The great chain of sympathetic ganglia which extends from the base of the skull to the pelvis, including the suprarenal medulla, accounts for the origin of the ganglioneuroma which compound with the matured ganglion cells and neural elements. The ganglioneuroma is non-functioning tumor, but occasionally this tumor accompanies with hypertension and diarrhea and increased excretion of vanilmandelic acid in urine. Recently we experienced a housewife with the bilateral ganglioma which developed at both suprarenal medulla and after successful removal of the tumors hypertension was controlled.
Diarrhea ; Ganglia, Sympathetic ; Ganglion Cysts ; Ganglioneuroma* ; Hypertension ; Pelvis ; Skull ; Vanilmandelic Acid

OBJECTIVETo establish a method for simultaneously determining vanilmandelic acid (VMA), 5-hydroxyindoleacetic (5-HIAA), 3, 4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in urine by high-performance liquid chromatography (HPLC).

METHODSAfter being filtered with a 0.45 µm membrane syringe filter, the urinary samples were injected directly into the HPLC system using a C18 chromatographic column and a fluorescence detector. The excitation and emission wavelengths were chose as 280 nm and 315 nm, respectively, and the urinary samples were carried with a mobile phase of methanol-0.1 mol/L phosphate buffered solution (V/V = 20:80) at a flow rate of 1.0 ml/min and an injection volume of 20 µl.

RESULTSUsing the method reported here, the correlation coefficients of VMA, 5-HIAA, DOPAC, and HVA were 0.9999, 0.9998, 0.9997, 0.9999, respectively, over linear ranges of 0-2.5, 0-2.0, 0-2.0, and 0-2.5 µg/ml, the minimum detectable concentrations were 0.006, 0.008, 0.012, and 0.0082 µg/ml, the average precisions were 4.2%, 3.7%, 4.9%, and 3.6%, and the recovery rates were 91%∼102%, 93%∼101%, 94%∼101%, and 89%∼ 102%.

CONCLUSIONThis determination method is simple, efficient, accurate, and sensitive for the simultaneous detection of VMA, 5-HIAA, DOPAC, and HVA in urine.

Biogenic Amines ; urine ; Chromatography, High Pressure Liquid ; Homovanillic Acid ; urine ; Humans ; Hydroxyindoleacetic Acid ; urine ; Vanilmandelic Acid ; urine

A 53-year-old woman had a 1.7 cm left adrenal mass on an abdominal computed tomography (CT) scan. She presented with paroxysmal headache, palpitation, sweating, and hypertension. The patient was highly suspected of having a pheochromocytoma, but measurements of 24-hour urinary metanephrine, catecholamines, and vanillylmandelic acid were normal. Plasma and urine catecholamine levels were within the normal range even during paroxysmal episodes. A scintigraphic study with 131I-metaiodobenzylguanidine (MIBG) revealed selective concentration of the radiotracer, corresponding to the CT mass. The patient underwent a left adrenalectomy and the pathological examination confirmed the diagnosis of pheochromocytoma. In this report, we describe a rare case of a symptomatic pheochromocytoma with normal catecholamine levels. Our case illustrates that routine nuclear scintigraphy, such as 131I-MIBG, should be performed even in cases with normal hormonal testing for all patients with high clinical suspicion of pheochromocytoma.
3-Iodobenzylguanidine ; Adrenalectomy ; Catecholamines ; Female ; Headache ; Humans ; Hypertension ; Metanephrine ; Middle Aged ; Pheochromocytoma ; Plasma ; Reference Values ; Sweat ; Sweating ; Vanilmandelic Acid

