Cerebrospinal fluid leptin in anorexia nervosa: correlation with nutritional status and potential role in resistance to weight gain.

Studies in rodents have shown that leptin acts in the central nervous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects included 11 female patients with anorexia nervosa studied at low weight and after treatment, and 15 healthy female controls.

Leptin concentrations in the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is characterized by menstrual disturbances, chronic anovulation and hyperandrogenism and is associated with insulin resistance and hyperinsulinemia. Leptin, the product of the ob gene, is an adipocyte-secreted molecule that signals the magnitude of energy stores to the brain and has been recently shown to have important effects on the reproductive axis of rodents. To assess the potential contribution of leptin to the pathogenesis of PCOS, we measured leptin levels in 24 obese women with PCOS and 12 weight- and age-matched controls and determined whether alterations in hyperinsulinemia produced by administration of the insulin-sensitizing agent troglitazone had an effect on serum leptin levels.

Human leptin levels are pulsatile and inversely related to pituitary-adrenal function.

Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty.

Leptin, the product of the ob gene, is an adipocyte-derived hormone that signals the amount of adipose tissue energy stores to the brain and exerts major effects on energy homeostasis and neuroendocrine function. Leptin has recently been shown to affect reproductive function in leptin-deficient and normal rodents. As puberty, the process of sexual maturation and acquisition of reproductive competence, has been proposed to be triggered by the attainment of a critical amount and/or distribution of fat, we examined whether changes in circulating leptin levels could represent the hormonal signal responsible for triggering the onset of puberty in humans.

Intractable hypercalcaemia due to parathyroid hormone-related peptide secretion by a carcinoid tumour.

Hypercalcaemia, a common complication of malignancy, may result from either the lytic effect of multiple osseous metastases or the effect of tumour-derived humoral factors. Excessive secretion of parathyroid hormone-related peptide (PTHrP), a major cause of humoral hypercalcaemia of malignancy, has been incriminated as the cause of hypercalcaemia in patients with lung, breast, renal, head and neck and, occasionally, haematological malignancies. Carcinoid tumours, while frequently the source of ectopic hormone secretion, are infrequently associated with hypercalcaemia.

Short-term hyperthyroidism has no effect on leptin levels in man.

Leptin, a 16-kDa adipocyte-derived protein whose circulating levels reflect energy stores, increases the resting metabolic rate and thermogenesis in rodents. Thyroid hormones also increase the basal metabolic rate, but nothing is known about possible interactions between leptin and thyroid hormone. Activation of beta-adrenergic receptors decreases leptin levels in rodents.

Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia.

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre.

Adult height and menarcheal age of young women in Greece.

Several factors contribute to the attainment of adult height, including genetic and environmental variables. To assess the relationship between menarcheal age and adult height, measured height was regressed on recalled menarcheal age in 286 young women, 18-24 years old, candidates for recruitment in the Greek army. Height was significantly associated with menarcheal age (b = 0.

Evidence for leptin binding to proteins in serum of rodents and humans: modulation with obesity.

Many hormones circulate bound to serum proteins that modulate ligand bioactivity and bioavailability. To understand the biology of leptin action, we investigated the presence of leptin binding proteins in serum. 125I-labeled leptin binds competitively to at least three serum macromolecules with molecular masses of approximately 85, approximately 176, and approximately 240 kDa in rodents and approximately 176 and approximately 240 kDa in humans.

Dehydroepiandrosterone sulfate and testosterone are independently associated with body fat distribution in premenopausal women.

To evaluate the relative importance of androgen and insulin concentrations in predicting body fat distribution, we measured their association with waist-hip ratio in a sample of 151 consecutively enrolled healthy premenopausal women age 18-24 years, after controlling for potential confounding variables. Dehydroepiandrosterone sulfate (DHEAS) and total testosterone were independently associated with waist-hip ratio, whereas insulin and free testosterone did not appear to play a role of comparable importance. Differences in concentrations of circulating DHEAS and total testosterone are independently associated with the waist-hip ratio in premenopausal women, providing epidemiologic support to the "neuroendocrine dysregulation" hypothesis for the pathogenesis of central obesity.

Role of leptin in the neuroendocrine response to fasting.

A total deficiency in or resistance to the protein leptin causes severe obesity. As leptin levels rise with increasing adiposity in rodents and man, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance. Starvation is also a threat to homeostasis that triggers adaptive responses, but whether leptin plays a role in the physiology of starvation is unknown.

Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice.

To examine potential interactions between leptin and the beta3 adrenergic system in the regulation of food intake, we determined the effects of treatment with a selective beta3 adrenergic receptor (AR) agonist (CL 316,243 [1 mg/kg]) on body weight, food intake, and leptin expression. Studies were carried out in C57Bl/6J and FVB male control mice as well as in mice with targeted disruption of the beta3 AR gene. These findings were correlated with measurement of the expression in hypothalamus of neuropeptide Y (NPY) and melanin concentrating hormone (MCH), two neuropeptides that may be involved in the central regulation of food intake.

