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In order to estimate the function of the pineal gland, the sympathetic nervous system and the adrenal medulla in patients with familial amyloid polyneuropathy relative to healthy subjects, we have quantified urinary 6-hydroxymelatonin, normetanephrine and metanephrine. Urinary 6-hydroxymelatonin level correlated with neither of two O-methylated catecholamine levels in healthy subjects. The excretion of both 6-hydroxymelatonin and metanephrine were reduced in the patient group as compared with the control group, and the normal daily rhythm of 6-hydroxymelatonin was undetectable in the most of the patients. This finding indicates that the function of the pineal gland is disturbed in familial amyloid polyneuropathy.

We describe a simplified fluorometric method for quantitatively determining metanephrines in urine. The method is based on the elution of metanephrines from an ion-exchange column followed by production of a fluorescent derivative that has excitation and emission maxima of 405 nm and 505 nm, respectively. Metanephrine concentrations as great as 7.0 mg/L were within the linear range of the assay. Analytical recovery of metanephrines was 82-87%. Cross contamination by catecholamines was insignificant. The upper range of normal was 520 micrograms/24 h. Within-run and between-run CV's were 5% and about 9%, respectively. Twenty-four-hour urine specimens from five patients with pheochromocytoma showed above-normal amounts of the metanephrines by this method.

Tested male Ss (N = 34) to determine how changes in the urinary excretion patterns of selected catecholamines and their metabolites affect the multivariate relationships involving variables that measure physical fitness condition and selected personality characteristics. Urine specimens were collected from each S after sleep and during occupational activities and analyzed for six catecholamine-related variables. Those measures were combined with six personality variables (MMPI) and a physical fitness score (Ismail Criterion), and subjected to first- and second-order factor analyses. The findings indicated an association between low physical fitness and high self-reported anxious depression during the occupational period, but not at rest. The changes in the factor structures were statistically mediated by changes in the concentrations of the biochemical variables across the collection periods. This suggests that the relationships between physical fitness and personality are augmented during catecholamine reactivity to occupational stress.

The 24-hour urinary catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol, normetanephrine, and metanephrine were measured in 23 hyperactive boys and 13 matched healthy controls. The hyperactive children excreted lower MHPG and higher NM (low MHPG/NM ratio) amounts than in controls. The administration of d-amphetamine in the dose of 0.5 mg/kg body weight divided over two doses daily for two weeks decreased MHPG excretion in the hyperactive children. When the hyperactive children group was divided into drug responders and nonresponders according to their pre- and post-treatment scores on the Conners Teacher Questionnaire, d-amphetamine administration decreased MHPG excretion in the responders and did not change it in the nonresponders. Percent decrease in MHPG excretion correlated significantly with percent change in the hyperactivity factor of the questionnaire on the Spearman Rank Order Correlation Coefficient. Pretreatment urinary metabolites did not differentiate the responders from nonresponders. It is suggested that a relationship between CNS norepinephrine metabolism and hyperactivity exists and that d-amphetamine may achieve its therapeutic action in hyperactive children by altering CNS NE metabolism.

Two patients who had removal of seemingly benign pheochromocytomas had recurrences 10 and 14 years later despite normal catecholamine excretion for 7 and 9 years postoperatively. The first patient returned with a myocardial infarction and an apparently solitary recurrence; the second patient with a stroke and metastatic disease. Both patients had recurrence of hypertension and increased catecholamine excretion. They were given phenoxybenzamine and are doing satisfactorily 7 and 9 years after their recurrences. Such patients should be followed after surgery for 15 or more years for early detection of recurrences. Prompt therapy should reduce the risk of undesirable complications.

The previous article in this series reported on the differences in urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in patients with various clinically defined subtypes of depressive disorders. We now report that further biochemical discrimination among depressive subtypes is provided by the following equation, derived empirically by applying multivariate discriminant function analysis to data on urinary catecholamine metabolits: Depression-type (D-type) score = C1(MHPG) + C2(VMA) + C3(NE) +C4(NMN + MN)/VMA + C0. In the original derivation of this equation, low scores were related to bipolar manic-depressive depressions, and high scores were related to unipolar nonendogenous (chronic characterological) depressions. Findings from a series of depressed patients whose biochemical data had not been used to derive this equation confirmed these differences in D-type scores among subtypes of depressions. The findings presented in this report further suggest that we can discriminate three biochemically discrete subgroups of depressive disorders.

