Feminizing Adrenocortical Carcinoma in Man
Masayuki NISHIKI, Kuniki AMANO, Hisao ITOH, Haruo EZAKI and Yukitaka MIYACHI*
ABSTRACT: A 37-year-old male with adrenocortical tumor presenting marked gynecomastia and impotence as initial symptoms was experienced. Abnormal elevations in urinary 17-KS, 17-OHCS and blood estrogen levels were noted. Total surgical removal of the tumor weghing 800g was per- formed. Postoperatively the gynecomastia disappeared and he regained libido with no signs of recurrence one year later.
KEY WORDS: gynecomastia, adrenocortical tumor, estrogen producing tumor, impotence, o,p’-DDD.
INTRODUCTION
Adrenocortical tumor presenting signs of feminization in males is rare. In 1965 Gabrilove reviewed sixty-one cases.3,4 Since then only a few cases have been added.1,5 Recently, Fang succeeded in the establish- ment a cell line of estrogen producing adrenal tumor and confirmed the con- tinuous production of estrogen.2 In Japan, two cases have been reported separately by Matsunaga9 and by Sakatoku.11 As we experienced a patient with a feminizing adrenocortical cancer who underwent opera- tion for the total removal of the tumor, the details are presented.
REPORT OF A CASE
A 37-year-old man was first seen in May, 1976, at the age of 35 years with the com- plaints of left gynecomastia and decreased libido. Gynecomastia disappeared after the administration of Mastizol (100 mg/week)
for 6 months but it appeared again on left side in May 1977. Gynecomastia persisted despite the additional Mastizol treatment and progressed to both sides. In August 1977, he noted anorexia and discomfort in the left upper quadrant of the abdomen. One March, 6, 1978, he was admitted to the Hiroshima University Hospital. He noted the onset of secondary sexual charac- teristics with pubic hair at the age of 13 years and axillary hair at 15 years of age. He had normal libido and potentia until 2 years prior to the admission. He has been married for five years but had no child.
He was a moderately built but rather slender. His voice was high-pitched, skin very smooth, and no facial hair, seborrhea or acne. The blood pressure was 120/80 mm Hg. The heart was not enlarged. No thrills nor murmurs were present. The lungs were clear to auscultation and percus- sion. Axillary and pubic hair showed an adult male pattern. Marked bilateral gy- necomastia was present. In the left upper quadrant of the abdomen, elastic soft, no tender, fixed mass with smooth surface was palpable. The liver was not palpable. The testes were almost normal in size but slightly soft. The penis was 8 cm in length. No
Second Department of Surgery, Hiroshima University School of Medicine, Hiroshima City, Japan.
* Third Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima City, Japan.
edema was present.
Urinalysis, hemogram, serum electrolytes, cholesterol, protein, fasting blood sugar, liver and renal function tests were all within normal limits. The electrocardiogram showed a normal pattern. Plain chest roentogenogram showed the presence of 3 coin lesions of about 2 cm in diameter in both lung fields suggestive of metastatic carcinoma (Fig. 1). On a flat plate of the
abdomen, a large mass was noted on the: left side of the abdomen. Following intra -. venous pyelography and pneumoretroperi- toneography, the retroperitoneal mass was seen above the left kidney compressing it inferiorly and laterally (Fig. 2). Adrenal venographic findings showed an avascular mass in the left adrenal gland compressing the dilated adrenal vein to the right (Fig. 3). The selective arteriogram revealed an ir- regular pattern of vascular supply charac- teristic of an adrenal neoplasm. The feeding artery branched from the inferior subphrenic artery. The adrenal scintigram showed. decreased uptake of the left adrenal gland. The liver scanning showed no space occupy- ing legion.
