Case report Successful pregnancy following surgery for a masculinizing adrenocortical carcinoma
A.A. Kasperlik-Załuska 1, B. Migdalska 1, J. Perkowicz 1, J. Nielubowicz 2 and M. Wysocki 3
Department of Endocrinology, Medical Centre of Postgraduate Education, 2 Institute of Surgery, Academy of Medicine, and 3 Department of Pathomorphology, Medical Centre of Postgraduate Education, 01 -809 Warsaw, Cegłowska 80, Poland
Accepted for publication 17 May 1983
KASPERLIK-ZAŁUSKA, A.A., MIGDALSKA, B., PERKOWICZ, J., NIELUBOWICZ, J. and WYSOCKI, M. (1983): Successful pregnancy following surgery for a masculinizing adrenocortical carcinoma. Europ. J. Obstet. Gynec. reprod. Biol., 16/2, 107-111.
A 16-year-old girl with a masculinizing adrenal carcinoma treated surgically is presented. Following surgery a full clinical and steroid remission has been achieved, without any adjuvant chemotherapy. In the 7th year after the surgical treatment the patient became pregnant. Pregnancy and labour were uncom- plicated. The patient continues in complete remission, and her son has been noted to have normal development at 21 mth of age.
masculinization; adrenocortical carcinoma; pregnancy
Introduction
In the last 18 yr eight adult patients with adrenal carcinoma (7 women and one man) ranging in age from 40 to 57 yr have been observed at the Department of Endocrinology, Medical Centre of Postgraduate Education, in Warsaw. All the women presented a clinical picture of Cushing’s syndrome, with hirsutism in four of them. Six female patients died within 1 to 3 yr after the onset of hypercorticism, despite surgery and/or chemotherapy. Only one woman with Cushing’s syndrome, treated with Mitotan (Lysodren - Bristol, New York) has been observed for 5 yr following surgical treatment. In this paper we present a young patient with mascu- linization syndrome due to an adrenocortical carcinoma, who achieved a complete clinical and hormonal remission after surgery, without any chemotherapy, and uneventfully completed pregnancy.
Case report
A 16-yr-old girl, B.F., was first seen in March 1973 with primary amenorrhoea and hirsutism of 8 yr duration. Her height was 150 cm, unchanged for 4 yr, her bone
age having not been delayed. She presented male body proportions and she had no breast development. Her weight was 52 kg and the blood pressure was 110/70 mmHg. Routine laboratory investigations were normal. The 24-h urinary 17-keto- steroids (17-KS) (Callow et al., 1938) excretion levels were significantly raised, and 17-hydroxycorticosteroids (17-OHCS) (Silber and Porter, 1954) were normal (Table I). A dexamethasone test showed no suppression of urinary 17-KS in response to 8 mg dexamethasone every 24 h for 2 days. On the basis of these studies the diagnosis of an adrenocortical carcinoma was made. An exploration via an abdominal approach was performed. A 535-g encapsulated tumor, yellowish on the cross-sec- tion, with multiple haemorrhagic and necrotic areas was found. On light microscopy dark and pinkish pleomorphic cells were observed with hyperchromatic nuclei and a high nuclear cytoplasmic ratio as well as a diffuse and trabecular pattern of growth. It is to be noted that mitoses were infrequent and the broad fibrous bands were scanty. Numerous neoplasmic emboli of blood and lymphatic vessles were also seen in the tumour (Fig. 1), and the tumour capsule was infiltrated with neoplasmic cells. In spite of the small extent of mitosis and not very marked fibrous bands, an adrenal cortical carcinoma was diagnosed after taking into account other histologic criteria (Hough et al., 1979).
There was no evidence of intraabdominal or hepatic metastases. Both ovaries appeared small and the right one was biopsied. Microscopic examination revealed numerous primary follicles, localized deeply in the cortex, part of them being degenerated. A subcapsular fibrosis was also present.
The postoperative course was uneventful. Urinary content of 17-KS dropped to low normal levels (Table I). The menarche appeared 5 mth postoperatively. During
| Month year | 17-KS (mg/day) 17-OHCS (mg/day) | |||||
|---|---|---|---|---|---|---|
| Baseline | Dexamethasone | Baseline | Dexamethasone | |||
| 2 mg/day | 8 mg/day | 2 mg/day | 8 mg/day | |||
| Before | ||||||
| 3/1973 | 257 | 190 | 326 | 6.7 | 3.6 | 3.6 |
| 228 | ||||||
| After | ||||||
| 5/1973 | 4.3 | 3.8 | 3.0 | 2.3 | 1.3 | 1.1 |
| 9/1974 | 5.2 | 1.2 | ||||
| 5/1977 | 6.6 | 1.6 | ||||
| 9/1978 | 15.6 | 5.8 | 4.7 | 3.0 | ||
| 4/1980 * | 18.0 | 4.8 | ||||
| 11/1980 | 16.5 | 4.5 | ||||
| 10/1981 | 10.2 | 1.8 | ||||
| 5/1982 | 17.5 | 4.3 | ||||
* 20 wk of pregnancy.
| LH (pu/ml) | PRL (ng/ml) | T4 (µg/dl) | TSH (pu/ml) | GH (ng/ml) | |
|---|---|---|---|---|---|
| Before pregnancy | |||||
| 9th day of cycle | 18 | 30 | 8.0 | 3.3 | 2.0 |
| 12th | 3.5 | ||||
| 14th | 18 | 16 | |||
| 15th | 100 | ||||
| 16th | 11 | ||||
| 19th | 33 | 19 | |||
| 24th | 7.5 | 10 | |||
| 20 wk of pregnancy | 78 | 120 | 12.5 | 4.0 | 6.2 |
| 3 mth after delivery | 16 | 11 | 9.0 | 3.5 | 3.6 |
| Normal range | 5-25 | 5-15 | 4-11.5 | 0.0-5.0 | 0.0-5.5 |
this time all signs of masculinization disappeared. Studies of the adrenocortical function carried out within the next 9 yr revealed normal values.
