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Adrenal vein sampling (obtención de muestras de sangre en vena suprarenal)

Introduction

There is an increasing requirement for adrenal vein sampling, which is driven by the appreciation that primary aldosteronism is far more common than previously recognized (1–3). Many centers throughout the world are reporting a prevalence of between 5% and 10% in unselected hypertensive patients (4–8).

Historically, adrenal vein sampling has been problematic, with many authors reporting difficulties with obtaining good samples, particularly from the right adrenal vein (9–11). This results from the small size of the right adrenal vein and the resulting difficulty in obtaining an adequate specimen, recognizing the typical vascular patterns, and distinguishing other vessels that may arise from the posterior wall of the inferior vena cava (IVC) close by. Lastly, the long anatomic segment that may give rise to the right adrenal vein may result in a prolonged search pattern. Superimposed on this is the frequency of anatomic variations of the left renal vein or left adrenal vein (12).

Furthermore, the realization that computed tomography (CT) is unreliable as a screening test, with increasing reports of inappropriate conclusions drawn from CT examinations (13–20), supports the premise that most patients with syndromes of adrenocortical excess production should undergo adrenal vein sampling to determine if the overproduction is unilateral or bilateral. Cure of hypertension occurs in 50%–80% of patients after adrenalectomy for an aldosterone-producing adenoma, and most of the remaining cases show improvement (1–3,21,22). Cases of bilateral aldosterone hypersecretion can usually be controlled simply with specific medications (1–3). The community cost benefit resulting from a reduction in hypertension medications and hypertension-associated morbidity is evident (23).

This article covers all aspects of adrenal vein sampling. Specific topics discussed are the reasons for performing the study, our clinical experience, aldosteronism, the shortcomings and value of CT, the anatomy of the adrenal veins, variations of the left renal vein, how to recognize the right adrenal vein, how to perform adrenal vein sampling, analysis of the results, and complications.

Why perform adrenal vein sampling?

Adrenal vein sampling is performed to assess whether autonomous hormone production is unilateral or bilateral. Adrenal vein sampling is most commonly performed in primary aldosteronism, as this is the most common hypersecretory adrenal disease (24–26). Less commonly, it is performed in biochemically proved pheochromocytoma when no source is visible at CT or other cross-sectional imaging. Rarely, it may be performed in adrenal Cushing disease or for syndromes of androgen excess (27).

Clinical experience

Queensland X-Ray has been performing adrenal vein sampling at Greenslopes Private Hospital since November 1994. Up to the end of August 2004, we had performed 800 examinations. Of these procedures, 716 were performed by two radiologists and 792 were performed for primary aldosteronism. Both cortisol and aldosterone were assayed in each sample (see the “Analysis of the Results” section). Because adrenal venous blood is rich in cortisol, this is used as a marker of successful adrenal vein sampling. Empirically, a cortisol gradient of 3 between the adrenal sample and a peripheral sample was considered to indicate adequate sampling (3); if the cortisol gradient was under 2, the sample was excluded from further analysis, as such levels have on occasion proved to be misleading. Cortisol gradients between 2 and 3 are assessed on their individual merits. Over the past 7 years, for the two experienced radiologists, the success rate has been 97% for left-sided samples and 96.6% for right-sided samples, with success defined as sample adequacy as outlined earlier (ie, an adequate gradient) and a study on the basis of which ongoing management can be planned.

Aldosteronism

Jerome Conn first described primary aldosteronism in 1954, the same year that the chemical structure of aldosterone was identified (28).

In April 1954, Conn managed the case of a 34-year-old housewife with severe hypokalemia, generalized muscle weakness, tetany, and hypertension, salient features of the soon to be recognized Conn syndrome. At surgery, a 4-cm cortical adenoma was removed from her right adrenal gland, resulting in cure of the hypertension. Over the next 10 years, it became evident that primary aldosteronism could be present even with normal potassium levels. By the mid-1960s, Conn suggested that the overall prevalence of aldosteronism among hypertensive persons was at least 7.6%. This idea aroused heated debate and was generally rejected by the medical community. Even today, some textbooks still suggest that the prevalence of aldosteronism among hypertensive persons is less than 1%.

