Pediatric Annals

Noninvasive Evaluation of Pediatric Hypertension

Julie R Ingelfinger, MD

Abstract

Evaluation of hypertension in a child or adolescent remains problematic and controversial. First, hypertension is a sign, and multiple causes, both primary and secondary, are known. Ruling in or out all the various etiologies often may be quite intricate, involving complicated, expensive, and painful tests. Second, the course and outcome of mild hypertension in children appears to be variable, with a substantial number of patients becoming normotensive without intervention. Severe hypertension clearly demands an extensive, careful evaluation, as adverse sequelae are likely. Thus, the extent of evaluation should be influenced by the severity of the blood pressure elevation: the more marked the hypertension, the more complete and rapid the evaluation ought to be.

An exhaustive evaluation of blood pressure elevation is extremely expensive and time consuming. Recent technologies are making it feasible to perform ever increasing portions of the hypertensive workup noninvasively. This article reviews some of the aspects of the noninvasive evaluation of pediatric hypertension.

HISTORY TAKING AS EVALUATION

The medical history, including recent events and family history, remains an indispensable part of the hypertension evaluation.1,2 Recent events in a child's life may serve to direct diagnostic tests by revealing, for example, signs of renal disease (red urine), renal trauma (flank trauma), or drug ingestion. Family history of primary or certain kinds of secondary hypertension, such as von Hippel-Lindau disease, may also serve to direct subsequent evaluation of elevated blood pressure. Table 1 lists aspects of the medical history that might lead to a focused battery of diagnostic tests. It is frequently worthwhile to take several medical histories, as facts relevant to hypertension diagnosis may surface only after repeated questioning.

PHYSICAL DIAGNOSIS

Certain physical findings may be helpful in pinpointing a particular category of secondary hypertension, while other findings may reveal end-organ damage due to the presence oí hypertension.1,2 Specific diagnostic clues or associations, ior example cafeau'lait spots in pheochromocytoma, are listed in Table 2. Physical examination procedures used for hypertension should always include four-extremity blood pressure, with concomitant testing ior radial-femoral pulse delay. Decreased relative lower limb blood pressure suggests aortic coarctation, as does femoral pulse delay.

Table

PHASED EVALUATION

The Second Task Force for Blood Pressure Control in Children1 suggests that evaluation of the hypertensive child he accomplished in phases or stages, with a full evaluation being reserved for the child who presents with severe hypertension or the child whose blood pressure fails to normalize after therapy (which is undertaken following a well-designed partial evaluation). The suggested phases of evaluation are listed in Table 3, which is modified from the 1987 Task Force report.

Phase I evaluation is designed to detect obvious renal disease - renal parenchymal and renovascular disease account for the vast majority of sustained hypertension - and to detect other cardiovascular risk factors, such as hypercholesterolemia. If renal parenchymal disease is already diagnosed, the remaining evaluative steps should be planned to define the degree of renal involvement; blood pressure evaluation should he secondary. Hypertension therapy in children and adolescents with intrinsic renal disease becomes important in preserving renal function.

NONINVASIVE IMAGING STUDIES

Ultrasonography and Radionuclide Renal Scan

Early in the evaluation of all but the mildest hypertension in children, kidney and urinary tract imaging is worthwhile because so many cases of secondary hypertension in the young are due to renal or renovascular diseases. In the past several years, it has become apparent that ultrasonography with or without radionuclide renal scintiscanning is more sensitive and specific than intravenous urography in the evaluation of hypertension.4,5

Ultrasonography can provide data on the size and configuration of the kidneys, and real-time examination may provide data on ureteral peristalsis…

Evaluation of hypertension in a child or adolescent remains problematic and controversial. First, hypertension is a sign, and multiple causes, both primary and secondary, are known. Ruling in or out all the various etiologies often may be quite intricate, involving complicated, expensive, and painful tests. Second, the course and outcome of mild hypertension in children appears to be variable, with a substantial number of patients becoming normotensive without intervention. Severe hypertension clearly demands an extensive, careful evaluation, as adverse sequelae are likely. Thus, the extent of evaluation should be influenced by the severity of the blood pressure elevation: the more marked the hypertension, the more complete and rapid the evaluation ought to be.

An exhaustive evaluation of blood pressure elevation is extremely expensive and time consuming. Recent technologies are making it feasible to perform ever increasing portions of the hypertensive workup noninvasively. This article reviews some of the aspects of the noninvasive evaluation of pediatric hypertension.

