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Primary Hyperaldosteronism (Conn Syndrome): MR Imaging Findings¹

¹ From the Departments of Diagnostic Imaging (S.A.S., P.D.P., R.H.R.) and Endocrinology (C.A., J.P.M., A.B.G., G.M.B.), Dominion House, 59 Bartholomew's Close, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. S.A.S. supported in part by a grant from the Joint Research Board, St Bartholomew's Hospital, London, England. Received January 29, 1999; revision requested March 22; revision received May 28; accepted August 30. Address reprint requests to S.A.S. (e-mail: S.A.Sohaib@mds.qmw.ac.uk).

	Abstract

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
PURPOSE: To describe the magnetic resonance (MR) imaging features of the adrenal glands in primary hyperaldosteronism and assess MR imaging in the detection and characterization of aldosterone-producing adenoma (APA).

MATERIALS AND METHODS: The authors retrospectively reviewed the cases of 20 patients (13 female and seven male patients; age range, 14–67 years; median age, 46 years) with primary hyperaldosteronism who underwent 1.5-T MR imaging between 1995 and 1998. All patients underwent transverse T1- and T2-weighted imaging, and chemical shift imaging was performed in 17 patients. Imaging results were correlated with findings at biochemical testing, venous sampling, or surgery.

RESULTS: Among the 20 patients, 10 (50%) had APA and 10 (50%) bilateral adrenal hyperplasia (BAH). In the detection of APA, MR imaging had a sensitivity of 70%, specificity of 100%, and accuracy of 85%. APAs (mean size, 20 x 16 mm) were iso- or hypointense relative to the liver on T1-weighted images and slightly hyperintense on T2-weighted images. With chemical shift imaging, the signal intensity decreased on the out-of-phase images in six of seven (86%) patients with APA and in eight of nine (89%) patients with BAH.

CONCLUSION: MR imaging has a high specificity in the detection of APA. As with nonhyperfunctioning adenoma, APA and BAH show evidence of intracellular lipid at chemical shift imaging.

Index terms: Adrenal gland, hyperplasia, 86.5412 • Adrenal gland, MR, 86.121411, 86.121412, 86.121414 • Adrenal gland, neoplasms, 86.317 • Magnetic resonance (MR), chemical shift, 86.121414

	Introduction

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
Primary hyperaldosteronism, or Conn syndrome, is most commonly due to an aldosterone-producing adenoma (APA) and less commonly to bilateral adrenal hyperplasia (BAH); other very rare causes include adrenocortical carcinoma (1–3). Identification of an underlying cause is important because surgery is usually considered the first treatment for APAs, whereas BAH is best treated medically. Many techniques have been used to distinguish between these two primary causes, but none has been entirely successful (4–7).

Recently, magnetic resonance (MR) imaging has been used to image the adrenal glands (8,9) as it offers a number of advantages. It uses no ionizing radiation and has superior soft-tissue contrast resolution compared with other cross-sectional imaging techniques. Findings in many studies have demonstrated the usefulness of MR imaging in the detection and characterization of adrenal gland masses (8,10–12); nevertheless, the role of MR imaging in primary hyperaldosteronism has not been well documented. To our knowledge, the sensitivity and specificity of MR imaging in primary hyperaldosteronism has been evaluated in only one study (7). Furthermore, descriptions of MR imaging characteristics of APA are limited (6). It has been postulated that there is a close relationship between the lipid content and the functional aspect of adrenocortical lesions, and hyperfunctioning adenomas may contain less cytoplasmic lipid than do nonhyperfunctioning adenomas (13). It is expected that chemical-shift imaging would reflect this difference in lipid content.

The aims of our study were to describe the MR imaging appearance of the adrenal glands in primary hyperaldosteronism; to assess the ability to detect APA at MR imaging; and to characterize the MR imaging features of APA, particularly the changes at chemical shift imaging.

	MATERIALS AND METHODS

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
We retrospectively studied the cases of all patients with a confirmed diagnosis of primary hyperaldosteronism at our institution between 1995 and 1998. There were 20 patients (13 female and seven male patients; age range, 14–67 years; median age, 46 years). The diagnosis of primary hyperaldosteronism was made with the standard series of biochemical tests, including venous sampling in all patients. The final diagnosis for the cause of primary hyperaldosteronism was APA in 10 (50%) patients and BAH in 10 (50%). The diagnosis in all cases of APA was confirmed at surgery and histologically. BAH was diagnosed on the basis of characteristic biochemical results including data from venous sampling and clinical and biochemical follow-up after medical therapy. None of the patients with BAH underwent surgery. We compared the age and sex distribution between the patients with APA and those with BAH.

