Barnett Zumoff

Impact of endocrine and diabetes team consultation on hospital length of stay for patients with diabetes

PURPOSEnTo determine whether consultation by an individual endocrinologist or by a multidisciplinary diabetes team (endocrinologist, diabetes nurse educator, and registered dietitian) can impact length of hospital stay of patients with diabetes.nnnPATIENTS AND METHODSnHospital stays of consecutive patients with a principal diagnosis of diabetes were compared. Forty-three patients were seen by an individual endocrine consultant and 27 were managed by the internist alone. Thirty-four patients were seen in consultation by the diabetes team. All consultations were performed at the request of the primary physician. There were no statistically significant differences among groups with respect to age, duration of diabetes, admitting diagnosis, glucose levels, or concomitant acute or chronic illness.nnnRESULTSnAverage length of stay of diabetes-team patients was 3.6 +/- 1.7 days, 56% shorter than the value, 8.2 +/- 6.2 days, of patients in the no-consultation group (P < 0.0001), and 35% shorter than the value, 5.5 +/- 3.4 days, of patients who received a traditional individual endocrine consultation (P < 0.05). The length of stay correlated with time from admission to consultation (regression equation: y = 3.92 + [1.09 x time to consultation]; r = .55; P < 0.0001). The slope (1.09) indicates that each 1-day delay in consultation resulted in a 1-day increase in length of stay.nnnCONCLUSIONSnLength of stay was lowest in patients who received diabetes-team consultation. Three million Americans are hospitalized annually with diabetes at a cost of

Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone

65 billion. A team approach to their inpatient care may reduce their hospital stays, resulting in considerable health and economic benefits.

Does Postmenopausal Estrogen Administration Increase the Risk of Breast Cancer? Contributions of Animal, Biochemical, and Clinical Investigative Studies to a Resolution of the Controversy:

Studies from this laboratory have shown that obese men have elevated serum estrogen levels and diminished levels of follicle-stimulating hormone (FSH) and free and total testosterone, all in proportion to their degree of obesity. The decreases in testosterone and FSH constitute a state of hypogonadotropic hypogonadism (HHG), and we have hypothesized that it results from feedback suppression of the pituitary by the elevated estrogen levels. We tested this hypothesis by lowering the serum estrogens of 6 health obese men (body mass index [BMI], 38 to 73) by administering the aromatase inhibitor testolactone (1 g daily for 6 weeks). Twenty-four-hour mean serum testosterone rose in every subject, from a mean of 290 +/- 165 ng/dL to a mean of 403 +/- 170 (P <.0003); 24-hour mean serum estradiol decreased in every subject, from a mean of 40 +/- 10.8 pg/mL to a mean of 29 +/- 6.7 (P <.004); and 24-hour mean serum luteinizing hormone (LH) increased in every subject, from a mean of 14.3 +/- 4.1 mIU/mL to a mean of 19.3 +/- 5.1 (P <.004). The rise in mean LH was due to an increase in the amplitude of the individual secretory pulses, especially at night. Twenty-four-hour mean serum estrone decreased nonsignificantly, from 48 +/- 14 pg/mL to 39 +/- 6.4, and 24-hour mean serum FSH increased nonsignificantly, from 13.5 +/- 5.3 mIU/mL to 15.0 +/- 5.4. The results are in accordance with the hypothesis, in that inhibition of estrogen biosynthesis (through administration of the aromatase inhibitor testolactone) results in alleviation of the HHG of our obese male subjects.