In 1981, Hiramatsu and colleagues (29) described a screening test—the aldosterone-to-renin ratio—and found aldosterone-producing adenomas in 2.6% of hypertensive patients. Because only those cases with a positive nuclear medicine (iodine 131 iodocholesterol) or CT study were accepted as positive cases, this figure would have underestimated the number of patients with primary aldosteronism, as all those cases with bilateral hyperplasia or small adenomas would have been missed.

There are now numerous published reports from all major continents and in many racial groups that confirm Conn’s original hypothesis, suggesting that the true prevalence of primary aldosteronism may be between 5% and 10% of all hypertensive persons (1–8).

Types of Primary Aldosteronism

The pathologic pattern of primary aldosteronism is very variable (1–3). The most common type is bilateral adrenal cortical hyperplasia, which may demonstrate several patterns including diffuse, micronodular, macronodular (30), or occasionally giant macronodular. Less frequent is unilateral secretion from a solitary adenoma, hyperplasia (23,31,32), or rarely carcinoma. When unilateral secretion is found and an adenoma is present, there is usually associated hyperplasia of the zona glomerulosa, the aldosterone-secreting portion of the adrenal gland, on the same side.

However, the macroscopic appearance, whether it be hyperplasia, nodular disease, or other, is irrelevant; the main differentiation is whether secretion is unilateral or bilateral, as those with unilateral secretion can be offered surgery (3).

There are two main types of familial hyperaldosteronism. Type 1 is glucocorticoid-remediable primary aldosteronism and is inherited as an autosomal dominant disease (1–3,21).

The second form of familial hyperaldosteronism, type 2, is now realized to be more common than type 1 (3). Type 2 familial hyperaldosteronism may be expressed as unilateral or bilateral disease and therefore needs to be investigated in the same manner as apparently sporadic primary aldosteronism.

Effects of Aldosterone and Rationale for Screening

Screening for primary aldosteronism by means of the aldosteronerenin ratio in venous blood is straightforward and reliable. Levels of renin and aldosterone are often within the normal range, but a ratio of the two levels is a robust screening test for primary aldosteronism (29). It requires care in interpretation, as there are numerous causes of false-positive and false-negative studies, particularly resulting from antihypertensive medication and diuretics (33). All of our cases are confirmed by use of a fludrocortisone suppression test (2,3,28).

A further important consideration is that inappropriate aldosterone secretion in excess appears to have direct cardiac effects that are independent of blood pressure elevation (34–38). A disproportionate extent of myocardial hypertrophy and fibrosis has been reported in patients with aldosteronism.

Shortcomings and value of CT

Previously, many had suggested that if primary aldosteronism was diagnosed and CT demonstrated a clear-cut adenoma, then surgery could be performed without adrenal vein sampling (39,40). It has become realized that such a process may lead to inappropriate surgery (13–20). In the most recent of these studies (13–20), Magill et al (20) compared adrenal vein sampling and CT in 62 patients and showed that CT results were inaccurate or noncontributory in 68%. Indeed, adenomas less than 1 cm in diameter account for nearly 50% of aldosterone-producing adenomas surgically removed at our center (3), and below this size detection at CT can become difficult. We have had several patients with adenomas at CT in whom disease was localized to the contralateral side at adrenal vein sampling (Fig 1).

Figure 1 CT scan shows a 13-mm-diameter
nonhyperfunctioning adenoma in the lateral limb of the left adrenal gland (arrow). At adrenal vein sampling, the patient’s disease was lateralized to the right adrenal gland. (The adrenal vein sampling was repeated to confirm the unexpected finding.) The patient’s hypertension was cured with right adrenalectomy.

However, the value of CT is twofold: (a) It allows assessment of mass lesions. A large adrenal mass greater than 2.5–4 cm in diameter may warrant consideration for surgical removal in its own right, on the basis of possible malignant potential, unless radiologic appearances are characteristic of other benign lesions such as myelolipoma or there are other clinical considerations such as metastatic disease. (b) CT demonstrates the anatomy and position of the adrenal veins, especially the right adrenal vein (Fig 2).

Figure 2 CT scan clearly shows the right adrenal vein (arrow).

