The diagnostic evaluation serves to identify other cardiovascular risk factors and end-organ damage in patients with high-normal blood pressure or hypertension. This information is used to identify 3 risk groups: Group A includes patients with no other cardiovascular risk factor, cardiovascular disease, or evidence of end-organ damage; group B includes patients who do not have cardiovascular disease or end-organ damage but have 1 or more of the major risk factors other than diabetes mellitus; and group C includes patients who have cardiovascular disease, other end-organ damage, or diabetes mellitus. The risk associated with hypertension and the intensity of recommended treatment increases progressively as a person moves from risk group A through risk group C.
The diagnostic evaluation may also reveal patients who are more likely to have an identifiable cause of hypertension. The probability of an identifiable cause of hypertension is increased by the onset of hypertension outside the normal age for essential hypertension (30-55 years), sudden onset or worsening of hypertension, stage 3 hypertension, and blood pressure that responds poorly to treatment. Elevated creatinine levels suggest hypertension caused by renal parenchymal disease. Abdominal or flank bruits, hypokalemia, or a significant rise in the serum creatinine level after an angiotensin-converting enzyme inhibitor is started suggests renovascular hypertension. Osteoporosis, truncal obesity, moon face, purple striae, muscle weakness, easy bruising, hirsutism, hyperglycemia, hypokalemia, and hyperlipidemia suggest Cushing syndrome. Labile hypertension, orthostatic hypotension, headache, palpitations, pallor, and diaphoresis suggests pheochromocytoma. Isolated hypokalemia may be caused by hyperaldosteronism.
Unfortunately, the accuracy of the history, physical examination, and preliminary diagnostic testing for patients presenting with hypertension has not been adequately studied. Therefore, estimating the pretest probability of a secondary cause of hypertension in a patient with specific clinical characteristics must be considered crude at best. The best available evidence is shown in Table 1.
Diagnostic Strategy
Patients whose initial history, physical, and laboratory evaluation suggest the possibility of a secondary cause of hypertension should undergo additional testing. The search for the secondary cause of hypertension should focus on chronic renal disease, renovascular hypertension, pheochromocytoma, Cushing syndrome, and primary aldosteronism, depending on the clinical scenario Table 2.
Chronic renal disease will be evident from the blood urea nitrogen, creatinine, and the urinalysis results. The diagnostic approach to other causes of hypertension is more complicated.
Although renal artery stenosis is suggested by the presence of an abdominal or flank bruit, it is an insensitive test (sensitivity=65%; specificity=90%). It is useful when positive (positive likelihood ratio=6.5) but does not rule out renal artery stenosis when negative (negative likelihood ratio=0.4). A clinical decision rule has been developed and validated that integrates several findings from the history and physical examination. Software to implement this decision rule in clinical practice, using Palm or PocketPC hand-held computers, is available at no charge from the JFP Web site at PC download.
Duplex sonography is very accurate (sensitivity=98%; specificity=98%) when the study is adequate but is often nondiagnostic in obese patients. For these patients, magnetic resonance angiography (MRA) is better (sensitivity=93%; specificity=95%). Captopril renal scanning (CRS) is less sensitive and less specific than either sonography or MRA. Renal artery stenosis is confirmed by the highly accurate but more invasive reference standard test of conventional angiography.
Pheochromocytoma is rare even in the presence of suggestive symptoms (headache, palpitations, and excessive and inappropriate perspiration), but failure to identify this disease can have disastrous consequences. Therefore, patients who have suggestive signs and symptoms should be screened for pheochromocytoma. However, the standard for screening pheochromocytoma remains controversial. A 24-hour urinary metanephrine (cutoff point of >3.70 nmol/day ) is highly sensitive and specific when done well, but urine collection is inconvenient and may be incomplete. Plasma metanephrines (metanephrine >0.66 nmol/L or normetanephrine >0.30 nmol/L) are easy to obtain, 100% sensitive, and may represent a good screening test for pheochromocytoma. Because they have limited specificity (85%), a positive plasma metanephrine should be confirmed by the 24-hour urinary metanephrine-to-creatinine ratio (cutoff point of >0.354; specificity=98%) before proceeding to anatomical localization of the tumor.
Two imaging studies are commonly used to localize pheochromocytomas. Metaiodobenzylguanidine (MIBG) scintigraphy is more specific but less sensitive than computed tomography (CT). Relying on CT to guide surgery is less likely to miss tumors than MIBG scintigraphy (CT sensitivity = 100% vs MIBG=88%) but is more likely to result in unnecessary surgery because of the lower specificity (CT specificity = 50%; MIBG=89%).
The 24-hour urinary free cortisol (cutoff point >90 mg/day; sensitivity=100%; specificity=98%) is a useful screening test for Cushing syndrome. It is very sensitive, but false-positives may be seen in patients with depression and polycystic ovarian syndrome. The single-dose (1 mg) overnight dexamethasone suppression test is equally sensitive but is a little less specific than the 24-hour urinary cortisol. However, this test is relatively simple for patients. The patient takes 1 mg of dexamethasone at midnight, and the plasma cortisol level is drawn in the morning (cutoff point >100 nmol). The combined dexamethasone and corticotropin-releasing hormone (CRH) suppression test, which has both a sensitivity and a specificity of almost 100%, can be used to confirm the diagnosis of Cushing syndrome. However, it is a little more complicated for the patient. The patient takes 0.5 mg of dexamethasone at noon on the first day and repeats this dose every 6 hours for a total of 8 doses (ending at 6 am on the third day). Two hours after the last dose the patient is given an intravenous bolus of CRH (1 μg/kg), and 15 minutes later a plasma cortisol is drawn. A cortisol level greater than 38 nmol is the cutoff point for this test.