MR imaging examination was performed with a 1.5-T unit (Signa Horizon; GE Medical Systems, Milwaukee, Wis). All imaging was performed with a phased-array multicoil in the transverse plane with a section thickness of 5–7 mm and intersection gap of 1 mm. All the patients underwent spin-echo T1-weighted imaging and fast spin-echo T2-weighted imaging, and chemical shift imaging was performed in 17 of the patients (seven with APA). The field of view was 32–35 cm in these pulse sequences. T1-weighted imaging (repetition time msec/echo time msec = 400–600/14–16) and fast spin-echo T2-weighted imaging (5,000–6,500/95–120 [effective], echo train length of eight) were performed with a matrix of 256 x 192–256, and two to three signals were acquired. Chemical shift imaging was performed with a breath-hold fast multiplanar spoiled gradient-echo sequence for in-phase images (150/4.2 with flip angle of 90°) and out-of-phase images (150/1.9–2.1), with a matrix of 256 x 128–192 and a breath hold of 20–30 seconds.

The images were analyzed by two radiologists (P.D.P., R.H.R.) unaware of the underlying cause of primary hyperaldosteronism. The images were reviewed independently, and in the cases in which there was a disagreement a consensus opinion was reached. The adrenal glands were classified as smooth, lobular if one or more glands showed undulating surface contour, or nodular if there were multiple nodules in the adrenal glands, or as showing only a single nodule (Figs 1–4). MR imaging diagnosis of an APA was made only if there was a single nodule with the remainder of the ipsilateral and contralateral adrenal glands appearing smooth and not enlarged. In the case of a single nodule, the diameters of the long and short axes were measured. The MR imaging findings and diagnosis were compared with the final diagnosis.

View larger version (152K): [in this window] [in a new window]   Figure 1. Transverse T1-weighted spin-echo image (500/14) in a 51-year-old man with BAH shows both adrenal glands (arrows) as not enlarged and smooth in contour.

View larger version (147K): [in this window] [in a new window]   Figure 2. Transverse T1-weighted spin-echo image (500/14) in a 43-year-old woman with BAH shows adrenal glands (arrows) as enlarged and lobulated in contour.

View larger version (109K): [in this window] [in a new window]   Figure 3a. Fast multiplanar spoiled gradient-echo MR images in a 55-year-old woman with BAH: (a) in-phase image (150/4.2 with 90° flip angle) and (b) out-of-phase image (150/2 with 90° flip angle). Multiple nodules can be seen in both glands (arrows), which show loss of SI in b.

View larger version (108K): [in this window] [in a new window]   Figure 3b. Fast multiplanar spoiled gradient-echo MR images in a 55-year-old woman with BAH: (a) in-phase image (150/4.2 with 90° flip angle) and (b) out-of-phase image (150/2 with 90° flip angle). Multiple nodules can be seen in both glands (arrows), which show loss of SI in b.

View larger version (120K): [in this window] [in a new window]   Figure 4a. Fast multiplanar spoiled gradient-echo MR images in a 45-year-old woman with a right APA (22 x 16 mm): (a) in-phase image (150/4.2 with 90° flip angle) and (b) out-of-phase image (150/2 with 90° flip angle). A nodule (straight arrow) is seen in the right adrenal gland, and the left adrenal gland (curved arrow) appears smooth and not enlarged.

View larger version (123K): [in this window] [in a new window]   Figure 4b. Fast multiplanar spoiled gradient-echo MR images in a 45-year-old woman with a right APA (22 x 16 mm): (a) in-phase image (150/4.2 with 90° flip angle) and (b) out-of-phase image (150/2 with 90° flip angle). A nodule (straight arrow) is seen in the right adrenal gland, and the left adrenal gland (curved arrow) appears smooth and not enlarged.

View larger version (12K): [in this window] [in a new window]   Figure 5. Diagram of adrenal gland illustrates body width (1) and limb width (2) measurements.

Statistical analysis was performed with a software package (SPSS, version 6.1.3; SPSS, Chicago, Ill), with a P value less than .05 considered significant. Data were subjected to the Student two-sample t test and nonparametric testing with the Mann-Whitney U and Fisher exact tests.

