☐ CASE REPORT ☐
A Functioning Black Adenoma of the Adrenal Gland
Yoshihide UEDA, Hidenori TANAKA, Hidehiro MURAKAMI, Tomoyuki NINOMIYA,
Yoshimasa YAMASHITA, Mikio ICHIKAWA, Toshifumi KONDOH and Tsutomu CHIBA*
A 53-year-old female had clinical and laboratory findings suggestive of Cushing’s syndrome. In contrast to the Cushing’s syndrome caused by cortical adenoma, a high level of urinary 17- ketosteroids (17-KS) was also noted. Imaging studies revealed a right adrenal tumor. Right adrenectomy was performed; the surgical specimen revealed a black adenoma consisting of compact cells with numerous pigments which seemed to be lipofuscin in nature. The present case indicates that black adenoma as well as adrenocortical carcinoma should be suspected, when patients with Cushing’s syndrome show an increased level of urinary 17-KS excretion. (Internal Medicine 36: 398-402, 1997)
Key words: lipofuscin, 17-ketosteroids (17-KS), Cushing’s syndrome
Introduction
Functioning black adenoma of the adrenal gland is a rare disorder. We report here a case of Cushing’s syndrome due to functioning black adenoma of the adrenal grand, together with a review of the Japanese language literature pertaining to functioning black adenoma. The diagnostic value of urinary 17- ketosteroids (17-KS) is also discussed.
Case Report
A 53-year-old woman had complained of general fatigue for 18 months. In addition, her symptoms such as peripheral edema, truncal obesity, moon face and buffalo hump had progressed gradually.
On admission, a ruddy faced obese woman had several characteristic features of overt Cushing’s syndrome; truncal obesity, moderate hypertension, moon face, buffalo hump, peripheral edema and proximal muscle weakness, but neither hirsutism nor purple abdominal striae was observed. Labora- tory findings and endocrinological data are listed in Table 1. Serum cortisol levels were around 20 µg/dl not only in the morning but also in the afternoon and were not suppressed by the oral administration of 1 mg dexamethazone. On the con- trary, adrenocorticotropic hormone (ACTH) levels remained less than 5 pg/ml. Urinary excretion of both 17- hydrocorticosteroids (17-OHCS) and 17-KS were also in- creased. Serum aldosterone levels were high, but furosemide
loading during upright posture revealed a normal reaction pattern. Glucose tolerance was well maintained. Data from endocrine function tests are summarized in Table 2. Dexam- ethasone administrations of 2 mg and 8 mg did not suppress the urinary excretion of 17-OHCS or 17-KS. Moreover the metopiron test showed no reaction. Abdominal computed tom- ography (CT) revealed a well-defined right adrenal tumor, 2.5 cm in diameter (Fig. 1). Magnetic resonance imaging (MRI) and ultrasound sonography also disclosed a right adrenal tumor. On MRI, the tumor showed a higher signal intensity on T2- weighted images than that of the liver (Fig. 2).
On the basis of the symptoms, laboratory findings and imaging studies, the existence of either an autonomous ad- enoma or carcinoma of the right adrenal cortex was suspected. After total right adrenorectomy, urinary 17-OHCS, 17-KS and serum cortisol levels became very low. Therefore, supplemen- tary treatment with cortisone acetate was necessary. The patient has been free of symptoms for one year.
Pathology
Gross appearance of the tumor
The removed adrenal gland, weighing 11 grams, contained a single, well circumscribed black nodule measuring 3.5 x 2.5 × 1.5 cm (Fig. 3). The residual adrenal grand which was adjacent to the nodule showed atrophic change of the cortex.
Microscopic appearance
The tumor consisted of compact cells (Fig. 4a); most of the
A FBA of the Adrenal Gland
| Hematology | |
| White blood cells | 5,600/ul |
| Neutrophil | 59% |
| Eosinophil | 1% |
| Lymphocyte | 31% |
| Monocyte | 9% |
| Red blood cells | 476×104/ul |
| Hemoglobin | 15.8 g/dl |
| Platelet | 20.4×104/ul |
| Chemistry | |
| Total protein | 6.5 g/dl |
| Albumin | 4.3 g/dl |
| Lactate dehydrogenase | 435 U// |
| Total cholesterol | 321 mg/dl |
| Triglyceride | 235 mg/dl |
| Fast blood sugar | 75 mg/dl |
| Na | 141 mEq/l |
| K | 4.0 mEq/l |
| Cl | 106 mEq/l |
Endocrinological Data
| Serum | |
| ACTH | <5 pg/ml |
| Cortisol | 21.1 µg/dl |
| Plasma renin activity | 2.27 ng/ml/h |
| Aldosterone | 343.8 pg/ml |
| Catecholamines | |
| Epinephrine | 0.03 ng/ml |
| Norepinephrine | 0.32 ng/ml |
| Dopamine | <0.01 ng/ml |
| Urine | |
| 17-OHCS | 9.40 mg/day |
| 17-KS | 9.60 mg/day |
| Catecholamines | |
| Epinephrine | 9.1 µg/day |
| Norepinephrine | 65.9 µg/day |
| Dopamine | 232.3 µg/day |
ACTH: adrenocorticotropic hormone.