Anatomy of the adrenal veins

The venous drainage of the adrenal glands is predominantly via a central vein on both sides (Fig 3) (41–44). On the right, the central vein drains directly into the IVC on its midposterior wall, and one researcher remarked on the constancy of this relationship in cadaver studies (42). Monkhouse and Khalique (44) noted that the central vein on the right may be duplicated and rarely triplicated; although some of these multiple veins may drain to the inferior phrenic or right renal vein, these authors noted that there was always a central vein entering the IVC. At least two authors have reported significant proportions of adrenal veins entering hepatic venous structures (43,45), with Bookstein (45) suggesting a frequency of 10%. The frequency stated in these two sources appears out of step with the frequency in other references, with none being reported in cadaver studies (42,44), and with the frequency in our experience, in which no convincing cases have been observed.

Figure 3 Diagram shows the anatomy of the adrenal veins.

The central vein on the left is also extremely constant (41–44), taking a caudal or downward path into the superior margin of the left renal vein and taking a tributary, the inferior phrenic vein with a variable-length common trunk, before entering the left renal vein. Rarely, the left adrenal and inferior phrenic veins enter the left renal vein separately (probably no more than 1% of cases). Both adrenal glands also have a number of superficial, emissary, or capsular veins that extend from the surface of the gland into the perirenal fat, even on occasion penetrating the renal capsule, particularly on the right (45). Such veins not infrequently communicate with inferior phrenic or intercostal veins; in addition, in two of our 800 cases, a connection with superficial hepatic veins was seen on the right (Figs 4, 5). On the right, they may enter the right renal vein (Fig 6). On the left, communications may be seen to the left renal vein as well as the azygos or hemiazygos vein. Visualization of these veins is an excellent method of confirming intraadrenal positioning.

Figure 4 Fluoroscopic image obtained with injection into the right adrenal vein shows opacification of small peripheral hepatic vessels (arrow).

Figure 5 Fluoroscopic image shows a Mikaelsson catheter passed distally in the right adrenal vein to superselect a medial limb branch; with this catheter position, drainage from a lateral limb adenoma could be missed. The wedged position of the catheter tip (open arrow) has resulted in some extravasation or staining around small branches inferiorly (arrowheads). More cephalad, there is possible filling of a hepatic branch (solid arrow).

Figure 6 Fluoroscopic image obtained with a C2 catheter in the central right adrenal vein shows superficial communications superolaterally and inferolaterally (arrows) and to the right renal vein (arrowhead).

Stack et al (46) recently described an anomalous central left adrenal vein draining directly into the IVC. I could find no other example of this in the literature, although we have seen several cases of superficial veins entering the IVC (Fig 7).

Figure 7 Fluoroscopic image obtained with injection into the left adrenal vein shows two separate left adrenal veins and extensive communicating veins draining into the left renal vein (1) and IVC (2).

In cadaver studies, the right adrenal vein may be 1–15 mm in length and averages 3.5–5 mm in caliber. The left adrenal vein measures 1–4 cm to the inferior phrenic confluence and 1–3 cm from there to the left renal vein and is usually 4–5 mm in caliber (42,44).

Variations of the left renal vein

A recent study by Trigaux et al (12) evaluated anomalies of the IVC and left renal vein with spiral CT, with bilateral IVCs recognized in 0.3% of patients. Ten percent had left renal vein variants, with 38 cases (3.7%) of retroaortic renal veins and 64 cases (6.3%) of circumaortic venous rings (Fig 8). Occasionally, the approach to the left adrenal vein will have to be made via a lower-positioned (usually at L3) retroaortic left renal vein (Fig 9). Retroaortic left renal veins usually lie some 4 cm below a normally sited vein.

Figure 8 Fluoroscopic image obtained with injection into the left adrenal vein shows numerous adrenal branches. Also noted is a renal vein ring, with a normal preaortic vein (top arrow) and a retroaortic vein inferiorly (bottom arrow).

Figure 9 Fluoroscopic image shows a C2 catheter passed via a retroaortic renal vein into the left adrenal vein, with injected contrast material draining into the normal preaortic renal vein.

