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DOI: 10.1148/rg.274065150
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RadioGraphics 2007;27:1145-1157
© RSNA, 2007

EDUCATION EXHIBIT

Role of Radiology in the Management of Primary Aldosteronism1

Shilpan M. Patel, BSc (Hon), MRCP, Ravi K. Lingam, BSc (Hon), MRCP, FRCR, Tina I. Beaconsfield, MSc, FRCRI, Tan L. Tran, FRCS (Eng), DMRD, FRCR, and Beata Brown, MRCP

1 From the Departments of Radiology (S.M.P., R.K.L., T.I.B., T.L.T.) and Endocrinology (B.B.), Central Middlesex and Northwick Park Hospitals, North West London Hospitals (NWLH) Trust, Watford Rd, Harrow HA1 3UJ, England. Presented as an education exhibit at the 2005 RSNA Annual Meeting. Received August 11, 2006; revision requested September 11 and received November 27; accepted December 4. All authors have no financial relationships to disclose. Address correspondence to R.K.L. (e-mail: raviklingam{at}yahoo.co.uk).


   Abstract
Top
 Abstract
Introduction
 Primary Aldosteronism
 Imaging-guided Therapeutic...
 Conclusions
 References
 
The diagnosis of primary aldosteronism, the most common form of secondary hypertension, is based on clinical and biochemical features. Although radiology plays no role in the initial diagnosis, it has an important role in differentiating between the two main causes of primary aldosteronism: aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). This distinction is important because APAs are generally managed surgically and BAH medically. Adrenal venous sampling is considered the standard of reference for determining the cause of primary aldosteronism but is technically demanding, operator dependent, costly, and time consuming, with a low but significant complication rate. Other imaging modalities, including computed tomography, magnetic resonance imaging, and adrenal scintigraphy, have also been used to determine the cause of primary aldosteronism. Cross-sectional imaging has traditionally focused on establishing the diagnosis of an APA, with that of BAH being one of exclusion. A high specificity for detecting an APA is desirable, since it will avert unnecessary surgery in patients with BAH. However, an overreliance on cross-sectional imaging can lead to the incorrect treatment of affected patients, mainly due to the wide variation in the reported diagnostic performance of these modalities. A combination of modalities is usually required to confidently determine the cause of primary aldosteronism. The quest for optimal radiologic management of primary aldosteronism continues just over a half century since this disease entity was first described.

© RSNA, 2007


   Introduction
Top
 Abstract
 Introduction
Primary Aldosteronism
 Imaging-guided Therapeutic...
 Conclusions
 References
 
Over half a century has passed since Conn originally described primary aldosteronism (1,2). Primary aldosteronism is now recognized as the most common form of secondary hypertension. There are two principal causes of primary aldosteronism: aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). The former is usually treated surgically and the latter medically. With hundreds of millions of hypertensive patients worldwide, recognition of primary aldosteronism and subsequent subtype classification, upon which treatment strategies are based, is clearly important.

BAH and APAs cannot be reliably differentiated clinically or biochemically, and radiology can play an important role in distinguishing between the two entities. Several imaging modalities have been used for this purpose, including computed tomography (CT), magnetic resonance (MR) imaging, scintigraphy, and adrenal venous sampling (AVS). In this article, we discuss primary aldosteronism in terms of screening, classification, and treatment and the use of the aforementioned imaging modalities in establishing the diagnosis and guiding the management of this pathologic condition. We also briefly examine imaging-guided therapeutic procedures in primary aldosteronism.


   Primary Aldosteronism
Top
 Abstract
 Introduction
 Primary Aldosteronism
Imaging-guided Therapeutic...
 Conclusions
 References
 
Primary aldosteronism is defined as the inappropriate autonomous hypersecretion of aldosterone in the absence of activation of the rennin-angiotensin-aldosterone axis (Fig 1). Primary aldosteronism is the most common cause of secondary hypertension and is estimated to be responsible for 5%–20% of all cases of hypertension (3). Aldosterone, a mineralocorticoid hormone produced by the outermost cortical zone of the adrenal gland, the zona glomerulosa, was first described by Simpson et al in 1952 (4). Soon after this discovery, in April 1954, the first case of primary aldosteronism was described by Conn (1,2) and by Conn and Louis (5).


