Subnormal plasma dehydroisoandrosterone to cortisol ratio in anorexia nervosa: a second hormonal parameter of ontogenic regression.
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Adult↗
Biomedical subjects
B Zumoff
Publications and source records attributed to B Zumoff.
Subnormal 24-hour mean plasma LH concentration and elevated plasma FSH/LH ratio in obese premenopausal women. A possible human counterpart of the slow-GnRH-pulsing model in primates.
The 24-hour mean plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured during the follicular phase of the menstrual cycle in 15 healthy, regularly cycling obese women (59-218% above desirable weight) and 9 healthy, regularly cycling nonobese women (14% below to 14% above desirable weight). The obese women showed slightly but not significantly higher FSH values (12.5 vs. 9.6 mIU/ml), definitely and significantly lower LH values (11 vs. 17 mIU/ml; p less than 0.005) and markedly and very significantly higher FSH/LH ratios (1.2 vs. 0.62; p less than 0.0005). These abnormalities may represent a human counterpart of the slow-GnRH-pulsing model of primates: monkeys in which the GnRH secretory centers have been ablated and that receive GnRH infusions at subnormal pulsing rates show slightly elevated FSH levels, markedly decreased LH levels, greatly elevated FSH/LH ratios and anovulation.
Adult↗
Paradoxical effects associated with supranormal urinary testosterone excretion in premenopausal women with breast cancer: increased risk of postmastectomy recurrence and higher remission rate after ovariectomy.
Urinary testosterone excretion was measured in 18 normal premenopausal women, 80 women studied shortly after mastectomy for primary operable breast cancer, and 93 women with either metastatic breast cancer (77) or primary inoperable breast cancer (16) who were to be ovariectomized. Forty-two of the 93 were restudied after the ovariectomy. The control women showed a normal distribution of testosterone excretion, up to 12 micrograms daily; the postmastectomy patients showed a bimodal distribution, with 14 patients (17.5%) having values above 12 micrograms (up to 39 micrograms) daily. In the metastatic group, 24 of 77 patients (31.1%) had urinary testosterone excretion greater than 12 micrograms daily (up to 77 micrograms). The difference in percentage of high excretors was significant (p less than 0.02). Of the patients treated by ovariectomy, 27 had supranormal testosterone excretion preoperatively, and 16 of these (59.2%) had remissions; 66 had normal excretion preoperatively, and 21 of these (31.8%) had remissions. The difference was significant (p less than 0.02). Urinary testosterone excretion was restudied postoperatively in 42 of the 93 ovariectomized patients. Values were normal preoperatively in 31, and these were unchanged postoperatively. Values were supranormal preoperatively in 11; all of these fell significantly after ovariectomy, to normal in 8 cases. These findings appear to confirm the ovarian source of the excessive urinary testosterone. The following conclusions were drawn. There is a subgroup of premenopausal women with primary operable breast cancer who have supranormal urinary testosterone excretion; the incidence of this abnormality in women with recurrent metastatic disease after mastectomy is nearly twice as high. It can be calculated that the finding of supranormal urinary testosterone shortly after mastectomy represents virtually a 100% risk of recurrence, in contrast to a recurrence rate of about 38% in women with normal testosterone excretion. Patients with supranormal testosterone excretion prior to therapeutic ovariectomy have nearly twice as high a remission rate as do those with normal testosterone excretion.
Adult↗
[24,25-3H]Cholesterol: presence of tritium at additional sites in the side chain.
In order to measure the distribution of radioactivity present in the side chain of [24,25-3H]cholesterol prepared by a sequence involving catalytic tritiation of 3 alpha, 5 alpha-cyclocholest-24-en-6 beta-ol 6-methyl ether, the cholesterol was oxidized to 4-cholesten-3-one, which was then cleaved between C-24 and C-25 to afford the C24 alcohol. Oxidation to the corresponding cholenoic acid, followed by alkali equilibration and esterification completed the sequence. It was found that about 20% of the tritium in the labeled cholesterol is not lost when this tracer is physiologically converted to bile acids. Consequently, measurements of bile acid formation using this tracer must be corrected upward by this amount.
Cholesterol↗
Effects of beta-blockers on post-infarction mortality.
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Adrenergic beta-Antagonists↗
Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory.
The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.
Age Factors↗
Sex difference in the influence of obesity on the 24 hr mean plasma concentration of cortisol.