How to recognize the right adrenal vein

Recognition of the right adrenal vein is the crux of adrenal vein sampling. In cadaver studies, it is usually some 4–5 mm in caliber (42,44). It often funnels down to the hilum of the gland. In our experience, it is usually angled caudally, although Monkhouse and Khalique (44) reported that 26 of 68 veins entered from above. We see five different patterns:

  1. A glandlike pattern with a main central stem and numerous branches (Figs 10, 11), usually with angles of less than 90° between the branches and the main stem, forming a characteristic glandlike pattern. This can occasionally be difficult to differentiate from an accessory hepatic vein (Fig 12).
  2. A delta pattern with little filling of internal structure (Figs 13–15).
  3. A triangular pattern with vessels fairly crowded together and a “blush-like” appearance (Figs 16, 17).
  4. No discernible adrenal vessels, but the main vessel position and attitude are characteristic and fit in with the position estimated at CT (Figs 18–20). Surprisingly, this occurs with some frequency, about one in 30 cases.
  5. A central vein leading to thin stellate or spidery branches (Figs 21–23).

Figure 10 Fluoroscopic image shows the classic glandlike pattern of injection into the right adrenal vein.

Figure 11 Fluoroscopic image shows the classic glandlike pattern of injection into the right adrenal vein with prominent lateral communicating veins.

Figure 12 Fluoroscopic image shows what appears to be a right adrenal vein injection but is actually injection into a hepatic radicle. The subtle upsloping vessel (arrow) arising from the superficial lateral border of the adrenal gland is the giveaway.

Figure 13 Fluoroscopic image shows the delta pattern of injection into the central adrenal vein. There are two or three major branches with acute angles between them.

Figure 14 Fluoroscopic image shows injection into the right adrenal vein with a reverse catheter. There is a basic delta pattern with extensive communications from superficial veins into the retroperitoneum and an intercostal vein (arrow).

Figure 15 Fluoroscopic image obtained with injection into the right adrenal vein shows mainly the central vein. The early branches of a delta configuration are also seen (arrows), thus confirming good catheter position; no more contrast material needs to be injected.

Figure 16 Fluoroscopic image obtained with adrenal vein injection shows a triangular pattern of veins (arrows) and minor blush with communicating superficial veins inferiorly.

Figure 17 Fluoroscopic image obtained with adrenal vein injection shows vessels in a triangular configuration with subtle background blush and an extremely large communicating superficial vein.

Figure 18 Fluoroscopic image obtained with injection into the right adrenal vein. It is difficult to make out any background adrenal structure; however, positive cortisol ratios were found at sampling.

Figure 19 Fluoroscopic image shows a right adrenal gland with an irregular intraglandular structure. Although no normal adrenal structure is discernible, there are large communicating vessels laterally.

Figure 20 Fluoroscopic image obtained with injection into the right adrenal vein. It is difficult to make out a normal background adrenal structure; however, the extensive inferolateral communicating veins support the premise of good catheter position.

Figure 21 Fluoroscopic image shows a barely discernible adrenal structure. However, there is a background spidery pattern with thin vessels and some communicating veins, which are also of small caliber.

Figure 22 Fluoroscopic image shows the spidery pattern of adrenal vein injection. There is a central adrenal vein with straight branches at multiple angles and with lateral communicating veins.

Figure 23 Fluoroscopic image obtained with injection into the right adrenal vein shows a poorly defined stellate or spidery pattern with inferior communicating veins.

Perhaps the most important finding is communication with superficial or emissary veins from the adrenal capsule; if appropriate, this finding gives a high confidence level for a satisfactory position (45). The emissary veins most commonly course laterally, medially, or inferiorly (Figs 6, 11, 16, 17, 20, 24) but sometimes pass cephalad in a straight fashion toward the IVC. They may communicate with the right renal vein (Fig 6), intercostal veins (Figs 14, 16, 17, 20, 24), phrenic vein, or IVC (Figs 6, 24). They must be contrasted with the sweeping, curvilinear, upward-passing veins that extend into the main hepatic veins in patients in whom a small accessory hepatic radicle has been injected (Fig 25). These accessory hepatic radicles often demonstrate marked tissue staining without patient discomfort, whereas injection into an adrenal gland, or for that matter, sometimes suction on a syringe to aspirate blood, may cause poorly defined upper quadrant or lower chest discomfort, particularly posteriorly. Tissue staining in the adrenal gland (Fig 5), which should be avoided at all costs, is also associated with acute discomfort or low-grade pain.