Figure 1
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  		Figure 1.  Diagram illustrates the renin-angiotensin-aldosterone axis. Physiologic release of aldosterone occurs if there is a reduction in the effective circulating volume (eg, hemorrhage). Aldosterone works by increasing sodium retention in the distal renal tubules, which in turn promotes water absorption and causes isotonic expansion of the effective circulating volume. Aldosterone is also a potent vasoconstrictor. Both of these mechanisms serve to increase blood pressure (BP). This increase is detected by cells of the juxtaglomerular apparatus, which suppress renin production as part of a negative feedback mechanism. In primary aldosteronism, this negative feedback mechanism is overridden by the pathologic excess of aldosterone, which occurs in the absence of an appropriate stimulus.

 
Conn originally described a 34-year-old patient with "a bizarre constellation of clinical and laboratory manifestations," which included hypertension, hyperaldosteronism, suppressed renin, hypokalemia, hypernatremia, metabolic alkalosis, and osmotic and neuromuscular symptoms (1). In this patient, surgical removal of a 4-cm right adrenal adenoma reversed all of the clinical and biochemical abnormalities. Today, the diagnosis of primary aldosteronism remains based on these clinical and biochemical features. However, it is now apparent that hypokalemia is not a universal finding and need not be present for the diagnosis to be made (3).

Screening
In 1976, Dunn and Espiner (6) first developed the concept of the aldosteronerenin ratio as a screening test for primary aldosteronism, based on the knowledge that aldosterone levels are elevated and renin levels suppressed in primary aldosteronism. This test soon gained widespread acceptance as a quick and inexpensive means of identifying patients with the condition and could also be performed prior to the onset of hypokalemia. However, controversy exists as to what the aldosteronerenin ratio threshold should be for the diagnosis of primary aldosteronism to be considered (3). Moreover, several large studies have questioned the test characteristics (specificity and sensitivity) of this ratio as a screening test, since many variables can affect the ratio (Table 1) (8–10).


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  		Table 1. Factors Affecting the Use of the Aldosterone-Renin Ratio as a Screening Tool for Primary Aldosteronism

 
Since the introduction of the aldosteronerenin ratio, the reported prevalence of primary aldosteronism among hypertensive patients has risen dramatically, from 1%–2% to as much as 20%, with a minority of investigators reporting even higher rates (3). However, it is likely that the variability of the reported prevalence of this condition is due to the different sample sizes and patient characteristics in these studies. Most studies have a referral bias, examining this ratio in patients referred for refractory hypertension or hypokalemia, resulting in a higher reported prevalence of primary aldosteronism. Perhaps a more accurate estimate of the prevalence of this condition (5%–15%) and the use of the ratio as a screening tool have come from studies in which the ratio has been applied to a large sample of unselected hypertensive patients in the primary care setting (11–13).

If the aldosteronerenin ratio is elevated, patients should undergo confirmatory tests. Failure of oral salt loading or the intravenous administration of saline solution or fluorocortisone to suppress plasma aldosterone levels is thought to be indicative of autonomous hyperaldosteronism. Fluorocortisone suppression is considered to be the standard of reference for confirming primary aldosteronism. However, these investigations are often not performed due to time and financial constraints (3,7,14–18).

Classification
Since Conn’s discovery, it is now apparent that there are many other causes of primary aldosteronism (Table 2). APA and BAH are the most common subtypes. APAs were traditionally thought to represent approximately two-thirds of cases of primary aldosteronism and BAH approximately one-third. However, recent evidence suggests that the reverse may be true (14).


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  		Table 2. Causes of Primary Aldosteronism

 
APAs are benign adrenocortical neoplasms associated with pathologic aldosterone excess. At gross examination, they are usually yellow, round or oval, and typically less than 2 cm in size, with a significant proportion less than 1 cm (19,20). APAs can occur in any age group but are often found in younger patients (<40 years old) (14).