HISTORY TAKING AS EVALUATION

The medical history, including recent events and family history, remains an indispensable part of the hypertension evaluation.1,2 Recent events in a child's life may serve to direct diagnostic tests by revealing, for example, signs of renal disease (red urine), renal trauma (flank trauma), or drug ingestion. Family history of primary or certain kinds of secondary hypertension, such as von Hippel-Lindau disease, may also serve to direct subsequent evaluation of elevated blood pressure. Table 1 lists aspects of the medical history that might lead to a focused battery of diagnostic tests. It is frequently worthwhile to take several medical histories, as facts relevant to hypertension diagnosis may surface only after repeated questioning.

PHYSICAL DIAGNOSIS

Certain physical findings may be helpful in pinpointing a particular category of secondary hypertension, while other findings may reveal end-organ damage due to the presence oí hypertension.1,2 Specific diagnostic clues or associations, ior example cafeau'lait spots in pheochromocytoma, are listed in Table 2. Physical examination procedures used for hypertension should always include four-extremity blood pressure, with concomitant testing ior radial-femoral pulse delay. Decreased relative lower limb blood pressure suggests aortic coarctation, as does femoral pulse delay.

Table

TABLE 1Medical History as Noninvasive Evaluation

TABLE 1

Medical History as Noninvasive Evaluation

In addition to general physical examination, the advent oí miniaturized computers has made possible ambulatory blood pressure monitoring which allows around-the-clock blood pressure recording in a child or adolescent's usual environmental settings. Blood pressure tends to vary over each 24-hour period, being lowest in the early hours oí the morning and highest in the late afternoon or early evening. The magnitude of the variation is large - up to 100 mmHg systolic and 50 mmHg diastolic. By obtaining a record of blood pressure during an entire day the diagnostician can learn whether the blood pressure is truly high or is elevated only in the office or clinic. The diagnostician can also note the Orcadian rhythm in a particular patient and see the percentage change over each 24-hour period during which blood pressure is elevated.

Most 24-hour monitors require electrocardiogram leads, as well as a portable pneumatic device attached to a sphygmomanometer cuff. 5 The heart rate output, electrocardiogram, and blood pressure are recorded. After the wearer has taken off the equipment, the data may be "down-loaded" into a computer and a printout created. Presently, several companies manufacture hardy and accurate equipment, and third-party insurers may pay tor this procedure. Adolescents and cooperative school-age children tolerate monitoring quite well, but younger or fidgety children may find the setup annoying. Even most adults report that sleep with this sort of device is difficult. Nonetheless, ambulatory blood pressure monitoring may be very helpful in hypertension evaluation.

As an adjunct to physical diagnosis, searching for end-organ effects of blood pressure elevation is important. A formal ophthalmologic examination may be invaluable, especially in a very young child or an infant. Echocardiography, and possibly exercise testing, may be helpful in assessing cardiac effects of high blood pressure. Although abnormalities will not pinpoint the cause of hypertension, they will alert the health professional to the presence of end-organ damage.

Table

TABLE 2Physical Examination as Noninvasive Evaluation

TABLE 2

Physical Examination as Noninvasive Evaluation

Table

TABLE 3Phases of Hypertensive Evaluation in Children and Adolescents

TABLE 3

Phases of Hypertensive Evaluation in Children and Adolescents

PHASED EVALUATION

The Second Task Force for Blood Pressure Control in Children1 suggests that evaluation of the hypertensive child he accomplished in phases or stages, with a full evaluation being reserved for the child who presents with severe hypertension or the child whose blood pressure fails to normalize after therapy (which is undertaken following a well-designed partial evaluation). The suggested phases of evaluation are listed in Table 3, which is modified from the 1987 Task Force report.

Phase I evaluation is designed to detect obvious renal disease - renal parenchymal and renovascular disease account for the vast majority of sustained hypertension - and to detect other cardiovascular risk factors, such as hypercholesterolemia. If renal parenchymal disease is already diagnosed, the remaining evaluative steps should be planned to define the degree of renal involvement; blood pressure evaluation should he secondary. Hypertension therapy in children and adolescents with intrinsic renal disease becomes important in preserving renal function.

