The use of sodium borate impregnated silica gel plates for the separation of 3-0-methyl catecholamines from their corresponding catecholamines.
The use of sodium borate impregnated silica gel plates for the chromatographic separation of the catecholamines noradrenaline, adrenaline, and isoprenaline from their respective 3-0-methylated derivatives, normetanephrine, metanephrine, and methoxy-isoprenaline, is described. The parent catecholamines remain at the origin of the plates while the 3-0-methylated derivatives concentrate in discrete bands at the upper edge of the borate impregnated area (the "borate front"). (+info)
Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease.
AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants. (+info)
Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.
BACKGROUND: The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel-Lindau disease or MEN-2. METHODS: We studied 26 patients with von Hippel-Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel-Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel-Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid. RESULTS: The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel-Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent). CONCLUSIONS: Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors. (+info)
Freedom from drug interference in new immunoassays for urinary catecholamines and metanephrines.
BACKGROUND: Determination of urinary free catecholamine and total (i. e., free plus conjugated) metanephrine excretion is considered the most clinically sensitive biochemical test for pheochromocytoma. In this study, we evaluated new immunoassay methods for the measurement of these analytes for potential drug-based interference. METHODS: Urine samples collected from patients on a variety of medications were grouped by specific drug type. The significance of any difference in the free catecholamine or total metanephrine concentrations in the different groups was assessed by one-way ANOVA. A group of patients receiving no medication was included as a control (no analytical interference). Additionally, analytical accuracy, detection limit, and precision were determined. RESULTS: No significant differences were found in the concentrations of free catecholamines or total metanephrines in urine from patients taking the medications investigated and the control group: P = 0.649 (fE), 0.221 (fNE), 0.149 (tM), and 0.170 (tNM). For free catecholamines, intraassay CVs were 4.6-18%; interassay CVs were 10-25%. For total metanephrines, intraassay CVs were 9.6-27%; interassay CVs were 5. 8-22%. Detection limits were 0.009 and 0.027 micromol/L for fE and fNE and 0.119 and 0.346 micromol/L for tM and tNM, respectively. CONCLUSIONS: None of the drugs examined in this study interfered in the measurement of free catecholamines or total metanephrines by these immunoassays. The technique is easier to use, requires less equipment, and is more accessible than HPLC. In combination, these assays are suitable as initial screening tests for pheochromocytoma. (+info)
Outcome in patients with adrenal incidentaloma selected for surgery: an analysis of 88 cases investigated in a single clinical center.
OBJECTIVE: The study was designed to evaluate the clinical, endocrinological and radiological parameters used to investigate adrenal incidentalomas and select patients for surgery. DESIGN AND METHODS: An analysis of 88 consecutive patients with adrenal incidentaloma selected for surgery and investigated in a single clinical center was performed. RESULTS: Mean (+/-s.d.) age of the patients was 53+/-14 years. Fourteen (16%) of the adrenal incidentalomas were malignant tumors (2 adrenocortical carcinomas, 3 metastases, 4 adenocarcinomas, 4 sarcomas and 1 mesenchymoma), 10 (11%) were pheochromocytomas, 32 (36%) were non-secretory benign adrenal adenomas and the remaining were benign adrenal (n = 8; 9%) or extra-adrenal (n = 24; 27%) masses. Endocrinological investigations revealed 1 Conn adenoma, 4 tumors responsible for Cushing's syndrome or silent hypercortisolism and 1 androgen secreting tumor. Abnormalities of endocrine evaluations were observed in the 2 malignant adrenocortical carcinomas. Elevated 24-h urinary metanephrine levels were observed in the 9 pheochromocytomas tested. Complications of surgery occurred in 14% of the cases. Regardless of the endocrine status, parameters associated with malignant tumors were: older age (mean age of patients harboring malignant tumors vs patients with benign incidentalomas: 62+/-17 years vs 52+/-13 years, P = 0.005), weight loss (39% vs 7%, P = 0. 005), and mass diameter greater than 60mm (69% vs 15%, P < 0.001). By multiple logistic regression analysis malignant tumors were associated with increased age, diameter greater than 60mm and bilateral masses. CONCLUSION: This study points to a high rate of pheochromocytomas and malignant tumors in patients selected for surgery. This high rate differs from some previous reports and might be explained by the criteria used to select patients for surgery. Among these two groups of tumors, careful systematic endocrinological investigations allow the detection of altered secretion in the vast majority - if not all - malignant tumors of adrenal origin and pheochromocytomas. Only 5% of the incidentalomas below 30 mm selected for surgery in this study were malignant, in keeping with the use of this criteria as an important parameter to select patients with normal hormonal investigations for careful follow-up. (+info)
Plasma metanephrines: a novel and cost-effective test for pheochromocytoma.
