Medscape is available in 5 Language Editions – Choose your Edition here.


Primary Aldosteronism Workup

  • Author: Gabriel I Uwaifo, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
Updated: Jun 30, 2016

Approach Considerations

Individuals with primary aldosteronism may present with hypokalemic metabolic alkalosis; however, as many as 38% of patients with primary aldosteronism may be normokalemic at presentation.[12]

Routine laboratory studies can show hypernatremia, hypokalemia, and metabolic alkalosis resulting from the action of aldosterone on the renal distal convoluted tubule (DCT) (ie, enhancing sodium reabsorption and potassium and hydrogen ion excretion).[18]

Historical tests

Adrenal phlebography

This procedure had been attempted in the 1980s and aimed to invasively visualize the venous patterns encircling adrenocortical adenomas. The procedure has fallen into disrepute because of the risk of adrenal infarction and is no longer used.

Therapeutic trial of spironolactone (Aldactone)

This procedure is also no longer used as a diagnostic test for primary aldosteronism, because easier and more rapid alternatives exist; hence, it is currently of historic value.

For reasons of completeness, the spironolactone therapeutic trial involved the administration of spironolactone orally at a dose of 100 mg 4 times daily for 5 weeks. A positive test would be characterized by a decrease in diastolic blood pressure of at least 20 mm Hg.


Screening (First-Tier) Tests

Serum potassium and bicarbonate levels

Hypokalemia and metabolic alkalosis have low sensitivities and specificities for primary aldosteronism when these levels are tested by themselves. Hypokalemia (serum potassium level < 3.6 mEq/L) has a sensitivity of 75-80% while the patient is on a normal sodium diet.[5] Typically, it is associated with mild metabolic alkalosis (serum bicarbonate level >31 mEq/L) and inappropriate kaliuresis (urinary potassium excretion >30 mmol/day).

Sodium and magnesium levels

Mild serum hypernatremia in the 143-147 mEq/L range and mild hypomagnesemia from renal magnesium wasting are other associated biochemical findings in established primary aldosteronism.[19] (See Medscape Reference Laboratory Medicine articles Serum Sodium and Magnesium.)

Plasma aldosterone/plasma renin activity ratio

Because the random plasma aldosterone/plasma renin activity (PRA) ratio is fairly constant over many physiologic conditions, it can be used for screening. Normal values are less than 270 when aldosterone concentration is expressed in pmol/L, or are less than 10 when aldosterone concentration is expressed in ng/dL. (See the chart below.)[20]

Algorithm for screening for potential primary aldo Algorithm for screening for potential primary aldosteronism.

When aldosterone is measured in ng/dL and PRA is measured in ng/mL/h, a plasma aldosterone/PRA ratio of greater than 20-25 has 95% sensitivity and 75% specificity for primary aldosteronism. When aldosterone is measured in pmol/L, a ratio greater than 900 is consistent with primary aldosteronism.[21, 22]


Limitations in the usefulness of the plasma aldosterone/PRA ration include the following:

  • A major limitation of these tests is the inherent variability of aldosterone secretion due to an intrinsic circadian rhythm
  • Most recommendations suggest performing the test while all antihypertensives that can affect the renin-angiotensin system (RAS) are withheld; this can be difficult to accomplish when severe disease dictates the continuation of some medications to control hypertension (HTN) and hypokalemia during testing.
  • Obtaining the plasma aldosterone/PRA ratio in the setting of chronic angiotensin-converting enzyme (ACE) inhibitor use (ie, >4 wk of use) increases the specificity of the ratio test but reduces the sensitivity
  • Although the usefulness of plasma aldosterone/PRA ratio testing has been well validated in whites and Asians, it has not been validated in other major racial groups.

Medication interference

The plasma aldosterone/PRA ratio should not be calculated when the patient is taking medications that can interfere with this measurement. Spironolactone, an aldosterone receptor antagonist, should be stopped for 6 weeks prior to testing. Eplerenone, another aldosterone receptor antagonist, can also interfere with testing and should be stopped for at least 2 weeks before testing.

Alpha-blockers, such as doxazosin, do not interfere with the PA/PRA ratio. Beta-blockers and calcium channel blockers do not affect the diagnostic accuracy of the ratio in most cases.

PRA after salt and water depletion and/or upright posture

In primary aldosteronism, PRA is less than 1 ng/mL/h and fails to rise above 2 ng/mL/h following salt and water depletion, furosemide administration, or 4 hours of erect posture. This test, along with the captopril suppression tests, has been used either as a screening test or as a confirmatory (second-tier) test for primary aldosteronism, depending on personal preferences of various groups involved in primary aldosteronism research.

