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Biomedical subjects

D K Fukushima

Publications and source records attributed to D K Fukushima.

At least 19 recordsLinked to original sources
PubMed1983

Influence of thyroid function on the in vivo cortisol in equilibrium cortisone equilibrium in man.

To evaluate the effect of thyroid function on the in vivo cortisol in equilibrium cortisone (F in equilibrium E) equilibrium, double-labeled cortisol tracer techniques were used to measure separately the rates of the F leads to E and E leads to F reactions in 4 euthyroid, 2 hypothyroid, and 2 hyperthyroid subjects. The rate of the F leads to E reaction was calculated from the appearance rate of 3H in body water after the i.v. injection of [11 alpha-3H]-cortisol; the rate of the E leads to F reaction was calculated from the difference in the plasma turn-over rates of [11 alpha-3H]-cortisol, and [4-14C]-cortisol after simultaneous i.v. injection of both tracers; the F in equilibrium E set-point was calculated by dividing the F leads to E rate by the E leads to F rate. In euthyroid subjects the F leads to E reaction rate averaged 1.6%/min, the E leads to F reaction rate averaged 1.0%/min, and the F in equilibrium E set-point averaged 1.6. In hyperthyroid subjects the two reaction rates were supranormal: the F leads to E rate averaged greater than or equal to 3.9%/min and the E leads to F rate averaged 1.54%/min; since the increase in the F leads to E rate was proportionally greater, the F in equilibrium E set-point (average greater than or equal to 2.6) was displaced towards cortisone. In hypothyroid subjects both reaction rates were equally slowed, to an average of 1.0%/min (F leads to E) and 0.68%/min (E leads to F); the F in equilibrium E set-point averaged 1.65, the same as in euthyroid subjects. Displacement of the F in equilibrium E equilibrium towards cortisone in hyperthyroid subjects appears to account for their elevated urinary THE/THF ratios, but the normal F in equilibrium E set-point in hypothyroid subjects makes it necessary to invoke a different mechanism for their depressed THE/THF ratio; it is suggested that increased conversion of THE to cortoic acids may be the responsible factor.

Adult↗
PubMed1983

Determination of plasma dexamethasone in the mother and the newborn after administration of the hormone in a clinical trial.

A RIA method is described for the measurement of dexamethasone in maternal, cord, and neonate plasma in a collaborative multicenter clinical trial to evaluate the efficacy of antenatal steroid therapy in the prevention of respiratory distress syndrome. The antiserum raised against dexamethasone-3-carboxymethyloxime-BSA conjugate was highly specific in that the endogenous steroids and 11-dehydrodexamethasone, a metabolite of dexamethasone, had a cross-reaction of less than 2.0%. Both pregnancy and cord plasma had to be purified by either gel filtration and/or paper chromatography. The overall recoveries of dexamethasone were 75.3 +/- 6.7% and 48.9 +/-6.7% for maternal and cord plasma samples, respectively. The intra- and interassay coefficients of variance for maternal plasma were 8.4% ad 9.1%, respectively, and for cord plasma were 11.9% and 10.9%, respectively. There was a good correlation between the dexamethasone values obtained by RIA when compared with those obtained by performance liquid chromatography in some cord plasma specimens. The recoveries of added dexamethasone and its metabolite by high performance liquid chromatography were also found to be good. The average maternal plasma dexamethasone level was 37 ng/ml 2 h after im injections of 5 mg dexamethasone phosphate every 12 h. The half-life of dexamethasone measured after the discontinuation of the drug was 216 min. Dexamethasone appeared too be cleared very rapidly from the circulation of the fetus and neonate. Because 11-dehydrodexamethasone was not present in significant amounts in the neonate, it was concluded that other factors in addition to the conversion of dexamethasone to its 11 dehydro metabolite were responsible for the rapid clearance of dexamethasone from fetal and neonatal circulation.

Antibody Specificity↗
PubMed1983

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↗
PubMed1983

Abnormal estrogen conjugation in women at risk for familial breast cancer at the periovulatory stage of the menstrual cycle.

The present study was designed to establish whether women with a family history of breast cancer exhibit endocrine abnormalities which could be responsible for their increased risk for the disease. Plasma hormone levels were measured every second day throughout the menstrual cycle in 30 women at risk for familial breast cancer and in an equal number of matched controls. Thirteen of the 14 substances measured exhibited no differences between the two populations, but plasma androsterone sulfate was significantly lower in the high-risk subjects. Thirteen urinary hormones were measured every day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in the periovulatory period of the cycle. These results suggest that the genetic risk for breast cancer is associated with an abnormality in estrogen conjugation at a specific time of the ovulatory cycle.

Androgens↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1982

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↗
PubMed1981

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↗
PubMed1981

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↗
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

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↗