A case is reported of a patient with a cerebral aneurysm in whom it was difficult to induce hypotension. The hyperadrenergic state mimicked, in some respects, that seen in patients with neural crest lesions. Possible mechanisms are discussed and the anaesthetic management described.

In a series of 53 pheochromocytoma patients operated on at Sahlgren's Hospital during 1956-82, a positive linear correlation is established between the 24-hour urinary excretion of vanilmandelic acid (mumol/24 h) and tumour mass (g). A similar correlation was found between the excretion of metanephrines and tumour mass in 33 subjects. The patients were subgrouped according to their type of hypertension. A statistically significant correlation between vanilmandelic acid excretion and tumour mass persisted in groups IA (sustained hypertension without attacks), IB (sustained hypertension with attacks), and II (paroxysmal hypertension) but not in group III (miscellaneous patients). There was also a correlation between metanephrine excretion and tumour mass in groups IB (n = 8) and II (n = 12). In 10 patients with the syndrome of multiple endocrine neoplasia, a positive correlation was found between tumour mass and the excretion of vanilmandelic acid, metanephrines and adrenaline.

Phaeochromocytomas are uncommon among patients with hypertension, and sometimes occur in persons without known hypertension, but are important to detect because they are often lethal but commonly curable, and because they are a clue to the presence of associated conditions. Paroxysmal symptoms (especially headache, palpitations, diaphoresis and anxiety), hypertension that is intermittent, unusually labile or resistant to conventional therapy, and conditions known to be associated raise the clinical suspicion of phaeochromocytoma. Biochemical confirmation is commonly achieved by measurement of urinary catecholamines, metanephrines or VMA. Plasma noradrenaline and adrenaline measurements may be superior to measurements of urinary catecholamine metabolites, but strict attention to the details of sample collection, handling and storage, the many sources of possible biological variation and the effects of drugs is critical if diagnostic error is to be avoided. Patients should be evaluated in the drug-free state if at all possible. Anatomical localization, in the abdomen in the vast majority of cases and usually in the adrenal medullae, can generally be accomplished with computed tomographic scans. Bilateral adrenomedullary tumours are the rule in familial phaeochromocytoma. Most phaeochromocytomas are benign and can be excised totally after medical preparation with an alpha-adrenergic antagonist.

The urinary excretion of dihydroxyphenylalanine (DOPA), catecholamines (CA) [dopamine (DA), norepinephrine (NE), and epinephrine (e)], their 3-O-methylated derivatives [3-O-methyldopamine (3-MT), normetanephrine (NMN), and metanephrine (MN)], and their deaminated metabolites [dihydroxyphenylacetic acid (DOPAC) and vanilmandelic acid (VMA)] was studied in six healthy men, at rest during short-term (15 min) or exhaustive submaximal exercise, and in the 2-h postexercise recovery period. During short-term exercise only NE and VMA excretions increased, whereas in postexercise period only DA output was enhanced. Exhaustive muscular work induced a rise in NE and E excretion during the test, and an increase in DA, NE, and NMN urinary levels during postexercise recovery, while the output of deaminated metabolites was unaltered. It is concluded that both release and synthesis of CA are stimulated by submaximal exercise, which induces, in addition to NE, a specific release of DA. A possible role of NE in lipid mobilization during recovery from exhaustive muscular work is evoked. The origin and role of released DA are also discussed.

A simple, but effective, procedure is described for the concurrent estimation of normetadrenaline (NMA) and metadrenaline (MA) in urine. The 3-methoxycatecholamines are adsorbed by a cation exchange resin, desorbed, separated by paper chromatography, and finally estimated spectrophotometrically after oxidation to vanillin. The mean (+/- 2 standards deviations) urinary outputs of NMA and MA from 123 normals (80 males, 43 females) in 24 hours was 2.15 +/- 1.04 and 1.79 +/- 0.96 mu mol respectively. There was no significant difference in the 24-hour urinary outputs of NMA between the male and female groups. However, the output of MA from the males was significantly higher than that from the females.