The 24 hr mean plasma cortisol concentration was measured in 65 healthy women ranging from 21% below to 218% above desirable weight and in 47 healthy men ranging from 5% below to 330% above desirable weight. In the women, there was a clear-cut inverse linear correlation between the plasma cortisol concentration and the percent deviation from desirable weight (y = 7.5 -- 0.3 x; r = -0.49; p less than 0.001); the relation of free to total cortisol concentration was weight-invariant; the MCR of cortisol in the most obese women was much higher than that of nonobese women (340 +/- 76 versus 211 +/- 31 liters/gm urinary creatinine; p less than 0.01). In the men, the plasma cortisol level and MCR were weight-invariant. To account for the finding in women of a linear correlation of the decrement in plasma cortisol level with the percent deviation from desirable weight (which in turn is nearly perfectly correlated with the total body fat content), we postulate that a given weight of adipose tissue in women takes up a constant amount of cortisol; this in turn suggests that their adipose tissue contains a saturable binding system such as corticosteroid receptor. By the same logic, the weight-invariance of plasma cortisol and MCR in men suggests the absence of significant amounts of corticosteroid receptor in their adipose tissue. The finding that the increased cortisol MCR of obese women results in decreased plasma cortisol levels rather than an increase in cortisol production (the latter, corrected for muscle mass, is normal in obesity: Strain et al, Metabolism 29:980, 1980) suggests a defect in their cortisol ACTH feedback system. Such a defect, presumably hypothalamic, is not unexpected in the light of reports of defective hypothalamic control of prolactin and growth hormone secretion in obesity.
Body Weight↗
Mild Hypogonadotropic hypogonadism in obese men.
To evaluate the pituitary-gonadal axis of obese men, we compared the 24-hour mean plasma concentrations of total and free testosterone and of dihydrotestosterone, FSH, and LH in 21 healthy obese men, aged 18-50, and 24 age-matched healthy nonobese men. In the obese men, we also measured the volume of ejaculate and the number and motility of sperm, and investigated libido by psychiatric interview, and potency by history and by measurement of nocturnal penile tumescence. As a group, the obese men had less than two-thirds the normal mean plasma levels of total testosterone, free testosterone, and FSH; the difference from normal was highly significant for all three. 24 hr LH levels were normal, which is inappropriately low in view of the subnormal testosterone levels. 24 hr mean levels of dihydrotestosterone and spermatogenesis, libido, and potency were essentially normal. Taken together, the findings represent a state of mild hypogonadotropic hypogonadism, which thus appears to be characteristic of obese men. This abnormality probably results from partial suppression of the pituitary by the elevated plasma estrogen levels we and others find in these men.
Adolescent↗
Metabolism of cortoic acids in man.
Administrated radioactive tracers of beta-cortolic or beta-cortolonic acids are excreted mostly unchanged, without significant alteration of the molecule at C-11 or C-20; a minor amount of cleavage to C-20 etianic acids occurs. Evidence was obtained for possible noncovalent complexing of the steroid acids to macromolecular components present in the enzyme preparation for hydrolysis of the urinary glucuronides; this complex can be dissociated by acidification to pH 2, and the acidic metabolites can then be readily extracted. The findings suggest that beta-cortoic acids are essentially terminal metabolites in man.
Adult↗
Age variation of the 24-hour mean plasma concentrations of androgens, estrogens, and gonadotropins in normal adult men.
The 24-h mean plasma concentrations of androgens (dihydrotestosterone and total and free testosterone), estrogens (estrone and estradiol), and gonadotropins (LH and FSH) were measured in 35 healthy men, aged 21-85 yr, who were rigorously screened to exclude factors known or suspected to alter endocrine function. The plasma total testosterone concentration showed a slow continuous decline with age, decreasing about 35% between 21 and 85 yr of age; the free testosterone level was closely correlated with that of total testosterone over the entire observed concentration range. The concentrations of dihydrotestosterone, estrone, estradiol, and LH were age invariant. The concentration of FSH showed a continuous linear increase with age; the level at age 85 was about 2.5 times the level at age 21. The following conclusions were drawn. 1) Testosterone secretion appears to decline slowly and continuously throughout adult life in men. 2) Measurement of the plasma free testosterone level adds no independent information in healthy men, since its level is closely correlated with that of total testosterone at all concentrations. 3) The continuous rise with age in FSH concentration while LH is age invariant cannot be explained by changes in testosterone or estrogen production, but might be due to a decline of inhibin production with age.
Adult↗
The mean 1300-1600 h plasma cortisol concentration as a diagnostic test for hypercortisolism.
The 24-h mean plasma cortisol concentration was compared with the mean plasma cortisol concentrations during short subperiods of the day in 88 normal subjects and 223 patients with a very wide range of mean 24-h cortisol levels. The correlation between the 1300-1600 h mean plasma cortisol concentration and the mean 24-h plasma cortisol concentration was extremely high in all groups. Mean cortisol concentrations during this short subperiod powerfully discriminate cortisol hypersecretors (patients with Cushing's syndrome, anorexia nervosa, or prostate cancer) from normal controls. Hence, it is suggested that the mean or integrated 1300-1600 h plasma cortisol concentration can be used as a reliable afternoon cortisol test for the presence of hypercortisolism.
