Single-voided urine metanephrine assays in screening for pheochromocytoma.

To facilitate the screening for pheochromocytoma, we have validated the use of single-voided, spot urine specimens for the determination of total metanephrines. Metanephrine excretion was found to be quite constant throughout the day and night in ten patients with essential hypertension and seven patients with pheochromocytoma. The levels in single-voided specimens were closely correlated to those in 24-hour specimens in 100 hypertensive subjects. The mean +/- 2 SD metanephrine excretion in single-voided urine specimens from 500 hypertensive subjects was 0.351 +/- 0.356 mug/mg of creatinine.

Glucagon-blood catecholamine test: use in isolated and familial pheochromocytoma.

In 149 cases, blood pressure response to glucagon test did not exceed 20/10 mm Hg more than the response in the cold pressor test control and was considered negative. Plasma catecholamine level increases may be seen in 95% of patients without pheochromocytomas. Among six patients with pheochromocytomas, urinary metanephrine levels were of diagnostic importance in two with isolated pheochromocytoma and in one with the multiple endocrine neoplasia of type 2 (MEN-type 2). Urinary metanephrine determinations yielded false-negative results in three patients with MEN-type 2, while vanilmandelic acid level was normal in one and nephrotomograms were positive in two of these three. These results suggest that the early diagnosis of pheochromocytoma in patients with MEN-type 2 may be difficult and may require multiple biochemical and roentgenographic investigations.

Evaluation of pindolol dosage in hypertension by automatic indirect BP monitoring.

Pindolol, a nonselective beta-adrenergic blocking drug, lowered systolic and diastolic BP equally well during once-daily and twice-daily dosage. Side effects were few. Absence of supine bradycardia distinguished this drug from other beta-adrenergic blockers and likely was attributable to the agent's intrinsic sympathomimetic activity. Blood pressure variability was less during therapy. Automatic indirect BP monitoring reliably confirmed office and home BP recordings and indicated good control throughout waking and sleeping periods.

Comparison of ketanserin and metoprolol in the treatment of essential hypertension.

Ketanserin, a serotonin receptor antagonist (S2), lowered blood pressure in patients with essential hypertension; at three months 72% (13/18) had a successful reduction in pressure. No marked orthostatic changes were noted. Older patients responded better when standing. Compared with metoprolol, ketanserin provided no significant difference in response at three months. With ketanserin, the heart rate was reduced only in the supine position, whereas it was reduced in the supine and standing positions with metoprolol. Response to ketanserin could not be predicted from baseline renin, aldosterone, or cortisol levels in blood, nor were there any changes in these factors or in plasma hydroxyindole levels with therapy. Ketanserin was generally well tolerated. Cholesterol values were significantly reduced with ketanserin, and there were no adverse hematologic or biochemical changes. Ketanserin should have a significant role in managing hypertension.

Cold pressor test as a predictor of hypertension.

To determine the usefulness of the cold pressor test as a predictor of hypertension, we compared the blood pressure recordings available from 142 patients in 1979 with readings obtained during performance of two cold pressor tests, the first in 1934 when these subjects were children, and the second in 1961. Forty-eight subjects were hyperreactors to the tests in either 1934 or 1961, and 94 were normoreactors. At last follow-up, blood pressures in 14 of the hyperreactors were between 140 and 160 mm Hg systolic or 90 and 100 mm Hg diastolic (Stratum 1) and in 20 exceeded 160 mm Hg systolic or 100 mm Hg diastolic (Stratum 2). Ten normoreactors had casual blood pressures in Stratum 1 and eight in Stratum 2. Hypertension had thus occurred in 71% of the hyperreactors and 19% of the normoreactors. Fifteen hyperreactors were receiving antihypertensive therapy, and this reduced the severity of the casual blood pressure elevation in most patients to Stratum 1. Antihypertensive therapy had been started in three normoreactors. The duration of follow-up, 45 years, and the mean age at follow-up, almost 57 years, were greater in this study than in any previously reported study. Early hyperreactivity was related to future hypertension in enough subjects to suggest that an abnormal response to an external cold stimulus may be useful as an indicator of future hypertension.

National standard for measurement of resting and ambulatory blood pressures with automated sphygmomanometers.

The Association for the Advancement of Medical Instrumentation develops voluntary standards for medical devices so that manufacturers might provide information on their product and basic safety and performance criteria that should be considered in qualifying the instrument for clinical use. American national standards are generated through a consensus process by committees consisting of experts in research, development, and design from user, industry, and government communities. Draft standards are made available for public review and may become American national standards after review by the American National Standards Institute. The first American national standard for electronic and automated sphygmomanometers was published in monograph form in 1987. The objective of the revised 1992 standard for electronic and automated sphygmomanometers is to provide updated labeling, safety, and performance requirements that help ensure that consumers and health care professionals are supplied with safe, accurate devices for the indirect measurement of blood pressure, including ambulatory blood pressure recorders. This standard permits validation of the automatic or electronic device by comparison with either direct, intra-arterial blood pressure measurements or the noninvasive cuff/stethoscope technique, based on Korotkoff sounds identified by individuals trained in auscultation. This summary report of the 1992 American national standard for automatic sphygmomanometers provides recommendations for the methods of comparison, statistical analysis of the data, presentation of the results, and criteria for acceptability. Users, researchers, and instrument designers should refer to the American national standard monograph for detailed requirements.