Measurements of urinary metanephrines by the Pisano procedure (Clin. Chim. Acta 5: 406, 1960) are unreliable in patients who are taking propranolol owing to the presence of 4-hydroxypropranolol in the urine. Three properties of this propranolol metabolite lead to interference: (a) it is absorbed and eluted from ion-exchange resins under the conditions Pisano used for metanephrine isolation, (b) at high pH it absorbs at 350 to 360 nm, and (c) it is oxidized by periodate to a substance with negligible absorption in this region. Because 350 to 360 nm is the wavelength used to quantitate vanillin, the product formed from periodate oxidation of metanephrines, and because the unoxidized eluate is used as a specimen blank, the presence of 4-hydroxypropranolol spuriously decreases the measured urinary metanephrines; this has special significance because patients being tested for increased metanephrines are also likely to be receiving propranolol for hypertension.

Urinary catecholamine levels were measured in 25 anorexia nervosa patients at the time when they were acutely ill with secondary depressive symptoms and again after treatment and weight gain to see whether changes in weight, activity levels, and symptoms of depression occurring during treatment might be associated with changes in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations. The latter was significantly lower in the acutely ill anorectics than in the control group. An increase in urinary MHPG concentration after treatment was significantly correlated with a decrease in depressive symptomatology. The increase in urinary MHPG level during treatment did not correlate significantly with change in patient's activity level. There seems to be a relationship between MHPG and the symptom of depression in a group of patients who do not carry a primary diagnosis of depression.

Many of the cardinal somatic symptoms associated with anxiety states are produced by the sympathoadrenal medullary discharge of catecholamines (CA) described over 50 years ago as 'fight or flight' responses. During the last decade, development of sensitive convenient assays for CA and their metabolites in tissues, cerebrospinal fluid, plasma and urine has made possible assessment of brain and peripheral adrenergic activity during stress, in neuropsychiatric disorders, and after administration of drugs. Studies in animal models of stress and anxiety parallel studies in humans. In rats, there are genetic differences in the graded adrenergic alerting responses to administered or anticipated stress, analogous to trait anxiety in humans. Behavioral responses to stress may be attenuated in rats by pharmacological blockade of peripheral CA release, suggesting a positive feedback process in which released CA augment behavioral responses, possibly analogous to use of clonidine or beta-adrenergic blocking agents to diminish somatic symptoms attending anxiety-provoking situations in humans. The biochemical evaluation of adrenergic responses by examination of CA and their metabolites in body fluids of humans with various levels of sympathetic activation will be discussed.

In five healthy selected volunteers with normal blood pressure and one pheochromocytoma patient, high performance liquid chromatography (HPLC) has been evaluated, with electrochemical detection for quantitation of urinary catecholamines and metanephrines during administration of the antihypertensive, alpha-methyldopa. The clinical usefulness of HPLC is compared with that of the conventional assay method--the trihydroxyindole (THI)-fluorometric procedure. The THI fluorometric method is known to suffer from true false-positive interference as a result of its inability to differentiate between alpha-methyldopa, its primary metabolic derivatives, and the structurally similar endogenous catecholamines. It is shown that the HPLC separation methodology yields accurate, reproducible results devoid of interference from the presence of alpha-methyldopa. Free urinary excretion rates of epinephrine, norepinephrine, and dopamine were elevated by alpha-methyldopa, P less than 0.001, for epinephrine, norepinephrine, and dopamine when measured by the trihydroxyindole technique but not with high performance liquid chromatography. With alpha-methyldopa treatment, urinary normetanephrine excretion rates were slightly increased, P less than 0.05, by fluorometric analysis and slightly decreased. P less than 0.05, when measured by HPLC. Of added interest, the formation of the normetanephrine analog of alpha-methyldopa, previously undetected, is suggested. Slightly elevated metanephrine levels are seen by the THI-fluorometric method in the presence of alpha-methyl metanephrines. Establishing that the HPLC assay procedure is suitable for clinical diagnosis of pheochromocytoma, despite the presence of alpha-methyldopa, makes it unnecessary to discontinue use of this antihypertensive in screening for pheochromocytoma.