Pheochromocytomas are rare chromaffin cell tumors that nevertheless must be excluded in large numbers of patients who develop sustained or episodic hypertension as well as in many others with suggestive symptoms or with a familial history of pheochromocytoma. Diagnosis of pheochromocytoma depends importantly on biochemical evidence of excess catecholamine production by a tumor. Imperfect sensitivity and specificity of commonly available biochemical tests and the low incidence of the tumor among the tested population mean that considerable time and effort can be expended in confirming or ruling out pheochromocytoma in patients where the tumor is suspected. Measurements of plasma free metanephrines provide a superior test compared to other available tests for diagnosis of pheochromocytoma. In particular, the high sensitivity of plasma free metanephrines means that a normal test result reliably excludes all but the smallest of pheochromocytomas so that no other tests are necessary. Measurements of plasma free metanephrines, when systematically combined with other diagnostic procedures outlined in this review, provide a more efficient, reliable and cost-effective approach for diagnosis of pheochromocytoma than offered by previously available approaches. (+info)
Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency.
BACKGROUND: Glucocorticoids are essential for the normal development and functioning of the adrenal medulla. Whether adrenomedullary structure and function are normal in patients with congenital adrenal hyperplasia is not known. METHODS: We measured plasma and urinary catecholamines and plasma metanephrines in 38 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (25 children with the salt-wasting form and 13 with the simple virilizing form), 39 age-matched normal subjects, and 20 patients who had undergone bilateral adrenalectomy. Adrenal specimens obtained from three other patients with 21-hydroxylase deficiency who had undergone bilateral adrenalectomy and specimens obtained at autopsy from eight other patients were examined histologically. RESULTS: Plasma epinephrine and metanephrine concentrations and urinary epinephrine excretion were 40 to 80 percent lower in the patients with congenital adrenal hyperplasia than in the normal subjects (P<0.05), and the values were lowest in the patients with the most severe deficits in cortisol production. Urinary epinephrine excretion and plasma epinephrine concentrations were at or below the limit of detection of the assay in 8 (21 percent) of the patients with congenital adrenal hyperplasia and in 19 (95 percent) of the patients who had undergone adrenalectomy. In the group of patients with congenital adrenal hyperplasia, plasma epinephrine and metanephrine concentrations and urinary epinephrine excretion were approximately 50 percent lower in those who had been hospitalized for adrenal crises than in those who had not. In three patients with congenital adrenal hyperplasia who had undergone bilateral adrenalectomy, the formation of the adrenal medulla was incomplete, and electron-microscopical studies revealed a depletion of secretory vesicles in chromaffin cells. CONCLUSIONS: Congenital adrenal hyperplasia compromises both the development and the functioning of the adrenomedullary system. (+info)
Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study.
OBJECTIVE: The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis. DESIGN: Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and 3 with MEN 2B (from 3 families). METHODS: Medullary thyroid carcinoma (MTC) was diagnosed by measuring plasma calcitonin in basal conditions or after pentagastrin stimulation. The search for pheochromocytoma consisted of clinical evaluation, 24 h determination of urinary catecholamines and adrenal imaging. The mean age at genetic diagnosis of MEN 2 was 14.0+/-7.0 years, the mean duration for the follow-up was 7.6+/-2.8 years. RESULTS: All 87 patients had a MTC detected at the same time as the genetic diagnosis was made. Urinary catecholamine measurements led to the diagnosis of pheochromocytoma and a combination of imaging techniques enabled the correct localization of both unilateral or bilateral adrenal involvement. Pheochromocytoma was detected simultaneously with MTC in only seven patients, and seven others were detected throughout the follow-up. Of the 14 patients with pheochromocytoma, 11 had bilateral involvement: nine were initially bilateral and two became so during follow-up. CONCLUSION: This study demonstrates that in MEN 2, MTC is the lesion which appears earliest. Pheochromocytoma develops later during the evolution of the disease, and necessitates regular clinical and biological monitoring throughout follow-up. Determination of urinary and/or plasma catecholamines and metanephrines should be performed to detect pheochromocytoma. Imaging techniques lead to the detection of both unilateral and bilateral pheochromocytoma, thus making video-assisted laparoscopic adrenalectomy possible. (+info)