In BAH, both adrenal glands are enlarged and may be smooth, micronodular, or macronodular in appearance. It has been postulated that these different appearances may be part of a pathologic spectrum ranging from a true solitary adenoma at one extreme to pure bilateral micronodular hyperplasia at the other, with intermediate degrees of unilateral or bilateral micro- and macronodular hyperplasia in between (21). Compared with APAs, BAH tends to be found in older patients (>40 years old) (14).

Treatment
APAs are usually managed surgically with adrenalectomy. Adrenalectomy for an aldosteronoma achieves long-term normalization of blood pressure in 30%–60% of patients. Predictive factors for a favorable outcome include a short history of hypertension, mild hypertension, young age, no family history of hypertension, and the absence of renal or cardiac dysfunction preoperatively (7,14). Surgery is also the treatment of choice for the much rarer causes of unilateral adrenal excess such as adrenocortical carcinoma and unilateral adrenal hyperplasia.

The practice of bilateral adrenalectomy in patients with BAH was abandoned in the 1970s when it became apparent that this procedure was seldom curative (17,22). Instead, these patients are treated with aldosterone antagonists. Traditionally, spironolactone has been used. However, spironolactone has dose-dependent antiandrogenic and progesterone-like effects and can cause impotence, painful gynecomastia, and dysmenorrhea. Eplerenone, a new selective aldosterone receptor antagonist, has been developed in recent years. Eplerenone has 0.1% and 1% of the binding affinity of androgen and progesterone receptors, respectively, found in spironolactone. It also has a side-effect profile similar to that of a placebo in clinical trials (14,23–25).

Determination of Cause
Once the diagnosis of primary aldosteronism has been established, it is important to distinguish between the principal causes of unilateral and bilateral adrenal excess, namely, APAs and BAH, respectively. However, differentiating between these two entities on clinical and biochemical grounds is often imprecise and seldom discriminatory (Table 3). It has long been appreciated that radiology plays no role in the initial diagnosis of primary aldosteronism. However, radiology does play an important role in differentiating between the different causes, thereby guiding management.


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  		Table 3. Clinical and Biochemical Differentiation between APA and BAH*

 
Adrenal Venous Sampling.— AVS was first described by Melby et al in 1967 (26). The procedure temporarily fell out of favor due to the technical difficulties and costs involved, but in the past two decades it has enjoyed a renaissance and is now considered the standard of reference for determining the cause of primary aldosteronism (27).

With use of a percutaneous femoral vein approach, samples are taken from the inferior vena cava (IVC) and both adrenal veins (Figs 2, 3). Aldosterone and cortisol levels are measured at each sample site. Many centers advocate the use of an infusion of adrenocorticotropic hormone during sampling to minimize the effect of stress-induced fluctuations in aldosterone and cortisol levels during the procedure and to augment side-to-side differences (27,28).


Figure 2A
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  		Figure 2a.  Left (a) and right (b) adrenal venograms demonstrate the normal ordered branching pattern of veins within the adrenal glands.

 

Figure 2B
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  		Figure 2b.  Left (a) and right (b) adrenal venograms demonstrate the normal ordered branching pattern of veins within the adrenal glands.

 

Figure 3
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  		Figure 3.  Adrenal adenoma in a 52-year-old man. Adrenal venogram demonstrates a left adrenal adenoma (arrow), a finding that was biochemically confirmed with AVS.

 
When AVS is performed by an experienced operator, complications (eg, adrenal hemorrhage [heralded by (a) flank pain necessitating strong analgesics and (b) fever], adrenal infarction, adrenal vein perforation, adrenal vein thrombosis) are rare. However, with smaller volumes of contrast material, these complications are much less common than previously described (22).

