PRIMARY HYPERALDOSTERONISM

This is a disease characterized by hypertension, hypokalemia, suppressed plasma renin and elevated levels of serum aldosterone. The various etiologies include the following: (1) unilateral aldosterone secreting adenomas (Conns syndrome); (2) bilateral adrenal hyperplasia; (3) adrenal cortical carcinoma (rare); (4) idiopathic hyperaldosteronism or (5) glucocorticoid suppressible hyperaldosteronism. Primary aldosteronism should be considered in cases of hypertension with associated hypokalemia, severe hypertension, refractory hypertension (hypertension which persists despite three different antihypertensives with a least one of the medications being a thiazide diuretic), excessive hypokalemia secondary to diuretic therapy, hypertension associated with an adrenal incidentaloma, hypertensive patients on ACEI's, ARB's or direct renin inhibitors with low or undetectable plasma renin activity levels, and hypertension at a young age (<20 years of age). Associated lab abnormalities include hypokalemia, mild hypernatremia, hypomagnesemia, metabolic alkalosis and hyperglycemia. It is important to consider this diagnosis in all cases of secondary/refractory hypertension even with normal potassium levels.

Elevated aldosterone levels characteristic of this disorder cause increased renal potassium wasting with resultant hypokalemia and increased sodium reabsorption with resultant plasma volume expansion and associated hypertension. Again, it is important to stress that potassium levels may be normal and the diagnosis should be considered in appropriate cases of secondary/refractory hypertension. The expanded plasma volume results in increased sodium delivery to the juxtaglomerular cells which suppresses renin release. In fact, a low plasma renin with a relatively fixed elevated aldosterone level is strong evidence for primary aldosteronism in a hypertensive patient. The serum values for renin and aldosterone are often expressed as the plasma aldosterone concentration/plasma renin activity ratio (PAC/PRA). A ratio of 10:1 is normal; whereas, ratios greater than 20:1 are suggestive of primary aldosteronism but are also seen in patients with chronic renal failure. These tests are less sensitive in African-American patients. The serum renin and aldosterone values should be obtained from after hypokalemia has been corrected and the specimens should be of a morning serum sample after the patient has been out of bed for at least 2 hours. Medications which may affect the plasma values (spironolactone, eplerone, amiloride, triamterene, potassium-wasting diuretics) should be discontinued before testing.

If the plasma aldosterone concentration/ plasma renin activity ratio is suggestive of primary hyperaldosteronism (>20), then the patient should undergo confirmatory testing with urinary aldosterone measurement after saline loading. Patients with primary aldosteronism will have elevated baseline aldosterone levels, which despite saline loading, will not suppress below 10 ng/dL (indicative of inappropriate aldosterone secretion). Saline loading is accomplished by having the patient ingest a high sodium diet (6,000 mg/day) for three days. then the finding of an elevated 24 hour urinary aldosterone level (which should be less than 12 micrograms/day) establishes the diagnosis. The 24 hour urinary sodium level and sodium concentration should also be measured to ensure patient was compliant on the high sodium diet. CT scanning of the adrenals can not distinguish between a hyperfunctioning mass and a benign asymptomatic adrenal cyst (incidentaloma). Also, hyperfunctioning adrenal adenomas may be microscopic rendering them undetectable with conventional imaging studies (CT or MRI).  Therefore, adrenal venous sampling is the next step to determine the pathologic adrenal gland. Once the pathologic adrenal or adrenals have been identified treatment may be offered. Unilateral adrenal pathology may be amenable to surgery with laparoscopic adrenalectomy or medication (aldosterone or eplerenone). Bilateral adrenal hyperplasia may be treated with medications.