Forty-one patients who had pheochromocytoma are described. These patients represent the experience of the authors over the last 19 years. The diagnoses, investigations, treatments, and pitfalls of this study and the management of these patients are described. The most sensitive screening test was the urinary measurement of catecholamines, vanillylmandelic acid (VMA), and metanephrines. The most useful localizing procedure was the metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT). After careful alpha and beta adrenergic blockade in 32 patients, no complications occurred during or after tumor resection. When this procedure was ignored even in patients who had normal blood pressure before surgery, severe cardiovascular complications occurred and two patients died. In familial pheochromocytoma, bilateral adrenalectomy with preservation of normal adrenal cortical tissue when possible may be the method of choice, but careful follow-up is warranted.

Diagnosis of pheochromocytoma has been made by the determination of urinary noradrenaline and adrenaline excretion for 24 hours. The assay procedure and the collection of urine for 24 hrs. are intricate. In the present study, we have ascertained the clinical significance of urinary normetanephrine (NM) and metanephrine (M), chemically stable metabolites of catecholamines, in single voided urine for a diagnosis of pheochromocytoma. Urine and plasma samples were collected from 361 normal subjects, 59 patients with essential hypertension, 22 patients with chronic renal failure and 22 patients with pheochromocytoma. Urinary NM and M concentrations were determined by radioimmunoassay with prior hydrolysis by acidification with 1N HCl. Plasma NM and M concentrations in normal subjects were 71.8 +/- 30.7 pg/ml and 41.5 +/- 8.61 pg/ml, respectively. Plasma NM was increased in 8 and plasma M was increased in 20 of 21 patients with pheochromocytoma, although many of these overlapped with those patients with chronic renal failure (NM, 285.9 +/- 175.1 pg/ml; M, 206.3 +/- 186.7 pg/ml) and essential hypertension (NM, 107.7 +/- 90.7 pg/ml; M, 46.7 +/- 20.2 pg/ml). Urinary NM and M concentrations did not show specific diurnal variation and there was significant correlations between the values in single voided urine and those in the 24 hour urine. Urinary NM and M concentrations in normal controls were 197.5 +/- 46.7 ng/mg Cr. and 125.3 +/- 37.1 ng/mg Cr., respectively. Urinary NM concentration was increased in 14 and urinary M concentration was increased in all of 17 patients with pheochromocytoma. In addition, urinary M concentration was higher in most of the 17 patients with pheochromocytoma than that in the patients with chronic renal failure and essential hypertension. However, the values in three patients with Sipple's syndrome with a small adrenal tumor or recurrent cases overlapped with those in other diseases. Relationships between urinary concentrations of NM and/or M and tumor size showed positive correlations. Urinary NM and M concentrations showed significant decreases after surgical removal of the tumors. These results suggest that NM and/or M concentrations in single voided urine could be a sensitive and specific diagnostic tool for pheochromocytoma.

The diagnosis of phaeochromocytoma is dependent on combined biochemical and radiological investigation, the biochemical studies being performed initially and followed later by both non-invasive and invasive radiological techniques. In 23 patients studied, a selection of biochemical studies allowed diagnosis and accurate localization of phaeochromocytoma in 16. In some patients, tumour localization was confirmed by radiographic methods. Biochemical estimations of catecholamines and/or metabolites in urine and/or plasma were also performed during and after operation, and these measurements allowed monitoring of the completeness of tumour excision, and of the possibility of recurrence, in both the short term and the long term follow up of patients.