Confirmatory tests are based on the concept that aldosterone is secreted in an unregulated fashion in primary aldosteronism and therefore cannot be suppressed by usual physiologic regulatory inputs. In a similar fashion, the PRA is chronically and tonically suppressed and cannot be stimulated

Captopril and losartan suppression tests

This involves the oral administration of a single dose of captopril (25-50 mg), an ACE inhibitor. In healthy individuals, aldosterone levels will be suppressed to less than 15 ng/dL. The test has a sensitivity of 90-100% but a specificity of only 50-80%.

In a study of 135 patients who underwent captopril and losartan (an angiotensin-II receptor blocker [ARB]) tests, Wu et al concluded that the values for the PRA ratio and aldosterone concentration derived using the losartan test were more accurate than those obtained through the captopril test for the diagnosis of primary aldosteronism.[23]

The authors found that when a PRA ratio (ng/dL per ng/mL/h) of greater than 35 and an aldosterone concentration of more than 10 ng/dL were used, the diagnostic specificity values for captopril and losartan were 89.1% and 93.8%, respectively, and the respective diagnostic sensitivity values were 66.2% and 84.5%. The authors recommend the preferential performance of the losartan suppression test.


Confirmatory (Second-Tier) Tests

Serum aldosterone level

After 3 days of an unrestricted sodium diet and 1 hour of full recumbency, healthy individuals have aldosterone levels of less than 15 ng/dL. When serum aldosterone is elevated above 22 ng/dL and renin is suppressed, the serum aldosterone (S-Aldo) test virtually confirms the diagnosis of primary aldosteronism. However, because aldosterone secretion is variable, the negative and positive predictive value of a single random aldosterone level is limited.

As many as 40% of patients with primary aldosteronism have serum aldosterone levels that remain within the reference range on repeated testing, as is typically the case in essential hypertension (HTN). (See the chart below.)

Algorithm for confirmation of primary aldosteronis Algorithm for confirmation of primary aldosteronism.

24-Hour urinary aldosterone excretion test

The 24-hour urinary aldosterone (U-Aldo) excretion test is one of the most useful confirmatory diagnostic tools because it is an index for total daily aldosterone secretion (in a fashion similar to the 24-h urinary free cortisol [UFC], which is typically elevated in patients with Cushing syndrome).

In most patients with primary aldosteronism, the 24-hour U-Aldo is greater than 14 mcg/day (after 3 days of salt loading). Only about 7% of patients with primary aldosteronism have values of less than 14 mcg/day.

Salt-loading test

The salt-loading test can be done by using either an intravenous salt-loading protocol or an oral salt-loading protocol. The oral protocol calls for daily ingestion of at least 10-12 g of sodium chloride for at least 5 days before the test is performed. When the oral protocol has been met, 24-hour U-Aldo, sodium, potassium, and creatinine excretions are measured, and serum aldosterone and PRA should be determined. In normal individuals, the major U-Aldo metabolite, urinary aldosterone-18-glucuronide, should fall below a level of 17 mcg/day. Nonsuppressibility of U-Aldo-18G is highly suggestive of primary aldosteronism. Nonetheless, this test is cumbersome and rarely performed.

The 24-hour urinary creatinine measurement validates the adequacy of the urine sample collection, while a 24-hour urinary sodium value of at least 250 mEq/day confirms an adequate salt load during the days prior to the test and therefore validates the other measurements.

The alternate version of the salt loading test involves the intravenous the infusion of 500 mL/h of isotonic sodium chloride solution over 4 hours (total of 2 L of fluid volume). The serum aldosterone level and PRA are measured at baseline, 2 hours, and 4 hours. In healthy individuals, aldosterone levels are suppressed to less than 8.5 ng/dL, while the PRA is suppressed to less than 0.6 ng/mL/h. Again, S-Aldo is highly suggestive of primary aldosteronism. Rapid infusion of isotonic saline should be avoided in patients with frank volume overload due to renal or cardiac failure or other medical reasons.


Determination of Primary Aldosteronism Subtype (Third-Tier) Tests

Once the diagnosis of primary aldosteronism has been confirmed by a first- or second-tier test, the next step is to determine the subtype of primary aldosteronism and to identify surgically curable disease. For practical purposes, this means distinguishing between an adrenal adenoma and idiopathic adrenal hyperplasia (IAH). (See the chart below.)[18, 24]

Algorithm for distinguishing subtypes of primary a Algorithm for distinguishing subtypes of primary aldosteronism.

