Differential Diagnosis of Solid Adrenal Masses Using Adrenocortical Scintigraphy
L. DOMINGUEZ-GADEA, L. DIEZ, C. BAS and A. CRESPO
Nuclear Medicine Service, Hospital ‘Ramón y Cajal’, Madrid, Spain
To evaluate the diagnostic contribution of adrenal scintigraphy with 75-Se-selenomethyl- cholesterol in adrenal masses, 42 patients have been studied. All of them had a solid adrenal mass discovered on computed tomography (seven bilateral). None of the patients showed any symptoms or clinical signs that might indicate the existence of adrenal dysfunction. Twenty-nine of them had known extra-adrenal primary malignant disease.
Forty-nine adrenal tumours were detected with an average size of 3.29 cm (range 1.5-12 cm). Eighteen lesions showed increased uptake of radiocholesterol on the side of the adrenal mass, all of which were either proven to be benign, or behaved in a benign fashion.
Twelve lesions showed normal uptake (10 in the benign group and one lung carcinoma metastasis), all but one (2.5 cm) being smaller than 2 cm.
Decreased uptake was observed in 20 lesions (15 metastases, two nonfunctional adrenal carcinomas, one myelolipoma and two tuberculous infectious lesions).
Adrenocortical scintigraphy provides functional information about adrenal masses, and is useful in differentiating between benign and malignant lesions. Dominguez-Gadea, L., Diez, L., Bas, C. & Crespo, A. (1994). Clinical Radiology 49, 796-799. Differential Diagnosis of Solid Adrenal Masses Using Adrenocortical Scintigraphy
Accepted for Publication 9 June 1994
According to autopsy data, adrenal nodules larger than 1 cm are found in 1.5-8.7% of patients [1]. Adrenal masses are found incidentally in 1% of patients with no signs of adrenal dysfunction who undergo CT [2]. The possible diagnoses include metastases, lymphoma or adrenal carcinoma, and benign lesions such as adenoma, myelolipoma or haemorrhage [1-3].
Some lesions, for example cysts or myelolipomas, show specific features on imaging, but the differentiation between malignant and benign lesions cannot be made reliably in a large number of cases [4,5]. A needle biopsy is needed in some patients [6], but this technique carries certain risks, and therefore, it should only be used in selected cases [7].
Adrenocortical scintigraphy allows noninvasive evaluation of adrenocortical function [8-10]. The degree of radiocholesterol uptake in adrenocortical tissue reflects the functional status of adrenal tumours [11]. Previous reports have proved the diagnostic value of scintigraphy in adrenocortical hyperfunction [12-14].
In this study, we have evaluated the efficacy of 75-Se-cholesterol adrenal scintigraphy in the differential diagnosis of solid adrenal masses found on CT scanning of patients with no evidence of adrenal dysfunction.
PATIENTS AND METHODS
During a 25-month period beginning in October 1989, 42 patients with adrenal masses were examined by scintigraphy. All masses had been discovered on CT.
Correspondence to: Dr L. Dominguez-Gadea, c/Marques de la Valdavia 94, 2 Esc, 3-C Alcobendas, 28100 Madrid, Spain.
In 29 cases the CT scan was performed to stage known malignancies or to look for tumours which were suspected clinically. The remaining patients had CT for unexplained abdominal pain (n = 6), pancreatitis (n= 3), hepatic disease (n=1), pneumonia (n=2) and cholelithiasis (n = 1). The group included 15 female and 27 male patients, with ages ranging between 37 and 77 (average 61.5). None of them had signs or symptoms suggestive of adrenal dysfunction.
Where possible, the diagnosis was confirmed by histological examination of material obtained by surgery or needle biopsy (18 patients). Those patients who did not undergo biopsy were considered to have a benign lesion when no change in size of the adrenal mass could be detected on a CT scan over at least 1 year (21 patients).
In the cases of patients with a known primary tumour, the mass was considered to be malignant when, over a 6 month follow-up period, there was either a significant increase in size after no treatment or a decrease after chemotherapy on a repeat CT (three patients). In cases of bilateral adrenal lesions, when the diagnosis was made using needle biopsy of one gland, we assumed that the enlargement of the contralateral gland was due to the same pathology.
Adrenal scintigraphy was performed with 11 MBq of 6-methyl-75-selenomethyl-19-norcholesterol, injected intravenously. Images were obtained on days 5 and 7 post-injection using a large field of view gamma camera, and a high-energy parallel-hole collimator. The 136 Kev and 265 Kev photopeaks of 75-Se were included with a 25% window. Posterior and lateral abdominal images were performed accumulating at least 300 000 counts per view in every patient. The effective dose equivalent for this examination is approximately 19 mSv.
Scintigraphic evaluation was based on the presence of a significant visual increase or decrease in uptake at the site of the adrenal mass. The examination was considered normal when uptake was symmetrical. Images were evaluated by two experienced observers, who knew which gland was abnormal on CT.
RESULTS
Forty-nine adrenal masses were detected. Masses were unilateral in 35 patients and bilateral in seven.
The final diagnosis was benign adrenal mass (adenoma or adrenocortical nodule) in 28 cases (proved by biopsy in 7 patients); neoplasm or space- occupying adrenal lesions in 21 cases (14 metastases, 2 adrenal carcinomas, 2 lymphomas, 1 myelolipoma and 2 tuberculous inflammatory lesions), proved by biopsy in 11 patients.
The size of the benign lesions ranged from 1.5 to 5 cm (average 2.53 ± 1.07 cm). The size of the neoplasms or space-occupying lesions ranged from 1.5 to 12cm (average 4.61 ± 3.02).
