A 5-Year Prospective Follow-Up Study of Lipid-Rich Adrenal Incidentalomas: No Tumor Growth or Development of Hormonal Hypersecretion

BACKGROUND: Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size 20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. CONCLUSION: None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years.

Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry Method for Quantification of Plasma Metanephrines for Differential Diagnosis of Adrenal Incidentaloma

High-resolution imaging techniques have increased the detection rate of adrenal incidentaloma. We developed a method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection of plasma free metanephrine (MN) and normetanephrine (NMN) and evaluated its analytical performance and clinical efficacy in differential diagnosis of adrenal incidentaloma. After solid-phase extraction, chromatographic isolation of the analytes and internal standard was achieved by column elution in the LC-MS/MS system. The analytes were detected in multiple-reaction monitoring mode by using positive electrospray ionization: MN, transition m/z 180.1-->165.1; NMN, m/z 166.1-->134.1. This method was validated for linearity, precision, accuracy, lower limits of quantification and detection, extraction recovery, and the matrix effect. Plasma concentrations of MN and NMN of 14 patients with pheochromocytoma were compared with those of 17 healthy volunteers, 10 patients with essential hypertension, and 60 patients with adrenal adenoma. The assay's linear range was 0.04-50.0 and 0.08-100.0 nmol/L for MN and NMN, respectively. Assay imprecision was 1.86-7.50%. The accuracy ranged from -7.50% to 2.00%, and the mean recovery of MN and NMN was within the range 71.5-95.2%. Our LC-MS/MS method is rapid, accurate, and reliable and useful for differential diagnosis of adrenal incidentaloma.

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of epsilon-Acetamidocaproic Acid in Rat Plasma

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of epsilon-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX C18 column (150 mm x 2.0 mm, i.d., 3 microm particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 microl/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.

Diagnostic Value of 24-hours Urinary Total Metanephrine As a Screening Test of Patients with Suspected Pheochromocytoma / 대한내분비학회지

BACKGROUND: A pheochromocytoma is a rare cause of secondary hypertension. Its diagnosis is important as the hypertension is usually curable by resection of the tumor, whereas the condition is potentially lethal if undetected. Biochemical confirmation of excessive catecholamine production is a prerequisite to a definitive diagnosis. Various studies from other countries have indicated that measuring of the urinary metanephrine, using a specific procedure, is the single most reliable screening test for all patients suspected of having a pheochromocytoma. However, the diagnostic value of urinary metanephrine has never been reported in Korea. We investigated the diagnostic value of 24-hours urinary metanephrine in patients with a suspected pheochromocytoma. METHODS: This was a retrospective evaluation study, which included 95 patients with sustained hypertension and paroxysmal symptoms, and 38 patients with asymptomatic adrenal incidentaloma at Seoul National University Hospital, between July 2000 and October 2002. We performed the 24- hour urinary total metanephrine test on all patients. The diagnosis of a pheochromocytoma was applied only when confirmed by pathological analysis of a resected specimen. The possibility of a pheochromocytoma was ruled out when all biochemical tests were normal, which were performed at least in duplicate, or there was no evidence of a mass in abdominal radiological studies or histological verification. We determined the upper reference limit for urinary metanephrine as 1.3mg/day and calculated the sensitivity and specificity of the 24-hour urinary metanephrine test. RESULTS: Seventeen patients were diagnosed with a pheochromocytoma. The total metanephrine measurement had sensitivities and specificities of 82.4 and 73.3% in all the patients, 90.9 and 66.7% in patients with hypertension and paroxysmal symptoms, and 66.7 and 90.6% in patients with adrenal incidentaloma, respectively. CONCLUSION: The urinary total metanephrine measurement had relatively lower sensitivities and specificities than in other countries(sensitivity: 83~100%, specificity: 80~98%). The sensitivity of urinary metanephrine was relatively high in patients with hypertension and paroxysmal symptoms, and the specificity was high in patients with an adrenal incidentaloma. We suggest that normetanephrine and metanephrine should be separately measured, and a reasonable upper reference limit be used. It may also be necessary to measure urinary metanephrine together with urinary catecholamine or VMA to improve the diagnostic value of the urinary metanephrine test.

Incidentaloma adrenal com elevaçäo de normetanefrinas urinárias: Caso 04/96 (MAM, RG 095.567-2, Santa Casa de Misericórdia de Belo Horizonte, MG) / Incidental adrenal masses with increase of urinary normetanephrine: Case 04/96 (MAM, RG 095.567-2, Santa Casa de Misericórdia de Belo Horizonte, MG)

O avanço tecnológico na obtençäo de imagens em medicina (ultrassonografia, tomografia computadorizada e ressonância nuclear magnética) tem proporcionado uma precisäo de detalhes cada vez maior. Por isso, a incidência de achados de massas acidentais está aumentando na mesma proporçäo, obrigando-nos a deparar com novos desafios diagnósticos e terapêuticos. O incidentaloma da adrenal apresenta-se nesta categoria, constituindo um problema diagnóstico e um dilema terapêutico. O feocromocitoma é um tumor raro, que incide em apenas 0,1 por cento dos indivíduos hipertensos e se carateriza por extrema variabilidade na sua expressäo clínica. Raramente o tumor é clinicamente silencioso, porém, frequentemente, seu diagnóstico é estabelecido somente após remoçäo de um incidentaloma adrenal ou autópsia. Neste relato de caso apresentamos uma paciente assintomática, portadora de feocromocitoma silencioso, com aumento apenas dos níveis de normetanefrinas urinárias, alertando para a importância da investigaçäo funcional destas massas encontradas incidentalmente. Os resultados alterados em apenas um dos metabólitos urinários de catecolaminas (HPLC) confirmam achados prévios, de serem estes os mais sensíveis para investigaçäo dos incidentalomas adrenais na detecçäo de feocromocitomas.

Separación de aminas biogénicas mediante cromatografía líquida de alta resolución / High-performance liquid chromatographic determination of biogenic amines

En este trabajo se han compilado los distintos modos cromatográficos y sistemas de detección utilizados en la cromatografía líquida de alta resolución de aminas biogénicas. Se indican las características generales del intercambio catiónico, fase reversa, fase reversa de pares iónicos y cromatografía de partición con fase reversa de pares iónicos. También se analizan comparativamente la detección UV, detección fluorimétrica usando fluorescencia nativa o bien derivatización pre- y postcolumna y detección electroquímica de gran utilidad para esta extensa familia de compuestos. Se dan ejemplos de aplicación de interés en el campo bioquímico-clínico, con el análisis de ácido homovainillínico, ácido 3,4-dihidroxifenilacético y ácido 5-hidroxiindolacético en líquido cefalorraquídeo, metanefrinas, ácido 3,4-dihidroxifenilacético, catecolaminas, ácidos urinarios y 3-metoxi-4-hidroxifenilglicol en orina, catecolaminas y 3-metoxi-4-hidroxifenilglicol en plasma, catecolaminas, 3-metoxi-4-hidroxifenilglicol y otros neurotransmisores en cerebro de rata. Se discuten, también, los tratamientos previos requeridos especialmente para orina y plasma, así como las condiciones de conservación y su incidencia en los resultados obtenidos