Figure 24 Fluoroscopic image obtained with right adrenal vein injection through a reverse Simmons 1 catheter shows no discernible adrenal structure. However, the large communicating veins extending into intercostal veins make it highly likely that the sample will be positive. At sample analysis, good cortisol gradients were obtained.

Figure 25 Fluoroscopic image obtained with right-sided venous injection shows what appears to be the delta pattern of an adrenal gland. However, the veins coursing upward and to the right are suggestive of hepatic vessels. Samples obtained at this point showed low cortisol values, findings typical of hepatic drainage.

Another major point is that the position of the adrenal gland at CT should have been assessed prior to the study and the area of gland filling should obviously not extend beyond the anticipated margins of the adrenal gland.

How to perform adrenal vein sampling

CT Scanning

High-quality CT examination is of enormous benefit in planning adrenal vein sampling. On a modern multisection scanner with reconstruction at 2 or 3 mm, the right adrenal vein can be identified in more than 50% of patients (Figs 2, 26). When we identify the right adrenal vein, we accurately assess its position in relation to the vertebral column and assign a disk end-plate or pedicle level as necessary. We then plan to place the catheter 1 cm higher to allow for the inspiration used for CT of the adrenal glands. This dramatically reduces the time taken for the search. If no vein can be identified, then the midpoint of the adrenal gland is used as the potential adrenal vein position.

Figure 26 Three sequential thin CT sections show the caudal alignment of the right adrenal vein (arrow), which drains into the mid posterior wall of the IVC.

Stimulation

Many authors use adrenocorticotropic hormone (ACTH) infusions before and during adrenal sampling to stimulate aldosterone release (24–26). The unit at Greenslopes Private Hospital has treated over 1,000 patients with primary aldosteronism over the past 20 years and for many years also used ACTH stimulation. However, we suspect that it increased the number of cases diagnosed as bilateral, perhaps falsely, and this will have eliminated the therapeutic possibility of unilateral adrenalectomy in some patients. Thus, we do not use ACTH stimulation for our adrenal vein sampling.

Peripheral Line

When each adrenal vein sample is obtained, it requires a peripheral blood sample for correlation of the cortisol and aldosterone levels. Although we routinely place a peripheral line for obtaining this blood, a sheath sample could equally well be used.

Catheters

We use 5- or 5.5-F catheters. Although many use a reverse catheter for the right adrenal vein, our unit has traditionally used a C2 Cobra catheter with one side hole 3 mm from the tip. With this catheter and the use of prior CT, the catheter normally drops immediately into the vein, with a very short search required. One side hole is used to facilitate drawing back of blood. We have found that using two side holes increases the number of samples with a low cortisol ratio, which may be a result of dilution by IVC blood. In a narrow IVC, a C1 catheter may often be helpful. Rarely, a reverse catheter such as a Simmons 1 or Mikaelsson may be required. The C2 catheter can often be used for accessing the left adrenal vein. However, more frequently we use an MK1B catheter (Cook, Bloomington, Ind), as this is purpose made for the left adrenal vein.

Puncture

In general, a right femoral vein puncture is performed. Occasionally, a referring endocrinology or hypertension department insists on bilateral adrenal vein sampling simultaneously. In such cases, after the initial femoral vein puncture, then under fluoroscopic guidance in the right inguinal region, a needle can be passed down toward the guidewire or catheter and a quick, easy second puncture can be performed within half a centimeter of the first. It is advisable to use a sheath for one of the catheters, preferably the right venous catheter, to prevent displacement of one catheter when the second is moved.

Often, a Valsalva maneuver aids in venous puncture. Very rarely, ultrasonographic guidance has been required.

Technique of Contrast Material Injection

It is important to inject gently into the adrenal veins, particularly that on the right, to prevent hemorrhage due to rupture of small intraglandular veins. A small amount of contrast material is used, perhaps 3 mL and no more. The injection is started slowly, and if satisfactory confirmation of adrenal position is obtained, then no more contrast material need be injected; a formal diagnostic venogram to outline the entire adrenal gland is not necessary (Fig 27). If little venous structure is seen due to backflow into the IVC (or into the left renal vein on the left), then the speed of injection and pressure are increased slightly in order to visualize the necessary vessels. When tumors are present, staining or a tumor outline is often seen, but this should not be aimed for (Figs 28, 29).