The plasma luteinizing hormone (LH) (Midgley, 1966) examinations performed 5 yr after surgery showed an evident peak in the midcycle (Table II) as if in an ovulatory cycle. In December 1979 she became pregnant. The course of pregnancy was uncomplicated. A physiological increase in serum luteinizing hormone, prolactin (Jeske, 1979) and thyrozine (Jeske et al., 1977) levels was observed. In September 1980 the patient was delivered of a healthy boy weighing 2350 g, 48 cm in height. The baby’s development has been normal. In May 1982 the boy was well and the mother remained in clinical remission from the masculinization syndrome.
Discussion
Patients with hormonally active adrenocortical carcinoma frequently have clinical evidence of virilization in addition to signs of Cushing’s syndrome. In our patient masculinization and primary amenorrhoea were the only clinical disorders: The diagnosis of an adrenocortical carcinoma was based on histologic criteria such as vascular invasion, cellular pleomorphism, mixed, diffuse and trabecular pattern of tumour growth, widespread necrosis of tumour cells and capsular invasion. Among nonhistologic criteria the weight of the tumour was considered to be the most important one. We have in our observation four other women with a masculinization syndrome due to adrenal adenoma (Kasperlik-Załuska et al., 1978). All of them underwent surgery within 2 to 4 yr after the onset of hirsutism. On microscopic examination in all the cases the neoplasm was composed of cells resembling zone reticularis. The tumour weight ranged from 25.5 to 149 g (mean, 85.6 g). In the present case the duration of the virilization syndrome was much longer, viz. 8 yr. One may speculate that in the initial stage an adrenal adenoma from zona reticularis cells had developed and the malignancy appeared at the age of puberty. A possibility exists that this type of malignant tumour would reveal biological characteristics different from those of carcinomas producing mainly cortisol.
The most striking observation in the presented case is the long-term survival, 9 yr after surgical treatment and 17 yr from the onset of masculinization. It is much longer than the median survival time in the series of Hogan et al. (1980). In most patients with Cushing’s syndrome due to an adrenocortical carcinoma the prognosis is poor (Hutter and Kayhoe, 1966).
However, Wohltman et al. (1980) described a 2-yr-old girl with feminizing adrenocortical carcinoma treated surgically, who was followed up for 10 yr. The longest period of survival after surgery, 21 yr with no clinical or laboratory evidence of recurrent tumour, has been reported by King and Lack (1979). Of special interest in our patient is a full recovery of the function of the ovaries, with ovulatory cycles, and an uneventful pregnancy with delivery of a healthy boy.
In the post-delivery period no clinical signs of recurrent malignancy have ap- peared and biochemical remission has also been retained.
Thus our observations have shown that surgical treatment may result in a complete cure of a masculinizing adrenocortical carcinoma and that a successful pregnancy is possible in such a case.
References
Callow, N., Callow, R. and Emens, C. (1938): Colorimetric determinations of substances containing the grouping -CH2CO- in urine extracts as an indication of androgen content. Biochem. J., 32, 1312-1331.
Hogan, T.F., Gilchrist, K.W., Westring, D.W. and Citrin, D.L. (1980): A clinical and pathological study of adrenocortical carcinoma. Therapeutic implications. Carcer, 45, 2880-2883.
Hough, A.J., Hollifield, J.W., Page, D.L. and Hartmann, W.H. (1979): Prognostic factors in adrenal cortical tumors. Amer. J. Clin. Pathol., 72, 390-399.
Hutter. A.M. and Kayhoe, D.E. (1966): Adrenal carcinoma. Clinical features of 138 patients. Amer. J. Med., 41. 572-580.
Jeske, W., Niewiadomska, A. and Czerwińska, A. (1977): The radioimmunoassay of total serum thyroxine and triiodothyronine. Endokr. pol., 28, 109-115.
Jeske, W. (1979a): The effect of metoclopramide, TRH and L-Dopa on prolactin secretion in pituitary adenoma and in “functional” galactorrhoea syndrome. Acta Endocrinol. (Kbh). 91, 385-396.
Jeske, W. (1979b): Prolactin secretion in man in selected physiological and pathological conditions. Habilitation project, Centre of Postgraduate Medical Education.
Kasperlik-Załuska, A., Hartwig. W., Nielubowicz. J., Rudowski, W., Midalska, B., Kobuszewska-Faryna, M. and Załuska, J. (1978): Clinical analysis of 111 cases of adrenocortical hyperfunction. Results of surgical treatment. Endokr. pol .. 29, 273-288.
King, D.R. and Lack, E.E. (1979): Adrenal cortical carcinoma. A clinical and pathologic study of 49 cases. Cancer. 44, 239-244.
Midgley. A.R. (1966): Radioimmunoassay: a method for human chorionic gonadotropin and human luteinizing hormone. Endocrinology, 79, 10-18.
Silber. R. and Porter, C. (1954): The determination of 17 .- 21-dihydroxy, 20-ketocorticoids in urine and plasma. J. biol. Chem., 210, 923-932.
Utiger. R.D. (1965): Radioimmunoassay of human plasma thyrotropin. J. clin. Invest., 44, 1277-1286.
Wohltmann, H., Mathur, R.S., Williamson, H.O., with technical assistance of Wesley. E., Moody, L. and Landgrebe, S. (1980): Sexual precocity in a female infant due to feminizing adrenal carcinoma. J. clin. Endocr. Metab .. 50, 186-189.