| Baseline | 2 mg | 8 mg | |
|---|---|---|---|
| Urinary 17-OHCS (mg/day) | 9.40 | 8.80 | 9.70 |
| Urinary 17-KS (mg/day) | 9.60 | 10.20 | 11.20 |
| Baseline | 24 hour | |
|---|---|---|
| Urinary 17-OHCS (mg/dl) | 1.34 | 0.30 |
| Urinary 17-KS (mg/dl) | 2.38 | 0.55 |
| Serum ACTH (pg/ml) | <5 | <5 |
cytoplasms were filled with numerous pigment granules with dark to golden brown colors on hematoxylin-eosin staining (Fig. 4b). These pigment granules were negative for Schmorl, Congo red, iron and mucicarmine staining, but they were positive for PAS and Fontana staining. In addition, they stained red with Ziehl-Neelsen stain. These features supported the lipofuscin nature of the pigment. Tumor cells showed neither necrosis nor mitosis and there was no finding of vascular invasion. The adenoma was divided by thin fibrovascular septa with small round cell infiltration.
Discussion
In addition to increased serum cortisol and associated Cush-
ing’s syndrome, the present case showed a right adrenal tumor and numerous lipofuscin granules in the tumor cells. The absence of mitosis, tumor cell necrosis or vascular invasion seems to exclude the possibility of malignancy of the present tumor (1,2). Therefore we diagnosed the present case as benign functioning black adenoma.
Non-functioning black nodule (NFBN) of the adrenal gland is a rather common autopsy finding. For instance, the occur- rence of NFBN in autopsy studies ranges from 10 to 37% (3, 4). In contrast, functioning black adenoma (FBA) of the adrenal
a
b
gland is comparatively rare (5-8) and only 41 cases have been reported to date in Japan. All of the reported cases were associated with Cushing’s syndrome.
A summary of 20 of the 41 cases, including a detailed description of the clinical data, is presented in Table 3 (4, 9-22). Cutaneous disorder, osteoporosis and hirsutism are said to be observed more frequently in FBA compared to in typical yellow adenoma (9, 12, 14, 16, 19, 23). However, Table 3 shows no significant differences in the occurrence of these symptoms between FBA and the typical yellow adenoma (24). Table 3 also indicates that FBA frequently shows an increased level of urinary 17-KS excretion. This is important, because this finding is in direct contrast to the well-known fact that an increased excretion of both 17-OHCS and 17-KS is rather specific for
a
b
A FBA of the Adrenal Gland
| Case | Ref. no. | Age (year) | Sex | Serum cortisol (µg) | Urinary 17-OHCS (mg/day) | Urinary 17-KS (mg/day) | Cutaneous disorder | Osteoporosis | Hirsutism |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 9 | 26 | F | 18.7 | 21.3 | 3.0 | + | + | + |
| 2 | 9 | 35 | F | 11.9 | 7.4 | 3.8 | + | + | - |
| 3 | 4 | 26 | F | 20.4 | 12.5 | 6.5 | + | - | - |
| 4 | 10 | 12 | F | 1 | 1 | 1 | |||
| 5 | 10 | 32 | M | 11.6 | 14.3 | 9.4 | + | - | |
| 6 | 10 | 34 | F | 1 | 1 | 1 | |||
| 7 | 11 | 38 | M | 30.5 | 7.3 | 10.8 | + | + | |
| 8 | 11 | 43 | F | 31.9 | 18.0 | 18.1 | + | - | - |
| 9 | 12 | 18 | F | 25.3 | 23.4 | 22.0 | + | - | - |
| 10 | 13 | 36 | F | 15.3 | 20.4 | 16.7 | + | + | |
| 11 | 14 | 34 | F | 19.5 | 14.7 | 10.0 | + | + | + |
| 12 | 15 | 57 | F | 25.0 | 11.6 | 5.5 | - | - | - |
| 13 | 16 | 24 | F | 25.2 | 27.2 | 17.0 | + | + | |
| 14 | 17 | 58 | M | 41.7 | 9.8 | 6.1 | - | - | |
| 15 | 18 | 59 | F | 18.8 | 10.4 | 2.9 | + | - | |
| 16 | 19 | 49 | F | 17.0 | 43.9 | 8.3 | + | + | |
| 17 | 20 | 64 | F | 12.1 | 7.6 | 4.4 | - | - | |
| 18 | 21 | 45 | F | 26.1 | 4.6 | 5.1 | + | + | |
| 19 | 22 | 40 | M | 24.0 | 15.6 | 1.1 | - | + | - |
| 20 | (our case) | 53 | F | 21.1 | 9.6 | 9.4 | - | - | - |
adrenal cortical carcinoma. Further, most patients with ordi- nary yellow adenoma are said to exhibit a normal or low level of urinary 17-KS (25, 26). Therefore, cortical adenoma associ- ated with elevated urinary 17-KS excretion may be diagnosed as black adenoma.
MRI of adrenal mass is said to have diagnostic value for the differential diagnosis between cortical adenoma and carcinoma (27-29). Most adrenal cortical adenomas show signal intensities similar to those of the liver on both T1- and T2-weighted sequences. However, the present case is not in agreement, because this case showed a hyperintense area as compared to the liver especially on T2-weighted sequences. These features of MRI are similar to those of adrenal carcinoma.
Therefore in patients with functioning black adenoma, the most important clinical problem may be the exclusion of malignancy.
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