Clinical significance of vanillylmandelic acid in neuroblastoma

Background: The second most common solid tumor in children is Neuroblastoma (NB). In about 90% of cases of NB, elevated levels of catecholamines or its metabolites are found in the urine or blood which includes Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA). Ferritin, Neuron-Specific Enolase (NSE) and Lactate Dehydrogenase (LDH) are commonly assessed in children suspected to have NB, and the levels of these markers are commonly used for differential diagnosis. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123(123I) Metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. To evaluate the utility of these marker present study was undertaken with 91 NB patients and 40 normal healthy control.Methods: The study comprised of blood samples and 24 hour抯 urine sample from 40 normal healthy subjects and 91 untreated patients with histologically proven Stage III and IV NB cases referred to our institute. Method used for NSE was Enzyme Immunoassay (Elisa), serum Ferritin was MIA, LDH-photometry and VMA by Column Chromatography.Results: Amongst the parameters studied VMA showed highest sensitivity (91%), specificity (94.4%) positive predictive value (97.8%) and 85% negative predictive value at the cut off levels of 7mg/ ml of creatinine as compared to other studied parameters.Conclusions: This study suggests that the detection of VMA in combination with routine histological examination, MIBG scan, serum NSE and LDH may improve the diagnosis of Neuroblastoma.

Plasma & urinary catecholamines & urinary vanillylmandelic acid levels in patients with generalized vitiligo

Background & objectives: Vitiligo is an acquired skin disease characterized by depigmented areas of the skin. Increased release of catecholamines from autonomic nerve endings in microenvironment of melanocytes in affected skin might be involved in the aetiopathogenesis of vitiligo. Levels of catecholamines are considered as being related to onset or worsening of the disease. Therefore, in this study, the role of catecholamines was evaluated in mapping disease stability and outcome of vitiligo patients undergoing melanocyte transfer. Methods: In this study, circulatory and urinary levels of catecholamine (CA) and vanillylmandelic acid (VMA) were determined in 45 individuals (30 vitiligo patients and 15 healthy controls) using ELISA. Results: A significant increase for plasma and urinary catecholamines along with VMA was observed as compared to healthy controls. When the pre- and post-intervention levels were analyzed in responders and non-responders, respectively, only dopamine showed significant decline in urine, rest of the molecules in plasma as well as urine showed non-significant decline except VMA which showed insignificant increase. Interpretation & conclusions: Levels of plasma/urinary epinephrine, and plasma dopamine, could not be established as biomarkers for disease stability or successful outcome of autologous melanocyte transfer in generalized vitiligo patients. However, dopamine (urine) might be of help in determining the stability in patients with generalized vitiligo undergoing melanocyte transfer. Further studies need to be done on a large sample of patients to confirm our findings.

Clinical Significance of Random Urinary Vanillylmandelic Acid in Patients with Neuroblastoma / 임상소아혈액종양

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.

Left-sided giant adrenal myelolipoma secreting catecholamine.

Adrenal myelolipoma (AML) is a rare benign tumor composed of mature adipose and hematopoietic tissue. Most of these patients are asymptomatic and the tumors are non-secreting. We present a case with a large functional adrenal myelolipoma, wherein the patient was hypertensive and biochemistry revealed increase in 24 hours urinary Vanillylmandelic Acid (VMA), a metabolite of catecholamine. The mass was removed surgically and diagnosed as adrenal myelolipoma on histopathological examination. Both his blood pressure and urinary VMA returned to normal following surgery, which suggested that the mass was functioning and was secreting catecholamine. To the best of our knowledge, a catecholamine secreting adrenal myelolipoma has been reported in the literature only once previously. The association of hypertension and adrenal myelolipoma may not be entirely coincidental, as it may be associated with secreting catecholamine, as seen in our case. We also review the literature on functioning adrenal myelolipoma.

The predictive value of urinary vanillylmandelic acid testing in the diagnosis of phaeochromocytoma at the University Hospital of the West Indies / El valor predictivo de la prueba del ácido vanilmandélico en orina para el diagnóstico de la feocromositoma en el Hospital Universitario de West Indies

OBJECTIVE: To investigate the positive predictive value (PPV) of urinary vanillylmandelic acid (VMA) testing in the diagnosis of phaeochromocytoma and to describe the features associated with phaeo chromocytoma at the University Hospital of the West Indies (UHWI). SUBJECTS AND METHODS: There were 551 VMA tests performed from January 2003 to June 2009 and 122 tests in 85 patients were elevated (ie > 35 µmol/24 hr). The study patients were categorized as: (i) 'surgical' (5 patients who underwent surgery) or (ii) 'non-surgical' (remaining 80 patients). Forty medical charts (out of 85) were reviewed using a standardized data extraction form. RESULTS: The median age for patients in the non-surgical group (with charts reviewed, n = 35) was 36 years (range 9-70) and the median VMA was 43 µmol/24 hr (IQR 38-51). Of these patients, 83% had one or no symptom typical of phaeochromocytoma. In the surgical group the median VMA was 58 µmol/24 hr (IQR 44-101); phaeochromocytoma was confirmed histologically in 3 patients, all of whom had several symptoms typical of catecholamine excess. VMA testing had a PPV of 8%, specificity of 79% and sensitivity of 100%. CONCLUSIONS: VMA testing at UHWI has poor specificity and high sensitivity. These results contrast with international data showing that VMA testing is poorly sensitive but highly specific. The use of assays with higher specificity (egplasma or urinary metanephrines) may represent a more cost-effective approach to biochemical screening at UHWI.

OBJETIVO: Investigar el valor predictivo positivo (VPP) de las pruebas del ácido vanilmandélico urinario (VMA) en el diagnóstico de la feocromositoma y describir las características asociadas con la feocromositoma en el Hospital de la Universidad de West Indies (HUWI). SUJETOS Y MÉTODOS: Se realizaron unas 551 pruebas de VMA de enero de 2003 a junio de 2009, y 122 de las pruebas en 85 pacientes tuvieron resultados elevados (ie > 35 µmol/24 hr). Los pacientes del estudio fueron clasificados como: (i) "quirúrgicos" (5 pacientes que se sometieron a cirugía) ó (ii) "no quirúrgicos" (los 80 pacientes restantes). Se revisaron cuarenta historias clínicas (de 85) mediante un formulario estandarizado de extracción de datos. RESULTADOS: El promedio de edad de los pacientes en el grupo no quirúrgico (con historias clínicas, n = 35) fue de 36 años (rango 9-70) y la mediana VMA fue 43 µmol/24 h (IQR 38-51). De estos pacientes, 83% tenían uno o ningún síntoma típico de la feocromositoma. En el grupo quirúrgico la mediana VMA fue 58 µmol/24 h (IQR 44-101). La feocromositoma fue confirmada histológicamente en 3 pacientes, cada uno de los cuales presentó síntomas típicos de exceso de catecolaminas. Las pruebas de VMA tuvieron un VPP de 8%, una especificidad de 79%, y una sensibilidad de 100%. CONCLUSIONES: Las pruebas de VMA en HUWI poseen pobre especificidad y alta sensibilidad. Estos resultados contrastan con los datos internacionales que muestran que la prueba de VMA es pobremente sensible pero altamente específica. El uso de ensayos con mayor especificidad (por ejemplo, metanefrinas plasmáticas o urinarias) puede representar un método costo-efectivo a la hora de realizar el pesquisaje bioquímico en HUWI.

Diagnostic Efficacy of Biochemical Studies and MIBG Scan in Pheochromocytoma / 대한비뇨기과학회지

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.