The interference of various foodstuffs on methods to determine epinephrine (E), norepinephrine (NE), vanillylmandelic acid (VMA), metanephrines (MN), homovanillic acid (HVA), and 6-hydroxyindole acetic acid (5-HIA) in the 24 h urine for diagnosis of pheochromocytoma and carcinoid syndrome, respectively, was investigated. The foodstuffs included were: tea, coffee, almonds, pineapples, cheese, walnuts, vanilla pudding, bananas, tomatoes, and chocolate. Further, the interference of cigarette smoking on the determination of E, NE, VMA, and MN was also investigated. Walnuts caused a rather high elevation of 5-HIA in the urine. After eating bananas elevated excretion of E, NE, VMA, MN, and 5-HIA was observed. Small increases of the MN values were noticed after coffee and pineapples. Smoking of 20-30 cigarettes/day had no influence on the variables measured. If the methods described are used, thus, only bananas and walnuts have to be restricted some days before and during urine sampling, but not coffee and pineapples if consumed in the usual small quantities. There is no reason to insist on diet restriction except for bananas and walnuts.

We studied the recently developed Abbott fluorescence polarization immunoassay (FPIA) for amphetamine and methamphetamine in urine and compared the results with those of the Syva enzyme-multiplied immunoassay technique (EMIT) and a gas-chromatographic assay. The FPIA method showed a limit of quantification of 0.3 mg/L, comparable with the lower cutoff of the EMIT assay. FPIA demonstrated greater specificity than the EMIT assay: phenylpropanolamine and ephedrine showed extremely limited cross reactivity with the FPIA antibody. Analysis of 249 urine specimens by all three methods clearly demonstrated the FPIA method to be acceptable for screening for amphetamine and methamphetamine in urine.

It is possible to separate metanephrine and normetanephrine from urine for the automated fluorimetric routine determination by means of a combination of liquid-liquid partition with ethylacetate and clean-up of the extract through Amberlite XAD-4. The differentiated fluorimetric determination is based on the oxidation with potassium hexacyanoferrate (III) in the presence of zinc ions and different pH values in an autoanalyzer. No quenching effects were observed. The recovery yields were in the range of 60%, the relative standard deviation being less than 10%.

A high-performance liquid chromatographic method has been developed for the determination of metapramine in human plasma and urine. After selective extraction and derivatization with dansyl chloride, metapramine and the internal standard (maprotiline) are chromatographed on a reversed-phase LiChrosorb RP-18 column using a mixture of water--acetonitrile (35:65) as mobile phase. The eluted compounds are measured using a fluorescence detector. The detection limit of the assay for plasma and urine samples is about 1 ng/ml. The method has been successfully applied in a pharmacokinetic study following intravenous administration of 35 mg of metapramine.

Catecholamines (dopamine [DA], norepinephrine [NE], epinephrine [E]), methoxyamines (3-methoxytyramine [MT], normetanephrine [NMN], metanephrine [MN]), DOPA, and acidic metabolites (3,4-dihydroxyphenylacetic acid [DOPAC], vanilmandelic acid [VMA]) were determined in human urines from one day of age to adulthood, in order to investigate sympatho-adrenal development during life. All adrenergic compounds are present in neonate urines on the first day of life, but their postnatal evolution is quite different according to the nature of metabolites. Daily E, MN and VMA amounts remain low until the 10th month of life; daily NE, MT and DOPA levels increase progressively, but, in contrast, NMN amounts are already high in the neonatal period and increase only beyond the fourth year of age. DA is at either age the predominant catecholamine but its elimination is relatively more important in the neonatal period.

We have reviewed 5 years' experience with the College of American Pathologists Urine Chemistry Survey--Series 2. Analytes studied include aldosterone, total free catecholamines, the fractionated catecholamines norepinephrine, epinephrine, and dopamine, total catecholamines, estriol, 5-hydroxyindoleacetic acid, 17-ketogenic steroids, 17-ketosteroids, vanillylmandelic acid, cortisol, metanephrines, coproporphyrin, and uroporphyrin. Interlaboratory precision achieved by participants did not reach levels reported by various investigators, but their studies do not reflect actual clinical laboratory conditions. The intralaboratory analytical precision may be adequate for clinical diagnosis but better interlaboratory agreement must await the preparation of standards verified by definitive analyses. Biases introduced by the use of many different standards probably are the origin of mediocre interlaboratory proficiency testing performance.