The principal difficulty with the technique relates to the failure to successfully catheterize the right adrenal vein. In a meta-analysis of 47 reports encompassing almost 400 patients, Young (14) reported a 74% success rate for right adrenal vein catheterization. However, at institutions where there is vast experience, some authors have higher success rates. For example, Daunt (20) recently reported success rates of 97% and 96.7% for left and right adrenal vein cannulation, respectively, in a cohort of 792 patients with biochemically confirmed primary aldosteronism who underwent AVS.

Sampling is generally considered successful if the cortisol ratio between the adrenal vein being sampled and the IVC is greater than 2, although an exact consensus for a cutoff has yet to be reached (19). To correct for dilution factors, most investigators express aldosterone-cortisol ratios (corrected aldosterone levels) for each sample site (20). The corrected aldosterone ratio of one adrenal vein divided by that of the other is known as the lateralization ratio. Young et al (22) proposed that a lateralization ratio of greater than 4 suggested unilateral aldosterone hypersecretion, a ratio of 3 or less indicated BAH, and ratios between 3 and 4 represented an area of overlap.

Some authors have examined the corrected ratio in the nondominant adrenal vein and compared it with that in the IVC, based on the premise that the ratio may be suppressed in the adrenal vein on the nondominant side in cases of unilateral excess to the extent that it is actually lower than that in the IVC. However, this finding has also been reported in a significant proportion of cases of BAH and therefore cannot be used alone as a reliable marker of unilateral adrenal excess (22).

Cross-sectional Imaging: Detecting APAs.— CT and MR imaging have increasingly been used to diagnose APAs (Fig 4). These modalities are quicker, cheaper, less invasive, more readily available, and less technically demanding than AVS. Most CT and MR imaging studies have concentrated on establishing the diagnosis of an APA, with the diagnosis of BAH being one of exclusion. However, it is now apparent that there is a wide variation in the reported diagnostic performance of CT (sensitivity, 40%–100%) and MR imaging (sensitivity, 70%–100%) in detecting APAs (27,29–36).


Figure 4A
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  		Figure 4a.  APA. (a) Unenhanced CT scan obtained in a 30-year-old woman with primary aldosteronism shows a 5-cm low-attenuation (– 16 HU) right adrenal mass (arrow), a finding that is in keeping with an APA. The left adrenal gland is normal (arrowhead). (b) T1-weighted MR image obtained in a 45-year-old woman with primary aldosteronism shows an APA of the medial limb of the right adrenal gland (arrow). The lateral limb of the right adrenal gland and the left adrenal gland (arrowhead) appear normal. Both patients underwent surgery, with postoperative histologic analysis leading to the diagnosis of APA.

 

Figure 4B
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  		Figure 4b.  APA. (a) Unenhanced CT scan obtained in a 30-year-old woman with primary aldosteronism shows a 5-cm low-attenuation (– 16 HU) right adrenal mass (arrow), a finding that is in keeping with an APA. The left adrenal gland is normal (arrowhead). (b) T1-weighted MR image obtained in a 45-year-old woman with primary aldosteronism shows an APA of the medial limb of the right adrenal gland (arrow). The lateral limb of the right adrenal gland and the left adrenal gland (arrowhead) appear normal. Both patients underwent surgery, with postoperative histologic analysis leading to the diagnosis of APA.

 
The lack of sensitivity for detection of an APA has been attributed to the small size of these adenomas, with CT failing to easily resolve those less than 5 mm (16,37,38). Indeed, in a series of 143 cases of surgically confirmed APAs, one in five adenomas measured less than 10 mm in size (19). In a more recent series, Daunt (20) reported that nearly one-half of all surgically confirmed APAs measured less than 10 mm.

A high specificity for the detection of an adenoma is desirable, since it will avert unnecessary surgery in patients with BAH. To obtain a high specificity, the number of false-positive findings must be kept to a minimum. Several reasons have been given for the lack of specificity for the detection of an adenoma, including the detection of a concomitant nonhyperfunctioning nodule, the presence of a dominant nodule in macronodular BAH, and increased nodularity with age and hypertension (37,38). To our knowledge, there are no specific data in the literature relating to the prevalence of nonhyperfunctioning adenomas as the sole abnormality in patients with primary aldosteronism.

