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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective, randomised case-control trial of an anorectic drug, fenfluramine was conducted on 30 patients of simple obesity. The study revealed that the drug was well tolerated, non-toxic and effective in reducing the body weight and normalising the thyroid profile. Reduction in body weight, rise in serum thyroxine (T4) and fall in serum triiodothyronine (T3) was highly significant (p less than 0.01) in drug treated group as compared to controls (p less than 0.05) after 12 weeks of therapy. There was also fall in serum thyroid stimulating hormone (TSH) levels but without any statistical significance.
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PMID:Effect of fenfluramine on serum T3, T4 and TSH levels in obesity. 151 14

In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 micrograms i.v.) was performed before and after administration of fenfluramine (FF) 60 mg b.d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FF, the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.
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PMID:Effect of fenfluramine on prolactin and thyroid-stimulating-hormone response to thyrotropin-releasing-hormone in obese and normal women. 212 37

Two cases of idiopathic hypothalamic dysfunction (one boy and one girl) are reported. Symptoms of hypothalamic dysfunction were noted by the age of 2 years: initial polyphagia and obesity with subsequent anorexia and emaciation were observed in one patient. Thermoregulation and thirst disorders, recurrent accesses of hypernatremia, acrocyanosis and profuse sweating were present. Impaired growth and delayed puberty in one case, and in the other hypogonadism, absence of growth hormone and gonadotrophins release in response to provocative stimuli were observed as well as abnormal thyroid stimulating hormone response to thyrotropin releasing hormone with hyperprolactinemia. Magnetic resonance imaging showed structural lesion in the lateral part of the lentiform nucleus in one case. Treatment with naltrexone, an opiate antagonist, had little if any effect.
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PMID:[Hypothalamic dysfunction. 2 cases: the contribution of nuclear magnetic resonance, therapeutic trial of naltrexone]. 266 35

Previous studies have indicated dysfunction of the hypothalamic-hypophyseal axis in obesity. We have studied 12 obese males to further characterize the extent of this dysfunction. The hypothalamic-hypophyseal-gonadal axis is normal as determined by the testicular response to human chorionic gonadotropin (hCG), the pituitary response to 200 micrograms gonadotropin-releasing hormone (GnRH), and the hypothalamic-pituitary-testicular response to clomiphene. Although L-dopa suppresses prolactin normally, the ability of thyrotropin releasing hormone (TRH) to stimulate the release of prolactin and thyroid stimulating hormone (TSH) is blunted. These latter responses are inversely related to the degree of obesity. The response to chlorpromazine, a hypothalamic stimulus for prolactin secretion, is also blunted, and to a greater extent than the prolactin response to TRH. These data indicate that exogenous obesity in males is associated with more extensive hypothalamic and pituitary dysfunction than previously realized. The abnormalities with regard to prolactin and TSH release become progressively worse when body weight exceeds 200 percent of ideal. In addition, when evaluating pituitary function with regard to gonadotropin release, obese males may have an abnormal response to 100 micrograms GnRH but respond normally to 200 micrograms.
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PMID:Hypothalamic and pituitary dysfunction in obese males. 680 59

Subnormal prolactin (PRL) and thyroid stimulating hormone (TSH) responses to thyrotropin releasing hormone (TRH) have been reported in massive obesity, while fasting and very-low-calorie diets have been shown to impair the reaction of PRL to TRH. The mechanism of these changes is poorly understood. We studied a group of moderately obese women on weight maintenance diets to determine whether PRL and TSH responses are reduced in moderate obesity, and repeated the TRH tests during treatment with a 320 kcal diet, with and without the addition of triiodothyronine (T3). Basal and maximal PRL levels after stimulation were not significantly different in the obese patients before dietary restriction from levels in non-obese controls. During the use of the diet the PRL response to TRH was significantly lower than the initial value (P less than 0.025) while basal PRL levels remained unchanged. The percentage reduction in PRL response showed a significant positive correlation with the percentage decrease in serum T3 (r = 0.80, P less than 0.05). Administration of 75 micrograms of T3 daily to the patients, however, was associated with a further significant decrease in the PRL response to TRH. Plasma oestradiol levels did not change with use of the diet. TSH response to TRH was normal in these patients and did not change with use of the diet alone. T3 treatment resulted in an almost complete suppression of the TSH response. In conclusion the reaction of prolactin to stimuli is normal in the moderately obese patient, but reduced during drastic caloric restriction. This decreased responsiveness is probably not due to changes in T3 or oestrogen levels.
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PMID:The effect of obesity and drastic caloric restriction on serum prolactin and thyroid stimulating hormone. 727 64