We evaluated the role of clinical symptoms, biochemical studies and metaiodobenzylguanidine (MIBG) scan in the diagnosis of pheochromocytoma. From August 1991 to June 1997, 42 patients with complaints of hypertension or adrenal mass were evaluated with MIBG scan, 24 hour urinary vanillylmandelic acid (VMA), serum and 24 hour urinary catecholamine and radiologic studies such as CT, MRI or ultrasonography. Initial 9 patients were evaluated with 131 I-MIBG scan and the rest 33 patients with 123 I-MIBG scan. Of 42 patients, histologic diagnosis was obtained in 32 patients including 23 patients with pheochromocytoma or paraganglioma and 9 patients with other adrenal or extra-adrenal tumors. Remaining 10 patients had no evidence of adrenal disease on radiologic studies. Paroxysmal symptoms or hypertension was noted in 14 patients with pheochromocytoma or paraganglioma, while it was also found in 12 out of 19 patients without pheochromocytoma or paraganglioma. Sensitivity, specificity and positive predictive value (PPV) of each diagnostic modality were 60.9%, 92.9% and 93.3% in 24 hour urinary VMA, 61.9%, 75.0%, and 81.3% in 24 hour urinary catecholamine, 82.6%, 94.7%, and 95.0% in MIBG scan, respectively. Sensitivity and specificity were improved to 86.9% and 100% when 24 hour urinary VMA and MIBG scan were combined. In conclusion, MIBG scan was the most useful single screening method for the diagnosis of pheochromocytoma, and combination of MIBG scan and 24 hour urinary VMA would enhance the diagnostic accuracy.
3-Iodobenzylguanidine* ; Diagnosis ; Humans ; Hypertension ; Magnetic Resonance Imaging ; Mass Screening ; Paraganglioma ; Pheochromocytoma* ; Sensitivity and Specificity ; Ultrasonography ; Vanilmandelic Acid

PURPOSE: The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. RESULTS: Malignant tumors were significantly larger than benign tumors (11.1+/-4.0 cm vs. 6.2+/-3.4 cm, p<0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 microg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p<0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (< or =5.5 vs. >5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (>2.1 vs. < or =2.1 mg/day/cm; 94.9% vs. 70.9%, p=0.019). CONCLUSIONS: Large tumor size (>5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (< or =2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.
Adrenal Gland Neoplasms ; Catecholamines ; Epinephrine ; Follow-Up Studies ; Humans ; Hypertension ; Neoplasm Metastasis ; Norepinephrine ; Pheochromocytoma ; Prognosis ; Retrospective Studies ; Survival Rate ; Tumor Burden ; Vanilmandelic Acid

The coexistence of extraadrenal pheochromocytoma and renal artery stenosis is extremely rare. The mechanisms of renal artery stenosis with pheochromocytoma include direct compression of the tumor mass on the renal artery and catecholamine-induced vasospasm, fibromuscular hyperplasia, and fibrous adhesion. We report a rare case of renal artery stenosis caused by extraadrenal pheochromocytoma in a 29- year-old female. She was admitted to the hospital because of palpitation and headache. She had been treated for hypertension for 2 years. On admission, her plasma epinephrine and norepinephrine levels were elevated as were her plasma renin activity, urinary vanillylmandelic acid (VMA) and metanephrine levels. Through the use of abdominal computed tomography, 131I-MIBG scan, and renal arteriography, a mass was found in the hilus of the left kidney which affected left renal artery stenosis. Surgical removal of the mass and left kidney restored the catecholamine excretion, plasma renin activity, and blood pressure to normal. Electronmicroscopic examination of the mass confirmed the pheochromocytoma.
Angiography ; Blood Pressure ; Epinephrine ; Female ; Headache ; Humans ; Hyperplasia ; Hypertension ; Kidney ; Metanephrine ; Norepinephrine ; Pheochromocytoma* ; Plasma ; Renal Artery Obstruction* ; Renal Artery* ; Renin ; Vanilmandelic Acid

Neuroblastomas originating from different sites might have different clinical and biological characteristics. In the present study, the clinical (age, sex and stage) and biological (N-myc amplification, Shimada pathology and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of patients with newly diagnosed neuroblastoma were compared according to the site of tumor origin (extra-abdominal versus abdominal). The event-free survival rate (EFS) was also compared between the two groups. Among 143 neuroblastomas, 115 tumors originated from the abdomen, 26 from extra-abdominal sites and 2 from unknown primary sites. Frequencies of stage 4 tumor and N-myc amplified tumor were lower in the extra-abdominal group than in the abdominal group (34.6% vs. 60.0%, P=0.019 and 4.2% vs. 45.0%, P<0.001, respectively). Levels of lactate dehydrogenase, ferritin and neuron-specific enolase were significantly lower in the extra-abdominal group than in the abdominal group. The probability of 5-yr EFS (+/-95% confidence interval) was higher in the extra-abdominal group than in the abdominal group (94.4+/-10.6% vs. 69.4+/-9.4%, P=0.026). Taken together, neuroblastomas originating from extra-abdominal sites might be associated with more favorable clinical and biological characteristics and a better outcome than neuroblastomas originating from abdomen.
Disease-Free Survival ; Female ; Ferritins/blood ; Humans ; L-Lactate Dehydrogenase/blood ; Male ; Neuroblastoma/*diagnosis/therapy ; Phosphopyruvate Hydratase/blood ; Prognosis ; Treatment Outcome ; Vanilmandelic Acid/urine