Relationships of sex hormone levels to dependence in activities of daily living in the frail elderly

Abstract Despite nearly six decades of epidemiological studies, meta-analyses, and reviews, there is still considerable controversy in the literature about the question, does postmenopausal estrogen administration increase the risk of breast cancer? In an effort to resolve the controversy, a number of animal, biochemical, and clinical investigative studies in this field have been reviewed. The following summary formulation is proposed: 1. Administration of estrogen is inherently capable of promoting the growth of breast cancer, and therefore of increasing the incidence of clinical breast cancer. 2. Human response to estrogen is like that of the low-cancer-incidence strains of mice studied by Lacassagne, in that large doses and prolonged administration are required to induce clinical breast cancer. 3. The blood levels of estradiol produced by the usual doses of postmenopausal estrogen are relatively low, equivalent to those of the follicular phase of the menstrual cycle. These levels may be near the threshold for producing breast-cancer-promoting effects; therefore, the tumor response will vary greatly in different populations, depending on genetic susceptibility factors: a. The prevalence of a family history of premenopausal breast cancer in a first-degree relative. b. The prevalence of abnormal BRCA1, BRCA2, and p53 genes. c. The prevalence of increased 16 α-hydroxylation of estradiol. d. The prevalence of smokers who are slow acetylators. 4. Consumption of alcohol (5 grams or more daily) along with the postmenopausal estrogen administration results in elevation of blood estradiol levels to values equivalent to those of the periovulatory peak of the menstrual cycle, which may be well above the threshold for producing breast-cancer-promoting effects in all women. The risk for cancer will therefore be uniformly increased in women who use alcohol and take estrogen. 5. Increased risk of breast cancer from postmenopausal estrogen administration can be eliminated by taking two synergistic steps: a. Eliminating alcohol consumption, or at least keeping it well below an average of 5 grams daily (equivalent to 2/3 ounce of whiskey or 3 ounces of wine). b. Diminishing the capacity to 16 α-hydroxylate estradiol, either through pharmacological agents such as indole-3-carbinol or through increased consumption of cruciferous vegetables.

Differential binding of dexamethasone to ammonium sulfate precipitates of human adipose tissue cytosols

OBJECTIVESnWe undertook this nursing home study in order to determine the relationships between dependency in activities of daily living (ADL) and blood levels of estrone, testosterone, androstenedione, and dehydroepiandrosterone (DHEA). Little is known about this issue.nnnMETHODSncross-sectional study of 370 nursing home residents. Hormone levels in blood specimens drawn in 1997 and 1998 were correlated with degree of ADL dependency recorded in medical charts.nnnRESULTSnBecause of multiple comparisons associations were deemed significant for P-values < or =0.017 for males and < or =0.0125 for females. In males, the following were inversely related: testosterone levels with dependency in transferring and eating; estrone with eating and a summary ADL index; and androstenedione with toileting and a summary ADL index (in all cases, r=-0.4; P=0.007-0.015). Inverse trends existed between testosterone levels and dependency in mobility and a summary ADL index; and androstenedione and eating (in all cases r=-0.3; P=0.030-0.055). Among females the following were directly related: estrone levels with dependence in mobility, toileting, transferring, and a summary ADL index; and DHEA with transferring and a summary ADL index (r=0.2-0.3, P=0.0001-0.01). Trends existed between estrone and eating, and DHEA and toileting (r=0.1-0.2, P=0.04).nnnCONCLUSIONnIn male residents, higher sex hormone levels are associated with better ADL performance. Among females the opposite is true. While further studies are needed to elucidate these relationships, our results and recent findings of others suggest sex hormone actions in older women differ from those in younger populations. A possible stress-related mechanism is also presented.

Androgen binding to ammonium sulfate precipitates of human adipose tissue cytosols

Saturation analysis of the binding of [3H]dexamethasone [( 3H]DEX) to ammonium sulfate precipitates (ASPs) confirmed the presence of a limited-capacity, high-affinity binder in human adipose tissue cytosols. Various non-radioactive steroids competed with [3H]DEX for binding to the ASPs in the following sequence: dexamethasone (DEX) approximately equal to triamcinolone acetonide (TA) greater than progesterone (P) much greater than estradiol (E2). The steroid specificity of the binder precipitated by AS was consistent with the specificities reported for glucocorticoid receptors in a number of systems. In order to investigate possible regional differences, glucocorticoid binding to ASPs derived from adipose tissues removed from two different sites in the same subject was quantitated. ASPs of human omental adipose tissue bound significantly more [3H]DEX than did similar preparations of subcutaneous adipose tissue from the abdominal wall (116 +/- 32 vs. 50 +/- 22 fmol/mg protein; mean +/- SD; p less than 0.02). The findings are consistent with reports from other laboratories suggesting that intra-abdominal fat is more responsive to glucocorticoids than is subcutaneous adipose tissue.