Figure 27 Fluoroscopic image obtained with injection into the central adrenal vein shows virtually no intraglandular structure (same patient as in Fig 12). This injection technique reduces the risk of extravasation to the minimum.

Figure 28 Fluoroscopic image obtained with right adrenal vein injection through a C2 catheter shows extensive distortion of the adrenal venous structure due to a large adenoma (arrows). At surgery, a 2.3-cm-diameter adenoma was removed.

Figure 29 Fluoroscopic image obtained with left adrenal vein injection shows the rounded configuration of an adenoma (arrow) in the lateral limb of the gland (same patient as in Fig 1).

Sampling Techniques

We are required by our laboratory service to provide a minimum of 5 mL and preferably 6 mL. We use a 10-mL syringe for aspiration. On the right, it is often difficult to obtain an adequate quantity of blood from the adrenal vein, as suction on the syringe results in presumed collapse of the vessel wall around the catheter tip. The presence of side holes in the catheter helps allay this problem, as may the following techniques: (a) intermittent gentle suction, (b) suction on the syringe with air in the syringe to reduce the effective suction pressure, and (c) free drainage (ie, letting blood drip from the catheter end into the sample bottle).

A recent article has also identified potential problems with too high a concentration of iodinated contrast material in the sample forming a gel layer that may alter concentrations (47). Therefore, it is advisable to eliminate all contrast material from the system before sampling.

Strategies for the Right Adrenal Vein

The C2 catheter is passed to the predetermined level (from CT) and rotated to the posterior wall of the IVC. Often, the catheter will “drop in” almost immediately. Catheter probing starts on the posterior wall and extends in an arc of 45° to the right and less so to the left. Although the catheter often appears to be pointing significantly one way or the other, CT suggests that this is illusory, as the vein always arises from the posterior wall. Occasionally, the search has to be extended a little cephalad, but rarely caudally. In this fashion, up to 90% of right adrenal veins are found within 5 minutes.

During this initial phase, the catheter usually engages a number of different vessels, such as short accessory hepatic vessels, retroperitoneal vessels, and phrenic vessels.

If the initial search fails, then the catheter can be exchanged for a C1 pattern; the tighter curve allows a more downward approach that may help in steeper right adrenal veins or narrower IVCs (Fig 30). If no vein is found with an extended search and by using these catheters, a reverse catheter such as a Simmons 1 or Mikaelsson may prove helpful. On at least two occasions, the MK1B catheter that I use for the left side has easily entered the right adrenal vein despite its inappropriate design (Fig 31). A reverse catheter may extend deeply into the right adrenal gland; this can potentially result in too selective sampling, which could result in missing the drainage from an adenoma (Figs 5, 32), and also could promote a wedged injection, which could increase the likelihood of extravasation (Fig 5).

Figure 30 Fluoroscopic image obtained with a C1 catheter in the central adrenal vein shows spindly intraglandular adrenal veins with superficial communications laterally.

Figure 31 Fluoroscopic image shows a reverse catheter (MK1B) deeply engaged within the central right adrenal vein.

Figure 32 Fluoroscopic image shows a reverse catheter (Mikaelsson) placed too selectively in the adrenal vein, with the catheter tip in the main medial limb branch (arrow).

In view of possible cephalic orientation of the right adrenal vein (44), other catheter shapes may on occasion be helpful.

If all else fails, an IVC sample obtained with the catheter tip on the mid posterior wall a few millimeters above the anticipated orifice may prove successful. The laminar flow of slow venous return that is characteristically observed from the renal veins at CT will also be observed from the adrenal veins, and this should promote a high likelihood of success with this method. This further highlights the importance of careful analysis of a good-quality CT study before adrenal vein sampling.

Strategies for the Left Adrenal Vein

After at least two right-sided samples are obtained, the C2 catheter is withdrawn to the left renal vein level. By gentle pushing, sometimes with a little rotation or twisting of the catheter around the wire, the C2 can often be advanced down the left renal vein. With the C2 catheter some 3–4 cm into the left renal vein, rotation on the catheter to direct the tip cephalad will result in this catheter engaging the left adrenal vein in at least 50% of patients. (Actually, the common trunk of the left adrenal and inferior phrenic veins is engaged, but I will refer to it as the left adrenal vein, as this is where sampling is usually performed.) The C2 catheter usually experiences some torque trying to expel it from this vein, but holding the catheter and applying an opposite torque should result in retention of a good position.