Small adrenal masses or nodules found in hypertensive patients have a differential diagnosis that includes pheochromocytomas and, in oncology patients, metastases. Adenomas have a propensity for intracellular lipid content (39), which can be evaluated with unenhanced CT densitometry and chemical shift MR imaging, and show rapid washout of contrast material enhancement (40). Evidence has accumulated that unenhanced CT densitometry (39,41), chemical shift MR imaging (39,42), and enhancement washout characteristics at CT (40,43,44) can be used to differentiate nonhyperfunctioning adenomas (incidentalomas) from nonadenomas and metastases. Using an algorithm that combined unenhanced CT densitometry and delayed enhanced CT densitometry (for enhancement washout calculations), Caoili et al (44) correctly characterized 160 of 166 masses as nonhyperfunctioning adenomas with a sensitivity of 98% and a specificity of 92%.

In an attempt to improve the specificity of detecting an APA, several studies have examined the intracellular lipid content of APAs compared with that of nonhyperfunctioning adrenal adenomas. The findings are equivocal, with one study suggesting that nonhyperfunctioning adenomas contain more intracellular lipid (45), whereas another study demonstrated no significant difference in the intracellular lipid content or CT attenuation between nonhyperfunctioning adenomas and APAs (46). Further lack of support for the use of intracellular lipid content of an APA as a specific diagnostic characteristic came from a chemical shift MR imaging study of 17 patients with primary aldosteronism by Sohaib et al (47). Their study showed no significant difference in signal intensity reduction on out-of-phase images compared with in-phase images between APAs and bilateral hyperplastic adrenal glands.

It is now apparent that an overreliance on CT in detecting an APA can lead to the incorrect treatment of patients with primary aldosteronism (17,22,27,33,34,36). The largest study illustrating this conclusion compared findings at CT with those at AVS in 203 patients with primary aldosteronism (22). In this study, had CT alone been used, 21.7% of patients would have been incorrectly excluded as candidates for adrenalectomy and 24.7% of patients might have undergone unnecessary or inappropriate adrenalectomy. Patients with unilateral aldosterone excess diagnosed with AVS included 41.4% of patients with "normal" CT findings, 51% of those with an ipsilateral micronodule (<10 mm) detected at CT, and 65.6% of those with an ipsilateral macronodule (>10 mm) seen at CT (22).

Several studies have directly compared CT with MR imaging in the detection of an APA (17,30,35,37). None of the studies reported any significant difference in diagnostic performance between the two modalities. However, there was a bias in patient selection in two of these studies, with only patients who had undergone adrenalectomy for unilateral aldosterone hypersecretion being included (17,35).

In the most recent comparative study, Lingam et al (37) retrospectively reviewed 34 cases of biochemically confirmed primary aldosteronism (17 patients with BAH and 17 with an APA) and demonstrated similar sensitivities and specificities for the detection of an APA for both CT (86% and 87.5%, respectively) and MR imaging (87.5% and 87.5%, respectively) with good inter-observer agreement. It was suggested that the choice of preferred imaging modality be based on the radiologist’s experience (37).

Cross-sectional Imaging: Detecting BAH.— Because of the wide variation in the performance of CT in the detection of an APA, Lingam et al (38) suggested differentiating the two main causes of primary aldosteronism by positively diagnosing BAH using adrenal gland size measurements. The method of measuring the adrenal gland was based on that used by Vincent et al (48), who documented "normal" adrenal size at CT (Fig 5).


Figure 5
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  		Figure 5.  Diagram illustrates width measurements of the body (1) and limbs (2, 3) of the adrenal gland (Reprinted, with permission, from reference 48).

 
The mean adrenal limb width was found to be significantly larger in BAH (Fig 6) than in APAs and normal control cases. The significantly larger mean adrenal limb width in BAH compared with APA was also documented in an MR imaging study (47).


