Nuclear Medicine Springer-Verlag 1984
Uptake of 75Se-selenocholesterol by an adrenal cortical carcinoma and its metastases
Eugenio Reschini and Maddalena Peracchi First Institute of Clinical Medicine, University of Milan, Italy
Abstract. Adrenal scintigraphy with 75Se-selenocholesterol was performed in a patient with Cushing’s syndrome due to a right adrenal tumor. The tumor was faintly but clearly imaged. The liver was sharply imaged and the liver uptake did not reveal the usual decrease after the first week postin- jection. The liver image was still clearly evident in the last scintiphotos taken 26 days after injection of radiocholes- terol. At operation a right adrenocortical carcinoma was removed and the right lobe of the liver was found to be almost completely replaced by metastatic adrenal tissue.
During the past decade much experience with adrenal scin- tigraphy has been obtained and it is now agreed that the main usefulness of the procedure is in localizing cortisol or aldosterone producing adrenal adenomas [12]. As far as carcinomas are concerned, the most frequent pattern is no imaging as a consequence of the low uptake per gram of neoplastic tissue usually displayed by adrenocortical car- cinomas [9, 12]. However, in rare instances adrenal carcino- mas could be imaged [1-4, 8]. Visualization of metastases is also rare and there are only seven published cases in whom uptake by metastases was sufficient for imaging [3, 5, 10, 13]. Interestingly enough, all these seven patients had their metastases imaged by radiocholesterol after the primary tumor had been resected. In this paper we report on a patient with Cushing’s syndrome due to adrenal corti- cal carcinoma in whom sufficient uptake for imaging was displayed by the tumor and in whom liver metastases were simultaneously visualized.
Case Report
The patient, a 67-year-old woman was admitted to our hos- pital for signs highly suggestive of Cushing’s syndrome present for about 1 year. The endocrinological study re- vealed elevated urinary steroid excretion in the range of 25 mg/24 h for both 17-hydroxycorticosteroids (Porter- Silber chromogens) and 17-ketosteroids. Steroid levels were not modified by either metyrapone, dexamethasone or ex- ogenous ACTH. Plasma cortisol was elevated at 40 µg/ 100 ml and did not show the normal circadian rhythm nor was suppressed by dexamethasone administration. With the exception of marked hypokalemia and glucose intolerance,
routine blood chemistry did not reveal abnormal findings. An adrenal scintiscan was performed after the IV injection of 250 µCi 75Se-6-selenomethylcholesterol (Radiochemical Centre, Amersham, England). The adrenal regions were ex- plored two to three times per week using a gamma camera equipped with a high-energy parallel-hole collimator, with the patient in either the sitting or prone positions. Exposure time was that sufficient to collect 100,000-150,000 counts per image, generally 20-30 min. From the early days after cholesterol injection there was the usual visualization of the liver and that of a mass located medially to the liver edge in the position of the right adrenal gland. However, the normal fading of the liver image was not observed as usual after the first week postinjection and the liver re- mained well outlined and was still clearly visible in the last scintiphotos taken 26 days after injection; the left adrenal was never clearly visualized (Fig. 1). Visualization of kid- neys by 197Hg-chlormerodrin confirmed that the mass im-
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Offprint requests to: Dr. Eugenio Reschini, I Clinica Medica, Un- iversità di Milano, 35 via F. Sforza, I-20122 Milano, Italy
| Tissue | Number of specimens | % dose per gram tissue | |
|---|---|---|---|
| Mean | (Range) | ||
| Adrenal tumor (yellow portion) | 2 | 0.037 | (0.035-0.039) |
| Adrenal tumor (grayish portion) | 4 | 0.0064 | (0.0052-0.0083) |
| Liver metastases | 6 | 0.010 | (0.0074-0.017) |
| Surrounding liver | 1 | 0.003 | |
age was located above the upper pole of the right kidney. The sum of endocrinological and scintigraphic studies led to the diagnosis of a right adrenal tumor. Computed axial tomography (CAT) confirmed the presence of a mass in the region of the right adrenal gland, but did not suggest abnormalities in the liver images. For this reason a liver scan with radiocolloids was not performed. Laparotomy was performed 39 days after radiocholesterol injection. A right adrenal tumor was found and removed. The right lobe of the liver was found to be almost completely replaced by metastatic tissue and the entire right lobe was resected. There was also metastatic invasion of the vena cava and of the hepatic veins. The adrenal tumor was capsulated and weighed 140 g; after section the tumorous tissue ap- peared grayish and necrotic for its greater portion; only in small areas the adrenal tissue displayed a canary yellow colour. The resected right lobe of liver was almost complete- ly represented by grayish tissue similar to that of the prima- ry tumor; there was virtually no normal liver tissue adjacent to metastatic tissue. The resected portion of liver weighed 850 g (Fig. 2). Microscopic examination of the adrenal tu- mor showed areas with clear cells showing little nuclear and cellular pleomorphism and areas of cells with eosino-
philic lipid-poor cytoplasm showing marked nuclear pleo- morphism, some mitotic figures, and vascular invasion. The metastatic tissue in the liver was closely similar to the more atypical areas of the adrenal tumor. Specimens of the tumor and metastatic tissue were counted for radioactivity and the results, expressed as per cent of the administered dose per gram of tissue, after correction for decay, are shown in Table 1.
