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Biomedical subjects

B Zumoff

Publications and source records attributed to B Zumoff.

At least 91 records · Page 5Linked to original sources
PubMed1981

Obese young men have elevated plasma estrogen levels but obese premenopausal women do not.

The 24 hr mean plasma concentrations of estrone (E2) and estradiol (E2) were measured in 18 healthy, regularly cycling obese women; 16 healthy, regularly cycling nonobese women; 18 healthy obese men; and 33 healthy nonobese men. The obese men showed significant elevations of both E1 (67 pg/ml versus 49 pg/ml control; P less than 0.005) and E2 (37 pg/ml versus 28 pg/ml; P less than 0.005), but the obese women showed no significant elevation of either E1 or E2. The most likely explanation for the absence of significant hyperestrogenemia in the obese women despite evidence that such women have increased androstenedione-to-estrone conversion is that the latter source of estrogen is too small in comparison with estradiol secretion to cause a statistically detectable increment in plasma estrogen levels.

Adult↗
PubMed1981

Sex difference in the influence of obesity on the retention of a tracer of 3H-estradiol.

The influence of obesity on the retention of a tracer of 3H-estradiol was studied in 15 nonobese premenopausal women, 15 obese premenopausal women (49%-274% above desirable weight), and 27 young men ranging in weight from 5% below to 330% above a desirable weight. The women showed a clear-cut inverse linear correlation between the 72 hr excretion of radioactivity and the percent deviation from desirable weight over the entire weight range examined (y equals 66 minus 0.10x, r equals -0.59, P less than 0.005); the average excretion in the 6 most obese women (145%-272% above desirable weight) was 45 plus or minus 11 (SD)%, significantly lower than the values of 65 plus or minus 12% in 15 nonobese women (P less than 0.025). The obese men showed no correlation whatever between excretion of radioactivity and relative body weight; the average excretion of the 6 most obese men was 55 plus or minus 7, not significantly different from the value of 56 plus or minus 12 in nonobese men. This sex difference makes untenable the hypothesis previously proposed by others that retention of estradiol tracers is obese women (men were not studied ) is due to simple solubility of estrogens in fat. Various alternative possibilities to explain the present data are discussed and it is concluded that a possibility worth examining is that the adipose tissue of women contains specific estrogen binding protein (? receptor) while the adipose tissue of men does not.

Body Weight↗
PubMed1981

The production rate of cortisol declines during recovery from anorexia nervosa.

The plasma concentration of cortisol is elevated in many patients with anorexia nervosa. It has remained unclear whether this elevation of plasma cortisol level is due only to a slowing of the rate of cortisol metabolism or whether there is, as well, an increase in adrenal secretory activity in anorexia nervosa. We studied adrenocortical activity in 9 female patients and one male patient with anorexia nervosa before and during recovery. The 24-h mean level of plasma cortisol and the rate of urinary free cortisol excretion decreased during recovery, from 11.4 to 7.4 micrograms/dl and from 225 to 116 micrograms/day, respectively (P less than 0.005 and P less than 0.10, paired t test). These changes were associated with a significant decline in the rate of cortisol production from 24.3 to 17.9 mg/day as measured by radioisotope dilution (P less than 0.005). These results suggest that adrenal secretory activity is increased in anorexia nervosa and that the elevation of plasma cortisol level observed in this syndrome reflects not only a slowing of cortisol metabolism but also a rise in cortisol production.

Adolescent↗
PubMed1981

Abnormal 24-hr mean plasma concentrations of dehydroisoandrosterone and dehydroisoandrosterone sulfate in women with primary operable breast cancer.

The 24-hr mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate were measured in 11 women with primary operable breast cancer, ages 31 to 78 years, and in 37 normal women, ages 21 to 75 years. In contrast to the marked and progressive decline of DHA and dehydroisoandrosterone sulfate concentration with age in the normal women, the concentrations of both steroids were age invariant in the cancer patients. The premenopausal patients had subnormal plasma DHA and dehydroisoandrosterone sulfate levels, while the post menopausal patients had supranormal levels. Since the plasma DHA/androsterone ratio was normal in the premenopausal patients and significantly elevated in the postmenopausal patients, it is postulated that the subnormal plasma adrenal androgen levels in the premenopausal patients were due principally to diminished production of these steroids, while the elevated plasma levels in the postmenopausal patients were due principally to slowed metabolic removal. Reports in the literature that DHA inhibits the development of breast cancer in mice suggest that the subnormal plasma DHA levels in premenopausal breast cancer may have clinical significance.

