At a Glance
Pseudoaldosteronism (sometimes also referred to as pseudohyperaldosteronism) clinically presents similarly to primary aldosteronism (see chapter on primary aldosteronism with hypertension, hypokalemia, and metabolic alkalosis. However, pseudohyperaldosteronism differs by having low plasma aldosterone.
There are several potential causes of pseudohyperaldosteronism:
ingestion of licorice-containing candy, herbal preparations, teas, or chewing tobacco
excess of glucocorticoids that also have mineralocorticoid activity
genetic deficiency of 11-beta-hydroxysteroid dehydrogenase type 2
Liddle syndrome, an autosomal dominant genetic disorder leading to increased activity of the amiloride-sensitive sodium channel
Accordingly, history of licorice ingestion, steroid treatment, or symptoms of Cushing’s syndrome suggest possible causes of pseudohyperaldosteronism. In pseudohyperaldosteronism, there is activation of the mineralocorticoid (aldosterone) receptor without an increase in aldosterone. This occurs because of functional increases in cortisol or other steroid hormones with some mineralocorticoid activity. The active agent in licorice, glycyrrhizin, inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol to cortisone in the kidney. Inhibition or genetic deficiency of this enzyme increases cortisol that binds to mineralocorticoid receptors.
In Cushing’s syndrome or high dose steroid therapy, the mineralocorticoid receptor can also be activated. Some tumors produce steroid hormones, such as 11-deoxycorticosterone that have substantial mineralocorticoid activity. Genetic deficiency of 11-beta-steroid hydroxylase can lead to overproduction of 11-deoxycorticosterone and decreased aldosterone. Genetic disorders, such as 11-beta steroid hydroxylase deficiency and Liddle syndrome, are suggested by onset at an early age and familial inheritance.
What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?
Electrolyte measurements will often show low potassium, normal or increased sodium, and increased bicarbonate (metabolic alkalosis). Plasma aldosterone and renin are decreased. The aldosterone measurement is a critical factor in ruling out true hyperaldosteronism. Urine potassium is inappropriately high for the serum potassium level. If there is clinical suspicion of glucocorticoid excess, measurement of cortisol or other steroid hormones is indicated. Measurement of the ratio of cortisol to cortisone serves as an indicator of whether there is decreased activity of the 11-beta-hydroxysteroid dehydrogenase 2. (Table 1)
|Plasma Aldosterone||Serum Potassium||Plasma Renin|
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?
Many factors affect the activity of the renin-angiotensin-aldosterone system (RAAS). These include posture, salt intake, and antihypertensive medicines. To assess plasma aldosterone and renin, 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.
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.
Licorice-containing substances include not only candy, but also some herbal preparations and chewing tobacco. Many therapeutically administered steroid hormones, such as cortisone and prednisone have some mineralocorticoid activity. Thiazide and loop diuretics affect electrolyte levels.
Hypokalemia with metabolic alkalosis may result from gastrointestinal fluid loss. Potassium loss can occur with loop or thiazide diuretics, diabetic ketoacidosis, renal tubular acidosis, and hypomagnesemia. Genetic disorders, including Bartter syndrome, Gitelman syndrome, and Liddle syndrome, result in altered activity of renal channels.
Deoxycorticosterone-secreting adenomas may be a source of increased mineralocorticoid activity.
What Lab Results Are Confirmatory?
Confirmatory testing depends on the suspected cause of pseudohyperaldosteronism. There is increasing availability of nucleic acid sequencing to identify genetic disorders. Suspected Cushing syndrome would lead to testing of cortisol production and dexamethasone suppression tests. History is an important factor in identifying ingestion of licorice-containing compounds or exogenous steroids. Measurement of 11-deoxycorticosterone helps identify mineralocorticoid secreting adenomas, whereas measurement of the ratio of cortisol to cortisone serves as an indicator of whether there is decreased activity of the 11-beta-hydroxysteroid dehydrogenase 2. Exogenous synthetic steroids can be identified by serum testing.
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.
- 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?