Catecholamine metabolites excreted by long-term methadone hydrochloride-dependent subjects were studied in a protocol involving a two-study design. After a two-week methadone maintenance period, 15 subjects underwent abrupt methadone withdrawal and 12 subjects, gradual methadone withdrawal. The first study compared levels of catecholamine metabolites excreted during the stable methadone period with those excreted during the abrupt withdrawal period, as well as with those eliminated by healthy nonaddicted controls. No changes in the excretion of 3-methoxy-4-hydroxyphenylglycol and normetanephrine were noted between the methadone maintenance period and the time of abrupt methadone withdrawal. These values did not differ from those obtained for controls. However, higher levels of metanephreine were excreted during the stable methadone period than those in controls. During withdrawal, levels of metanephrine dropped a statistically significant amount in comparison with levels observed during the stable methadone period. The gradual withdrawal study confirmed these findings.

This study describes the secretion of cortisol, growth hormone, prolactin and catecholamines before, under, and following gynaecological surgery in electrostimulation anaesthesia combined with nitrous oxide (ESA). The hormonal stress reactions of ESA were compared to inhalation anaesthesia with enflurane-nitrous oxide ( EFL ). Twenty-two patients undergoing laparotomy were allocated evenly to one of these procedures. In both groups serum levels for cortisol, growth hormone, and prolactin increased during surgery. Growth hormone showed a considerably higher increase during ESA at the end of the operation, whereas prolactin was higher at all periods of surgery during EFL . Cortisol, however, was identical for both groups. Renal excretion rates of adrenaline and noradrenaline were not significantly different. During surgery more metanephrine and normetanephrine were excreted in the urine under ESA than under EFL . There is no advantage with ESA intra- or postoperatively as compared to other routine procedures of anaesthesia for abdominal gynaecological surgery with regard to the so-called stress hormones or sympathetic activity.

Chronic iron deficiency in rats resulted in decreased MAO activity both in vitro and in vivo. Since MAO is an important enzyme in inactivation of catecholamines, urinary excretion of DA, NE, E, MN-NMN, and VMA was measured in 24-hour samples from 11 iron-deficient children before and after treatment with intramuscular iron. Pretreatment NE excretion was abnormally high and returned to normal (P=0.001) within one week of therapy. VMA excretion also was higher before than after treatment (P greater than 0.05), but most values were within the normal range for healthy children of comparable size. There was no significant difference between DA, E, and MN-NMN excretion before and after iron therapy. Anemic, non-iron-deficient children had normal urinary NE, E, and VMA excretion before and after transfusion. These findings suggest that the irritability, lack of attentiveness, and low performance scores of iron-deficient children may be related to alterations in catecholamine metabolic pathways secondary to dependence of MAO on adequate iron stores.

A method is described for quantitative analysis of urinary free and conjugated catecholamines and metanephrines. The compounds are isolated from the urine by cation exchange on Amberlite CG 50. Separation is performed by ion-pair reversed-phase high-performance liquid chromatography. For detection of the amines their native fluorescence emitted at 313 nm on excitation at 285 nm was monitored. There was good separation of the compounds of interest, while interference by exogenous compounds other than the catecholamines or metanephrines was minimal. The method is rapid and precise, and it has a broad linear working range for all six DOPA metabolites, making it suitable for clinical analysis. Reference values for children of 0-16 years were established. Examples are shown of excretion patterns of DOPA metabolites from patients with different types of neurogenic tumour.

Between 1982 and 1984, 48 studies with 131I-meta-benzylguanidine were carried out in Erlangen in patients with suspected pheochromocytoma or neuroblastoma. Scintigraphy with MIBG was found to be highly specific. False positive findings can be avoided if with weak uptakes an exact correlation with the results of morphological studies such as CT or sonography is sought and if follow-up observations ensure that they are not caused by activity residues in the biliary, intestinal or urinary pathways. False negative findings are made in 5-10% of the investigations in pheochromocytoma and in 41% of those in neuroblastoma patients. In pheochromocytoma the uptake rates are generally low (1-2%), whereas in neuroblastoma they may reach 10% and more.