Figure 6A
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  		Figure 6a.  BAH in a 55-year-old woman. Unenhanced CT scans (a, b) and T1-weighted MR image (c) demonstrate bilateral smooth enlargement of the adrenal glands (arrows). BAH was diagnosed with AVS.

 

Figure 6B
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  		Figure 6b.  BAH in a 55-year-old woman. Unenhanced CT scans (a, b) and T1-weighted MR image (c) demonstrate bilateral smooth enlargement of the adrenal glands (arrows). BAH was diagnosed with AVS.

 

Figure 6C
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  		Figure 6c.  BAH in a 55-year-old woman. Unenhanced CT scans (a, b) and T1-weighted MR image (c) demonstrate bilateral smooth enlargement of the adrenal glands (arrows). BAH was diagnosed with AVS.

 
Lingam et al (38) went on to propose and test a diagnostic algorithm, based on adrenal limb measurements, to differentiate BAH from APA (Fig 7). With use of this algorithm, in a small study of 28 patients, a 100% specificity for diagnosing BAH was achieved with a mean adrenal limb width greater than or equal to 5 mm and a 100% sensitivity with a mean width greater than 3 mm. Although all the cases were correctly managed with this algorithm, 13 of 28 patients (46%) required AVS because the adrenal width fell between the two thresholds. Therefore, it was suggested that a larger study be conducted to validate the proposed algorithm (38).


Figure 7
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  		Figure 7.  Diagram illustrates an algorithm proposed by Lingam et al (38) for diagnosing BAH. Although all cases were correctly managed in their study, the sample size was small, and it was suggested that a larger study would be necessary to validate the algorithm.

 
Adrenal Scintigraphy.— Almost four decades have passed since radiopharmaceuticals were first developed to image the adrenal cortex. Radio-pharmaceuticals allow noninvasive assessment of adrenal function and can be used to differentiate between an APA and BAH (Fig 8). The most commonly used adrenocortical imaging agents are cholesterol based and include iodine-131–6-ß-iodomethylnorcholesterol (NP-59) and selenium-75–6-ß-selenomethylcholesterol. These agents circulate in the bloodstream bound to low-density lipoproteins and are taken up by low-density lipoprotein receptors in the adrenal cortex. The overall radiation dose to the patient is similar for both agents. It is preferable that all drugs that may interfere with the renin-angiotensin-aldosterone system be withdrawn prior to performing adrenal scintigraphy to prevent misdiagnosis (49,50).


Figure 8A
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  		Figure 8a.  APA in a 66-year-old woman. Adrenal scintigrams obtained immediately (a), 7 days (b), and 11 days (c) after the administration of NP-59 with the patient prone demonstrate unilateral increased uptake, a finding that was surgically confirmed to represent a left-sided APA. It is worth noting that this study was performed after a long dexamethasone-suppressed period, so that the timing of appearances of unilateral abnormalities does not conform to the interpretative convention outlined by Gross et al (49,50). (Case courtesy of Adil Al-Nahhas, MBBS, FRCP, Hammersmith Hospital, London, England.)

 

Figure 8B
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  		Figure 8b.  APA in a 66-year-old woman. Adrenal scintigrams obtained immediately (a), 7 days (b), and 11 days (c) after the administration of NP-59 with the patient prone demonstrate unilateral increased uptake, a finding that was surgically confirmed to represent a left-sided APA. It is worth noting that this study was performed after a long dexamethasone-suppressed period, so that the timing of appearances of unilateral abnormalities does not conform to the interpretative convention outlined by Gross et al (49,50). (Case courtesy of Adil Al-Nahhas, MBBS, FRCP, Hammersmith Hospital, London, England.)

 

Figure 8C
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  		Figure 8c.  APA in a 66-year-old woman. Adrenal scintigrams obtained immediately (a), 7 days (b), and 11 days (c) after the administration of NP-59 with the patient prone demonstrate unilateral increased uptake, a finding that was surgically confirmed to represent a left-sided APA. It is worth noting that this study was performed after a long dexamethasone-suppressed period, so that the timing of appearances of unilateral abnormalities does not conform to the interpretative convention outlined by Gross et al (49,50). (Case courtesy of Adil Al-Nahhas, MBBS, FRCP, Hammersmith Hospital, London, England.)

