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Biomedical subjects

B Zumoff

Publications and source records attributed to B Zumoff.

At least 109 records · Page 6Linked to original sources
PubMed1979

The effects of psychotropic drugs and diuretics on blood glucose levels in diabetes mellitus.

It has been clearly established that most diuretics and most tranquilizers can raise blood glucose levels in diabetics, while antidepressants can lower them. The extent of these effects is variable but can be highly significant clinically. Chlorpromazine has very likely been responsible for a considerable increase in the prevalence of diabetes in hospitalized psychotics, while antidepressants can produce useful improvement of diabetic control, especially in brittle diabetics.

Blood Glucose↗
PubMed1978

Absorption of sodium from hypertonic sodium phosphate enema solutions.

Absorption of sodium from hypertonic sodium phosphate enema solutions has been studied in 11 patients by means of labeling the contained sodium with added 24Na and determining the radioactivity of body fluids after administration of the enemas. The sodium absorption thus estimated is a maximal figure and may represent an overestimate, since radioactivity can enter the body fluids by ion exchange without net transport of sodium. An average of 5.5 per cent of the instilled radioactivity was absorbed, corresponding to not more than 228 mg sodium. Absorption of such a quantity of sodium does not appear to represent a source of concern in the management of salt-restricted patients.

Adult↗
PubMed1978

Adrenal activity in anorexia nervosa.

Adrenocortical activity was studied in 19 emaciated women with anorexia nervosa. Relative to body size the patients' mean cortisol production rates of 0.591 mg/kg/day and 16.4 mg m2/day were significantly elevated compared to those of 0.322 mg/kg/day and 11.4 mg/m2/day for age and sex matched normal controls (p less than 0.001 and 0.02, respectively). The 24-hr mean plasma cortisol concentration in 18 patients was 10.6 microgram/dl and was significantly higher than that of the controls (6.8 microgram/dl, p less than 0.001). The average excretion of urinary free cortisol in nine patients was 205 microgram/day, significantly greater than that of 65 microgram/day in the controls (less than 0.01). Three patients underwent overnight suppression with 1 mg of dexamethasone and had inadequate responses. These data suggest that cortisol production is excessive in emaciated patients with anorexia nervosa due to a disturbance of the hypothalamic-pituitary mechanisms regulating adrenocortical function. The excessive adrenal activity may reflect certain psychobiological disturbances as well as the effects of malnutrition.

Adolescent↗
PubMed1978

Effect of flutamide on cortisol metabolism.

The effect of flutamide on cortisol metabolism was studied in eight patients with prostate cancer. Flutamide markedly decreased the formation of 3 alpha, 17,21-trihydroxypregnane-11,20-dione (THF), and the 11-oxy-17-ketosteroid metabolites by 72%, 50%, and 46% respectively; however, 3 alpha, 11 beta, 17,21-tetrahydroxy-5 alpha- pregnan-20-one was increased by 46%. The 24-h mean plasma cortisol concentration was not altered. The cortisol production rate decreased by an average of 53% (from 32.7 to 15.5 mg/24 h). The effect of the drug on plasma cortisol kinetics was studied in three patients. This showed that flutamide increased the t1/2 (from 80 to 108 min) but decreased the distribution volume (from 17.8 to 13.8 liters) and the MCR (from 222 to 130 liters/24 h). The changes in THE and THF formation and in the t1/2 and MCR of [C]cortisol are similar to the effects observed in patients with intrahepatic cholestasis. It is suggested that in the case of flutamide these changes were also due to a cholestasis-producing effect of the drug on the liver. As the clinical response to the drug did not correlate with the cortisol metabolic changes, its therapeutic effect was probably not mediated by its effects on cortisol metabolism.

Aged↗
PubMed1978

Metabolism of cortisol-21 glucosiduronate in man.

The metabolism of cortisol-21-glucosiduronate has been studied in two subjects. Urinary excretion was about 65% in both subjects, with cortisol glucosiduronate as the principal metabolite accompanied by small amounts of 11 beta, 17,21-trihydroxypregnane-3,20-dione (THF) glucosiduronate. The absence of the other normal metabolites of cortisol [17,21-dihydroxypregnane-3,11-20-trione (THE), 3 alpha, 11 beta, 17, 20xi, 21-pentahydroxypregnane, and 3 alpha, 17, 20xi, 21-tetrahydroxypregnan-11-one] indicates that negligible hydrolysis at C-21 occurred and that an unoccupied C21 position is required for oxidation at C-11 and reduction at C-20. The limited conversion to THF suggests that a pathway through cortisol-21-glucosiduronate does not contribute significantly to the differences in specific activity of urinary THF and THE observed after administration of labeled cortisol.

Humans↗
PubMed1978

Extraadrenal effects of metyrapone in man.

