Medline ® Abstracts for References 2-5

In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), "refractory" hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.

Primary aldosteronism is caused by bilateral idiopathic hyperplasia in approximately two-thirds of cases and aldosterone-producing adenoma in one-third. Most patients with primary aldosteronism are normokalemic. In the clinical setting of normokalemic hypertension, patients who have resistant hypertension and hypertensive patients with a family history atypical for polygenic hypertension should be tested for primary aldosteronism. The ratio of plasma aldosterone concentration to plasma renin activity has been generally accepted as a first-line case-finding test. If a patient has an increased ratio, autonomous aldosterone production must be confirmed with an aldosterone suppression test. Once primary aldosteronism is confirmed, the subtype needs to be determined to guide treatment. The initial test in subtype evaluation is CT imaging of the adrenal glands. If surgical treatment is considered, adrenal vein sampling is the most accurate method for distinguishing between unilateral and bilateral adrenal aldosterone production. Optimal treatment for aldosterone-producing adenoma or unilateral hyperplasia is unilateral laparoscopic adrenalectomy. The idiopathic bilateral hyperplasia and glucocorticoid-remediable aldosteronism subtypes should be treated pharmacologically. All patients treated pharmacologically should receive a mineralocorticoid receptor antagonist, a drug type that has been shown to block the toxic effects of aldosterone on nonepithelial tissues.

Great strides have been made in our understanding of the pathophysiology of primary aldosteronism syndrome since Conn's description of the clinical presentation of a patient with an aldosterone-producing adenoma (APA) more than 50 years ago. It is now recognized that the APA is just one of the seven subtypes of primary aldosteronism. APA and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism. Although most clinicians had thought primary aldosteronism to be a rare form of hypertension for more than three decades, it is now recognized to be the most common form of secondary hypertension. Using the plasma aldosterone to plasma renin activity ratio as a case-finding test, followed by aldosterone suppression confirmatory testing, has resulted in much higher prevalence estimates of 5-13% of all patients with hypertension. In addition, there has been a new recognition of the aldosterone-specific cardiovascular morbidity and mortality associated with aldosterone excess. Although thought to be daunting and complex in the past, the diagnostic approach to primary aldosteronism is straightforward and can be considered in three phases: case-finding tests, confirmatory tests and subtype evaluation tests. Patients with hypertension and hypokalaemia (regardless of presumed cause), treatment-resistant hypertension (three antihypertensive drugs and poor control), severe hypertension (>or= 160 mmHg systolic or>or= 100 mmHg diastolic), hypertension and an incidental adrenal mass, onset of hypertension at a young age or patients being evaluated for other forms of secondary hypertension should undergo screening for primary aldosteronism. In patients with suspected primary aldosteronism, screening can be accomplished by measuring a morning (preferably between 0800 and 1000 h) ambulatory paired random plasma aldosterone concentration (PAC) and plasma renin activity (PRA). An increased PAC:PRA ratio is not diagnostic by itself, and primary aldosteronism must be confirmed by demonstrating inappropriate aldosterone secretion. Aldosterone suppression testing can be performed with orally administered sodium chloride and measurement of urinary aldosterone or with intravenous sodium chloride loading and measurement of PAC. Unilateral adrenalectomy in patients with APA or unilateral adrenal hyperplasia results in normalization of hypokalaemia in all these patients; hypertension is improved in all and is cured in approximately 30-60% of them. In bilateral adrenal forms of primary aldosteronism, unilateral or bilateral adrenalectomy seldom corrects the hypertension and they should be treated medically with a mineralocorticoid receptor antagonist.