FEMINIZING ADRENOCORTICAL TUMORS IN MALE PATIENTS: ADENOMA VERSUS CARCINOMA
MEHUL B. DESAI* AND SAMIR N. KAPADIA From the Department of Radiology, Jaslok Hospital, Bombay, India
ABSTRACT
We report a case of a feminizing adrenocortical adenoma in a 8-year-old boy and feminizing carcinoma in a 25-year-old man. Because diagnosis of adrenal malignancy in such tumors by histopathological criteria is not always conclusive, a clinicoradiological approach may be used in the evaluation. (J. Urol., 139: 101-103, 1988)
Feminizing adrenocortical tumors in male subjects are rare. There have been reports of adrenocortical carcinomas in male patients1-3 but feminizing adrenocortical adenomas are ex- tremely rare.4-11 During evaluation of such adrenal masses a combined clinicoradiological approach is important, since his- tology often is inconclusive as to whether the tumor is malig- nant.3,7 We report an estrogen-secreting feminizing adrenocor- tical adenoma in an 8-year-old boy and feminizing adrenocor- tical carcinoma in a 25-year-old man.
CASE REPORTS
Case 1. An 8-year-old boy was evaluated for bilateral gyne- comastia that had been present for 3 years. The breasts were large in size (Tanner stage 5) with pigmented nipples. Weight was 25 kg. (95th percentile) and height was 125 cm. (95th percentile). Developmental milestones were normal. Physical examination revealed normal prepubertal testes and penis, and no pubic or axillary hair. Blood pressure was 120/90.
Abdominal examination was normal. The karyotype was 46XY. The serum estradiol level was increased (table 1). An x-ray of the wrist and elbow showed a bone age of 12 to 16 years. Computerized tomography (CT) of the abdomen revealed a well defined, poorly enhanced, homogeneous 3 × 2 cm. mass in the left adrenal (fig. 1). The right adrenal gland was normal. Diagnosis was adrenal adenoma.
A well encapsulated 3 cm. left adrenal tumor, weighing 10 gm., was removed at operation. There was no invasion of the surrounding structures. The tumor had a homogeneous appear- ance on cut section, and it was composed of pleomorphic cells with abundant granular cytoplasm. The cells were arranged in sheets and alveolar patterns, and they possessed pleomorphic, hyperchromatic nuclei. Mitotic activity was not evident. The surrounding adrenal tissue was compressed and atrophied. Tu- mor diagnosis was adrenocortical adenoma.
A month postoperatively serum estradiol had returned to normal, and a year later the boy appeared normal and the gynecomastia was regressing.
Case 2. A 25-year-old man, father of 1 child, presented with bilateral gynecomastia, generalized edema and impotence 1 year in duration. Physical examination revealed features of Cushing’s syndrome. Blood pressure was 200/130. The breasts were enlarged with pigment areolae (Tanner stage 3). Both testes were flabby and small with diminished sensations. Serum estradiol and cortisol (total cortisol) levels were increased (table 2). Abdominal CT revealed an enhancing 13 x 8 cm., solid contrast-enhancing left adrenal tumor with central speckled calcification and some necrotic areas (fig. 2). Tentative diag- nosis was adrenal carcinoma. The right adrenal gland was normal.
Accepted for publication May 20, 1987.
* Requests for reprints: 27201 Valleymont Rd., El Toro, California 92630.
A 300 gm. adrenal tumor, which appeared to invade the renal vein, was removed at operation. The tumor was homogeneous and grayish white on cut section. Microscopy showed an encap- sulated surface without any break-through into the capsule. Tumor cells resembled adrenocortical cells. They were arranged in sheets and had a monomorphic appearance except in the center where a few pleomorphic cells were noted. There was no convincing evidence of vascular or capsular invasion. Histolog- ical diagnosis was adrenocortical adenoma. At 1 month post- operatively the serum estradiol and cortisol levels had returned to normal.
| Tests | Pt. Value | Normal Male Range |
|---|---|---|
| Serum: | ||
| Estradiol (pg./ml.) | 621.9 | 7-36 |
| Testosterone (ng./ml.) | 0.29 | 3-9 |
| Dehydroepiandrosterone (mcg./ml.) | 0.86 | 0.8-5.6 |
| Cortisol (mcg. %) | 10 | 6-20 |
| Androstenedione (ng./ml.) | 3.4 | 8-20 |
| Progesterone (ng./ml.) | 0.33 | 0.47-1.2 |
| L-triiodothyronine (ng./ml.) | 181 | 88-133 |
| Thyroid-stimulating hormone (uU/ml.) | 2 | 2-7 |
| Electrolytes (sodium/potassium/chloride) | 139/4.6/100 | |
| Urine (mg./24 hrs.): | ||
| 17-ketosteroid | 6.3 | 5-18 |
| 17-ketogenic steroid | 16.7 | 5-18 |
| Postop. serum estradiol (pg./ml.) | 10 |
Investigations performed at our hospital by radioimmunoassay technique.