In general, patients with adenomas are younger than patients with hyperplasia and have more severe hypertension (HTN) and hypokalemia, as well as higher urinary aldosterone (U-Aldo) levels, than do patients with IAH. However, these clinical parameters are not reliable enough to accurately distinguish adenoma from IAH.

Postural stimulation test

Aldosteronomas are associated with an anomalous decrease in the aldosterone level with upright posture, in contrast to patients with idiopathic adrenal hyperplasia (IAH), in whom a renin-angiotensin system (RAS)–mediated increase in aldosterone level occurs with upright posture.

Similarly, a serum aldosterone level surge occurs in patients with renin-responsive adenomas (RRAs), low-renin essential HTN, and very rare cases of unilateral adrenal hyperplasia (the latter presenting with features intermediate between idiopathic adrenal hyperplasia [IAH] and aldosterone-producing adrenal adenoma; occasionally designated as “intermediate aldosteronism”).[25]

When abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans are combined with postural stimulation, the positive predictive value (PPV) of an abnormal postural test in predicting surgically correctable primary aldosteronism due to a single adenoma is 98%.

The standard postural test protocol involves obtaining baseline values for serum aldosterone (S-Aldo) and plasma renin activity (PRA) levels, as well as these levels 2 hours after the patient has assumed an erect posture. S-Aldo levels typically rise in this setting at least 50% above baseline in healthy persons, in persons with essential HTN, and in the subgroup of patients with primary aldosteronism who have either idiopathic adrenal hyperplasia (IAH) or RRAs.

Among patients with aldosteronomas (aldosterone-producing adenomas; APAs), S-Aldo levels typically do not rise or paradoxically fall to this level. The sensitivity and specificity of this test in the differential diagnosis of the main causes of primary aldosteronism have been reported to be as high as 80-85%.

Furosemide (Lasix) stimulation test

This test is often combined with the upright posture test. The typical test involves the oral administration of 40 mg of furosemide the night before as well as the morning of the test. On the morning of the test, after the furosemide dose has been administered, the patient remains upright 2-3 hours; then, S-Aldo and PRA levels are assayed. The interpretation of the test results is similar to that described above for the postural stimulation test.

Diurnal rhythm of aldosterone

The circadian rhythm of aldosterone secretion in healthy individuals parallels that of cortisol and is corticotropin-dependent. The lowest values are observed around 11:30 pm to midnight, and the highest values occur early in the morning around 7:30-8:00 am (assuming a normal sleep-wake cycle). While this is preserved in patients with aldosteronomas, it is typically lost in patients with IAH.

Elevated levels of 18OH corticosterone and/or 18OH cortisol in plasma and urine may be found in some patients with aldosteronomas but are uncommon in IAH.[26, 27]


CT Scanning and MRI

CT scanning

The initial radiologic investigation in the workup of primary aldosteronism is high-resolution, thin-sliced (2-2.5 mm) adrenal CT scanning with contrast.

Aldosteronomas tend to be small, in contrast to cortisol-producing adrenocortical adenomas; only aldosteronomas that are at least 1 cm in diameter can be detected reliably and consistently.

The overall sensitivity of high-resolution, thin-slice adrenal CT scanning is greater than 90%, but the picture is complicated by the many false-positive findings associated with incidentalomas, which are reported in some series to be found in up to 10-15% of the general population (their prevalence increases with age).[28]

Moreover, high-resolution CT studies can actually be detrimental, because these scans often detect the hyperplasia accompanying adenomas and may result in a tendency to overdiagnose idiopathic adrenal hyperplasia (IAH). Similarly, because long-term adrenal hyperplasia is associated with pseudonodule and nodule formation, this radiographic picture may often be confused with the diagnosis of autonomous adenomas.

Surgical indications

Some investigators suggest that when a solitary, unilateral macroadenoma (>1 cm) is detected on a CT scan in a young patient in the setting of unequivocal aldosteronism, unilateral adrenalectomy is indicated. However, because of the age-dependent risk that a solitary, unilateral adrenal macroadenoma may be a nonfunctioning adenoma, some experts believe that adrenal vein sampling[18] should be performed in patients older than 40 years.


It is generally accepted that MRI is not superior to contrast-enhanced CT scanning for adrenal visualization. High-resolution CT scans may actually have better adrenal definition. (See the image below.)

Magnetic resonance imaging (MRI) scan in a patient Magnetic resonance imaging (MRI) scan in a patient with Conn syndrome showing a left adrenal adenoma.

If the screening (CT scanning and/or MRI) of a patient with primary aldosteronism is completely normal, a 6- to 12-month treatment trial with aldosterone antagonists is generally recommended, after which the imaging studies should be repeated. Treatment with glucocorticoids may also be considered for glucocorticoid-remediable aldosteronism (GRA), if this condition is suspected.