 
Dexamethasone suppression is commonly used to enhance the diagnostic accuracy of adrenal scintigraphy in patients with primary aldosteronism (51), although controversy exists (52). Dexamethasone suppression is thought to work by suppressing NP-59 uptake by the glucocorticoid- and androgen-producing portions of the adrenal cortex. Theoretically, this suppression prevents masking of radiopharmaceutical uptake in the outermost portion of the adrenal cortex, the zona glomerulosa, which is responsible for aldosterone production (49). The most commonly used regime for dexamethasone suppression results in scans on which the normal adrenal glands are not visualized before 5 days (49,50). Patterns of scintigraphic uptake are outlined in Table 4.


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  		Table 4. Patterns of Radiotracer Uptake at Adrenal Scintigraphy in Patients with Primary Aldosteronism

 
NP-59 is also taken up by the liver, excreted in bile, and subject to enterohepatic circulation, potentially leading to significant gut activity, which can interfere with analysis. Therefore, some centers advocate the use of laxatives (50).

The reported sensitivity of adrenal scintigraphy for detecting an APA varies widely, ranging from 50% to 100% (30,32,49,50,52–56). Perhaps smaller adenomas are missed due to their size, based on the observation that adrenal NP-59 uptake strongly correlates with the estimated adrenal volume (56).

Although it is known that radiotracer accumulation can occur in nonhyperfunctioning adrenal adenomas, there is insufficient evidence from the literature relating to the use of scintigraphy alone in differentiating between hyperfunctioning adenomas (APAs) and nonhyperfunctioning adenomas. Most investigators agree that scintigraphy should be performed only after the clinical and biochemical diagnosis of primary aldosteronism has been confirmed so as to minimize the potential interpretative problems caused by scintigraphic detection of nonhyperfunctioning adrenal adenomas (50).

However, adrenal scintigraphy may provide information to help differentiate nonhyperfunctioning from hyperfunctioning adenomas if bilateral adrenal masses are detected at CT. Several case reports have suggested that an APA demonstrates greater radiotracer uptake than does a contralateral nonhyperfunctioning adenoma (57,58). Following adrenalectomy on the side of the scintigraphically predominant lesion, the biochemical and blood pressure data returned to normal, and follow-up CT scans demonstrated no significant change in the size of the contralateral adenoma, all of which findings indicate a diagnosis of nonhyperfunctioning adenoma on that side. However, one case report suggested that a large nonhyperfunctioning adenoma can take up sufficient radiotracer to mimic an APA (59). Therefore, even if scintigraphic findings are interpreted in the context of anatomic imaging, it is unclear whether scintigraphy can help differentiate between hyperfunctioning (aldosterone-producing) and nonhyperfunctioning adenomas in patients with confirmed primary aldosteronism.

Several studies have compared scintigraphy with CT and MR imaging in determining the cause of primary aldosteronism. The diagnostic performance of scintigraphy varies greatly relative to that of CT and MR imaging (17,35,55). In practice, scintigraphy can be used in a supplementary role if cross-sectional imaging is equivocal in determining the cause of primary aldosteronism.

Multimodality Diagnostic Approach.— Because of the limitations of AVS and the problems inherent in the diagnostic performance of CT, MR imaging, and scintigraphy, various multimodality diagnostic algorithms or flow charts have been proposed (7,14,15,17,22) in attempting to differentiate between the two main causes of primary aldosteronism. All of these algorithms include CT prior to AVS. Some of them attempt to maximize diagnostic performance without an overreliance on AVS by considering the probability of an APA or BAH prior to selecting cases for AVS. As yet, however, none of these diagnostic algorithms has been rigorously tested for efficacy.