Detection and control of high blood pressure in the community : Do we need a wake-up call?

At the community level, the effect of national programs in increasing hypertension awareness, prevention, treatment, and control is unclear. This study evaluated the degree of detection and control of high blood pressure in a random population-based sample of Olmsted County, Minnesota, residents >/=45 years old, of whom 636 subjects among 1245 eligible residents agreed to participate. Home interview and home and office measurements of blood pressure were used to estimate awareness, treatment, and control rates for hypertension in the community. Mean blood pressures (+/-SD) were 138/80+/-20/12 mm Hg for men and 137/76+/-23/11 mm Hg for women. The overall prevalence of hypertension was 53%. The percentage of subjects with treated and controlled hypertension was 16.6%. Thirty-nine percent of subjects were unaware of their hypertension. Despite clinical trial evidence of reduced morbidity and mortality with antihypertensive therapy, recently reported national data suggest a leveling-off trend for treatment and control of hypertension. This population-based study supports these observations and suggests that at a community level, hypertension awareness and blood pressure control rates are suboptimal, presumably because of decreased attention to the detection and control of hypertension.

Pharmacodynamics of midodrine, an antihypotensive agent.

Midodrine is an orally active adrenergic agonist useful in the treatment of hypotension. We have investigated the pharmacodynamics of its active metabolite after oral midodrine therapy in nine patients with severe orthostatic hypotension. Peak plasma levels of the metabolite were reached in 60 to 90 minutes and ranged from 25 to 56 ng/ml. The mean values for distribution volume, plasma clearance, and t1/2 were 4.0 L/kg, 23 ml/min/kg, and 2.1 hours, respectively. Heart rate increased after 5 to 10 mg doses and the increases were statistically significant (P less than 0.05) at 120 minutes. An apparent increase in blood pressure was not statistically significant. The patients said that they felt better.

Prospective study of immune response to hydralazine and development of antideoxyribonucleoprotein in patients receiving hydralazine.

To examine the relationship between the immune responses to hydralazine, a drug known to induce systemic lupus erythematosus, and to deoxyribonucleoprotein (DNP) we followed prospectively 21 hypertensive patients treated with hydralazine for the first time. Within one year, antibodies to hydralazine developed in 16 of these patients and anti-DNP in seven of these. In one patient whose serum had a positive antinuclear antibody test prior to treatment, a mild hydralazine systemic lupus erythematosus syndrome developed preceded by rises in the levels of both anti-hydralazine and anti-DNP. Studies by radioimmunoassay on serums of three additional patients, not followed in this study but known to have hydralazine-induced systemic lupus erythematosus, revealed no evidence for either (1) cross-reactivity between anti-DNP and anti-hydralazine or (2) antibodies specific for a hydralazine-DNP complex. In some way, perhaps related to the mechanism by which carrier molecules enhance the immunogenuity of haptens, hydralazine increases the antigenicity of DNP. This effect depends on the development of immunity to hydralazine as well.

Catecholamine-secreting paraganglioma of the interatrial septum.

A 29-year-old woman was found to have clinical and biochemical evidence of a functioning paraganglioma (pheochromocytoma) five years after the onset of symptoms. Despite extensive investigation of known potential sites of paragangliomas (including laparatomy), the suspected tumor eluded localization. Adrenergic blocking agents controlled her blood pressure but did not affect the other manifestations of catecholamine excess. Ischemic perforation of the colon and refractory gram-negative sepsis resulted in death. At autopsy, a large paraganglioma was found within the heart; the unique tumor location was an important factor in the fatal clinical course.

Familial pheochromocytoma and islet cell tumor of the pancreas.

The occurrence of pheochromocytoma(s) or pancreatic islet cell tumor(s), or both, in two or more members of three unrelated families in a manner consistent with autosomal dominant inheritance suggests that this tumor association is a genetically determined syndrome. Among 11 affected patients (aged five to 53 years), 10 had pheochromocytoma (bilateral in six), four had islet cell tumor (multicentric in one), and three had both tumors. Clinical presentation was due to pheochromocytoma in 10 cases (symptoms or signs commencing before age 10 years in three patients) and islet cell carcinoma in one case. Four patients are dead as a result of the tumors--two from pheochromocytoma and two from islet cell carcinoma.

Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2.

We studied the gross and microscopic pathology of the adrenal gland in 69 cases of sporadic phenochromocytoma in order to develop a profile of the neoplasm to compare with that of pheochromocytoma observed in the syndrome of multiple endocrine neoplasia, type 2 (MEN 2). The results showed that sporadic pheochromocytoma was a unicentric (93%), unilateral (100%) neoplasm, which was associated with normal extratumoral adrenal medulla (100%). The findings contrast with those encountered in the adrenal gland in MEN 2, in which the tumor involvement is frequently multicentric, usually bilateral, and associated with extratumoral medullary hyperplasia in cases of early involvement. Therefore, the interpretation of the results of pathologic examination of a pheochromocytoma should be immediately communicated to the surgeon.

Diagnostic evaluation of pheochromocytoma.

Progress in the diagnostic evaluation of pheochromocytoma has taken place in biochemical studies and localization techniques. Measurement of fractionated catecholamines and their metabolites has been subjected to sensitivity and specificity assessment. Magnetic resonance imaging and isotopic imaging have led to much better localization of extra-adrenal tumors. Flow cytometry of the DNA of the tumor cells very likely indicates the malignant nature of the tumor.

Echocardiographic findings in pheochromocytoma.

M-mode and 2-dimensional echocardiography were used to study 26 consecutive, unselected patients with pheochromocytoma over a 3-year period. Only 1 patient had congestive heart failure; more than half had no cardiac symptoms or abnormalities. The most common (80% of patients) echocardiographic pattern was normal left ventricular (LV) mass with normal or even increased systolic performance. When LV mass was increased, LV systolic function was either normal or only borderline depressed in most of the patients. Patients with echocardiographic LV hypertrophy had symmetric thickening of ventricular walls; no case of asymmetric septal hypertrophy was found. There was no correlation between 24-hour urinary norepinephrine excretion and any of the echocardiographic variables studied. In some patients, increased LV wall thicknesses did not correlate with increased LV mass as calculated by the Woythaler echocardiographic method. Left atrial enlargement was not seen in any patient, including those with increased LV mass. The electrocardiogram and echocardiogram may be discordant: Electrocardiographic LV hypertrophy was seen in 6 patients, of whom 5 had normal echocardiographic LV mass. In patients with pheochromocytoma who have no cardiac symptoms or other clinical evidence of cardiac involvement, echocardiographic findings are usually normal.

Cardiovascular complications of pheochromocytoma crisis.

Two patients with hypertensive crises due to pheochromocytoma presented with unusual features suggestive of cardiovascular disorders other than pheochromocytoma. These features included transient cortical blindness and other neurologic deficits, electrocardiographic changes indicative of transmural infarction and peripheral arterial spasm. In both patients the diagnosis of pheochromocytoma was made later; removal of the tumor was followed by ready reversal of the clinical and biochemical abnormalities. Management of such cases includes suspicion of the diagnosis in the presence of atypical features, early initiation of therapy with alpha and beta adrenergic blocking agents and a definitive surgical procedure before peripheral vascular changes become irreversible. When an apparent myocardial infarction occurs, the diagnosis of coronary artery disease cannot always be excluded, but rapid stabilization of the clinical and electrocardiographic changes after adrenergic blockade would favor the diagnosis of a catecholamine-induced myocarditis. The coexistence of coronary artery disease and uncontrollable arrhythmias presents an increased risk but, if pheochromocytoma is suspected, surgery may be necessary despite the increased risk.

Verapamil and 24-hour ambulatory blood pressure monitoring in essential hypertension.

The antihypertensive effects of oral regular and slow-release verapamil, a calcium-channel blocking agent, were evaluated in 22 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95 to 112 mm Hg). The dose required to control blood pressure varied from 80 to 120 mg, 3 times a day. All patients received regular verapamil for a further 3 to 4 months, when systolic blood pressure (SBP) and DBP had risen from the end of the open-label phase. During a double-blind phase patients were randomly assigned to continue the same dose of regular verapamil, 3 times a day, or an equivalent daily dose of sustained-release verapamil (240 to 360 mg once a day). Seven of the 11 patients on regular and 3 of the 11 on sustained-release verapamil were also taking diuretics. This antihypertensive program was continued for at least 4 weeks. During the efficacy period, 24-hour ambulatory blood pressure monitoring was carried out. Mean 24-hour SBP and DBP were 133 +/- 20 and 89 +/- 13 mm Hg, respectively, on regular and 131 +/- 22 and 87 +/- 12 mm Hg, respectively, on sustained-release verapamil. There were no statistically significant differences noted between the 2 groups. Mean SBP and DBP varied similarly during awake and sleep hours with both formulations of verapamil. With regular verapamil, SBP was 139 +/- 18 and 124 +/- 20 mm Hg and DBP 92 +/- 11 and 84 +/- 13 mm Hg during awake and sleep hours, respectively; with sustained release, SBP was 138 +/- 21 and 122 +/- 22 mm Hg and DBP 92 +/- 10 and 80 +/- 10 mm Hg during awake and sleep hours, respectively. Heart rate fell during the entry period and continued during the entire study period. No other adverse effects were noted during the double-blind phase. In summary, verapamil is an effective antihypertensive medication and can be administered once a day as a sustained-release preparation; it is most useful in patients in whom adrenergic blocking drugs are indicated.