NP-59 Iodo-methyl-norcholesterol Scintigraphy

Although fairly difficult to set up and not routinely available, this test can be useful in select cases for distinguishing between adenomas and hyperplasia. In large nuclear medicine referral centers, the discriminant value of the test approaches that of adrenal venous sampling (ie, close to 90%), especially with larger tumors of 1.5 cm in diameter or larger. (See the image below.) The typical administered activity is 37 MBq (1 milliCurie; mCi).

Scintigram obtained by using iodine-131-beta-iodom Scintigram obtained by using iodine-131-beta-iodomethyl-norcholesterol (NP-59) in a 59-year-old man with hypertension shows fairly intense radionuclide uptake in the right adrenal tumor. At surgery, a Conn tumor was confirmed.

The test results are improved if there has been previous dexamethasone suppression of the adrenals using 0.5-1 mg of oral dexamethasone every 6 hours. In this setting, adenoma images remain visible, while hyperplastic gland images fade after 2-3 days of dexamethasone therapy.

Standard scanning may produce a false-negative result for small aldosteronomas; however, the diagnostic yield can be increased by coadministration of spironolactone. This is the major diagnostic alternative to adrenal venous sampling (AVS).


Adrenal Venous Sampling

Because this procedure is highly dependent on the availability of technically proficient interventional radiologists, it cannot (and should not) be performed universally, despite the fact that it is the criterion standard for the confirmation of lateralizable aldosterone excess.[29, 30, 31] Indeed, AVS may be performed selectively only when preoperative imaging cannot definitively lateralize a presumed unilateral aldosteronoma.

Adrenal venous sampling probably has its greatest utility when adrenal imaging findings are completely normal despite biochemical evidence for primary aldosteronism and in settings in which bilateral adrenal pathology is present on imaging and the biochemistry suggests the presence of a functional aldosteronoma.

The test also has utility in resolving the exact etiology in cases of primary aldosteronism in which discordance exists between the biochemical findings and the radiologic findings with regard to whether the primary aldosteronism is due to idiopathic adrenal hyperplasia (IAH) or an aldosteronoma.

One series reported that 41% of patients with a normal adrenal CT scan who had biochemical evidence of primary aldosteronism actually had lateralizable disease, while 49% of patients with bilateral micronodules on CT scan also had lateralizable disease.[32] Even in cases in which only a single adrenal nodule was found on imaging, when AVS was performed, it confirmed lateralizable disease in just 51-66% of cases.


The adrenal veins are catheterized via a percutaneous femoral venous approach. Right and left venous catheters should be placed in the ipsilateral adrenal veins to prevent errors in handling the samples. (Cannulation of the right adrenal vein is technically difficult because of the short length of this vessel. The left adrenal vein is longer, allowing for more stable catheter placement.)

At baseline and following corticotropin stimulation (preferably by continuous infusion at 50 mcg/h for the duration of the sampling study), blood samples are obtained simultaneously from both adrenal veins, as well as from the inferior vena cava, and the samples are assayed for aldosterone and cortisol.

In order to document the placement of the catheters within the adrenal veins, an adrenal-to–vena cava cortisol ratio (post corticotropin) is calculated; it should be greater than 5-10.


The accuracy of the test exceeds 95% when the procedure is technically successful. If autonomous, unilateral secretion of aldosterone is present on either side, the ratio of aldosterone concentrations between the right and left adrenal veins generally exceeds 10:1. False-positive results can occur when renal artery stenosis is present; hence, renal artery stenosis needs to be thoroughly excluded, especially before a highly invasive test is performed.

Most patients with a unilateral source of aldosterone have adrenal-to-adrenal aldosterone-to-cortisol ratios of greater than 4. Ratios of less than 3 suggest hyperplasia, and values of 3-4 are considered indeterminate results.


Adrenal venous sampling is not without risks. Adrenal and iliac venous thrombosis, adrenal hemorrhage, adrenal insufficiency, or even major venous hemorrhage due to transmural tears and catheter dislocations are among the potential complications.


Hydroxycorticosterone and Oxocortisol-Hydroxycortisol Assays

Because of the different adrenocortical zones involved in idiopathic hyperplasia, in comparison with adenomas, assays of plasma 18-hydroxycorticosterone (18-OHB) or plasma and/or urine 18-oxocortisol (18-oxo-F)/18-hydroxycortisol may be of diagnostic use. (See the image below.)[26, 27]

Transitional zone adrenocortical steroids. Transitional zone adrenocortical steroids.