Adult↗
PubMed1981

Influence of obesity and malnutrition on the metabolism of some cancer-related hormones.

It has been suggested that the well-documented relationship of dietary composition to the incidence of human breast cancer is mediated by the effects of dietary constituents on hormone levels. There is fairly good evidence for diet-hormone relationships in animals, but the evidence in humans is unconvincing. In this paper, we describe three of our findings relating nutrition to hormone levels: (a) that obesity causes retention of a tracer of estradiol in women but not in men, a finding we attribute to the presence of specific estrogen receptor in the adipose tissue of women but not men; (b) that obese men have elevated plasma estrone and estradiol levels but obese women do not, a finding we attribute to greater androstenedione-to-estrone conversion in the adipose tissue of men than in that of women; and (c) that cachectic girls with anorexia nervosa fail to have the normal nocturnal surge of prolactin secretion, a finding that we attribute to deficiency of tryptophan, which is an adequate stimulus for prolactin secretion. These findings give support to the concept that dietary factors affect hormone secretion and/or metabolism in humans.

Anorexia Nervosa↗
PubMed1981

Plasma levels of thyroxine and triiodothyronine in women with breast cancer.

24-hour mean plasma levels of T3 and T4 were compared in 29 rigorously selected breast cancer patients (all stages) and 27 healthy women, and 8 A.M. "spot" plasma T4 levels were compared in 43 consecutive unselected breast cancer patients (all stages), 22 women with other-than-breast cancer, 21 women with miscellaneous non-cancerous illnesses, and the same 27 healthy women. The 24-hour T3 levels were the same in the breast cancer patients and healthy controls, but the 24-hour T4 levels were significantly higher in the cancer patients (7.7 vs 5.8 micrograms/dl, p less than 0.001); equal elevations were present in all stages of cancer. Spot T4 levels were likewise significantly higher in the breast cancer patients than in the healthy controls (8.8 vs 7.3 micrograms/dl, p less than 0.005). The women with other-than-breast cancer and the women with miscellaneous non-cancerous illnesses also showed significant elevations of spot T4 levels, indistinguishable from those of the breast cancer patients. It is concluded that breast cancer patients as a group show significant hyperthyroxinemia and that this finding may represent a second nonspecific abnormality of thyroid hormones in disease, hypotriiodothyroninemia (low-T3 syndrome) being the first.

Adult↗
PubMed1980

Cortisol production in obesity.

Absolute cortisol production was estimated from the urinary excretion of tetrahydro metabolites of cortisol in 74 healthy women varying in weight from 12% below to 218% above desirable weight, and in 37 healthy men varying in weight from 3% below to 139% above desirable weight, and was measured by isotope dilution (after 14C tracers) in 26 of the women and 23 of the men. The relationship of both parameters to urinary creatinine excretion (as a measure of lean body mass) and to percent deviation from desirable weight (relative weight) was determined. Both absolute cortisol production and urinary creatinine excretion showed a significant positive linear correlation with relative weight in the men and women, but cortisol production/g urinary creatinine excretion (by isotope dilution or by tetrahydro metabolite excretion) was weight-invariant in both sexes. The geometric mean of cortisol production/g creatinine was 12.9 mg/g in men and 14.5 mg/g in women; the difference was not statistically significant. The geometric mean of tetrahydro metabolite excretion/g creatinine was 3.7 mg/g in men and 3.8 mg/g in women; the difference was not statistically significant. The average ratio of cortisol production to tetrahydro metabolite excretion was 3.5 in men and 3.8 in women, values not significantly different from one another and closely confirming our previously reported value of 3.6, based on the conversion of cortisol tracers to radioactive urinary tetrahydro metabolites. It is concluded that there is no functionally significant elevation of cortisol production in obese men or women: the increase in absolute production is solely a consequence of greater lean body mass, and the production/U lean body mass is weight-invariant. It appears desirable to make any comparisons of one group of patients with another in terms of cortisol production/g urinary creatinine in order to eliminate body size and obesity as confounding factors, so that disease-related differences may emerge clearly.

Carbon Radioisotopes↗
PubMed1980

Stability of ego defenses and endocrine responses in women prior to breast biopsy and ten years later.