Zinc status and serum testosterone levels of healthy adults.

Zinc deficiency is prevalent throughout the world, including the USA. Severe and moderate deficiency of zinc is associated with hypogonadism in men. However, the effect of marginal zinc deficiency on serum testosterone concentration is not known.

Conicity index as a predictor of blood pressure levels, insulin and triglyceride concentrations of healthy premenopausal women.

Conicity index (C index), an index of abdominal obesity that was developed based on a model of geometric reasoning, proved to be a sensitive and better than the waist to hip ratio indicator of risk for hyperlipidemia in Western populations. To evaluate comparatively the C index and the Waist-to-Hip Ratio (WHR) as predictors of blood pressure levels, insulin and triglyceride concentrations, we performed a cross-sectional study on 280 healthy women, 18-24 year-old. C index was found to be within the expected range (0.

Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer.

Serum concentrations of estrone, androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured postoperatively in 122 postmenopausal women with incident breast cancer and 122 age-matched population controls. After mutual adjustment, through conditional logistic regression, between the hormonal variables and body mass index (BMI), the odds ratios for increasing control-defined quartiles of estrone and androstenedione, respectively, were 1.00, 1.

Outcome of percutaneous transluminal coronary angioplasty in patients with subclinical hypothyroidism.

To determine the outcomes of percutaneous transluminal angioplasty (PTCA) in patients with subclinical hypothyroidism and to compare them with those in euthyroid patients, we studied retrospectively 48 hypothyroid (4 overtly and 44 subclinically hypothyroid) and 122 euthyroid patients who had a PTCA in Boston's Beth Israel Hospital between 1984 and 1994. No significant differences were detected in bradycardia (relative risk, RR: 0.96), tachyarrhythmia (RR: 0.

Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance.

A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration.

Body mass and physical activity are important predictors of serum androgen concentrations in young healthy men.

The relative importance of body mass index (BMI), demographic, and life-style factors in predicting androgen and sex hormone-binding globulin (SHBG) concentrations of young healthy men has not been clearly established. We evaluated the role of age, BMI, height, habitual physical activity, education, smoking, coffee and alcohol intake as predictors of serum testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG concentrations in 100 healthy men 18-22 years old. BMI was the only independent predictor of dihydrotestosterone and dehydroepiandrosterone sulfate, and both BMI and physical activity were independent predictors of serum testosterone concentrations, whereas other variables did not appear to play a role of comparable importance.

Genetic variability in the TNF-alpha promoter is not associated with type II diabetes mellitus (NIDDM).

Recent evidence suggests that expression of tumor necrosis factor-alpha (TNF-alpha) by adipocytes is a molecular mediator of insulin resistance in obesity. We have therefore tested the hypothesis that variations within the regulatory region of the TNF-alpha gene, which might cause increased adipocyte or generalized TNF-alpha synthesis, are associated with NIDDM, a state in which insulin resistance is routinely observed. Neither the previously known variants within the TNF-alpha promoter at position -308 and -238, nor two newly identified polymorphisms at position -376 and -163, were found at a significantly higher frequency in Caucasian NIDDM patients compared to non-diabetic controls.

Relative androgenicity, blood pressure levels, and cardiovascular risk factors in young healthy women.

To test the hypothesis that androgens may play a role in the pathogenesis of atherosclerosis and hypertension, we investigated the association of delta 5 dehydroepiandrosterone sulfate [DHEAS]) and delta 4 (free testosterone [FT]) androgens with the resting, seated blood pressure (BP) levels and cardiovascular risk factors in 280 young, healthy women 18 to 24 years of age. After application of multiple regression analysis, systolic BP was positively and independently correlated with the ratio of dehydroepiandrosterone sulfate to free testosterone (DHEAS/FT), fasting insulin levels, and the diastolic BP with DHEAS/FT only. The DHEAS/FT ratio proved to be a stronger predictor of the BP levels than either hormone alone.

Insulin resistance in a patient with ovarian stromal hyperthecosis and the hyperandrogenism, insulin resistance and acanthosis nigricans syndrome. Report of a case with a possible endogenous ovarian factor.

Insulin resistance is a common feature of ovarian stromal hyperthecosis and is usually accompanied by hyperandrogenemia. A patient had ovarian stromal hyperthecosis, and her hyperandrogenemia resolved, possibly due to the development of a type of ovarian fibrosis similar to so-called ovarian fibromatosis, without a concomitant improvement in her insulin resistance. The insulin resistance improved markedly, however, after bilateral oophorectomy.

Imaging of the sella in the syndrome of inappropriate secretion of antidiuretic hormone.

Objective: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results either from ectopic production or inappropriate release of antidiuretic hormone from the neurohypophysis. Although magnetic resonance imaging (MRI) has provided new insights into the morphological changes of the hypophysis in health and disease, no previous studies have evaluated its use in SIADH: The aim of this study was to evaluate the MRI appearance of the neurohypophysis in patients with SIADH:

Design: Retrospective case-control study.

Setting: Tertiary care teaching hospital.