[14C]Cortisol was injected iv into three subjects during a control period and while receiving metyrapone. The plasma kinetics of the tracer cortisol and the patterns of its urinary metabolites were measured. Metyrapone caused an increase in the volume of distribution of cortisol (34%) and in the MCR (75%); the half-life was decreased by 25%. There were marked changes in the urinary metabolite pattern: 3 alpha,11 beta,17,21-tetrahydroxy-5 alpha-pregnan-20-one, 3 alpha,17,21-trihydroxy-pregnane-11,20-dione(THE), pregnane-3 alpha,11 beta,17,20 alpha,21-pentol, plus pregnane-3 alpha,11 beta,17,20 beta-21-pentol (cortol), and 3 alpha,17,20 alpha,21-tetrahydroxypregnan-11-one (cortolone) all decreased by an average of 62%, 44%, 38%, 45%, and 25% respectively. In contrast, there was an increase of 296% in 3 alpha,17,20 beta,21-tetrahydroxypregnan-11-one (beta-cortolone). To account for these effects it is postulated that metyrapone has the following extraadrenal actions: 1) it inhibits the back reduction of cortisone to cortisol and 2) it stimulates the 20-ketosteroid reductase that converts THE to beta-cortolone.

Adult↗
PubMed1978

Preparation of [24,25-3H] cholesterol. Oxidation in man as a measure of bile acid formation.

In order to devise a convenient method for measuring the rate of formation of bile acids from cholesterol in man, [24,25-3H] cholesterol was prepared by catalytic tritiation of desmosterol where the delta5-unsaturation was protected by conversion to the 3 alpha, 5 alpha-cyclosterol-6-methyl ether. It was shown that tritium in the purified labeled sterol was located exclusively in the side chain. Measurements of 3H2O and the specific activity of plasma cholesterol at timed intervals up to 96 hours after administration of the tracer to three subjects afforded values for cholesterol oxidation (equals bile acid formation) in good agreement with accepted figures for bile acid formation determined by other techniques.

Adult↗
PubMed1977

Cortisol secretion and metabolism in anorexia nervosa.

We studied cortisol secretion and metabolism in 10 women with anorexia nervosa. The 24-hour mean plasma cortisol concentration was 8.9 mug per deciliter (controls, 4.9) (P less than 0.01). Secretory patterns showed normal circadian rhythms. Cortisol half-life was prolonged from 60 to 78 minutes (P less than 0.01), and metabolic clearance rate was decreased from 359 to 177 liters per day (P less than 0.001). Cortisol production was normal (19.4 mg per day). Urinary cortisol was slightly elevated in two of five patients. These findings, as well as the increased tetrahydrocortisol/tetrahydrocortisone ratio (1.2 vs 0.65, P less than 0.01), also appear in hypothyroid patients. Thyroid-function studies showed normal total and free thyroxine and thyrotropin, but low plasma tri-iodothyronine levels (52.7+/-13.2 vs. 137.8+/-24.1 ng per deciliter in the controls, P less than 0.001). In five additional patients with anorexia nervosa studied before and after short-term tri-iodothyronine administration, metabolic abnormalities decreased as plasma tri-iodothyronine levels rose to or above normal.

Adolescent↗
PubMed1977

Studies in the biotransformation of cortisol to the cortoic acids in man. II. The central role of tetrahydrocortisol and tetrahydrocortisone as intermediates.

The possible role of THF and THE as intermediates in the biotransformation of cortisol to the cortoic acids was studied by giving 3H-THF + 14C-cortisol tracers and 3H-THE + 14C cortisol tracers to two subjects each, measuring the 3H/14C isotope ratios of the urinary cortoic acid metabolites and relating these ratios to the dose ratio. Isotope ratios substantially higher than the dose ratio indicate that the tetrahydro compound is a better precursor than cortisol, and isotope ratios that are essentially identical to that of urinary THF or THE, respectively, indicate that the tetrahydro compound may be an obligatory intermediate in the cortisol leads to cortoic acids pathway. The isotope ratio data in these studies clearly establish that THF was a preferential precurosor of the 11 beta-hydroxy cortoic acids (cortolic and beta-cortolic) and THE was a preferential precursor of the 11-ketone cortoic acids (cortolonic and beta-cortolonic). Furthermore, the data strongly suggest that THF and THE may be obligatory intermediates in cortoic acid formation.

Carboxylic Acids↗
PubMed1977

The effect of 7beta, 17alpha-dimethyltestosterone (calusteron) on testosterone metabolism in women with advanced breast cancer.

Calusterone (7beta, 17alpha-dimethyltestosterone) is a 17-alkylated, orally active androgenic steroid used in the treatment of breast cancer. The effect of this steroid on the metabolism of 14C-testosterone and the excretion of endogenous urinary androgen metabolites has been studied in four patients with breast cancer. Total glucuronide metabolites of the tracer decreased significantly, the andorsterone/etiocholanolone ratio rose by a factor of 2-4, and there was increased formation of uncharacterized polar metabolites. There was no significant change in either the sum of the excretion of endogenous androgen metabolites or the androsterone/etiocholanolone ratio. The changes resemble those we have seen in cirrhosis of the liver. It is concluded that the effects of Calusterone on testosterone metabolism, like its effects on cortisol or estradiol metabolism, represent nonspecific effects of an orally administered 17-alkylated steroid on hepatic structure and function, and probably bear no relationship to its therapeutic effect in breast cancer.