The metabolites of catecholamines were determined in 24-hour urine samples of patients with genital carcinoma and treated by radio therapy. The patients were irradiated first with gamma-rays of radium and then with X-rays. The radium sources (80 mCi) were placed intracavitarily for 46 hours twice within 2 weeks. X-irradiation (800 R daily), applied 1 month after radium treatment, was delivered on four abdominal fields over 15 days. The quantities of excreted catecholamine metabolites during irradiation were compared with control values (obtained before irradiation) in the same patients. Gamma-irradiation provoked a significant increase in the excretion of 3-methoxy-4-hydroxy-mandelic acid, metadrenaline and normetadrenaline, as well as of homovanillic acid, whereas X-irradiation provoked only a significant increase in the excretion of free 3-methoxy-4-hydroxy-phenylglycol. The increased excretion might be explained: (1) in the case of radium application, by direct radiation-induced release of catecholamines from the peripheral symphathetic nerves; (2) in the case of X-irradiation, by putting in the motion the complex of early neuroendocrine reactions via irradiated adrenal medulla.

To validate the clinical usefulness of recently developed normetanephrine (NM) and metanephrine (M) RIA for the diagnosis of pheochromocytoma, urinary excretion of catecholamines and these metabolites were determined in 30 normal subjects, 40 patients with essential hypertension, 30 patients who were suspected to have but ultimately proven not to have a pheochromocytoma (pheochromocytoma-suspect), and 31 patients with a surgically verified pheochromocytoma. Abnormally high catecholamine excretion (epinephrine plus norepinephrine) was found in patients with pheochromocytoma compared with that in the normal subjects and the essential hypertension group. However, 3 of 31 patients with pheochromocytoma had urinary catecholamine excretion that overlapped the values in the pheochromocytoma-suspect group. Both urinary NM and M excretion also were elevated in patients with pheochromocytoma, but in 4 of 31 patients with pheochromocytoma urinary M excretion was within the range found in 1 or more of the other groups. Total M (NM plus M) excretion of more than 5485 nmol/day (as NM) was found in all patients with pheochromocytoma, and all patients had values that were higher than the highest values in the normal subjects or the patients with no evidence of pheochromocytoma. To save time and simplify the diagnostic work-up of patients suspected of having a pheochromocytoma, we also determined the NM and M concentrations in randomly voided 1-h urine samples in 24 patients with pheochromocytomas, 31 patients with essential hypertension, and 16 normal subjects. Abnormally high total M excretion was found in all patients with pheochromocytomas, and there was no overlap with the values in the patients with essential hypertension or the normal subjects. We conclude that total M measurements in both 24-h and random 1-h urine samples are useful in diagnosing pheochromocytomas.

A glomus jugulare tumor secreted a large quantity of noradrenaline (NA) and produced symptoms of tinnitus, palpitation, sweating, and labile hypertension. The NA content of the tumor was 0.75 mg/gm of tissue. Electron microscopical study of the tumor demonstrated many membrane-limited osmiophilic granules. This indicates the capacity of the tumor not only to synthesize but also to store NA in the tumor. Continuous blood pressure recording showed a cyclic change of blood pressure with a cycle length of 10 to 17 minutes that terminated after intravenous doses of phentolamine (0.1 mg/kg) or diazoxide (4.5 mg/kg) and surgical removal of the tumor.

Blood pressure, alcohol withdrawal symptoms and plasma levels of cortisol, aldosterone and renin activity and serum dopamine beta-hydroxylase concentrations were measured in 65 alcoholics on the first and fourth days after admission for detoxification. On the day after admission blood pressure was elevated (greater than 140/90 mmHg) in 32 patients (49%) and was 160/95 mmHg or more in 21 (32%). Plasma renin activity was elevated in 41 patients and plasma aldosterone concentration in 14, but neither correlated with blood pressure. Plasma cortisol levels were elevated in 13 patients and were positively correlated with systolic blood pressure. Blood pressure and all biochemical measures fell significantly by the fourth day while urine volume and sodium output, low on admission, increased significantly. Urinary metanephrine levels were elevated in four of 31 patients in whom they were measured on admission. Alcohol withdrawal was accompanied by raised blood pressure and high plasma concentrations of cortisol, renin and aldosterone but only plasma cortisol concentrations and withdrawal symptoms were significantly related to blood pressure.

The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column. L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism of L-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oral L-threo-DOPS were essentially equal to those of twice as large a dose of DL-threo-DOPS.