We suggest using the diagnostic algorithm shown in Figure 9, which is largely representative of the other proposed algorithms (7,14,15,17,22) but has also been modified in the light of the current literature, although it has not been tested for efficacy. CT and AVS remain the mainstays of the algorithm, although there is also a proposed place for MR imaging and scintigraphy, should the radiologist or clinician prefer to use them. Using cross-sectional imaging (CT, MR imaging), the radiologist should not only detect an APA but should also attempt to positively diagnose BAH.


Figure 9
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  		Figure 9.  Diagram illustrates a proposed algorithm for differentiating APA from BAH in patients with primary aldosteronism. The algorithm has not yet been tested for efficacy.

 
If an adrenal nodule or mass is seen in one adrenal gland but the contralateral gland appears normal, surgery should be considered for the resection of an APA. In older patients, however, owing to the higher prevalence of bilateral (nodular) hyperplasia, the clinician may prefer to use AVS prior to surgery to confirm the diagnosis of an APA. In the unlikely event of a localized adrenal carcinoma manifesting as an adrenal mass at CT or MR imaging, surgery would be indicated if the algorithm shown in Figure 9 is used. When multiple nodules are seen, the radiologist could assess for limb enlargement (Fig 7) to differentiate bilateral nodular hyperplasia from multiple adenomas (consisting of a combination of hyperfunctioning and nonhyperfunctioning adenomas). When bilateral adrenal gland enlargement with or without nodules is seen at CT or MR imaging, the likely diagnosis is bilateral (nodular) hyperplasia, and medical treatment is indicated. If the diagnosis of bilateral (nodular) hyperplasia is challenged by failure to respond clinically to appropriate medical treatment, AVS can be used to reestablish the cause of primary aldosteronism. If the adrenal glands appear normal at CT or MR imaging, AVS is indicated to exclude the possibility of a small adenoma that was not detected at cross-sectional imaging.


   Imaging-guided Therapeutic Procedures in Primary Aldosteronism
Top
 Abstract
 Introduction
 Primary Aldosteronism
 Imaging-guided Therapeutic...
Conclusions
 References
 
There are few studies that have described and evaluated imaging-guided therapeutic procedures for APAs (60–64). The main procedures include CT-guided ablation and transarterial embolization of aldosteronomas. Proponents of these techniques argue that they offer a quicker and cheaper alternative to surgery and can be used in patients for whom surgery is not an option.

Liang et al (60) described the results of CT-guided ablation in two patients with APAs. In both patients, there was a sustained correction of biochemical abnormalities, and the blood pressure remained normal after 18 months. Follow-up CT scans obtained at 6 and 12 months demonstrated cystic necrosis of the ablated lesions. In another study, four of five patients with aldosteronomas who underwent CT-guided ablation with acetic acid experienced a good outcome (61).

The largest study, which investigated the results of transarterial embolization of APAs, included 33 patients. The study demonstrated a success rate of 82%, although some of the patients required more than one session of ablative treatment (64).

Both percutaneous CT-guided ablation and transarterial embolization are not without side effects, including transient increases in blood pressure, flank pain, and mild pyrexia. There is also the theoretic risk of pneumothorax, adrenal hematoma, and adrenal infarction (60–64). Another disadvantage of both procedures is the lack of histologic confirmation of ablated lesions.


   Conclusions
Top
 Abstract
 Introduction
 Primary Aldosteronism
 Imaging-guided Therapeutic...
 Conclusions
References
 
The diagnosis of primary aldosteronism is made on clinical and biochemical grounds. Imaging plays an essential role in differentiating between the two main causes of primary aldosteronism: APA and BAH. Imaging modalities including AVS, CT, MR imaging, and scintigraphy are currently used for this purpose, but their capabilities and limitations make radiologic management less clear cut. The quest for optimal radiologic management of primary aldosteronism continues just over a half century since Conn’s original description of this disease entity.


   Footnotes
 

Abbreviations: APA = aldosterone-producing adenoma, AVS = adrenal venous sampling, BAH = bilateral adrenal hyperplasia, IVC = inferior vena cava


   References
Top
 Abstract
 Introduction
 Primary Aldosteronism
 Imaging-guided Therapeutic...
 Conclusions
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