highest systolic blood pressure (SBP)was 240 mmHg(1 mmHg-0.133 kPa) and highest diastolic blood pressure (DBP) was 160 mmHg.20 cases were occult PHEO without hypertension.217 cases accepted preoperative preparation of alpha-blocker [phenoxy-benzamine,dosage ranging from 5 mg Q12h to 40 mg Q8h,maximum dosage not exceeding 1 mg/(kg· 24 h)].2 cases did not accept preoperative preparation.All cases accepted open or endoscope surgery.The patients were divided into 2 groups depending on the presence or absence of hypertensive attack at the time of surgery.Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to hypertensive attack.Results Histopathological results showed that all cases were PHEO or PGL,while 205 cases were benign,14 cases were malignant.Hypertensive attack were recorded in 112 cases(51％).The diameter of tumors in the hypertensive attack group were larger than that in the non-hypertensive attack group[(6.70 ± 2.95)cm vs.(3.95 ± 1.70) cm,P =0.005].There was no significant difference between the two groups among age [(51.0 ± 10.8) years vs.(38.5 ± 17.6) years,P =0.105],preoperative catecholamine level [norepinephrine (111.20 ± 41.49) μg/24 h vs.(419.15 ± 154.81) μg/24 h,P =0.075],time of use of alpha blockers [(53.0 ± 7.5) d vs.(38.0 ± 6.4) d,P =0.139],daily dosage of alpha blocker [(40.0 ±7.2)mg vs.(27.1 ± 1.8) mg,P =0.111] and blood pressure at diagnosis[(173.75 ± 26.69) mmHg vs.(155.0 ± 20.75) mmHg,P =0.139].Among 219 cases,2 case had emergency hemostasis after operation,1 case had catecholamine cardiomyopathy after operation for occult pheochromocytoma,and no perioperative death occurred.Conclusions Patients with large tumor tend to have hypertensive attack during operation so that should be better prepared.

Optimal Management of a Synchronous Diagnosis of Phaeochromocytoma and Colorectal Neoplasia.

The incidence rates of phaeochromocytoma and colorectal cancer (CRC) are approximately 1 and 65 per 100,000 per year, respectively. Simultaneous presentation of these conditions is rare and poses unique management challenges. We report on treatment strategies and clinical outcomes in a series of patients with colorectal neoplasia and phaeochromocytoma. Demographic and clinical details of four patients over a 4-year period were reviewed. The median (range) age at first presentation was 66 (52-70) years. Phaeochromocytoma (2.5-12.5 cm) was confirmed on biochemistry after incidental detection of an adrenal mass on CT scan-three had CT for staging of CRC and one had CT scan for weight loss. Adrenalectomy (three retroperitoneoscopic and one open procedure) was first performed after maximally tolerated alpha blockade; no significant complications were observed. Normalisation of biochemistry was confirmed and the patients then underwent colorectal surgery-laparoscopic right hemicolectomy, open right hemicolectomy (with further extensive surgery) for locally advanced cancer, laparoscopic low anterior resection and open high anterior resection. One respiratory infection and a seroma were the post-operative complications seen. In patients with a simultaneous diagnosis of phaeochromocytoma and CRC, surgical interventions should be staged. Adrenalectomy should first be performed to avoid haemodynamic instability during colorectal resection. A retroperitoneoscopic approach to the adrenal in patients with ipsilateral colonic tumours avoids transgressing the planes for colorectal resection. The synchronous diagnosis of these two rare conditions and the reported stimulatory effect of catecholamines on colorectal epithelia raise the possibility of an increased incidence of colorectal neoplasia in patients with phaeochromocytoma.

Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease.

Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.

An Update on Kawasaki disease (Research): Animal Model

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology in young children. There has been many trials to find out the causes of KD all over the world since Dr. Kawasaki published the first KD cases in Pediatrics (1973). The studies using animal models have been carried out noticablly in Japan and North America, initiated by Dr. Murata (1979) and Dr. Lehman (1985). The medical doctors and scientists have used many animals for their studies, for example, dog, rabbit, swine and mice. Nowadays, mice is the most popular animal model for patho-physiologic research of KD. However, there is no report about animal model research of KD in Korea. I emphasize that we have to start to search the causes of KD through experimental trials. Candida albicans extract and Lactobacillus casei cell wall extract were used to make coronary arteritis in animal models as in case of KD in humans. Recently, there is a good result in developing new drugs (TNF-alpha blockade) for the treatment of KD patients who are resistant to intravenous immunoglobulin and methylprednisolone through animal model research of KD.

Alpha-blockade therapy in alternating day dose in the management of benign prostatic hyperplasia

This study was conducted to compare the efficacy of Terazosin given in alternate day doses with that of the same drug given in daily doses in the medical management of benign prostatic hyperplasia (BPH) using the following parameters: International Prostate Symptom Score (IPSS), urine flow rate, residual urine volume and quality of life. Ninety patients were randomly assigned to Daily Dose, Alternate Day Dose and Placebo groups. Symptom scores using the IPSS were measured at pre-treatment, and at 1st, 3rd and 6th week treatment periods. Pre- and post-treatment measurements of urine flow rate, residual urine volume and quality of life were done. Two-way ANOVA and Wilcoxon Matched Pair Signed Ranked Test was used to determine the level of significance. The study showed that there was significant improvement in the symptom score in both Daily Dose (15.80 +/- 1.74 to 5.93 +/- 1.03) (p 0.001) and Alternate Day Dose group (16.06 +/- 1.87 to 6.13 +/- 1.45) (p 0.001) compared to the placenta group. Likewise there was significant improvement in the urine flow rate in both groups, (4.82 +/- 0.75 to 5.76 +/- 0.67) (p (65.66 +/- 17.54 to 46.46 +/- 12.77) (p = 0.001) in the Alternate Day Dose group. The quality of life improved (3.26 +/- 0.88 to 1.66 +/- 0.72) (p = 0.002) in the Daily Dose group and (3.66 +/- 0.81 to 1.80 +/- 0.77) (p = 0.001) in the Alternate Day Dose group. (Author)