Androsterone↗
PubMed1977

Studies in the biotransformation of cortisol to cortoic acids in man. III. 21-Oxidation of 4-14C,21-3H-desoxycorticosterone.

The metabolism of (4-14C, 21-3H) desoxycorticosterone (DOC) in man has been studied. DOC, like cortisol, undergoes oxidation at C-21 with the formation of acidic metabolites (2.3-8.2% of the dose). The release of 3H into the body water, either by oxidation or exchange, is approximately twice as great as the actual formation of acidic metabolites (as judged from the recovery of 14C in the urinary acidic fraction), but both parameters were considerably smaller than the corresponding values for cortisol. The principal metabolite isolated from the urine was 21-hydroxypregnanolone, which had an isotope ratio (3H/14C) greater than that of the dose; the pregnanetriols, which were formed in lesser amounts, had significantly lower isotope ratios than the dose. The absence of the 17-hydroxy group in DOC appears to modify C-21 oxidation, decreasing its magnitude and altering the character of the products.

Biotransformation↗
PubMed1977

The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins.

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.

Aged↗
PubMed1976

The influence of age and sex on the metabolism of testosterone.

The influence of age and sex on the peripheral metabolism of testosterone was studied by giving intravenous tracers of 14C-testosterone to 21 prepubertal children (13 boys and 8 girls), 39 young adults 18-43 years old (23 men and 16 women), and 10 elderly adults 68-86 years old (6 men and 4 women). Studies were also carried out in 2 sexually immature young adults, one 18-year-old 45 XO phenotypic female with gonadal agenesis and one 18-year-old 45 XO, 46 XX mosaic female with gonadal dysgenesis; the latter was restudied after prolonged estrogen-progestagen therapy. Age and sex influences were observed only with respect to the androsterone/etiocholanolone (A/E) ratio; a sex difference in diol metabolite formation was not observed. Prepubertal children showed no sex difference in A/E ratio, which averaged 1.7 +/- 0.28 in boys and 1.9 +/- 0.42 in girls. Young adult men showed a slightly lower A/E ratio, averaging 1.5 +/- 0.10, while females showed a much greater decrease in A/E ratio, to 0.9 +/- 0.09, so that there was a highly significant (P less than .001) sex difference in this age group. The decreased averages were due to disappearance of the higher end of the ranges seen in prepubertal children; the lower limit of the ranges remained the same. Elderly adult men showed a further fall in the A/E ratio, to 1.0 +/- 0.11, and elderly women also showed a further fall, to 0.4 +/- 0.04; a highly significant (P less than .005) sex difference remained. Once again, the fall in average A/E ratio from young adults to elderly adults was due to disappearance of the higher end of the ranges in the former, the lower limits of the ranges were the same in both groups. Of the 2 sexually immature young women, one showed an A/E ratio of 1.3, just below the upper limit for young adult women, and the other showed a ratio of 1.8, well above that limit and thus typical of prepubertal girls. Estrogen-progestagen therapy of the second girl decreased the A/E ratio to 1.4, the upper limit for young adult women. It was concluded that there is a fundamental aging effect in both sexes which causes a gradual progressive decrease of the mean A/E ratio as a result of progressive disappearance of the higher individual A/E values while the lower end of the range of values remains constant; superimposed on this gradual decrease is an acute pubertal decrease in females, probably mediated by the development of the estrogen-progestagen milieu characteristic of sexually mature women.

Adolescent↗
PubMed1976

The effect of medroxyprogesterone acetate on the pituitary-adrenal axis.

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.

Adrenocorticotropic Hormone↗
PubMed1976

Effect of 7beta, 17alpha-dimethyltestosterone (calusterone) on cortisol metabolism in women with advanced breast cancer.

It was demonstrated that oral administration of 7beta, 17alpha-dimethyltestosterone (Calusterone) reversibly alters cortisol production and metabolism in women with advanced breast cancer. There was a 30% decrease in cortisol production rate, a 50% decrease in transformation to tetrahydrocortisone (THE) glucuronide, a 50% prolongation of plasma cortisol half-life and decreased conversion to C-19 metabolites. The plasma cortisol concentrations (means and 24-hour profiles) remained unchanged by Calusterone despite the reduction in adrenocortical function. We have concluded that the beneficial effect of Calusterone in breast cancer is probably not due to its effects on cortisol production.

Adult↗
PubMed1976

Hypothyroid-like alterations in testosterone metabolism in anorexia nervosa.

The metabolism of 14C-testosterone was studied in 8 severely underweight young women with anorexia nervosa. The urinary androsterone/etiocholanolone (A/E) ratio was uniformly low, in a range characteristic of hypothyroidism; the patients also showed low plasma concentrations of triiodothyronine (T3). Clinical remission as manifested by weight gain was accompanied by concomitant increases of the A/E ratio and the plasma T3 concentration to or toward normal. The administration of T3 also resulted in a shift of the A/E ratio toward normal. These data demonstrate that the low plasma T3 concentrations in patients with anorexia nervosa may be related to the development of one of the characteristic biochemical abnormalities found in clinical hypothyroidism, namely a decreased A/E ratio. These data suggest that the "low T3 syndrome" may be associated with biochemical hypothyroidism.

Adolescent↗