The results of scintigraphy are summarized in Table 1. The 18 benign lesions which showed increased uptake (Fig. 1) had an average size of 2.72, S.D. 1.24cm (between 1.5 and 5cm). The other 10 benign lesions showed normal adrenal uptake. The largest of these measured 2.5 cm, and the rest of them measured 2 cm or less.
Twenty of the 21 lesions diagnosed as metastasis, malignant lesions or space-occupying lesions, showed diminished uptake (Fig. 2). The average size in this group was 4.57, S.D. 2.81 cm (between 2 and 12 cm). The lesion with normal adrenal uptake was a metastatic lung carcinoma of 1.5 cm in size.
Four of the 18 lesions which showed increased uptake had ipsilateral uptake without visualization of the contralateral gland.
Five of the seven patients with bilateral lesions showed a noticeable decrease or absence of adrenal uptake; four were malignant lesions and one was a tuberculous infection. The remaining two patients have presumed benign cortical nodules, one of which showed a significant increase in uptake; the other was normal.
DISCUSSION
The management of asymptomatic adrenal masses is controversial. Most of them are benign nodules [1,15,16]. These nodules are most frequently found in elderly patients with arteriosclerotic disease, hypertension or diabetes mellitus.
Due to the relation between the size of the lesion and the likelihood of malignancy, the majority of authors make a size-dependent decision. But the range in size of the different types of lesions is very wide; therefore the size alone cannot reliably differentiate benign from malignant. Besides, there is no agreement on the threshold size above which surgery is needed. According to previous authors, this varies between 3 and 6 cm [1,2,15,17-19].
In our study the size of malignant lesions was greater than non-malignant ones, but malignant disease could not be excluded solely on the basis of size as they ranged from 1.5 to 12 cm.
34 OGNISTNO
X# +0 00cm y. . 0 00cm
R
(a)
L
R
(b)
When imaging is not conclusive in the differential diagnosis of a solid adrenal mass, some authors propose the use of peripheral hormone analysis [19]. However, this is of limited value as so few adrenal tumours produce enough hormone to affect blood levels (2).
| Diagnosis | Number cases | Adrenal scintigraphy uptake | ||
|---|---|---|---|---|
| of | Increased | Decreased | Normal | |
| Adenoma/benign nodule | 28 | 18 | 10 | |
| Metastases | 14 | 13 | 1 | |
| Adrenocortical carcinoma | 2 | 2 | ||
| Lymphoma | 2 | 2 | ||
| Inflammation | 2 | 2 | ||
| Myelolipoma | 1 | 1 | ||
| Total | 49 | 18 | 20 | 11 |
(a)
Ra
0
0
9
(b)
Charles et al. [20] propose that when there is an adrenal nodular lesion without peripheral hormone alterations, the only criterion for making a decision should be its size (bigger or smaller than 6cm). We think that scintigraphy should be used as a preliminary step to a cortical hormonal profile, leaving the latter only for the high-uptake lesions. Gross et al. [21] have proved that the adrenal vein cortisol levels were higher from the adrenal that demonstrated the high uptake nodule.
In some cases nodules may be responsible for the production of practically all the adrenocortical hormone, including a relative suppression of the hormonal secretion of the contralateral gland, without causing increasing peripheral adrenocortical hormone levels. This clinical condition has been called pre- Cushing’s syndrome [22]. Usually, the adenomas that produce this condition are found incidentally, and are larger than 3 cm [23]. In these cases, surgery to remove
the enlarged gland can produce post-operative adreno- cortical insufficiency [19,24]. At the present time, scintigraphy is the most sensitive non-invasive method to evaluate the function of a silent adrenal mass [21,23], and will also provide information about the degree of suppression of the contralateral gland [23].
Phaeochromocytoma is the only lesion not recorded in our series that could have hormonal function as well as reduced uptake on scintigraphy with selenocholesterol. This uncommon tumour causes symptoms in 95% of cases [25], and the prevalence of phaeochromocytoma in patients with an incidentally discovered adrenal mass is low [1,15-19]. Adrenal scintigraphy with meta- iodobenzyl guanidine (MIBG) would be indicated when there are signs or symptoms suspicious of adrenal medullary pathology [26,27].
According to autopsy studies, patients with a primary extra-adrenal carcinoma have adrenal metastases in about 26% of cases [3]. Because of the higher prevalence of malignant adrenal lesions in oncological patients, some authors propose the performance of fine-needle aspiration biopsy in order to reach a definitive diagnosis [28,29]. In our study, none of the malignant lesions showed increased uptake on scintigraphy, suggesting that in cases where there is increased uptake correspond- ing to the radiological lesion, biopsy or surgery can be avoided.
Scintigraphy was always normal in small lesions (2 cm or less) which are at the resolution limits of planar scintigraphy. Gross et al. [30] found similar results. Although most of these lesions are benign, normal scintigraphy does not help to make a decision; therefore according to the level of suspicion of malignancy, repeated radiological examinations (CT, MRI) or more invasive tests might be necessary. Possibly SPECT (single photon emission computed tomography) techniques could improve the results in these cases.
In conclusion, we think that to evaluate a silent solid adrenal mass between 2 and 6 cm, adrenocortical scinti- graphy should be, in most cases, the next diagnostic test after a CT examination. The visualization of increased uptake in the lesion is indicative of benign aetiology that could be followed up radiologically, assuming there are no biochemical adrenocortical alterations.
Decreased or absent uptake in the gland indicates the existence of a non-functional space-occupying lesion. Therefore, in order to reach a diagnosis, fine- needle aspiration biopsy should be performed, leaving biochemical studies of the adrenal medulla and MIBG scintigraphy for those cases where a phaeochromocytoma is suspected.
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