A black adrenocortical adenoma causing Cushing’s syndrome not imaged by radiocholesterol scintigraphy
Eugenio Reschini1, Marina Baldini2, and Luigi Cantalamessa2
1 Service of Nuclear Medicine, Ospedale Maggiore di Milano, pad. Granelli, via F. Sforza 35, 1-20122 Milan, Italy
2 Institute of Internal Medicine, Infectious Diseases and Immunopathology, University of Milan, Italy
Received September 20, 1989 and in revised form February 9, 1990
Abstract. In a 33-year-old female patient with left adre- nal tumour and Cushing’s syndrome, adrenocortical scintigraphy with radiocholesterol did not image the tu- mour nor the suppressed contralateral gland. Histology showed a black adrenocortical adenoma composed only of compact cells; there was no evidence of malignancy. This demonstrates that non-visualization of the adrenal glands in a patient with Cushing’s syndrome is not in- variably due to adrenal carcinoma. The literature on black adrenal adenomas causing Cushing’s syndrome is reviewed.
Key words: Adrenal scintigraphy - Adrenocortical ad- enoma - Cushing’s syndrome
Eur J Nucl Med (1990) 17:185-187
Introduction
It is well established that benign adrenocortical ad- enomas causing Cushing’s syndrome concentrate radio- cholesterol avidly, and their scintigraphic picture is char- acterized by visualization of the tumour and non-visual- ization of the contralateral gland due to long-lasting ad- renocorticotropic hormone (ACTH) suppression by the cortisol secreted by the adenoma (Gross et al. 1984). No exception to this rule has been reported to date. On the contrary, carcinomas concentrate radiocholester- ol to a lower degree, the most freqeunt finding being insufficient concentration to obtain visualization, al- though in some patients carcinomas and even their me- tastases have been imaged (Seabold et al. 1977; Schteingart et al. 1981; Reschini and Peracchi 1984).
We have recently studied a patient with a benign black adenoma, which was composed exclusively of lip- id-poor compact cells and had too low a radiocholesterol concentration to be imaged at scintigraphy. This demon- strated that non-visualization of the adrenal glands in a patient with Cushing’s syndrome is not invariably due to adrenal carcinoma.
Case report
A 33-year-old woman presented with a typical clinical picture of Cushing’s syndrome of 5-years’ duration. The endocrinological study (Table 1) revealed elevated levels of plasma cortisol and urinary 17-hydroxycorticoster- oids not modified by metyrapone, dexamethasone or corticotropin releasing hormone (CRH); plasma ACTH was undetectable under basal conditions and was not stimulated by CRH. These findings indicated a typical ACTH-independent Cushing’s syndrome of primary ad- renal origin.
Serum cholesterol levels were moderately increased (251 mg/dl; normal value <220) as were those of trigly- cerides (242 mg/dl; normal value <200). Computerised tomography of the abdomen revealed a mass about 3 cm in diameter in the region of the left upper renal pole; its radiologic density was higher than that of the average adrenal adenoma and higher than that of the renal pa- renchyma (Fig. 1). Adrenocortical scintigraphy was per- formed with 6-selenomethylcholesterol Se 75, 9.25 MBq i.v. (Radiochemical Centre, Amersham, UK). The adre- nal regions were imaged daily for 18 days after injection with a gamma-camera equipped with a high-energy par- allel-hole collimator; the 265 and 280 keV photopeaks of 75Se were included in a 30% window; about 100000 counts per image were collected, exposure time being 20-30 min. Some images were also taken centering on the 136 keV photopeak of the radionuclide (Hawkins
| Measured substances | Stimulus | Basal | Stimu- lated | Normal basal range |
|---|---|---|---|---|
| Plasma ACTH | CRH 100 µg i.v. | <10 | <10 | 10-70 |
| (pg/ml) | ||||
| Plasma cortisol | CRH 100 µg i.v. | 25.3 | 23.3 | 5-25 |
| (µg/dl) | Dexa 1 mg p.o. at 12 p.m. | 27.9 | 29.4 | |
| Urinary 17-hydroxy- | Dexa 8 mg/day p.o. | 19.4 | 19.4 | 3-10 |
| corticoids | Metyrapone | 16.1 | 20.3 | |
| (mg/day) | 4.5 g/day p.o. | |||
| Urinary 17-keto- | Dexa 8 mg/day p.o. | 17.4 | 16.1 | 5-15 |
| steroids | Metyrapone | 17.2 | 12.8 | |
| (mg/day) | 4.5 g/day p.o. | |||
| Plasma aldosterone (ng/dl) | Postural stimulus | 5.3 | 16.9 | 2-12 |
| Urinary aldosterone | None | 3.8 | - | 5-20 |
| (ug/day) | ||||
| Plasma renin activity (ng/ml·h) | Postural stimulus | 1.8 | 4.2 | 0.2-2.8 |
ACTH, adrenocorticotropic hormone; CRH, corticotropin releas- ing hormone; Dexa, dexamethasone
A
B
et al. 1980). The liver was imaged as usual in the early post-injection days, but the adrenal glands were not visu- alized (Fig. 1).