	RESULTS

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A summary of the demographic details is shown in Table 1. There was no difference in the sex distribution in the patients with APA and those with BAH (Fisher exact test). However, patients with BAH were older (mean age, 50 years; age range, 37–67 years) than those with APA (mean age, 39 years; age range, 14–63 years), but this difference was not statistically significant (two-sample t test, P = .06).

View larger version (159K): [in this window] [in a new window]   Figure 6. Transverse T1-weighted spin-echo image (640/14) in a 63-year-old woman with a right APA that was prospectively diagnosed as BAH owing to the lobulated contour of the adrenal glands (arrows). Findings at venous sampling suggested APA in the right adrenal gland, which was confirmed after right adrenalectomy as a 12-mm-wide APA.

View larger version (11K): [in this window] [in a new window]   Figure 7. Adrenal gland width (size) in primary hyperaldosteronism. Scattergram shows the relationship between mean adrenal gland body and limb widths in seven patients with APA and 10 with BAH. Note that patients with BAH have larger adrenal glands, but only the limb width is significantly larger than that in the patients with APA (P < .05). Horizontal bar indicates the median value.

Chemical shift imaging was performed in seven of the 10 patients with APA and in all 10 of the patients with BAH. Qualitative assessment of the SI change on the out-of-phase compared with SI on the in-phase images showed that SI decreased in six of the seven (86%) patients with APA and in eight of nine (89%) patients with BAH. In one patient with BAH, the SI decrease could not be assessed qualitatively owing to movement artifact. The SI change was quantitatively assessed in the seven patients with APA but in only five of the patients with BAH because their adrenal glands were large enough to allow accurate region-of-interest readings. Quantitative measurements in all 12 of these patients showed a decrease in SI, but the difference in SI index was not significant between patients with APA (SI index median, 53%; range, 42%–65%) and those with BAH (SI index median, 58%; range, 43%–89%). Control values for SI index for the spleen (SI index median, 2%; range, -6% to 8%) showed no significant difference in SI between the in-phase and out-of-phase images.

	DISCUSSION

TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 
In primary hyperaldosteronism, a diagnostic test for APA that has a high specificity (ie, a low false-positive rate) is important, as this will avert unnecessary surgery in patients without APA. Findings in our study, albeit in a small number of patients, show that MR imaging is a specific test for the detection of APA with sensitivity comparable to that reported with CT (4–6). However, we were unable to demonstrate the very high sensitivity previously reported for MR imaging in one series (7).

The lack of specificity in a test is due to a high false-positive rate. In primary hyperaldosteronism, a false-positive diagnosis of APA may be made owing to a dominant nodule in macronodular hyperplasia or concomitant nonhyperfunctioning adenoma (15). In our series, we did not encounter a nonhyperfunctioning adenoma, and all hyperplastic glands were correctly identified as BAH (hence, the specificity of 100%) on the basis of the adrenal gland size or contour abnormality.

MR imaging has a very high specificity but a lower sensitivity. The sensitivity of MR imaging and CT may remain relatively low because better spatial resolution may lead to the detection of more nodularity within normal adrenal glands. The demonstration of multiple nodules may then be misinterpreted as nodular hyperplasia rather than as a solitary adenoma, with multiple unrelated nodules resulting in a false-negative diagnosis for APA. Furthermore, the increase in adrenal gland nodularity with age and hypertension may further limit the accuracy of these tests (15).

In view of the very high specificity of MR imaging, if a unilateral mass with a normal contralateral adrenal gland is depicted on MR images and the clinical and biochemical features suggest APA, then this diagnosis is relatively ensured, and a unilateral adrenalectomy can be recommended without further investigation (15,16). However, if MR images depict bilateral adrenal gland masses or a unilateral mass with a hyperplastic contralateral gland, then venous sampling is recommended (15).

The adrenal gland measurements obtained in this study show that adrenal glands are larger in patients with BAH than in patients with APA. To our knowledge, this has not previously been quantified or compared for MR imaging. In a comparison at CT, adrenal glands were larger in BAH, but the pattern of enlargement between APA and BAH was not clear (17). Our data show that the size of the adrenal gland limb is affected more than adrenal gland body size in primary hyperaldosteronism. This would reflect the predominance of adrenocortical tissue in adrenal gland limbs (18). Unlike for CT, a simple criterion for normal adrenal gland size is not yet available for MR imaging (14,19,20). In primary hyperaldosteronism, a comparison between adrenal gland sizes in APA and BAH is more important than is a comparison with healthy subjects as patients are referred with a clinical diagnosis of Conn syndrome. However, there is a substantial overlap in size of the adrenal gland in patients with APA and those with BAH. The adrenal glands in a proportion of patients with BAH are quite small; thus, the diagnosis cannot be made at MR imaging on the basis of size alone.

