Watch for Clinical Clues of Secondary Hypertension

June 3, 2007
Wayne Kuznar

Internal Medicine World Report, July 2006, Volume 0, Issue 0

From the American Society of Hypertension

NEW YORK CITY?Several clinical indicators can be clues to secondary forms of hypertension, which increase in prevalence with age, said L. Michael Prisant, MD, professor of medicine and director of hypertension and clinical pharmacology, Medical College of Georgia, Augusta, at the 21st annual scientific meeting of the American Society of Hypertension.

"There's a marked increase in the prevalence of secondary hypertension after age 50,"

L.Michael Prisant, MD

"There's a marked increase in the prevalence of secondary hypertension after age 50," Dr Prisant said. Other than age, the history and severity of hypertension may provide clues to secondary forms.

The causes of secondary hypertension are many, and the clinical clues can help physicians suspect this overlooked condition (Table). Suspect a secondary cause if the hypertension is resistant, if blood pressure (BP) begins to increase for uncertain reasons after being well controlled, and if the onset of hypertension is severe, he advised.

Table. Clinical clues to secondary hypertension

Abrupt onset

Age <30 or >55 y

Abdominal bruit w/diastolic component

Acute azotemia w/ACE inhibitor or ARB

Atherosclerotic disease elsewhere

Negative family history of hypertension

Recurrent pulmonary edema

Renal failure without proteinuria

Severe/resistant hypertension Smokers w/bruits: femoral, carotid, abdominal

ACE = angiotensin-converting enzyme;

ARB = angiotensin receptor blocker.

Renovascular causes are common among the secondary forms. Others are hypothyroidsim and hyperthyroidsim, obstructive sleep apnea (OSA), primary aldosteronism, and renal insufficiency, and to a lesser extent pheochromocytoma and Cushing's disease.

In a 1991 study, 11% of hypertension was attributed to secondary causes, although the investigators did not look for sleep apnea as one of the causes.

Renal parenchymal diseases that can cause secondary hypertension include diabetic nephropathy, hypertensive nephrosclerosis, polycystic kidney disease, and chronic glomerular nephritis. "As part of the evaluation, you should do an estimated glomerular filtration rate," said Dr Prisant. "A renal ultrasound is at the very least the first test that we should do" for patients at risk.

Renovascular hypertension is fairly common, he said. A careful abdominal examination, listening for bruits, should be conducted if secondary hypertension is suspected. If palpating the abdomen reveals oversized kidneys, consider polycystic kidney disease.

Scleroderma renal crisis is "something to think about in patients presenting with acute renal failure or heart failure," he said.

OSA may be one of the most common secondary causes of hypertension. "I really think that we need to be screening more patients for this," he said. "I have been very surprised at the number of positives." Following periods of snoring, oxygen saturation stimulates the sympathetic nervous system and ultimately increases BP. Sleep deprivation may be just as important a cause of secondary hypertension as sleep apnea.

Clues to OSA are snoring, witnessed apneas, obesity, excessive daytime sleepiness, a family history, previous tonsillectomy, and nonrestorative sleep.

A sensitive thyroid-stimulating hormone test is a useful screening tool for hypothyroidism or hyperthyroidism as a secondary cause of hypertension. Treatment for hyperthyroidism, such as surgery and radioactive iodine, are successful at reducing BP, more so in younger patients than in older patients, with a concomitant reduction in heart rate, said Dr Prisant.

Gynecomastia, another clue to secondary hypertension, can be present in patients with hyperthyroidism, chronic renal failure, and adrenal hyperplasia tumors. Although spironolactone is most often blamed for drug-induced gynecomastia, other drugs such as amphetamines, calcium antagonists, anabolic steroids, cyclosporine (eg, Gengraf, Neoral), methyldopa, angiotensin-converting-enzyme (ACE) inhibitors, and alpha-1 blockers may also cause gynecomastia.

Clues to Cushing's syndrome include truncal obesity, Moon facies, purple striae, glucose intolerance, and chronic steroid therapy. When Cushing's is suspected, a dexamethasone suppression test is recommended; give 1 mg, orally, between 11 PM and 12 PM, and then measure plasma cortisol early in the morning (normal cortisol level is <5 ?g/dL).

If the cortisol level is abnormal, "call an endocrinologist to sort out the various causes," said Dr Prisant.

Symptoms of pheochromocytoma are headache, sweating, tremor, pallor, and palpitations; 90% of cases arise in the adrenal medulla. "Blood pressure with pheochromocytoma is not always labile; it can be consistently up," he said. "If you just focus on labile, you may miss something."

A plasma-free metanephrine is the most sensitive test for pheochromocy-toma at present. Plasma catecholamine levels can be falsely positive in patients with congestive heart failure, cerebrovascular accident, and chronic renal failure. False positives can also be caused by use of alpha blockers, beta-blockers, stimulants, tricyclic antidepressants, sinus and cough medicines, and nose drops. False negatives are possible with alpha-2 stimulants, ACE inhibitors, and calcium antagonists.

Computed tomography scans can localize 95% of adrenal tumors &#8805;1 cm in size, and 90% of extra-adrenal tumors &#8805;2 cm.

An iodine-131-meta-iodobenzylguanidine is a test used to confirm the presence of pheochromocytoma. Uptake is inhibited by many medicines that need to be stopped a week before performing the test, reminded Dr Prisant.

Unprovoked hypokalemia is an important clue to primary aldosteronism. The causes can include adrenal adenoma, adrenal carcinoma, and bilateral adrenal hyperplasia. Remember that a 24-hour aldosterone level should be performed if primary aldosteronism is suspected. Because the workup is complex, patients with elevated levels should be referred to an endocrinologist.


The prevalence of secondary hypertension after age 50 is increasing.

Suspect a secondary cause if the hypertension is resistant, if BP begins to increase for unclear reasons after being well controlled, or if the onset of hypertension is severe.

Renovascular conditions are common causes of secondary hypertension.

Other causes include hypo-/hyperthyroidism, obstructive sleep apnea, primary aldosteronism, and renal insufficiency.

When considering secondary causes, a renal ultrasound is a must.