Aldosteronomas are typically associated with 18-OHB levels of greater than 100 ng/dL. Similarly, glucocorticoid-remediable aldosteronism (GRA; type 1 familial hyperaldosteronism), though a hyperplastic disease by definition, is also associated with an increased production of these 18-oxo/hydroxy derivatives. This distinct biochemistry is not present in renin-responsive adenomas (RRAs). At this point, few centers send out for these specialized biochemistry tests, and their current value is mainly historical.


Fludrocortisone Suppression Test

This test works on the same principle that the sodium chloride intravenous infusion or the oral salt-loading tests are based on for confirming a diagnosis of primary aldosteronism. The fludrocortisone suppression test has lost much of its popularity, however, because it requires hospitalization of the patient and 4-5 days to complete, and it currently is mainly of historical interest.

For reasons of completeness, the description of this test is as follows: fludrocortisone is administered orally at a dose of 0.1-0.2 mg every 6 hours, along with supplemental sodium chloride and potassium. In the healthy individual, following this stimulation, the serum aldosterone (S-Aldo) level is typically suppressed to less than 8 ng/dL, with a corresponding urinary aldosterone (U-Aldo) excretion of less than 12 mcg/day.

In patients with primary aldosteronism, neither the urinary aldosterone level nor the plasma aldosterone level suppresses to the above-noted thresholds.


Dexamethasone Suppression Test

This test is relevant only in the setting of possible familial aldosteronism. Customarily, in patients with primary aldosteronism, dexamethasone is associated with a transient slight-to-moderate reduction of plasma and urinary aldosterone levels, although not into the normal reference range.[7]

In the subset of primary aldosteronism patients with glucocorticoid-remediable aldosteronism (GRA), small doses of dexamethasone (1-2 mg/day) induce full normalization in plasma and urinary aldosterone levels. This is invariably associated with improvement in hypertension (HTN) in these patients. Other reports suggest a cut-off level for plasma aldosterone of less than 4 ng/dL and/or a relative plasma aldosterone suppression of greater than 80% of the baseline for the diagnosis of GRA following the dexamethasone challenge.

Three variants of familial primary aldosteronism exist. Type 1 familial primary aldosteronism (also called GRA) is associated with improvement in HTN using low-dose dexamethasone. Types 2 and 3 familial primary aldosteronism are not dexamethasone suppressible.


Metoclopramide (Reglan) Test

This is a noninvasive test for distinguishing between aldosteronomas and idiopathic adrenal hyperplasia (IAH). It takes advantage of the differential expression of the dopamine receptors on the cell membrane of adrenocortical cells.

Under normal conditions, dopamine causes tonic inhibition of aldosterone, whereas serotonin (5-HT) causes increased aldosterone secretion in vivo. Metoclopramide is a D2 dopamine receptor antagonist, as well as a serotonin receptor-4 (5-HT4) partial agonist, and, hence, its administration leads in increased aldosterone levels. This normal pattern of response is retained in patients with aldosteronomas and low-renin hypertension (HTN), but not in patients with IAH.[33]

Following a 10-mg intravenous injection of metoclopramide, serum aldosterone levels increase significantly in patients with aldosteronomas, but they remain either unchanged or paradoxically reduced in patients with IAH. This test saw some increased usage in the mid 1990s, especially in Europe, but is rather rarely used in the United States today.


Additional Laboratory Studies

Corticotropin stimulation test

The corticotropin stimulation test uses the standard 250-mcg intravenous injection. In aldosteronomas, a robust aldosterone response is typically observed. In idiopathic adrenal hyperplasia (IAH), the aldosterone surge is considerably more feeble. The test is no longer used, because the discriminant value of the test is rather poor.[6]


Angiotensin-II infusion test

This test involves evaluating the response of plasma renin activity (PRA) and serum aldosterone (S-Aldo) to a continuous angiotensin-II infusion. The response characteristics are similar to those observed in the posture tests, with an appropriate increase in aldosterone level observed in IAH but not in aldosteronomas.

The angiotensin-II infusion test is much less popular than other aldosteronism tests because it requires continuous infusion and close hemodynamic monitoring, and it is rarely used today.


Histological Findings

Histologic findings vary according to the type of primary aldosteronism that a patient has. Typical aldosteronomas are characterized by adenomatous tissue, usually with zona fasciculata–type morphology. Most of these tumors are small (< 3 cm in diameter), and most of the cells are lipid-laden cells arranged in acini or cords. Associated focal and/or diffuse hyperplasia often occurs.

Renin-responsive adenomas (RRAs) are characterized by zona glomerulosa–type morphology. The only other distinctive features are predictable, unique biochemical features.

