Hypogonadism following prostate-bed radiation therapy for prostate carcinoma.

BACKGROUND: The degree of testicular damage resulting from primary treatment of prostate carcinoma by external beam radiation therapy (EBRT) to the prostate bed has not been determined. If significant testicular damage has occurred, the resulting endocrine changes may result in modified tumor behavior, contribute to postradiation impotence, and may aggravate other signs and symptoms of hypogonadism, potentially influencing a patient's choice of primary treatment for his tumor. METHOD: Three to eight years after primary treatment for localized prostate carcinoma, serologic evaluation for hypogonadism was undertaken in 33 men who had received EBRT and in 55 similar men who had received radical prostatectomy (RP). No subjects had developed recognized tumor recurrence, and none had undergone hormonal treatment since primary therapy. RESULTS: Among men of similar age, prior treatment with EBRT was associated with significantly more frequent hypogonadism than prior treatment with RP. In men with EBRT, total testosterone levels averaged 27.3% less, free testosterone levels 31.6% less, dihydrotestosterone levels 33.4% less, luteinizing hormone (LH) levels 52.7% greater, and follicle-stimulating hormone (FSH) levels 100% greater than those values in men who had prior treatment with RP. Differences between postradiation and postsurgical men in LH and FSH levels were most prominent in men older than 70 years. CONCLUSIONS: Three to eight years after primary treatment for prostate carcinoma, striking hormone differences were present between men who had received EBRT to the prostate bed and those with prior RP. These differences strongly suggested that prominent and permanent testicular damage was sustained during EBRT, frequently severe enough to cause hypogonadism.

Progressive osteoporosis during androgen deprivation therapy for prostate cancer.

PURPOSE: Hypogonadism is a prominent risk factor for osteoporosis in older men. However, bone loss during androgen ablation therapy for prostate cancer has rarely been quantitated. MATERIALS AND METHODS: Femoral neck bone mineral density was determined in 26 men before orchiectomy or chemical castration as initial hormone therapy for prostate cancer and at 6-month intervals thereafter for 6 to 42 months. Measurements were made in 16 other men at 12 to 24 months beginning 3 to 8 years after the onset of castration. Baseline and post-castration bone loss was related to several host and tumor characteristics, and compared to similar measurements in 12 control subjects. RESULTS: Average age corrected baseline femoral neck bone mineral density was higher in controls than in treated men and remained essentially unchanged for 2 years. Following orchiectomy average bone mineral density decreased 2.4% and 7.6%, respectively, during years 1 and 2 (2-year loss 2.5% to 17.0%), with similar losses documented in men undergoing chemical castration. Average bone mineral density decreased 1.4% to 2.6% per year 3 to 8 years after uninterrupted androgen deprivation. Age corrected baseline bone mineral density was greater in men who were obese, younger than 75 years or participated in regular exercise but the influence of each characteristic could not be isolated. Post-castration bone loss was greater in men who were obese, younger than 75 years without regular exercise. CONCLUSIONS: Chemical or surgical castration in men with prostate cancer is usually followed by greatly accelerated bone loss which may be superimposed on a bone mass already depleted before hormonal therapy. Baseline bone mass and subsequent bone loss may be influenced by host obesity, age and exercise habits.

T cell subpopulations in alopecia areata.

Alopecia areata remains a disease of unknown cause and unsatisfactory treatment. Histologically it is characterized by a lymphocytic infiltrate that surrounds the lower half of the hair follicle. Our findings show that 64% to 92% of this infiltrate is composed of T lymphocytes bearing the Leu 3a (helper-inducer) phenotype. The remaining lymphocytes demonstrate the Leu 2a (cytotoxic-suppressor) phenotype. This helper T cell predominance is present in all patients, irrespective of clinical activity or duration of disease. The Leu 3a/Leu 2a ratio ranged from 2.6 to 19.8, the higher ratios being seen in patients with clinically active disease. The cutaneous infiltrate also is Ia-positive, indicating the activated nature of these lymphocytes.

Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma.

We have studied the clinical effects of a murine monoclonal anti-human T-cell antibody in seven patients with T-cell lymphoma. Four to 17 treatments with anti-Leu-1 were given to each patient over periods of 14-75 days. Doses of antibody ranged from 250 micrograms to 100 mg. Antibody treatments usually caused a rapid fall in circulating T cells, with return to baseline levels within 24-48 hr. The optimum dose appeared to vary for each patient. Clearance of circulating tumor cells correlated with the amount of antibody bound to cells. Other than dyspnea in one patient, no serious toxicity was noted. Five patients had definite tumor responses, but these were of short duration (1.5-4 mo). Four patients developed anti-mouse immunoglobulin (Ig) antibodies, and in three patients, this was responsible for tumor escape from therapy. Although 95% of the host anti-mouse Ig response was directed against mouse Ig constant region determinants, a small but significant component was found to be antiidiotype.

LPS-induced differentiation of a murine B cell leukemia (BCL1): changes in surface and secreted IgM.

We examined the effect of LPS-induced differentiation on surface and secreted IgM in a cloned BCL1 in vitro cell line. Incubation of this cell line with LPS resulted in a decrease in the amount of membrane IgM, measured by both immunofluorescence and immunoprecipitation, and an increase in IgM secretion, measured by plaque-forming cells (PFC). Activation to high rate secretion was independent of cell cycle in synchronized cells and was independent of DNA synthesis because PFC formation was not inhibited by hydroxyurea. Almost all cells in the in vitro line were shown to contain large quantities of intracytoplasmic IgM before LPS activation. Thus, it would appear that the in vitro cell line represents a partially activated stage of differentiation compared to normal resting B cells or to the in vivo line of BCL1. Analysis of the two forms of mRNA coding for membrane and secreted IgM showed that, at least for cells at the level of differentiation examined here, the control of membrane IgM expression is post-transcriptional. The differentiation of resting B cells to the plasma cell level appears to consist of multiple stages of differentiation. The present data suggest that LPS provides at least two signals of activation. One induces the resting cell to synthesize cytoplasmic IgM, increase surface IgM, and to begin cell division. The second induces the secretion of intracytoplasmic IgM associated with a decrease in surface IgM.