In those cases where the C2 catheter will not pass down the left renal vein, a guidewire—we use a double-ended wire to give us two options—can often be directed deep into the renal veins and the catheter advanced over the wire, often again with a rotary force applied to the catheter stem. The C2 catheter is advanced or pulled back and rotated to try to select the left adrenal vein, as described earlier.

If the C2 catheter cannot be persuaded down the left renal or adrenal vein, a reverse catheter is required. An MK1B catheter is ideal and was designed for the job (Fig 33). This should be deployed over the guidewire with the wire deeply seated in the left renal vein. If this proves difficult, sometimes success can be achieved by using the right renal vein. On occasion, an adequate length of guidewire cannot be passed down either renal vein, in which case the catheter can be re-formed down the left common iliac vein. The MK1B catheter is then passed up the IVC with the guide-wire at the apex of the catheter until the tip is just above the left renal vein. The wire is advanced to the tip of the catheter, causing the main convexity of the catheter to open, pushing the tip of the MK1B against the left lateral wall of the IVC. On pulling back from this position, the MK1B catheter always engages the left renal vein.

Figure 33 Fluoroscopic image shows an MK1B catheter in the left adrenal vein (common trunk). Although the catheter points slightly toward the inferior phrenic vein (arrow), there is excellent filling of only the adrenal venous structure with contrast material injection.

The wire is then withdrawn several centimeters, and the catheter is slowly pulled back while its tip is watched with fluoroscopy. It enters the adrenal vein in most cases; occasionally, a little advancing of the catheter is required to obtain a good stable position. The left adrenal vein is usually about 3 cm from the confluence of the left renal vein and IVC. It is very rare that the left adrenal vein is not found in this way. Once in the common trunk, sampling is performed, preferably with the catheter tip pointing toward the central adrenal vein rather than the inferior phrenic vein (Figs 33–35). I advance the catheter into the central vein only rarely (Figs 36, 37), only in repeat studies, as passage deeper into the gland must increase risk and poor studies are so uncommon.

Figure 34 Fluoroscopic image shows an unusually large common trunk and central left adrenal vein with good demonstration of the entire intraglandular venous system.

Figure 35 Fluoroscopic image shows an MK1B catheter in the common trunk just beyond the confluence and pointing laterally toward the adrenal veins. An unusual aberrant vein joins the central vein at the confluence (arrow).

Figure 36 Fluoroscopic image obtained with an MK1B catheter deep in the central left adrenal vein shows extensive communicating veins laterally, medially, and inferiorly. The catheter position is too deep (arrow); as a result, venous supply from some parts of the left adrenal gland could be missed.

Figure 37 Fluoroscopic image shows a catheter deep in the central adrenal vein, past some of the early branches. In addition, the inferior phrenic vein is filled by an unusual communicating superficial vein superiorly (arrow).

In our experience, there have been only eight cases where the left adrenal vein could not be selected in this way: five cases of retroaortic veins with or without a vascular ring, one case where no vein was found in the normal position, and two cases of complex venous anomalies.

If no left adrenal vein can be cannulated in this way, a retroaortic vein is looked for at L2–3; this will often be apparent at CT. If one is present, a guidewire can often be passed up the vein. A C2 catheter is passed over the guidewire (Fig 9), which may require a combination of twisting and advancing, and contrast material is injected to identify the position of the adrenal vein. Lastly, if all else fails, a left renal vein sample is obtained in the same way as in the IVC on the right; that is, medially to the anticipated adrenal vein orifice on the cephalic border of the renal vein.

When contrast material is injected on the left side, numerous communicating veins are seen to the phrenic vein, retroperitoneal fat, hemiazygos system, left renal vein, and even IVC (46) (Figs 36–40).

Figure 38 Fluoroscopic image obtained with left adrenal vein injection shows the tip of the catheter just past the confluence and in the central adrenal vein. An unusual, extensive varicose branch arises from the common trunk and passes inferiorly.

Figure 39 Fluoroscopic image shows injection into the common trunk with no inferior phrenic vein seen. Extensive corkscrew communicating veins extend from the gland inferiorly and laterally.