Idiopathic adrenal hyperplasia (IAH) is characterized by diffuse hyperplasia that may be micronodular, macronodular, or a mixture of both. The morphology of the cells is commonly akin to the zona glomerulosa.

In primary adrenal hyperplasia (PAH), diffuse hyperplasia, which is unilateral and has zona fasciculata morphology, is typically observed.

Primary aldosteronism syndrome rarely occurs in the setting of adrenal carcinoma, whereby the cause of the hypersecretion of aldosterone is a malignancy (rather than a benign adenoma). In such cases, histopathology reveals the typical features of adrenocortical carcinoma (ACC), including mitotic figures, local invasion, and locoregional lymph node metastases.

Contributor Information and Disclosures

Gabriel I Uwaifo, MD Associate Professor, Section of Endocrinology, Diabetes and Metabolism, Louisiana State University School of Medicine in New Orleans; Adjunct Professor, Joint Program on Diabetes, Endocrinology and Metabolism, Pennington Biomedical Research Center in Baton Rouge

Gabriel I Uwaifo, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Society of Hypertension, Endocrine Society

Disclosure: Nothing to disclose.


Nicholas J Sarlis, MD, PhD, FACP Vice President, Head of Medical Affairs, Incyte Corporation

Nicholas J Sarlis, MD, PhD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Association of Clinical Endocrinologists, American College of Physicians, American Federation for Medical Research, American Head and Neck Society, American Medical Association, American Society for Radiation Oncology, American Thyroid Association, Endocrine Society, New York Academy of Sciences, Royal Society of Medicine, Association for Psychological Science, American College of Endocrinology, European Society for Medical Oncology, American Society of Clinical Oncology

Disclosure: Received salary from Incyte Corporation for employment; Received ownership interest from Sanofi-Aventis for previous employment; Received ownership interest/ stock & stock option (incl. rsu) holder from Incyte Corporation for employment.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.


Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law, Medicine &Ethics, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Serge A Jabbour, MD Associate Professor, Department of Medicine, Division of Endocrinology, Jefferson Medical College of Thomas Jefferson University

Serge A Jabbour, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, and Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, andInternational Society for Clinical Densitometry

Disclosure: Nothing to disclose.

  1. Rossi GP, Ragazzo F, Seccia TM, Maniero C, Barisa M, Calò LA, et al. Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma. Hypertension. 2012 Aug. 60(2):431-6. [Medline].

  2. Dluhy RG, Lifton RP. Glucocorticoid-remediable aldosteronism. Endocrinol Metab Clin North Am. 1994 Jun. 23(2):285-97. [Medline].

  3. Funder JW. The genetic basis of primary aldosteronism. Curr Hypertens Rep. 2012 Apr. 14(2):120-4. [Medline].

  4. Choi M, Scholl UI, Yue P, et al. K+ channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science. 2011 Feb 11. 331(6018):768-72. [Medline]. [Full Text].

  5. Young DB. Quantitative analysis of aldosterone's role in potassium regulation. Am J Physiol. 1988 Nov. 255(5 Pt 2):F811-22. [Medline].

  6. Stowasser M, Klemm SA, Tunny TJ, et al. Plasma aldosterone response to ACTH in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol. 1995 Jun-Jul. 22(6-7):460-2. [Medline].

  7. Litchfield WR, New MI, Coolidge C, et al. Evaluation of the dexamethasone suppression test for the diagnosis of glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 1997 Nov. 82(11):3570-3. [Medline]. [Full Text].

  8. Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab. 2004 Mar. 89(3):1045-50. [Medline].

  9. Born-Frontsberg E, Reincke M, Rump LC, et al. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: results of the German Conn's Registry. J Clin Endocrinol Metab. 2009 Apr. 94(4):1125-30. [Medline].

  10. Bernini G, Galetta F, Franzoni F, Bardini M, Taurino C, Bernardini M, et al. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens. 2008 Dec. 26(12):2399-405. [Medline].

  11. Apostolopoulou K, Künzel HE, Gerum S, Merkle K, Schulz S, Fischer E, et al. Gender differences in anxiety and depressive symptoms in patients with primary hyperaldosteronism: A cross-sectional study. World J Biol Psychiatry. 2012 May 8. [Medline].

  12. Cruz DN, Perazella MA. Hypertension and hypokalemia: unusual syndromes. Conn Med. 1997 Feb. 61(2):67-75. [Medline].

  13. Cesari M, Letizia C, Angeli P, Sciomer S, Rosi S, Rossi GP. Cardiac Remodeling in Patients With Primary and Secondary Aldosteronism: A Tissue Doppler Study. Circ Cardiovasc Imaging. 2016 Jun. 9 (6):[Medline].