At operation, the left adrenal gland contained a nod- ule and was excised. The gland was composed mainly of the nodule surrounded by a thin atrophic cortex. The nodule was well encapsulated and weighed 12 g. Its cut surface was nearly black, without evidence of yellow tissue. Histologic examination of the nodule showed only lipid-poor compact cells, with no clear cells; there was no cytologic or histologic evidence of malignancy. The surrounding cortex was atrophic and composed only of clear cells. On the 9th post-operative day plasma cortisol under dexamethasone substitution was almost undetectable (0.7 µg/dl). The signs of Cushing’s syn- drome cleared rapidly; when last seen, a year after sur- gery, the patient was in good health.
Portions of the tumour and attached cortex were counted for radioactivity, and the results, as percentage of administered dose per gram of tissue, after correction for radionuclide decay, are shown in Table 2. The table also shows the results obtained in eight patients with yellow or mixed yellow-brown adenomas and two with carcinomas for comparison. The concentration of radio- activity in the black adenoma was markedly lower than in the other adenomas and approximated the low values found in the two patients with carcinomas.
Discussion
In addition to the present patient we have studied 11 patients with benign adrenocortical adenomas causing Cushing’s syndrome. The adenomas were of yellow or mixed yellow-brown type, and all were clearly imaged at scintigraphy. Measurements of radiocholesterol in the surgical specimens performed in 8 of them showed a marked, albeit variable concentration. In the present pa- tient with black adenoma, the concentration value was 13 times lower than the mean of the other adenomas studied and 4 times lower than the lowest value of that group. The reason for this low radiocholesterol concen-
| Adrenal pathology | Tissue | Weight (g) | Percentage % uptake per g | Percentage % total uptake | Days from injection to surgery |
|---|---|---|---|---|---|
| Yellow or mixed adenomas (n=8) | tumour | 12 | 0.13 | 1.62 | 25 |
| (6-16) | (0.04-0.25) | (0.48-2.75) | (13-47) | ||
| Black adenoma | tumour | 12 | 0.01 | 0.12 | 26 |
| cortex | 2 | 0.017 | 0.034 | ||
| Carcinoma Carcinoma | tumour | 1800 | 0.0037 | 6.6 | 13 |
| tumour | 140 | 0.0064 | 0.9 | 39 | |
| liver metastasis | 850 | 0.01 | 8.5 |
tration is unclear. Seven previous patients with black adenoma were studied with scintigraphy, six by Komiya et al. (1985) and one by Dixon et al. (1983), and all were visualized, but no data on concentration or uptake values were provided. Black adenomas are composed exclusively of lipid-poor, compact cells without clear cells, and it is conceivable that the radiocholesterol con- centration may be lower than in the average adrenal adenoma and that in extreme situations the concentra- tion may be insufficient for visualization. Scintigraphic imaging is the result of a combination of tracer concen- tration and organ mass. In this black adenoma the total uptake (0.12%) was not extremely low and would prob- ably have been sufficient for visualization if concentrated in a normal adrenal gland of about 4-5 g; however, the radioactivity was contained in a volume 3 times larger, and this was probably the critical factor of non-visual- ization. This concept is well exemplified by the two carci- nomas we studied. Both of them were extremely large tumours with a very high total uptake in the tumour or tumour plus metastases (6.6% and 9.4% of admin- istered activity, respectively). However, in one patient, the radioactivity was contained in a tumour of 1800 g, and the concentration per gram was very low, leading to an insufficient photon concentration compared with background, while in the second one the concentration values in the primary tumour and liver metastasis were 2-3 times higher, and these tumours were clearly visual- ized (Reschini and Peracchi 1984).
Other possibilities to explain non-visualization of the black adenoma were considered. The uniformly benign histologic appearance and the full remission after sur- gery virtually excluded malignancy. It seems improbable that the radiopharmaceutical was altered since the at- tached atrophic adrenal cortex concentrated more radio- cholesterol than the tumour. Severe hyperlipidaemia has been described as a possible cause of non-visualization of the arenals at scintigraphy (Gordon et al. 1980; Valk et al. 1980); again, this seems unlikely in our patient whose cholesterol and triglyceride levels were only mod- erately increased.
Black adrenal adenoma causing Cushing’s syndrome has been considered a rare entity, initially reported as single cases (Bahu et al. 1974; Visser et al. 1974; Tseng et al. 1978; Uras et al. 1978; Zaniewski and Sheeler 1980). However, in the study by Komiya et al. (1985) of a Japanese population, these tumours represented 35% of patients with Cushing’s syndrome due to adrenal adenoma (6 of 17), and in a British population Neville and O’Hare (1982) found a prevalence of 15% (4 of 26). To our knowledge, the patient studied is the first black adrenal adenoma described in Italy and is the only one in our series of 12 adenomas (8%). There are likely differences in the prevalence among various populations, but black adenomas causing Cushing’s syndrome are probably less rare than initially thought. No substantial differences in endocrine function between black and
other adenomas causing Cushing’s syndrome have been found by Komiya et al. (1985). These authors found, interestingly, that black adenomas have a radiological density with computerised tomography higher than that of the average adrenal adenoma; this was observed also in our patient and is not surprising considering that these tumours are exclusively composed of lipid-poor, com- pact cells.
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