As is true of CT, MR imaging cannot differentiate APA from BAH in cases of bilateral nodules. The criteria of SI patterns or SI change at chemical shift imaging cannot be used to improve the sensitivity of MR imaging. The patterns of SI changes in APA and BAH on the T1- and T2-weighted images are also similar to those reported for nonhyperfunctioning adenomas and normal adrenal gland tissue (8). This in part reflects that the overall composition of these tissues is similar, and small differences cannot be readily detected at imaging. The one patient in our series with atypical SI at MR imaging proved to have a mixed tumor that secreted cortisol and aldosterone, and this tumor was also much larger than the other adenomas.

In terms of characterization of APA with respect to the fat content and changes at chemical shift imaging in our study, most APAs contained lipid. This finding is in keeping with those in other studies in which APAs were shown to have a large fat component (21,22). The relationship between fat in an adenoma and function is not clear-cut, as nonhyperfunctioning adenomas also contain intracellular lipid (10,21,23). The authors of a previous study postulated that hyperfunctioning adenomas may contain less cytoplasmic lipid than do nonhyperfunctioning adenomas, and they found that the SI index in nonhyperfunctioning adenomas was significantly higher than that for hyperfunctioning adenomas (13). However, it must be noted that there is not a linear relationship between the SI index and the amount of fat (24). Although the SI on the out-of-phase images reflects the difference in water and fat SI, it is not possible to identify whether the fat or water signal is the dominant signal. On out-of-phase images, the SI of a lesion with more than 50% fat could be similar to that of a lesion with less than 50% fat. Therefore, the relationship between functional status of an adenoma and lipid content cannot be linked directly with this method.

In a study that quantified the amount of lipid present at histologic analysis in functioning and nonhyperfunctioning adenomas, no difference was found (21). In a study of attenuation at CT, values for APA were lower (implying more intracellular lipid) than those for an adenoma that secreted cortisol (22). In both these studies, however, the sample size was small. Features of APA described in our series do not differ markedly from those in other published series of nonhyperfunctioning adenoma (8). Therefore, MR imaging is not likely to help distinguish between a nonhyperfunctioning adenoma and APA.

There are a number of limitations in our study. First, our institution is a referral center for endocrine disorder; thus, the patient population is skewed toward patients with more difficult diagnoses. Hence, the number of cases with BAH as a cause for the primary hyperaldosteronism may be overrepresented in our study. Second, definite proof of diagnosis in our series was available in only the patients who underwent surgery for APA. In the remaining patients, the diagnosis was based on results at venous sampling and follow-up of medical treatment. This is a common problem with most studies of this condition.

In summary, our data suggest that MR imaging is a specific test for the detection of APA. Hence, in the clinical setting of a suspected APA, if a unilateral nodule is identified with a normal contralateral adrenal gland at MR imaging, then the diagnosis of APA can be assumed and the patient treated surgically; otherwise, further investigation with venous sampling or other imaging is recommended. At MR imaging, APA and BAH show evidence of a substantial amount of intracellular lipid and SI characteristics similar to those of other adenomas. The adrenal glands, in particular the adrenal gland limbs, are in general larger in patients with BAH than in patients with APA.

	Acknowledgments

 
We thank Janice M. Thomas, PhD, for statistical advice.

	Footnotes

 
Abbreviations: APA = aldosterone-producing adenoma BAH = bilateral adrenal hyperplasia SI = signal intensity

Author contributions: Guarantor of integrity of entire study, R.H.R.; study concepts and design, S.A.S., R.H.R.; definition of intellectual content, S.A.S., R.H.R.; literature research, S.A.S., P.D.P.; clinical studies, C.A., A.B.G., J.P.M., G.M.B.; data acquisition, S.A.S., C.A., P.D.P., R.H.R.; data analysis, S.A.S., C.A., R.H.R.; statistical analysis, S.A.S.; manuscript preparation, S.A.S.; manuscript editing and review, P.D.P., C.A., A.B.G., J.P.M., G.M.B., R.H.R.

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TOP Abstract Introduction MATERIALS AND METHODS RESULTS DISCUSSION References

 

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This Article Abstract Figures Only Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sohaib, S. A. Articles by Reznek, R. H. Search for Related Content PubMed PubMed Citation Articles by Sohaib, S. A. Articles by Reznek, R. H.