Search

Alterations in the metabolism of testosterone (T) and dihydrotestosterone (DHT) induced by diethylstilbestrol (DES) or medroxprogesterone acetate (MPA) could account for the beneficial therapeutic effect of these agents in prostatic carcinoma. To investigate this possibility we sutdied plasma kinetics of T and DHT in 17 elderly patients with prostatic carcinoma, before and after treatment with DES (1 or 5 mg/d) or MPA (10 or 30 mg/d) for 30 days. Metabolic clearance rates (MCR) were determined with the single injection technique and by use of two compartment model, plasma concentrations (PC) of T and DHT by radioimmunoassay, the per cent of T bound to plasma protein (T-binding) by charcoal adsorption of the unbound steroid. Production rate (PR) and PC of T were lower, PR and PC of DHT were higher in our patients than in normal men. With both DES regimens, PR, PC and MCR of either androgen declined; however, T was suppressed to a much greater extent than DHT. In either instance, the decrease may have been caused by direct suppression of testicular androgen synthesis and/or by decreased gonadotropin stimulation. Enhanced T-binding played an additional role in reducing the free testosterone index. High and low dose of DES were equally effective. The low dose regimen of MPA did not influence androgen metabolism. MPA in the higher dose suppressed PR and PC of T and DHT, possibly due to effects on testicular synthesis or by gonadotropin suppression as suggested for DES. In contrast to DES, MPA failed to cause profound changes in MCR of either androgen or in T-binding. When judged by its influence on the metabolism of T and DHT in prostatic carcinoma, MPA in higher doses is much less effective than either dose regimen of DES.

Blood and breast cyst fluid were drawn simultaneously for hormonal determination. There was no difference between serum and cyst fluid values of PRL and TSH. A significant difference was noted for LH (p less than 0.01) and FSH (p less than 0.05), serum concentrations being higher than cyst fluid concentrations.

Measurements of cardiac output, blood volume, plasma renin activity (PRA), serum aldosterone, plasma and urinary catecholamine levels, serum and urinary electrolyte levels, and of transfusion and fluid therapy have been made in eight hypertensive and seven normotensive burned children. Studies were conducted during the acute phase of burn injury when hypertension was first diagnosed and were repeated just before discharge from the hospital. Hypertensive patients perfused at an inappropriately high total peripheral resistance and hypervolemia was demonstrated in the hypertensive patients. No differences could be demonstrated between hypertensive or normotensive patients in PRA, aldosterone, catecholamine, or electrolyte levels. These data indicate that both the hypervolemia and the vasoconstrictor activity of PRA and/or catecholamines are present when hypertension develops in these patients. These data suggest that the renin-angiotension-aldosterone system is directly stimulated as part of the neuroendocrine response to trauma.

A unique case of Sheehan's syndrome is characterized by deficiencies of growth hormone, prolactin, thyrotropin, and ACTH. Clinically, it was manifested by adrenal and thyroid insufficiency with regular cyclical menses. Normal menstrual cycles do not preclude extensive hypothalamic-pituitary destruction.

In an attemp- to clarify the clinical importance of glucose intolerance associated with acute thyrotoxicosis, 22 patients had evaluations performed for glucose tolerance while thyrotoxic and at mean follow-up times of 8.8 months and 11.6 years after adequate antithyroid treatment. High incidences of glucose intolerance at long-term follow-up (32%) and of histories suggestive of diabetic diathesis (43%) support the hypothesis that there is an inherited relationship between diabetes mellitus and thyrotoxicosis and suggest that initial testing of all thyrotoxic patients for glucose intolerance is advisable. In addition, all thyrotoxic patients displaying diabetic glucose intolerance after a return to the euthyroid state should be considered to have permanent diabetes mellitus until proved otherwise.

Low plasma renin activity (PRA) has been reported in patients with long-term diabetes mellitus complicated by hypertension and nephropathy. We have assayed PRA in twelve normal subjects and in eight age- and sex-matched juvenile diabetics of greater than twelve years' duration without hypertension and nephropathy under control conditions and following stimulation with diazoxide. During control conditions PRA did not decrease with time in the diabetics as it did in the normals. Following diazoxide infusion, PRA increased in both groups, and although the levels were often higher in diabetics than in normals, the mean differences were not statistically significant. The findings are consistent with the suggestion that PRA is normal or possibly elevated in clinically uncomplicated insulin-dependent diabetes mellitus and decreases with establishment of hypertension and nephropathy.

Measurements of the serum levels of pituitary hormones were made in six patients with uncomplicated head injury. Samples were obtained at 4-hour intervals for 72 hours to evaluate diurnal rhythms. Three of the six patients revealed elevations of serum growth hormone (GH) and prolactin, but no trends could be established. Likewise, three patients had marked elevations of luteinizing hormone and lesser elevations of follicle-stimulating hormone, but no pattern was discernible. The level of thyroid-stimulating hormone was stable and remained in the normal range throughout. GH was measured after intravenous glucose loading. A paradoxical rise reverted to normal at the late follow-up evaluation. It is suggested that the abnormal levels were related to abnormal hypothalamic function rather than to pituitary damage.

Sixteen children with familial hypertriglyceridemia were studied to determine whether there were any distinctive insulintriglycerid-obesity relationships in pediatric familial hypertriglyceridemia. Eleven of 16 children had calculated fat mass greater than the 97th percentile for age, height, and sex. When compared with 16 normal control subjects matched for degree of obesity immunoreactive insulin and glucose response during oral glucose tolerance was similar for normal and hypertriglyceridemic children. By either simple correlation or multiple regression analysis, plasma, triglycerides did not correlate significantly with measurements of insulin or obesity in hypertriglyceridemic or normal children. Within the limits of a small sample size, and in the presence of obesity, insulin does not appear to play a predominant role in the genesis of hypertriglyceridemia in children with familial hypertriglyceridemia. With a small mean weight loss of 1.8 kg and adherence to a diet with 20% of calories as protein, 40% each as fat and carbohydrate, polyunsaturate to saturate ratio of 1.5:1, mean plasma triglycerides were reduced from 238 to 140 mg/100 ml in the 11 obese children with familial hypertriglyceridemia (P less than 0.02). Speculation In spite of the complicating role of obesity, adolescence, and the small sample size, it is interesting to note that the correlation coefficients between triglyceride and insulin/glucose area (0.36), and insulin area (0.30), although not significant (P less than 0.1), were considerably higher in hypertriglyceridemic children than in normal subjects in whom comparable correlation coefficients were 0.08 and 0.08. This infers that the potential role of insulin in triglyceride metabolism in children with familial hypertriglyceridemia might be discerned with longitudinal follow-up into adulthood.