NONINVASIVE IMAGING STUDIES

Ultrasonography and Radionuclide Renal Scan

Early in the evaluation of all but the mildest hypertension in children, kidney and urinary tract imaging is worthwhile because so many cases of secondary hypertension in the young are due to renal or renovascular diseases. In the past several years, it has become apparent that ultrasonography with or without radionuclide renal scintiscanning is more sensitive and specific than intravenous urography in the evaluation of hypertension.4,5

Ultrasonography can provide data on the size and configuration of the kidneys, and real-time examination may provide data on ureteral peristalsis and contour. s Using classic ultrasound techniques, the vessels of the renal pedicle may be imaged clearly, but no flow data can be obtained with this method. Using Doppler technique with ultrasound, renal artery flow and turbulence may be estimated, although in native kidneys, this technique is difficult to apply accurately.6 In contrast, in transplanted kidneys, where the vessels are more easily accessible, quite accurate determination of flow may be accomplished. Because the sensitivity of ultrasound techniques is increasing, this noninvasive method of imaging may become useful for quantitative estimation of renal arterial flow.

Ultrasound studies do not provide renal functional data concerning glomerular filtration rate or renal plasma flow. Although not generally used quantitatively, both the intravenous pyelogram and the radionuclide renal scan provide some information about renal function. However, the radionuclide scan can provide much more quantitative data. The Second Task Force1 recommends radionuclide scan as preferable to the intravenous pyelogram, as the scan not only appears more sensitive, but also averts the need for using intravenous pyelogram dye, which is usually highly ionic and high in Na+ content. Despite the recent use of "nonionic" contrast media in many centers, most data suggest that the radionuclide scan remains preferable. Although both methods require intravenous injection of tracer radioactivity (radionuclide scan) or ionic contrast media (intravenous pyelogram), better functional data are obtained with the scan.

Two types of radionuclide renal scan are in general use5: the technetium 99m dimercaptosuccinic acid (DMSA) scan and the technetium 99m diethylene triamine pentacetic acid (DTPA) scan. The DMSA scan is a "static scan" because the isotope concentrates in the renal parenchyma (50% within 1 hour), especially in cortex. The DMSA scan is especially useful for identifying areas of relative hypoperfusion, so that the correlation between regions of ischemia or scarring and renal artery abnormalities is high. Another use for the DMSA scan is in identifying small kidneys with poor function, for finding renal tumors, or for providing relative renal function data for individual kidneys or regions of a given kidney.

The DTPA scan relies on the fact that DTPA is filtered yet neither reabsorbed nor secreted. It is possible to determine relative renal perfusion, glomerular filtration rate, and renal transit times using this type of scan. Although the DTPA scan may reveal decreased renal perfusion in renal artery stenosis of a main renal artery, it is less helpful in discerning bilateral disease or intrarenal arterial disease.

In addition or as an adjunct to the radionuclide renal scan, a converting enzyme inhibitor such as Captopril may be used to search for relative hypoperfusion.7 This class of agents acts to decrease the glomerular hypertension often seen in renovascular hypertension, which in turn decreases the function in affected areas of the kidney. There are several ways to perform a "Captopril challenge" test.7'9

1. Captopril, in a single dose of 0.35-0. 5 mg/kg orally 1 hour prior to a radionuclide scan using Tc99m DTPA and 151I orthoiodohippurate is thought to improve predictability of renovascular disease, especially in helping to select patients who might benefit from angioplasty or surgical repair of renovascular lesions. Experience with this test in children and adolescents, however, is limited.

2. A child or adolescent may be placed on Captopril as a therapeutic trial. A baseline scan is obtained prior to pharmacotherapy. A second scan is obtained after a week or more of therapy. The area(s) of the kidney(s) affected by renovascular disease is emphasized by the decrease in apparent function after Captopril therapy.

3. A young patient is given an oral dose of Captopril as in #1 above. A patient whose blood pressure drops more than 25% is likely to have renovascular disease and requires further study. In my experience, this test is not sufficiently specific to warrant its use.

Given that the combination of ultrasonographic and scan studies will identify the majority of patients with renovascular hypertension, when should intravenous pyelography be used? The use of intravenous pyelogram should be reserved for situations where adequate sonar and scan techniques are unavailable or when genitourinary tract structural disease, which requires the sort of anatomic definition only obtainable from contrast study, is apparent.

Digital Subtraction Angiography

The question as to whether other imaging techniques, such as digital subtraction angiography (DSA)10·11 with venous injection, ought to be used is often raised. This type of vascular study is noninvasive compared with classic arteriography, although heavy sedation is required for a young child to hold still. The DSA study in a young child usually requires rapid injection of a large amount of radiocontrast material via a central vein and cannot be considered noninvasive in that age group. Digital subtraction angiography with venous injection should, therefore, be reserved for the latter phases of a hypertension evaluation.

