POSTPUBERAL CASTRATION AND PROSTATIC CARCINOMA
NORBERT EGLE, M.D. JENS E. ALTWEIN, M.D.
From the Department of Urology, Kantonsspital, St. Gallen, Switzerland
ABSTRACT - The occurrence of prostatic carcinoma after postpuberal castration is rather unique since only one other case has been reported. However, there was no lack of androgens in the patient in this report, because the testicular ablation was compensated by nodular hyperplasia of the adrenal cortex maintaining a normal plasma testosterone.
Growth and development of the prostate gland require the availability of androgens, particularly testosterone. Therefore testicular ablation is fol- lowed by prostatic atrophy.1 This observation has been confirmed through repeated laboratory ex- periments.2 The time of castration, particularly in regard to the onset of puberty, is critical in regard to the extent of prostatic atrophy. Prepuberal castration interferes with the growth of the pros- tate which in turn remains minute and dem- onstrates no secretory activity,3 whereas post- puberal castration results in regressive changes of an organ already enlarged and functioning. Ob- servations by Priesel4 and Altmann5 support the latter statement.
It would appear reasonable to assume that these atrophic prostates might be protected from malignant transformation. However, the occur- rence of prostatic cancer in men castrated in their third decade appears to put the former assump- tion into question. Such a patient was seen by Scott.2 Another case is reported herein.
Case Report
A sixty-year-old man was hospitalized November 28, 1970, in acute urinary retention with 200 cc. residual urine. The pertinent history disclosed that thirty-five years prior to admission a bilateral inguinal orchiectomy had been carried out for sexual deviation.
On physical examination three firm nodules were palpated within the confines of a moderately enlarged prostate. Transperineal biopsy revealed a solid, moderately differentiated adenocar- cinoma of the prostate interspaced with clear cells (Fig. 1A). This was confirmed by the cytologic examination of an additional transrectal aspiration biopsy. The scrotum was empty, and bilateral inguinal scars were noted. The radiologic evalua- tion did not demonstrate any pathologic changes related to the carcinoma of the prostate.
Pertinent laboratory data included the follow- ing: alkaline phosphatase 140, acid phosphatase 10, prostatic phosphatase 1.1, and osteoclastic phosphatase 6.2 mU. per milliliter; creatinine 0.9 mg. and blood urea nitrogen 17 mg. per 100 ml .; and erythrocyte sedimentation rate 22 per 50 mm. (Westergren). The plasma testosterone measured 1,080 ng. per 100 ml.
On December 12, 1970, a retropubic radical prostatectomy was performed. Histologic study revealed a solid prostatic carcinoma with a crib- riform pattern (Fig. 1B). The postoperative course was uneventful. Six months after the oper- ation a voiding cystourethrogram divulged adequate funneling of the bladder neck and free urine passage.
A follow-up examination on August 8, 1973, revealed a local tumor recurrence. Transperineal biopsy of a nodule adjacent to the bladder base showed a poorly differentiated adenocarcinoma.
B
At this time serum testosterone measured 940 ng. per 100 ml. Despite estrogen administration bone metastases developed. Local invasion of the tumor lead to bilateral ureteral obstruction and the patient died March 4, 1974.
Autopsy demonstrated the poorly differen- tiated tumor involving the bladder, prevesical portion of both ureters, and the rectum. Multiple metastases were present in the retroperitoneal lymph nodes, liver, lungs, and pelvis (Fig. 2). Both testes were absent. The adrenals revealed nodular hyperplasia of their cortex.
Comment
In Scott’s2 patient castration had been carried out at twenty-eight years of age, and the prostatic carcinoma was histologically confirmed at the age of sixty years. These two observations are seem- ingly in contradistinction to the beneficial effects of castration on cancer of the prostate. Two expla- nations may be proposed.
First, the occurrence of a hormone-resistant prostatic tumor may be responsible. Statistically, estrogen responsiveness is lacking in 16 per cent of prostatic cancer.” The hormone dependence
was found to be related to the degree of differenti- ation being rare in well-differentiated prostatic cancers and prevailing in poorly differentiated prostatic cancers.7,8 However, in the case pre- sented the carcinoma of the prostate did not fall into the category of “poorly differentiated” when first diagnosed.
Second, the influence of extragonadal andro- gens could have overcome the postpuberal tes- ticular ablation. The appearance of adrenal corti- cal adenomas has been observed in castrated ani- mals,9 an effect attributed to the postcastration release of gonadotropins. Altmann5 described the development of adrenal cortical adenoma in a postpuberal castrate. In the patient presented, nodular hyperplasia of the adrenal cortex was seen at the time of death. Moreover, the plasma testosterone was in the upper normal range on two occasions. This demonstrated the androgen re- lease from the adrenal glands compensating the adrogen deficit. The ability of the adrenal cortex to secrete testosterone has been proved before. 10
University of Mainz Medical School 6500 Mainz West Germany (DR. ALTWEIN)
References
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