Figure 40 Fluoroscopic image obtained with injection into the common trunk shows filling of left adrenal venous structures and communicating veins, with extension into an aberrant branch draining retroperitoneal structures (arrow).

Analysis of the results

For each adrenal vein sample collected, a peripheral sample is simultaneously obtained (3). The adrenal vein sample should have significantly higher levels of cortisol than the peripheral sample if the vein selected is truly draining the majority of adrenal cortical blood. On rare occasions, despite an obviously adequate position with good demonstration of adrenal vasculature, cortisol levels are only slightly raised, if at all, over those of the peripheral samples. In these cases, it may be that the majority of the blood is draining via a different “central” vein or via superficial or emissary veins. Oddly enough, in our experience, this is more commonly a problem on the left side and may be due to the occasionally extraordinary size of communicating or emissary veins on the left (John Rutherford, FRACS, oral communication, 1995) (Figs 38, 39). Monkhouse and Khalique (44) reported a positive case from right atrial sampling due to azygos inflow from a pheochromocytoma on the left side when adrenal vein samples were negative.

Ideally, our referral hypertension unit seeks a cortisol ratio that is three times the peripheral value from the selected vein (3). In practice, ratios between 2 and 3 often provide useful information even though they are not ideal. Ratios below 2 have the potential to create a false diagnostic impression. To correct for dilution from inflow of adjacent veins, the ratio of aldosterone to cortisol is calculated in the selected venous sample and compared to those in the corresponding peripheral sample. Adrenal glands that are producing aldosterone show an aldosterone-cortisol ratio higher than the peripheral value; normal glands give a ratio equal to or less than the peripheral value. In the case of an adenoma on one side, the contralateral normal adrenal gland shows suppressed aldosterone excretion.

Rarely, adrenal vein sampling results in aldosterone-cortisol ratios that are no higher than the peripheral value, despite good cortisol gradients confirming successful adrenal vein catheterization. Possibilities that might be considered are (a) a quiescent phase of aldosterone production, (b) venous drainage of an aldosterone-producing adenoma being via veins other than those cannulated (eg, superficial emissary veins), (c) superselective sampling from an area of gland that does not house an adenoma (Figs 5, 32), or (d) an ectopic source of aldosterone overproduction. More detail can be found in the article by Stowasser et al (3).

Complications

The major complication of adrenal vein cannulation is rupture of an adrenal vein and subsequent intraglandular and widespread periadrenal hemorrhage. Bookstein (45) quotes a complication rate of some 4% and suggests that complications are more common with Conn and Cushing syndromes due to vein fragility. Walters and Thomson (48) suggest that complications including adrenal infarction and venous rupture occur in 5%–10% of patients, more commonly on the right.

Gross et al (10) suggest that hematoma, infarction, adrenal vein thrombosis and perforation, as well as hypertensive crisis and adrenal insufficiency are not infrequent. Doppman and Gill (25) outline the occasional occurrence of painful extravasation or rarely bilateral infarction. The sequence of events indicating intraadrenal hemorrhage is persistent pain after an injection, increasing in intensity over 30–60 minutes and requiring large doses of analgesics with pain and fever often persisting for 24–48 hours. This sequence of events is frequently associated with complete and permanent destruction of the gland. With the move away from venography and only small injections, the complication rate is undoubtedly much lower. We have had only one documented case of intraadrenal hemorrhage in the past 8 years, for a frequency of less than 0.2% over that time.

It should be noted that local hemorrhage makes laparoscopic surgery far more difficult due to the extensive retroperitoneal adhesions that are found.

Conclusions

Adrenal vein sampling should be a rapid, safe, and reliable procedure. In our experience, most studies are performed within 15–25 minutes from local anesthetic infiltration to the finish of the procedure, and indeed our quickest procedure took 7 minutes. Avoidance of strong injections and adrenal venography gives a very tolerable complication rate that should be well under 1%.

The procedure should be reliable and accurate. With CT planning on the right and with a thorough appreciation of different right adrenal vein patterns, catheterization should be achieved in 90% of cases within 5 minutes, although it is admitted that obtaining good volume from the right adrenal vein can be a frustrating experience. The rationale for adrenal vein sampling particularly in primary aldosteronism should be appreciated, and the importance of the procedure in the treatment of these patients is emphasized.

IVC = inferior vena cava

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