Neuroblastomas originating from different sites might have different clinical and biological characteristics. In the present study, the clinical (age, sex and stage) and biological (N-myc amplification, Shimada pathology and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of patients with newly diagnosed neuroblastoma were compared according to the site of tumor origin (extra-abdominal versus abdominal). The event-free survival rate (EFS) was also compared between the two groups. Among 143 neuroblastomas, 115 tumors originated from the abdomen, 26 from extra-abdominal sites and 2 from unknown primary sites. Frequencies of stage 4 tumor and N-myc amplified tumor were lower in the extra-abdominal group than in the abdominal group (34.6% vs. 60.0%, P=0.019 and 4.2% vs. 45.0%, P<0.001, respectively). Levels of lactate dehydrogenase, ferritin and neuron-specific enolase were significantly lower in the extra-abdominal group than in the abdominal group. The probability of 5-yr EFS (+/-95% confidence interval) was higher in the extra-abdominal group than in the abdominal group (94.4+/-10.6% vs. 69.4+/-9.4%, P=0.026). Taken together, neuroblastomas originating from extra-abdominal sites might be associated with more favorable clinical and biological characteristics and a better outcome than neuroblastomas originating from abdomen.
Disease-Free Survival ; Female ; Ferritins/blood ; Humans ; L-Lactate Dehydrogenase/blood ; Male ; Neuroblastoma/*diagnosis/therapy ; Phosphopyruvate Hydratase/blood ; Prognosis ; Treatment Outcome ; Vanilmandelic Acid/urine

BACKGROUND: To evaluate the value of random urinary vanillylmandelic acid (VMA) as a surrogate marker for monitoring tumor response and predicting outcome in patients with neuroblastoma (NB). METHODS: Medical records of 91 patients newly diagnosed with NB at the Samsung Medical Center between June 2014 and August 2017 were reviewed. Clinical associations and other prognostic factors, including age at diagnosis, stage, pathologic subtype, MYCN amplification, and other cytogenetic aberrations, were analyzed. Furthermore, the significance of random urinary VMA level in predicting outcome and tumor response was also evaluated. RESULTS: The median random urinary VMA level at diagnosis was 27.9 (range: 1.7–600) mg/g creatinine. Abdominal primary site, male sex, advanced stage, less differentiated pathology (poorly differentiated, undifferentiated), 11q deletion, and high-risk tumor were associated with a higher VMA level at diagnosis. The VMA level decreased during chemotherapy (28.4%, 16.9%, and 9.6% of the VMA level at diagnosis after 3, 6, and 9 cycles of chemotherapy, respectively). A higher VMA level at diagnosis tends to be associated with a better overall survival in high-risk patients with borderline significance (58.3±18.6% vs. 76.5±13.4%, P=0.050). However, in the multivariate analysis, the VMA level was not a significant predictor of survival. A slower reduction in VMA level during chemotherapy was not associated with a worse overall survival. However, event free survival was significantly better in the rapid responder group. CONCLUSION: A higher VMA level was associated with high-risk features at diagnosis of NB. Random urinary VMA is a valuable marker for monitoring NB response during chemotherapy.
Biomarkers ; Chromosome Aberrations ; Creatinine ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Male ; Medical Records ; Multivariate Analysis ; Neuroblastoma* ; Pathology ; Prognosis ; Vanilmandelic Acid*

Two external quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests using tandem mass spectrometry, were performed in 2015. A total of 44 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetics tests.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Galactosemias ; Homocystinuria ; Humans ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid