At a Glance
Bilateral hyperplasia is one cause of primary aldosteronism (also sometimes referred to as primary hyperaldosteronism). Other causes are adrenal adenomas, adrenal carcinoma, and inherited glucocorticoid responsive aldosteronism.
Bilateral hyperplasia often presents as hypertension relatively resistant to antihypertensive medications. The cause of hypertension in most patients is unknown (essential hypertension), but several factors suggest a need for further evaluation of hypertension and the possibility of bilateral hyperplasia:
moderate or extreme hypertension
resistance to therapy
Cardiac palpitations may be another symptomatic presentation of bilateral hyperplasia. Patients with hypokalemia can present with muscle weakness or paralysis. Hypokalemia is no longer needed to make the diagnosis of bilateral hyperplasia or primary aldosteronism.
Primary aldosteronism results from secretion of aldosterone without the usual stimulus by the renin-angiotensin system. Nonregulated aldosterone production may result from a single adrenal adenoma, bilateral adrenal hyperplasia, a mineralocorticoid producing adrenal carcinoma, or a rare inherited disorder, glucocorticoid suppressible aldosteronism. The term Conns syndrome was originally applied to adrenal adenomas producing aldosterone.
The primary effect of aldosterone is on distal renal tubules, sweat glands, and salivary glands. Aldosterone stimulates sodium-potassium exchange. In the kidney, aldosterone increases sodium uptake and potassium excretion. Retention of sodium results in slight volume expansion and increased blood pressure. Volume expansion tends to suppress renin and angiotensin production. Under normal physiology, aldosterone production then would fall. Other tissues, including the heart, have the mineralocorticoid receptors, which bind aldosterone. Aldosterone, thus, may directly promote left ventricular hypertrophy and heart failure.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
The primary screening test for primary aldosteronism or bilateral hyperplasia is the plasma aldosterone:renin ratio. Aldosterone production is increased, and renin release is suppressed; therefore, the ratio is increased in primary aldosteronism or bilateral hyperplasia. Serum potassium used to be considered a key diagnostic factor. Although hypokalemia does support the diagnosis, most patients with primary hyperaldosteronism are now recognized to have potassium within reference limits.
Increased urine potassium concentration (>30 mmol/L) in a random urine specimen suggests increased mineralocorticoid effect.
Some tumors may produce increased amounts of other mineralocortoids in addition to aldosterone. 11-deoxycorticosterone and 18-hydroxycorticosterone, for example, have significant mineralocorticoid effect. Increases in serum 11-deoxycorticosterone or 18-hydroxycorticosterone suggest presence of an adrenal adenoma or adrenal carcinoma.(Table 1)
|Aldosterone:renin ratio||Serum potassium||Urine potassium|
|Increased||Low or normal||Increased|
Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?
Aldosterone production is stimulated by angiotensin generation by renin, high serum potassium concentration, and, to a lesser extent, adrenocorticotropic hormone (ACTH).
Many factors affect the activity of the renin-angiotensin-aldosterone system (RAAS). These include posture, salt intake, and antihypertensive medicines. To assess the plasma aldosterone:renin ratio, patients should have a normal salt intake and should not be taking spironolactone or licorice, which is present in some candies, herbal preparations, and chewing tobacco. Reference ranges are different for ambulatory (upright) patients versus recumbent patients.
Factors expanding vascular volume, such as increased salt intake, intravenous fluid infusion, mineralocorticoids, and recumbency, suppress the RAAS. Factors contracting vascular volume, such as low salt intake, dehydration, diuretics, and upright posture, activate the RAAS. Thiazide and loop diuretics promote potassium loss and need to be considered in assessing hypokalemia. Several antihypertensive agents are considered to have minimal effects on aldosterone levels (e.g., verapamil, hydralazine, prazosin, doxazosin, and terazosin).
The aldosterone:renin ratio is increased slightly by beta blockers, clonidine, nonsteroidal anti-inflammatory agents, renin inhibitors, and renal impairment, possibly leading to false positive results for the screening test. The ratio is lowered by most diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, some calcium channel blockers, sodium restriction, pregnancy, and renovascular hypertension. Blood specimens for testing of plasma renin activity should be kept at room temperature; refrigeration of specimens may cause activation and higher values.
What Lab Results Are Confirmatory?
Confirmatory tests that can be applied when the plasma aldosterone:renin ratio is high include the oral sodium loading test, saline infusion test, fludrocortisones suppression test, and captopril challenge test. All of these challenge tests tend to physiologically suppress aldosterone, and failure to achieve suppression indicates loss of normal physiological regulation. Other tests may be employed to help confirm the diagnosis and direct further therapy. Treatment with dexamethasone can assess whether aldosterone production is steroid responsive. A trial of spironolactone helps confirm aldosterone is a cause of hypertension.
Imaging studies with computerized tomography (CT) can identify the presence of adrenal masses, but it does not indicate whether masses are functional. Adrenal venous sampling to collect specimens for measuring aldosterone and renin is a technically difficult procedure that helps assess whether aldosterone production is unilateral or bilateral.
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- At a Glance
- What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
- Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?
- What Lab Results Are Confirmatory?