To assess the effect of the new, selective, reversible MAO A inhibitor, CGP 11305 A (4-(5-methoxy-7-bromo-benzofuranyl-2-)piperidine HCl), on MAO A and B activity in man, the daily excretion of total normetanephrine (NMN), metanephrine (MN), 3-methoxytyramine (3-MT) and beta-phenylethylamine (PEA) was measured in the urine of healthy volunteers treated with weekly increasing doses from 40 to 150 mg/d. A similar study was carried out with tranylcypromine in weekly increasing doses from 10 to 25 mg/d. Both compounds increased the excretion of NMN; with CGP 11305 A, a plateau was obtained at 50 mg/d, and tranylcypromine 20 mg was more effective than 10 mg, and was also more active than the highest dose of CGP 11305 A. Increases in MN and 3-MT produced by the latter compound were comparable to that in NMN, whereas tranylcypromine had a biphasic effect on MN excretion, and caused only a small increase in 3-MT excretion. CGP 11305 A up to 150 mg/d did not alter total tyramine excretion, whereas tranylcypromine at 20 mg caused a definite increase. Tranylcypromine led to 4-6 fold increases in PEA output at 20 and 25 mg/d, but not at 10 mg. No such effect could be demonstrated for CGP 11305 A up to 150 mg/d. These results suggest that in man MAO A was inhibited by CGP 11305 A in daily dose of 40 mg or more, whereas it did not affect MAO B at up to 150 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

A simple high-performance liquid chromatographic procedure was developed for the simultaneous determination of catecholamines and metanephrines in urine. One-step sample preparation was achieved with Bio-Rex 70 ion-exchange resin. The extract was assayed on a C18 reversed-phase column. Dihydroxybenzylamine was used as an internal standard. The eluent was monitored by an electrochemical detector with an oxidation potential of +0.85 V. The use of 1-heptanesulphonic acid in the mobile phase permitted the separation of norepinephrine, epinephrine, dopamine, normetanephrine and metanephrine in a single chromatogram. The corresponding detection limits were 5, 9, 14, 10 and 30 nmol/l, respectively. For the between-day precision, the coefficients of variation at physiological and pathological concentrations were less than 11%. Compounds with similar chemical structures and drugs commonly prescribed for the treatment of hypertension were assayed and found not to cause interferences in the chromatogram. The assay is reliable and is suitable for the analysis of clinical specimens. Reference values were established for normotensive Chinese patients with no neurological or endocrine disorders and also for patients suffering from essential hypertension.

A psychiatric and biochemical study was undertaken at the request of two patients who were thought to be terminally ill by the medical staff. One patient accepted dying and expired from her disease. The other patient wished to continue living and did not die. The dying patient exhibited abnormally high levels of catecholamine excretion which were not associated with verbal reports of anxiety or discomfort and did not seem upset or uncomfortable to the physician and nurses caring for her. The patient who lived had relatively low levels of catecholamine excretion and was anxious, irritable and uncomfortable. The behavior of these two patients differed during the period of acute respiratory failure. The dying patient had given up and felt that she was engaging in goal-directed activity which she would or could not shut off. The patient who lived was frightened of dying and felt that she would overcome her current difficulties and that she was not ready or willing to die. The major cardiovascular differences were those of a significantly lower blood pressure and higher heart rate in the patient who died.

From 1949 to 1974, urine samples of 1669 patients with unclarified arterial hypertension were tested for non-conjugated catecholamines. Chromaffine tumours--among them one pheochromoblastoma and two families with inherited forms--were found in 1.1% of all cases. With the procedure applied, adrenergic alpha- and/or beta-mimetic actions on the circulation of cats can be identified when the excretion of total catecholamines is increased by the factor 1.5 to 2.0. Hence, chromaffine tumours with smaller excretion rates (about 200 mug/24 h) are also detectable, so in one case where the excretion of vanillyl-mandelic acid was normal. Thus all prerequisites concerning sensitivity and specificity of a screening method are fulfilled. The large variety of symptoms of chromaffine tumours becomes obvious from the catamnestic data of 19 patients indicating problems which may arise in differential diagnosis.