Biological and endocrinological insights into the possible breast cancer risk from menopausal estrogen replacement therapy

Although androgens are believed to influence the distribution of human adipose tissue and have been detected in human fat, receptors for these sex hormones have yet to be identified. These studies demonstrate that a high-affinity, limited-capacity binding component for the synthetic androgen methyltrienolone (R1881) exists in ammonium sulfate precipitates of human adipose tissue cytosols. The equilibrium dissociation constant (Kd = 0.1 to 0.4 nmol/L, n = 6) and the number of binding sites (2 to 26 fmol/mg protein, n = 22) are consistent with those reported for androgen receptors in rat prostate, human prostatic carcinoma, MCF-7 cells, and baboon myocardium. The relative steroid-binding specificities of the human adipose tissue androphile (R1881 approximately 5 alpha-dihydrotestosterone greater than testosterone greater than estradiol approximately progesterone much greater than dexamethasone) are similar, but not identical, to those reported for androgen receptors in rat prostate (R1881 greater than 5 alpha-dihydrotestosterone approximately testosterone greater than estradiol greater than progesterone much greater than cortisol) and baboon myocardium (R1881 greater than 5 alpha-dihydrotestosterone greater than testosterone greater than progesterone greater than estradiol much greater than cortisol). The function of the androgen-binding component in human adipose tissue is not known.

Relationship of Endogenous Levels of Sex Hormones to Cognition and Depression in Frail, Elderly Women

The question of whether estrogen therapy increases the risk of breast cancer is reviewed. Despite more than 60 epidemiological studies and several meta-analyses over a five-decade period, there is no consensus about the answer. At present, the majority of investigators agree that short-term or medium-term therapy (less than 10 years) poses no measurable risk; some, but not all, investigators feel that there is a modest risk with long-term therapy (more than 15 years). Even this semi-consensus is clouded by the startling and clear-cut finding of the largest ever epidemiological study, the Nurses Surveillance Study, that a small increase in risk with estrogen therapy occurred only in women who also ingested alcohol, itself a known risk factor for breast cancer; women who did not ingest alcohol were at no increased risk. Because virtually none of the other epidemiological studies has controlled for alcohol ingestion, the conclusions of all of them are placed in doubt. To try to shed light on this problem, the 60-year-old studies of Lacassagne et al. on the induction of breast cancer in mice by estrogens were reviewed. They found that the magnitude and timing of the inducing effect of estrogen depended on the spontaneous breast cancer incidence in the mouse strain studied: in no-incidence strains, no cancer was induced; in high-incidence strains, induction was rapid and universal; in low-incidence strains, only a low percentage of animals had cancer induced, and it required prolonged estrogen administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Defensive maturity ratings and sustained weight loss in obesity

Neuropsychological evaluations and sex hormone assays for 188 elderly, female nursing home residents (mean age: 87.8 years; standard deviation: 7.0 years) revealed inverse relationships for dehydroepiandrosterone (DHEA) blood levels and cognition scores based on the Mini-Mental State Exam and the Test for Severe Impairment, as well as for scores of the Immediate Recall, Copy, and Recognition tests of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised (WMS-R; VR). A positive correlation between estrone and depression approached significance, as did the inverse relationships between the Recognition scores of the WMS-R; VR with androstenedione. These results and findings of others suggest that sex hormone actions in elderly women may differ from those in younger populations. A possible stress-related mechanism is also posited.

Norethandrolone produces temporary loss of the ability to escape from salt-retaining steroids

Abstract Twelve highly obese patients were studied to determine if “defensive maturity” ratings might correlate with sustained weight loss (SWL). Six patients with SWL averaging 24.2% had significantly (P