Adrenocortical Hyperfunction↗
Streptozocin-induced eosinophilia and fever: a case report.
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Adenocarcinoma↗
Allopurinol hepatotoxicity potentiated by tamoxifen.
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Aged↗
Relationship of obesity to blood estrogens.
It has become conventional wisdom that estrogenic stimulation of breast tissue has something to do with the causation of breast cancer and that the reason obesity is a risk factor for breast cancer is that obese women are hyperestrogenized. However, it has been very difficult to demonstrate that excessive exogenous estrogen increases the incidence of breast cancer, that endogenous estrogen excess is present in breast cancer, or that obese women are hyperestrogenized. We have examined the last question by measuring 24-hr mean plasma estrone and estradiol levels in the midfollicular phase in 18 healthy, regularly cycling, very obese (53 to 218% above ideal weight) women and 16 regularly cycling, age matched, nonobese control women. Unlike obese men, the obese women showed no significant elevation of either estrone or estradiol. Their average estrone level was 72 compared with 64 pg/ml in controls; their average estradiol level was 65 compared with 57 pg/ml in controls. In the combined group (obese plus nonobese), there was a significant correlation of percentage of deviation from ideal weight with plasma estrone (y = 63 + 0.12x; p less than 0.05) but not with estradiol. This correlation supports the current hypothesis that there is increased androstenedione leads to estrone conversion (i.e., increased aromatase activity) in obesity. The reason plasma estrone levels are not significantly elevated in obese women is that the small amount derived from androstenedione is swamped by the much larger amount derived from ovarian secretion, which is apparently unaffected by obesity. Unless there is increased local formation of estrogens in the breast tissue of obese women, the absence of elevated plasma estrogens in them means that their breasts are not "seeing" increased estrogen levels. Thus, endogenous hyperestrogenization is unlikely to be a causative factor of breast cancer in obese women.U
Aromatase↗
Effect of tamoxifen treatment on cortisol metabolism and the course of the disease in advanced breast cancer.
Twenty-nine postmenopausal women with advanced breast cancer were treated with Tamoxifen, a nonsteroidal antiestrogen. The effect of the drug on the plasma concentration, production rate, and metabolism of cortisol was measured, and the relationship of the changes in these parameters to the course of the disease was investigated. After six weeks of Tamoxifen treatment the plasma cortisol concentration and the cortisol-binding globulin concentration increased by 26 and 64%, respectively, but the production rate of cortisol and the urinary excretion of its tetrahydro metabolites THF, ATHF, and THE decreased by 35 and 13%, respectively; all of these changes were statistically significant. When the group consisting of complete or partial responders was compared with one consisting of patients whose disease remained stable or worsened, no significant difference was detected between these two groups in the change in any of the above parameters. It was concluded that any improvement due to Tamoxifen was not related to changes in cortisol metabolism.
Aged↗
Cortisol measurements in patients receiving oral corticosteroid replacement treatment.
Eight women receiving corticosteroid replacement in the form of 50 mg cortisone acetate or 40 or 50 mg cortisol orally daily were studied. The cortisol "urinary productions rate" and "blood production rate" measurements suggested that the steroid was rapidly metabolized in the gut or in the first passage through the liver. The 24-hour mean plasma cortisol concentration obtained from blood samples drawn every 20 minutes over a 24-hour period and the "blood production rate" were close to the values in normal women. However, since the normal 24-hour plasma cortisol concentration profile could not easily be reproduced and this may be relevant for optimal physiologic function, the patient's clinical status will continue to be the main guide to the choice of the appropriate replacement dose.
Adrenal Cortex Hormones↗
Selective elevation of plasma free cholesterol concentration by administration of estrogen in the presence of total biliary obstruction.
On the basis of clinical observations suggesting interactive effects of biliary obstruction and estrogen therapy on plasma cholesterol levels, a prospective study of the effect of ethinyl estradiol on plasma lipid levels was carried out in a patient with total biliary obstruction. A daily dose of 50 micrograms of ethinyl estradiol raised the plasma free cholesterol concentration from 265 mg/dl to 550 mg/dl over a period o 3 weeks; there was no change in plasma ester cholesterol concentration. Withdrawal of the estrogen was followed by a fall to baseline of the free cholesterol concentration over a 45-day period; once again there was no change in ester cholesterol. Plasma phospholipid concentration rose and fell in direct proportion to the changes in free cholesterol; plasma triglyceride concentration was unaffected by the estrogen. To account for the results of this study, it is suggested that the already elevated plasma levels of lipoprotein-X in biliary obstruction are further elevated by estrogen administration.
Aged↗