  14. Hall JE, Granger JP, Smith MJ Jr. Role of renal hemodynamics and arterial pressure in aldosterone "escape". Hypertension. 1984. 6:1183.

  15. Yokota N, Bruneau BG, Kuroski de Bold ML, et al. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest. 1994 Nov. 94(5):1938-46. [Medline]. [Full Text].

  16. Vallon V, Rieg T. Regulation of renal NaCl and water transport by the ATP/UTP/P2Y2 receptor system. Am J Physiol Renal Physiol. 2011 Sep. 301(3):F463-75. [Medline]. [Full Text].

  17. Schiffrin EL, Chrétien M, Seidah NG, et al. Response of human aldosteronoma cells in culture to the N-terminal glycopeptide of pro-opiomelanocortin and gamma 3-MSH. Horm Metab Res. 1983 Apr. 15(4):181-4. [Medline].

  18. [Guideline] Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008 Sep. 93(9):3266-81. [Medline].

  19. Quamme GA. Control of magnesium transport in the thick ascending limb. Am J Physiol. 1989 Feb. 256(2 Pt 2):F197-210. [Medline].

  20. Seiler L, Rump LC, Schulte-Mönting J, Slawik M, Borm K, Pavenstädt H, et al. Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication. Eur J Endocrinol. 2004 Mar. 150(3):329-37. [Medline].

  21. Tzanela M, Effremidis G, Vassiliadi D, et al. The aldosterone to renin ratio in the evaluation of patients with incidentally detected adrenal masses. Endocrine. 2007 Oct. 32(2):136-42. [Medline].

  22. Diederich S, Mai K, Bahr V, et al. The simultaneous measurement of plasma-aldosterone- and -renin-concentration allows rapid classification of all disorders of the renin-aldosterone system. Exp Clin Endocrinol Diabetes. 2007 Jul. 115(7):433-8. [Medline].

  23. Wu VC, Chang HW, Liu KL, et al. Primary aldosteronism: diagnostic accuracy of the losartan and captopril tests. Am J Hypertens. 2009 Aug. 22(8):821-7. [Medline].

  24. Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, et al. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. J Clin Endocrinol Metab. 2012 Jan. 97(1):100-9. [Medline].

  25. Otsuka F, Otsuka-Misunaga F, Koyama S, et al. Hormonal characteristics of primary aldosteronism due to unilateral adrenal hyperplasia. J Endocrinol Invest. 1998 Sep. 21(8):531-6. [Medline].

  26. Stowasser M, Bachmann AW, Tunny TJ. Production of 18-oxo-cortisol in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol. 1996 Jun-Jul. 23(6-7):591-3. [Medline].

  27. Hamlet SM, Gordon RD, Gomez-Sanchez CE, et al. Adrenal transitional zone steroids, 18-oxo and 18-hydroxycortisol, useful in the diagnosis of primary aldosteronism, are ACTH-dependent. Clin Exp Pharmacol Physiol. 1988 Apr. 15(4):317-22. [Medline].

  28. McAlister FA, Lewanczuk RZ. Primary hyperaldosteronism and adrenal incidentaloma: an argument for physiologic testing before adrenalectomy. Can J Surg. 1998 Aug. 41(4):299-305. [Medline].

  29. Georgiades CS, Hong K, Geschwind JF, et al. Adjunctive use of C-arm CT may eliminate technical failure in adrenal vein sampling. J Vasc Interv Radiol. 2007 Sep. 18(9):1102-5. [Medline].

  30. Young WF, Stanson AW, Grant CS, et al. Primary aldosteronism: adrenal venous sampling. Surgery. 1996 Dec. 120(6):913-9; discussion 919-20. [Medline].

  31. Webb R, Mathur A, Chang R, Baid S, Nilubol N, Libutti SK, et al. What is the Best Criterion for the Interpretation of Adrenal Vein Sample Results in Patients with Primary Hyperaldosteronism?. Ann Surg Oncol. 2011 Nov 3. [Medline].

  32. Young WF, Stanson AW, Thompson GB, et al. Role for adrenal venous sampling in primary aldosteronism. Surgery. 2004 Dec. 136(6):1227-35. [Medline].

  33. Naruse M, Naruse K, Yoshimoto T, et al. Dopaminergic regulation of aldosterone secretion: its pathophysiologic significance in subsets of primary aldosteronism. Hypertens Res. 1995 Jun. 18 Suppl 1:S59-64. [Medline].