A year later the patient was rehospitalized with similar symptoms. Serum estradiol and cortisol levels again were in- creased (table 2). Repeat CT showed recurrence of the left adrenal tumor and hepatic metastases (fig. 3). A chest x-ray revealed a metastatic lesion in the right lung. The patient died 2 months later.
DISCUSSION
The causes of pathological gynecomastia are numerous.12 Adrenal tumors are a rare cause and gynecomastia in such tumors usually is owing to production of increased substrate for peripheral aromatase, for example a massive increase in androstenedione production associated with high serum estro- gen level due to extraglandular aromatization.13 In rare in- stances adrenal tumors may secrete estrogen directly as in our case 1.
In patients with adrenocortical carcinomas the pattern of symptoms may shift during the course of the disease so that feminization, Cushing’s syndrome and masculinization may predominate at various times.14 Sometimes estrogens are the
| Serum Tests | Pt. Value | Normal Male Range |
|---|---|---|
| Preop: | ||
| Estradiol (pg./ml.) | 2,600 | 7-36 |
| 1:2 dilution | ||
| Cortisol (mcg. %) | 29 | 6-20 |
| Adrenocorticotropic hormone (pg./ml.) | 15 | 17.2-59.6 |
| Follicle-stimulating hormone (mIU/ml.) | 10 | 5-20 |
| Luteinizing hormone (mIU/ml.) | 5-20 | 5-20 |
| Electrolytes (sodium/potassium/chloride) | 142/4/100 | |
| 1-yr. postop .: | ||
| Estradiol (pg./ml.) | 3,600 | |
| Cortisol (mcg. %) | 50 | 6-20 |
| Testosterone (ng./ml.) | 4.8 | 3-9 |
Investigations performed at our hospital by radioimmunoassay technique.
major functioning products and there is no evidence of Cushing’s syndrome.7 Histopathology is not diagnostic of the nature of such tumors. A histologically benign tumor may show evidence of metastasis at followup3,7 as in our case 2. Anaplastic adrenocortical carcinomas may not be associated with clinical or biochemical evidence of hormone production. The liver and lungs are common sites for metastases. 15,16
CT criteria for separating benign and malignant adrenal masses have been proposed.17 Size, contrast enhancement and irregular consistency are significant discriminators of malig- nant from benign adrenal masses. Malignant adrenal lesions tend to be larger than benign lesions, with a 6 cm. diameter being considered significant. Malignant masses show signifi- cant (20 CT density units) enhancement after administration of intravenous contrast material. Benign masses do not en- hance to this extent. Malignant adrenal masses usually are of irregular consistency with hypodense and soft tissue areas mixed haphazardly. Calcification in an adrenal mass favors malignancy.18 When these criteria are considered it usually is possible to differentiate malignant from benign adrenal masses. Functional status of the mass also is an important determinant about the nature of the lesion. Cushing’s syndrome in infancy with virilizing or feminizing signs suggests the presence of adrenal carcinoma.19 High serum estrogen levels suggest carci- noma.14 The findings in our cases are in keeping with these concepts.
Adrenal adenomas, ovarian tumors and pheochromocytomas have been known to produce immunoreactive adrenocorticotro- pic hormone, although it is not secreted into the circulation.20 When the level of serum adrenocorticotropic hormone is deter- mined by radioimmunoassay in patients with functioning ad- renal tumors, a falsely elevated value may be seen. In case 1 the serum adrenocorticotropic hormone value was 551 pg./ml. (normal 17.2 to 59.6). Sometimes such a phenomenon occurs in adrenocorticotropic hormone radioimmunoassay without ex- traction.20 There are 2 possibilities to explain the discrepancy between an elevated adrenocorticotropic hormone associated with a normal cortisol level. Some materials in the plasma might interfere with adrenocorticotropic hormone radio- immunoassay, causing it to be falsely elevated. The interfering materials can be determined by measuring the nonspecific binding protein in the radioimmunoassay, the adrenocortico- tropic hormone binding protein in plasma and the stability of tracer in the radioimmunoassay during incubation. Another rare possibility would be that adrenocorticotropic hormone in the plasma might have little bioactivity to stimulate the adrenal gland (for example big adrenocorticotropic hormone or frag- ments of adrenocorticotropic hormone). Characterization of plasma adrenocorticotropic hormone by gel filtration chroma- tography and bioassay then would be necessary.21
The infrequent occurrence of feminizing adrenal tumors in male subjects and their unpredictable behavior make patient management difficult. Histopathology may prove to be mis- leading and, therefore, the best approach is combined clinico-
F
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radiological and histopathological studies with prolonged fol- lowup.
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