Carney's triad: guidelines for management.

Carney's triad--gastric leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma--is a syndrome that occurs primarily in young women. To date, 28 patients with at least two of these individually unusual or rare neoplasms have been described. This updated case report of one of the originally described patients with Carney's triad highlights several clinically important features of this unusual syndrome: (1) the multicentricity of both the paragangliomas and the epithelioid leiomyosarcomas, (2) the often indolent progression of metastatic leiomyosarcoma, (3) the potential for late recurrences, and (4) the importance of distinguishing intra-adrenal from periadrenal catecholamine-producing tumors (paragangliomas). Localization of paragangliomas is facilitated by two relatively new techniques--131I-metaiodobenzylguanidine scanning (a scintigraphic technique with high specificity for catecholamine-producing tumors) and two-dimensional echocardiography (which can noninvasively localize and demonstrate the anatomic relationships of aorticopulmonary paragangliomas). In patients with this syndrome, new or recurrent tumors frequently manifest after unusually long asymptomatic intervals. We outline an approach for continued follow-up of patients with one or more of the three neoplasms that constitute the syndrome. Rigorous long-term screening of these patients should not only lead to early recognition and resection of recurrent or new tumors but also enhance our understanding of this intriguing syndrome.

Current role of automated ambulatory blood pressure and self-measured blood pressure determinations in clinical practice.

OBJECTIVE: To discuss the clinical indications for use of automated indirect blood pressure measurement (ABPM) and self-monitoring of blood pressure. DESIGN: Available equipment, variations in blood pressure, and settings in which ABPM may be useful are reviewed. RESULTS: Measurement of blood pressure in the physician's office may not reflect the usual blood pressure in other nonmedical environments, such as at work, at home, or during sleep. Self-measurement of blood pressure at home and work and ABPM can provide this additional information. These procedures can be useful not only for determining the presence of office or "white-coat" hypertension but also for assessing patients with both borderline hypertension in the office and target organ damage, those with drug resistance, and cases of episodic hypertension or hypotension. ABPM can also be used to assess very abrupt changes in blood pressure (hypertension or hypotension) and changes in heart rate and blood pressure during sleep. An abbreviated (6-hour) ABPM can be used to confirm increased office blood pressure measurements. Thus, a 6-hour ABPM has the potential to decrease the misclassification of subjects with hypertension or normotension and to limit costs. CONCLUSION: Accurate self-monitored blood pressure measurements can be integrated with office blood pressure determinations to assist in the management of many patients with hypertension. Both ABPM and self-monitoring of blood pressure can improve blood pressure control and practice efficiencies.

Management of patients with hypertension: a hypertension clinic model.

OBJECTIVE: To describe a successful system for managing outpatients with hypertension. DESIGN: The establishment of a Hypertension Clinic in the Division of Hypertension at the Mayo Clinic was reviewed. MATERIAL AND METHODS: The assignment of responsibilities in the use of a team approach was evaluated, and the various types of patients encountered were compared. RESULTS: Our experience has shown optimal control of hypertension in outpatients with use of a team approach, including hypertension medical specialists, nurses, dietitians, and nurse-educators. Patients also assume an active role in their own care, particularly for compliance with medications and recommended lifestyle changes, attendance at the Hypertension Clinic for follow-up monitoring, and reporting of symptoms or side effects of drugs. Individual goals are established, and patients are managed by the nurse-clinicians. The physician reviews each patient's course at regular intervals or as needed for specific situations. Short-term patients, long-term patients, and those undergoing liver transplantation have successfully participated in this type of a program. CONCLUSION: The team approach for management of outpatients with hypertension effectively provides a support system for prompt attention to any questions or medical problems that arise. With such an approach, decreased morbidity and mortality from hypertension and associated cardiovascular disease have been achieved.

Hypertension.

Hypertension, a health problem of epidemic proportions, has not been controlled successfully. Screening efforts are increasing the detection of cases, and current emphasis on treatment rather than detailed evaluation is increasing the incidence of control of hypertension. Patient compliance is crucial, however, because all of the currently available treatments require daily taking of pills by patients who commonly do not understand their disease or the need for treatment. Efforts at increased public education and improved doctor-patient relationships are important if the epidemic is to be overcome. This paper reviews diagnosis, evaluation, treatment, public education, and patient compliance.