Digital subtraction angiography may be most helpful in ruling out the presence of a vascular lesion in a hypertensive older child whose blood pressure elevation does not seem to warrant an intra-arterial study. For example, if a teenager has moderately elevated blood pressure (140/95 to 100 mmHg) unresponsive to either a low-salt diet or low-dose hypotensive medication, it would be important to rule out a major vascular lesion prior to further therapy. Thus, digital subtraction angiography, which may be done on an outpatient basis, would be a worthwhile study. When a vascular lesion is likely, the plan to perform transluminal angioplasty, possibly at the time of diagnosis, makes an invasive DSA study via the arterial route a more sensible approach. In a young child, arteriography by any route is invasive and ought to be performed in the hospital or where the child can remain in a holding unit for ample observation following the procedure.

Additional Imaging Studies

Computerized tomography or magnetic resonance imaging scans are occasionally recommended during hypertension evaluation. 1,8,12,13 However, neither scan is especially useful for determining either the common type of renal parenchymal disease causing hypertension or renovascular disease. Rather, their use may be helpful in localizing small tumors within the kidneys or discovering small renal stones, which are unlikely to cause hypertension in isolation. These scans are more helpful in diagnosing extrarenal causes of secondary hypertension such as neural crest tumors.

PHARMACODIAGNOSIS

Pharmacologic therapy may be used in the evaluation of hypertension in two ways: the therapeutic trial and the test using a pharmacologic agent. Both have their place in the evaluation of pediatric hypertension.

Before using a drug for a therapeutic trial the physician should be convinced that nothing will be lost by using a medication prior to a full and possibly invasive evaluation. In a practical sense, this means that a very young child with severe hypertension must be evaluated prior to therapy, and that one must be fairly sure that there will be no danger in using the contemplated agent. Once proceeding along this route, the expectation is that the medication not only will improve blood pressure control but may shed light on the cause of the hypertension. For instance, salt-sensitive hypertensives will often respond to use of a diuretic, whereas children with substantial secondary hypertension will probably not respond to such medication.

A formal test with a pharmacologic agent may also be used in pharmacodiagnosis. Such tests include use of:

* Furosemide in a single dose to stimulate plasma renin levels, as an alternative to determining salt balance.

* Captopril as noted previously.

* Clonidine14 as a means of distinguishing primary hypertension with "catecholamine overdrive," in which elevated plasma catecholamines are suppressed with Clonidine, from neural crest tumors, in which Clonidine fails to suppress catecholamine levels.

* Phentolamine acutely (short acting a-blocker) or longer acting oral a-blocker to diagnose and control hypertension in pheochromocytoma or other neural crest tumors.15

* Spironolactone to suppress aldosterone, which should occur in primary hypertension but not in primary aldosteronism.2

OTHER NONINVASIVE STUDIES

Other noninvasive techniques involve the use of radioisotopes to study extrarenal organ systems; eg, the adrenal gland, in which 131I metaiodobenzylguanidine has been used1·16 to locate sources of catecholamine secreting tissue, and 131I-19iodocholesterol17 has been used to localize adrenal tissue in Cushing's syndrome. The sensitivity and specificity of either of these adrenal scans is unclear in children, and many centers hesitate to use these techniques, owing to apparent lack of specificity and the high radiation dose involved.

HORMONE LEVELS

Much has been written on determining levels of vasoactive hormones, catecholamines, and steroids in the evaluation of pediatric hypertension.1·2-8 For instance, measurement of various components of the renin angiotensin system in peripheral blood is a matter of some controversy because dietary salt, posture, and certain medications may increase or decrease levels. Furthermore, in children, levels vary with age, so it is important to know normal values for the particular laboratory doing measurements. In most circumstances either a very high plasma renin activity (suggesting renin-mediated hypertension) or very low renin activity (suggesting primary aldosteronism) may be helpful, whereas midrange levels are not. Some knowledge of salt intake makes interpretation more reliable; alternatively, a single dose of intravenous furosemide may stimulate renin activity and somewhat standardize the condition of the patient. In view of these considerations, the determination of reninangiotensin system components should be reserved for the patient in whom renin-mediated hypertension (eg, renal arterial stenosis) or primary adrenal hyperactivity is highly suspected. Several other vasoactive hormones can also be measured in peripheral blood, such as the cardiac-produced peptide hormone atrial peptin (atrial natriuretic factor) and endothelin (a newly described vasoconstrictor). However, the importance of these substances in children is unclear and routine determination seems unwarranted.