Thirty women with breast masses were evaluated psychologically and endocrinologically ten years ago while they were awaiting breast biopsy (3). Eight of these women proved to have benign fibrocystic disease and 22 had breast cancer. A significant (p < 0.05) positive correlation was found between extent of failure of psychological "defenses" and cortisol metabolite excretion rate in these 30 women. On follow-up, 12 women had died (11 with cancer and one who had had benign disease); 7 women were lost to follow-up. Of the remaining 11, one refused to participate, leaving 10 women for follow-up study (7 who had had mastectomy for breast cancer and 3 with benign breast lesions). They were reevaluated using the same assessment techniques as 10 years before. The psychological parameters and cortisol metabolite excretion rates did not show a significant change over the span of ten years. These data support the hypothesis that these psychological parameters and cortisol metabolite excretion rates reflect relatively abiding characteristics and are not as much affected by a "psychosocial threat" as previous research has suggested.

17-Hydroxycorticosteroids↗
PubMed1980

Acidic metabolites. V. Isosteroids as intermediates in cortoic acid formation.

The role of steroid-17-aldols, 20 beta-isocortisol (11 beta, 17,20 beta-trihydroxy-3-oxo-pregn-4-en-21-al) or 20 beta-iso THE (3 alpha,17,20 beta-trihydroxy-11-oxo-pregnan-21-al), as preferred intermediates for the biosynthesis of cortoic acids was studied in human subjects. The results demonstrated that the isosteroids were converted moe efficiently than cortisol to cortoic acids and hexahydro neutral metabolites. In all cases, the oxidation state at C-11 was largely conserved. After the administration of the 20 beta compounds both 20 alpha and 20 beta epimers of the acidic and neutral metabolites were isolated. This inversion occurred without oxidation at C-20 and provided evidence for the mediation of an epimerase in this transformation. The results further indicate that reversion of the isosteroids to ketolic intermediates (i.e. cortisol, tetrahydrocortisol, and tetrahydrocortisone did not occur.

Carbon Radioisotopes↗
PubMed1980

Sex differences in the twenty-four-hour mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio in normal adults.

The 24-h mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate (DHAS) and the DHA to DHAS ratio were determined in 37 normal women, aged 21-75 yr, and 32 normal men, aged 21-72 yr. As predicted from our study of sex differences in the metabolism of DHAS, women showed a markely higher DHA to DHAS ratio than men at all ages; the geometric mean for women was 7.5 x 10(-3) and that for men was 3.9 x 10(-3) (P less than 0.0001); and the mean for premenopausal women (6.7 x 10(-3) did not differ significantly from that for postmenopausal women (8.6 x 10(-3)). The two steroids showed a clear-cut linear inverse correlation between concentration and age in both sexes, and menopause was "nonevent" in the age progression for both steroids in the women. The slopes of the concentration vs. age curves were considerably greater in the women, as a reuslt of which the sex differences in concentrations of these steroids changed with age. Under age 50 yr, the plasma DHA concentration of women was considerably higher than that of men [462 +/- 187 (mean +/- SD) vs. 336 +/- 103; P less than 0.025], while the concentrations of DHAS showed no significant sex difference ((77 +/- 38 vs. 101 +/- 67; P greater than 0.1). In persons 50 yr of age or over, plasma DHA concentrations were about the same in women and men (238 +/- 119 vs. 287 +/- 121; P greater than 0.1), but plasma DHAS concentrations were very much lower in women (31 +/- 21 vs. 83 +/- 49; P less than 0.0001).

Adult↗
PubMed1980

Subnormal plasma adrenal androgen levels in men with uremia.

The 24-h mean plasma concentrations of 8 hormones were measured in 11 men with chronic uremia and 32 normal men. Our findings confirm previous reports of subnormal levels of testosterone, T3, and T4 and elevated levels of LH, PRL, and cortisol. In addition, we observed a new finding: markedly subnormal levels of the adrenal androgens dehydroisoandrosterone (DHA) and DHA sulfate. The mean DHA level in the patients was 164 +/- 46 (SD) ng/dl, compared with 320 +/- 124 in age-matched controls (P < 0.0001); the geometric mean DHA sulfate level was 40 micrograms/dl (95% confidence limits, 11-113) in the patients and 76 micrograms/dl (95% confidence limits, 26-214) in age-matched controls (P = 0.005). The depression of adrenal androgen levels in the face of elevated cortisol levels suggests a biosynthetic block in the adrenal cortex at the step where the C-19 and C-21 pathways diverge, namely the removal of the 2-carbon side chain by C-17, 20-lyase. If a similar defect were present in the testes, it could account for the diminished synthesis of testosterone, which is a further metabolite of DHA in the testes.

Adult↗
PubMed1979

Effect of flutamide on estradiol metabolism.

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.

Anilides↗
PubMed1979

Plasma cortisol profiles in Cushing's syndrome.

Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27%; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14%. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.

Adenoma↗