The postoperative course was characterized by massive intraabdominal hemorrhage and the patient died 2 days after surgery.
Discussion
In this case the liver metastases showed a cholesterol uptake roughly similar to that of the primary tumor. Due to the greater mass of the metastatic tissue, the liver image was sharper than that of the adrenal tumor. The total uptake of radiocholesterol by the adrenal tissue (tumor plus metas- tases) approximates 10% of the injected dose. This is by far the greatest value ever reported. Bossuyt and Somers [1] measured a total uptake of 4% in a very large (2.5 kg) nonfunctioning adrenal carcinoma showing a very modest uptake (0.0016% of administered dose per gram). In adre- nal adenomas or hyperplasia the uptake per gram of tissue is much greater, but due to the smaller mass of adrenal tissue, the total uptake generally does not exceed 2%-3% of the injected dose in Cushing patients with these underly- ing abnormalities [6, 7, 11, 12]. This case is the first one in whom metastases were imaged simultaneously with the primary tumor. In the seven previously reported cases me- tastases were detected with radiocholesterol after removal of the primary tumor [3, 5, 10, 13]. Seabold et al. [10] specu- lated that prior removal of the adrenal carcinoma might have improved the metastatic uptake in their cases and that this effect might have been strengthened by concomitant administration of cortisone acetate due to its suppressive effect on the remaining adrenal gland. These explanations seem unconvincing since the uptake of radiocholesterol by the adrenal tissue is always a small percentage of the admin- istered dose and this means that there is always a large fraction available for uptake if a tissue is able to concentrate the tracer. The fact that in previous cases metastases were detected after removal of the primary tumor is probably mere coincidence, since only one of the cases was studied also prior to operation. In this case, reported by Chatal et al. [3], the adrenal carcinoma was detected in the initial study and metastases became evident only in a subsequent study 1 year later. The ability to concentrate radiocholes- terol to a sufficient degree for imaging is probably an intrin- sic property of the carcinomatous tissue of each individual patient. It is interesting to note that the uptake of various tissues in our patient (Table 1) is closely similar to that found in the one patient of the series of Seabold et al. [10] studied in a similar way. The previous cases of metastases detection with radiocholesterol were imaged with 131I-iodo- cholesterol. Experience with the recently introduced agent 75Se-selenocholesterol is still limited [4, 7, 11]. However, our preliminary experience indicates that its behavior in imaging adrenal tissue is similar to that of iodocholesterol. In particular, the fading of the liver image takes place at a time similar to that observed with iodocholesterol. The persistent liver image in this case was difficult to explain prior to operation. The possibility of metastases was consid-
ered, but in this event we would have expected a less homo- geneous image. Therefore, an unknown metabolic cause of persistency of selenocholesterol in the liver was taken into consideration. The operation findings solved the problem and also explained the normal appearance of liver on the CAT scan, since the right lobe was found to be almost completely replaced by isodense metastatic tissue. In con- clusion, the present case demonstrates that when the liver image persists after the first week after radiocholesterol in- jection, the presence of metastases should always be consid- ered. In such cases 75Se seems preferable to 131I as a label- ing agent since its longer half-life permits a longer period of study, and imaging of the adrenal tissue can be per- formed for over 1 month after injection, when cholesterol concentration in other organs has almost completely disap- peared.
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Received January 10, 1984