  34. Carey RM. Primary aldosteronism. Horm Res. 2009 Jan. 71 Suppl 1:8-12. [Medline].

  35. Hood SJ, Taylor KP, Ashby MJ, et al. The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio. Circulation. 2007 Jul 17. 116(3):268-75. [Medline]. [Full Text].

  36. Ronconi V, Turchi F, Appolloni G, di Tizio V, Boscaro M, Giacchetti G. Aldosterone, Mineralocorticoid Receptor and the Metabolic Syndrome: Role of the Mineralocorticoid Receptor Antagonists. Curr Vasc Pharmacol. 2011 Oct 21. [Medline].

  37. Minowada S, Fujimura T, Takahashi N, et al. Computed tomography-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenoma. J Clin Endocrinol Metab. 2003 Dec. 88(12):5814-7. [Medline]. [Full Text].

  38. Sukor N, Gordon RD, Ku YK, et al. Role of unilateral adrenalectomy in bilateral primary aldosteronism: a 22-year single center experience. J Clin Endocrinol Metab. 2009 Jul. 94(7):2437-45. [Medline].

  39. Celen O, O'Brien MJ, Melby JC, et al. Factors influencing outcome of surgery for primary aldosteronism. Arch Surg. 1996 Jun. 131(6):646-50. [Medline].

  40. Waldmann J, Maurer L, Holler J, Kann PH, Ramaswamy A, Bartsch DK, et al. Outcome of surgery for primary hyperaldosteronism. World J Surg. 2011 Nov. 35(11):2422-7. [Medline].

  41. Letavernier E, Peyrard S, Amar L, et al. Blood pressure outcome of adrenalectomy in patients with primary hyperaldosteronism with or without unilateral adenoma. J Hypertens. 2008 Sep. 26(9):1816-23. [Medline].

  42. Milsom SR, Espiner EA, Nicholls MG, et al. The blood pressure response to unilateral adrenalectomy in primary aldosteronism. Q J Med. 1986 Dec. 61(236):1141-51. [Medline].

  43. Giacchetti G, Turchi F, Boscaro M, Ronconi V. Management of primary aldosteronism: its complications and their outcomes after treatment. Curr Vasc Pharmacol. 2009 Apr. 7(2):244-49. [Medline].

  44. Amar L, Baguet JP, Bardet S, et al. SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook. Ann Endocrinol (Paris). 2016 Jun 14. [Medline]. [Full Text].

  45. Baguet JP, Steichen O, Mounier-Vehier C, Gosse P. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA?. Ann Endocrinol (Paris). 2016 Apr 15. 86 (20):1002-8. [Medline]. [Full Text].

  46. Douillard C, Houillier P, Nussberger J, Girerd X. SFE/SFHTA/AFCE Consensus on Primary Aldosteronism, part 2: First diagnostic steps. Ann Endocrinol (Paris). 2016 May 10. [Medline]. [Full Text].

  47. Reznik Y, Amar L, Tabarin A. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 3: Confirmatory testing. Ann Endocrinol (Paris). 2016 Jun 15. [Medline]. [Full Text].

  48. Bardet S, Chamontin B, Douillard C, et al. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis. Ann Endocrinol (Paris). 2016 Mar 29. [Medline]. [Full Text].

  49. Zennaro MC, Jeunemaitre X. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 5: Genetic diagnosis of primary aldosteronism. Ann Endocrinol (Paris). 2016 Jun 14. [Medline]. [Full Text].

  50. Steichen O, Amar L, Chaffanjon P, Kraimps JL, Menegaux F, Zinzindohoue F. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 6: Adrenal surgery. Ann Endocrinol (Paris). 2016 Jun 10. [Medline]. [Full Text].

  51. Pechère-Bertschi A, Herpin D, Lefebvre H. SFE/SFHTA/AFCE consensus on primary aldosteronism, part 7: Medical treatment of primary aldosteronism. Ann Endocrinol (Paris). 2016 Jun 14. [Medline]. [Full Text].

Magnetic resonance imaging (MRI) scan in a patient with Conn syndrome showing a left adrenal adenoma.
Scintigram obtained by using iodine-131-beta-iodomethyl-norcholesterol (NP-59) in a 59-year-old man with hypertension shows fairly intense radionuclide uptake in the right adrenal tumor. At surgery, a Conn tumor was confirmed.
Effects of main antihypertensives on the renin-angiotensin system.
Potential causes of primary aldosteronism.
Transitional zone adrenocortical steroids.
Algorithm for screening for potential primary aldosteronism.
Algorithm for confirmation of primary aldosteronism.
Algorithm for distinguishing subtypes of primary aldosteronism.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.