The results of endocrine function studies were listed in Table 1. The urinary excre- tion of 17-ketosteroids was 27.0 mg/day and of 17-hydrocorticoids was 26.0 mg/day. The plasma cortisol level was 19.1 ug/dl with normal response to intravenous administra- tion of synthetic ACTH (250 µg). Under basal conditions, the plasma levels of estrone and estradiol were extremely high and
| preop. | postop. | |
|---|---|---|
| Urine 17-KS(mg/24hrs) | 27.0 | 3.7 |
| Urine 17-OHCS(mg/24 hrs) | 26.0 | 4.4 |
| Serum estrogen E1 | 1545 | <5 |
| (pg/ml) E2 | 300 | <5 |
| E3 | <5 | <5 |
| FSH (IU/1) | 1.0 | 1.0 |
| LH (IU/1) | 1.0 | 6.8 |
| TSH (uU/1) | 8.0 | 5.0 |
| GH (ng/ml) | 1.0 | 4.0 |
| Cortisol (ug/dl) | 19.1 | 13.0 |
| Aldosterone (ng/dl) | 34.6 | 41.6 |
| Testosterone (ng/dl) | 124 | nd |
| Progesterone (ng/dl) | 0.492 | 0.641 |
| E1 | E2 | E3 | |
|---|---|---|---|
| 1. heart | 831 | 81 | 5 |
| 2. vena cava inf. | 708 | 102 | 5 |
| 3. renal vein | 2,612 | 200 | 5 |
| 4. adrenal vein | 1,397 | 131 | 5 |
| (pg/ml) | |||
ranged from 1,545 to 2,335 pg/ml for estrone and from 200 to 300 pg/ml for estradiol. Estriol was not elevated. The plasma levels of LH, FSH and testosterone were very low. The estrone and estradiol levels in venous blood samples collected from various parts of the venous system were shown in Fig. 4. The samples from left adrenal vein showed 2,612 pg/ml for estrone and 200 pg/ml for estradiol. Estrone and estradiol values from the left renal vein were high suggesting that the draining vein from the tumor mainly flows into the left renal vein.
Under the diagnosis of the estrogen pro- ducing left adrenocortical tumor, surgical exploration was performed by transabdo- minal approach on March 16, 1978. Left adrenal gland exploration showed a large tumor compressing the spleen, pancreas, inferior vena cava and left kidney. Nor- mally appearing adrenal tissue was noted in the upper inner portion of the tumor. There was no metastasis to the liver, spleen
pancreas
diaphragmiatic
artery
Stomach
spleen
Tumor
kidney
Colon
and lymph nodes. The right adrenal gland appeared normal by palpation (Figs. 5 and 6). Total excision of the tumor was per- formed by separating it from the adherent organs. The tumor weighed 800 g and
measured 14x11x7 cm. The cut surface was of yellowish brown color with extensive areas of necrosis and hemorrhagic foci (Fig. 7).
On microscopic examination, the tumor contained large oval or polygonal cells with clear or eosinophilic cytoplasma which formed trabecular structure with sinusoid rich in vascularity. The nuclei are oval or poly- morphic, and mitoses were observed (Fig. 8). The capsular invasion was identified and massive foci of necrosis were observed, which established one diagmosis of the left adrenal gland cancer.
The postoperative course was uneventful over one year period with administration of Fluorouracil, o,p’-DDD and prednisone (15
mg/day). Postoperatirely the gynecomastia regressed and the patient recovered sexual potentia. The plasma estrogens, gonado- tropins, testosterone levels and urinary 17- hydroxycorticoid and 17-ketosteroid were all returned to normals. The coin lesions in the lungs remained unchanged.
DISCUSSION
A rare case of a feminizing adrenocortical cancer was reported. In this patient, the plasma levels of estrone and estradiol were extremely high, while the plasma estriol level was much less than in the patient reported previously.4 The short incubation study of excised tissues of adrenal cancer showed significant production of the estro- gens in vitro (unpublished observation). The production of the estrogens from the adrenal cancer caused the suppression of pituitary LH and FSH secretion via negative feedback, resulting in the decrease of testo- sterone production and sexual potentia. In spite of the increased excretion of urinary 17-hydroxycorticoids, no symptoms of Cush- ing’s syndrome was present. This may be partly due to the decreased activity of 11 B-hydroxylase in the tumor with the impaire- ment of the transformation of 11-deoxy- cortisol to cortisol, as pointed out by Green- wood and Gabrilove.5 All clinical symptoms and laboratory abnormalities returned to normal after the extirpation of the tumor.
The prognosis of the advanced adrenal cancer is generally poor.1 The large size of the tumor, histological findings and the probable metastasis to the lung observed in this patient indicate the malignant nature of one tumor and showed the advanced stage suggestive of poor prognosis.
However, recently Hutter6 and Kumagai? reported the beneficial effects of o,p’-DDD for the treatment of adrenal cancer. Fur- thermore, Ostumi10 reported a case of the adrenal cancer with massive metastasis which was cured by combined administration of o,p’-DDD and Fluorouracil. The com-
bination chemotherapy with o,p’-DDD, Fluorouracil and prednisone was done in the present patient with satisfactory effects. At present the patient leads an active life and long survival may be expected.
ACKNOWLEDGEMENT
We are grateful to Mr. Hanji Ishida for his excellent technical assistance.
(This case was presented at the 26th Western Japan Regional Meeting of the Japan Endocrine Society held in Hiroshima on Sep. 29, 1978.) Reprint requests: Masayuki Nishki, M.D., Second Department of Sur- gery, Hiroshima University School of Med- icine, Kasumi 1-2-3, Minamiku, Hiroshima City 734, Japan.
(Received for publication on May 19, 1979)
References
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