Most forms of endocrine hypertension are rare (pheochromocytoma accounts for only 0.5% of secondary hypertension), so that routine measurement of catecholamine levels is not necessary. Urinary collections for catecholamines may prove unwieldy, yet plasma catecholamines may become elevated by even the manipulation required for venipuncture in normal patients. In the presence of a rapid heart rate and even mild postural hypotension, plasma catecholamine levels may help differentiate primary hypertension with catecholamine overdrive from catecholamine-secreting mass.

Measurement of plasma aldosterone and glucocorticoid levels, as well as various stimulation or depression tests, should be reserved for those instances in which there is a high index of suspicion. Aldosterone elevation as a cause of hypertension should be sought in the presence of: (1) hypokalemia, high total carbon dioxide level, and low plasma renin activity; or (2) unexplained hypertension that does not respond to attempts at blood pressure control undertaken after other tests have been unrevealing. Glucocorticoid levels are usually not measured unless the patient appears to have endogenous Cushing's syndrome.

WHEN TO DO INVASIVE TESTS

The younger the child and the more severe the level of blood pressure elevation, the more important a "full" invasive evaluation becomes - ie, one in which formal arteriography or cavai sampling of renin or catecholamines is conducted. However, for most children with hypertension, an extensive noninvasive evaluation is usually satisfactory.

REFERENCES

1. Task Force on Blood Pressure Control: National Heart. Lung, and Blood Institute: Report of the Second Task Force on Blood Pressure Control in Children - 1987. Pediatrics 1987; 79:1.

2. Ingelfinger JR: Pediatric Hypertension. Philadelphia, Saunders. 1982, pp 1-297.

3. Stein IM. Peterson R, Lee A: Amhulatory blood pressure recorder. Medical Instrumentation 1983; 17:352.

4. Rosen PR. Treves S. Ingelfinger J: Hypertension in children. Increased efficacy of Tc -99m succimer in screening for renal disease. AmJ Dis Child 1985; 139:173.

5. Siegel M), St. Amour TE, Siegel BA: Imaging techniques in the evaluation of pediatric hypertension. fVdiatnc Nephmlogy 1987; 1:76.

6. Greene ER, Venters MD, Avasthi PS, et al: Noninvasive characterization of renal artery blood flow. Kidney lnt 1981; 29:523.

7. Willems CD, Shah V, Uchiyama M, et al: Captopril as an aid to diagnosis in childhood hypertension. Clin Exp Hypertens 1986; A8:747.

8. Dillon M): Investigation and management of hypertension in children: A personal perspective, fVdiatnc Nephrology 1987; 1:59.

9. M imJ M, Potter BM, Guyetta PC, et al: Captopril enhanced renal scintigraphy lor detection of renal artery stenosis - An update, abstracted. ) Nucl Med 1986; 27:962m.

10. Hillman B]. Ovitt TW, Capp MP. et al: The potential impact of digital video subtraction angiography on screening for renovascular hypertension. Rudiolog-v 1982; 142:577.

1 1 . Tonkin IL, Stapleton FB, Roy S: Digital subtraction angiography in the evaluation of renal vascular hypertension in children. Pediatrics 1988; 81:150.

12. DunnickNR. DoppmanJL, GiII)R. et al: Localization of functional adrenal tumors by computed tomography and venous sampling. Radiology 1982; 142:429.

13. Farrelly CA. Daneman A. Martin D], et al: Pheochromocytoma in childhood: The important role of computed tomography in tumor localization. Pedun Radiol 1984; 14:210.

14. Bravo EL. Tarazi RC Fouad FM: Clonidine-suppression test. A useful aid in the diagnosis of pheocWiomocytoma. N Engl J Med Í981; 305.6ZÎ.

15. Lewis D. Dalton N. Ridger S: Phaeochromocytoma: Report of three cases. Pediatric Nephrology 1987; 1:46.

16. Francis IR, Glazes GM. Shapiro B, et al: Complementary roles of CT and "1I-MIBG scintigraphy in diagnosing pheochromocytoma. American Journal of Roentgenography 1983; 141:719.

17. Gifford RW. Kirkendall W. O'Connor DT, et al: Office evaluation of hypertension: A statement for health professionals by a writing gnxip of the Council for High Blood Pressure Research. American Heart Association. Hypertension 1989; 13:283.

TABLE 1

Medical History as Noninvasive Evaluation

TABLE 2

Physical Examination as Noninvasive Evaluation

TABLE 3

Phases of Hypertensive Evaluation in Children and Adolescents

10.3928/0090-4481-19890901-07

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