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A wide variety of medications may produce drug-mediated hypertension that is correctable once the condition is recognized and the offending agent withdrawn (table 2). These drugs can be divided into three categories:

Phenylephrine, pseudoephedrine, phenylpropanolamine (used in cough mixtures and cold medications) and other sympathomimetic amines, anti-adrenergic agents withdrawal, appetite suppressants, and monoamine oxidase inhibitors treatment combined with tyramine-containing foods or medications.

Glucocorticoids, estrogens especially at high doses as in oral contraceptives, non-steroidal anti-inflammatory agents that inhibit prostaglandins.

Psychotropic drugs that interfere with sympatholytic antihypertensive agents, cyclosporine, immunosuppressants, and erythropoietin (used in treatment of anemia in end stage renal disease).

Several clinical and laboratory features suggest a more extensive work-up for secondary hypertension (table 3). However, most of the features are non-specific and - in view of the low frequency of secondary hypertension - the selection of patients for further evaluation should be based on reasonable doubt.

Table 3. Clues for Secondary Forms of Hypertension

· Onset of hypertension before age 25 or after age 60 years.

· Sudden onset, change from normal blood pressure to severe hypertension in less than a year.

· Resistant hypertension.

· Poor response to prior effective drug therapy.

· Paroxysmal attacks of hypertension with palpitation, pallor, sweating and tremors.

· Multiple system involvement on initial evaluation.

· Delayed and weak femoral pulses with lower blood pressure in the lower extremities.

· Continuous abdominal bruit.

· Renal masses.

· Advanced end organ damage: more than grade 2 retinopathy or serum creatinine >2.0 mg/dl .

· Laboratory abnormalities: (e.g., hypokalemia, or hypercalcemia).

Table 4 summarizes the important clinical clues and diagnostic tests of some forms of secondary hypertension.

Table 4. Summary of Diagnosis and Treatment of Some Forms of Secondary Hypertension

Cause and Frequency

Clinical Clues

Screening Test

Definitive Test

Treatment

Renal parenchymal hypertension (3-5 %)

- History of renal disease

- Abnormal urine sediments

Urinary sediments, pyuria, elevated creatinine.

- Abdominal ultrasonography.

- Radiologic examination.

- Renal biopsy.

- Drug therapy for hypertension.

- Specific urologic treatment.

Renovascular hypertension. (1-2%)

- Onset before 30 or after 50 years.

- Abrupt onset.

- Resistant hypertension.

- Multi-site atherosclerosis.

- Abdominal bruit.

- Flash pulmonary edema.

- Azotemia on ACE-I

Captopril renography

- sensitivity 83%

- specificity 93%

Renal Duplex

- sensitivity 95%

- specificity 93%

- Renal arteriography

- Digital subtraction angiography.

- Spiral CT*

- Angioplasty + stenting

- Drug therapy

- Surgery

Aortic Coarctation

(< 0.5%)

- Delayed / absent femoral pulse

- ¯ arm / leg blood pressure difference

- LVH^**

- Precordial systolic ejection murmur

- Systolic / continuous back murmur

- Chest X-ray: rib notching

- ECG: LVH^**

- Echocardiography

- Aortography.

- Surgical repair.

- Balloon angioplasty.

Primary aldosteronism

(< 0.5%)

- Polyuria

- Muscle weakness

- Hypokalemia

- Excess urinary K⁺ loss

- High plasma and urinary aldosterone, not suppressible

- Low renin, persistent with standing or frusemide

- CT^* / MRI^†

- Surgical removal

- Frusemide + spironolactone

Pheochromocytoma

(< 0.3%)

- Proxysmal hypertension

- Headache, chest or abdominal pain

- Sweating, palpitations, pallor

- 24h urinary metanephrin & nor-metanephrin (sensitivity and specificity >95%).

- CT^* / MRI^† / MIBG scan^‡

- Angiography

- Surgical removal after medical preparation.

* CT: Computerized Tomography.

† MRI: Magnetic Resonance Imaging.

** LVH: Left Ventricular Hypertrophy.

‡ MIBG: 131-I- Metaiodobenzylguanidine.

SECONDARY HYPERTENSION