Examination of thyroxine usage in a study in the United States of America revealed that many patients were prescribed thyroxine for non-thyroid indications, such as obesity and fatigue. Many of those receiving thyroxine had high or low serum thyroid stimulating hormone levels, indicating prescription of incorrect doses or lack of patient compliance with therapy. Long term thyroxine therapy may have effects upon the risk of osteoporosis. The aims of this study were to investigate indications for thyroxine prescription in the United Kingdom and to examine the frequency of abnormal serum thyroid stimulating hormone concentrations in those prescribed thyroxine for hypothyroidism. This was in order to determine the relevance of measurement of thyroid stimulating hormone level in monitoring thyroxine therapy. Subjects receiving thyroxine were identified from the computerized prescribing records of four general practices in the West Midlands. Of 18,944 patients registered, 146 (0.8%) were being prescribed thyroxine; 134 of these had primary hypothyroidism and the remainder had other thyroid or pituitary diseases prior to treatment. Of the 97 patients with primary hypothyroidism who agreed to have their thyroid stimulating hormone level measured, abnormal serum levels were found in 48%, high levels in 27% and low levels in 21%. There was a significant relationship between prescribed thyroxine dose and median serum thyroid stimulating hormone level: high hormone levels were found in 47% of those prescribed less than 100 micrograms thyroxine per day, while low levels were found in 24% of those prescribed 100 micrograms or more. Thus, thyroxine prescription was common in the four practices sampled, although indications for its use were appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroxine prescription in the community: serum thyroid stimulating hormone level assays as an indicator of undertreatment or overtreatment. 812 26

Smoking exerts influences on the secretion of several hormones which are abnormal in obesity. Previous studies have mainly been performed in non-obese men, and data from non-obese and obese women are scarce. The aim of the present study was therefore to identify the effect of smoking on hormone secretions in obese and lean female smokers. The study was performed in 10 obese and 8 lean, premenopausal, healthy smokers. All subjects were tested once under experimental and once under control conditions (not smoking) in randomized order. The women smoked two non-filtered cigarettes during 4 minutes each. Blood pressure and heart rate were measured 30 minutes before smoking, at the start of smoking (time 0) and then after 5, 10, 20, 30, 45 and 60 minutes. Blood samples were taken for determination of serum concentrations of adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH) at the same time points except at 5 minutes. Heart rate rose in both groups during smoking. Systolic and diastolic blood pressure was increased only in the obese subjects. Cortisol and ACTH increased in both groups, while TSH, PRL and GH were unchanged in both groups. We conclude that lean and obese smoking women seem to respond rather similarly to smoking in the hemodynamic and endocrine variables measured in this report with the possible exception of blood pressure where the obese women tended to show more pronounced increases.
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PMID:Influence of smoking on hormone secretion in obese and lean female smokers. 882 56

The frequency of endocrine abnormalities during the follicular phase in non-pregnant women with a history of recurrent abortion was investigated in a case-control study. A total of 42 consecutive women with recurrent spontaneous abortion (three or more consecutive abortions, mean +/- SD: 3.9 +/- 1.1 range 3-8) with no parental chromosome rearrangement or uterine abnormality were studied during the early follicular phase under standardized conditions. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, androstenedione, testosterone, dehydroepiandro-stenedione, 17-OH-progesterone, oestradiol, progesterone and thyroid stimulating hormone (TSH) were measured by commercially available radioimmunoassays. Controls were 42 nulligravid females with tubal or male factor infertility without miscarriage. Mean (SD) concentrations of prolactin and androstenedione were 14.2 +/- 6.7 ng/ml versus 10.5 +/- 3.5 ng/ml (95% CI 0.8-6.1) and 2.3 +/- 0.9 ng/ml versus 1.7 +/- 0.6 ng/ml (95% CI 0.2-0.9) in the study and control groups respectively. The other endocrine parameters were comparable in both groups. Obesity [BMI weight (kg)/height (m2) > or = 25] was more prevalent (23 versus 5 women, P = 0.0001) in the study than the control group. Recurrent spontaneous abortion is associated with abnormalities in prolactin and androgen secretion during the follicular phase, suggesting an endocrine aetiology in this disorder. Reduction of body weight and correction of hyperprolactinaemia and of hyperandrogenism may reduce the rate of miscarriage in a subsequent pregnancy in these women.
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PMID:Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion. 1037 87

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.
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PMID:Endocrine and metabolic abnormalities involved in obesity associated with typical antipsychotic drug administration. 1177 42

In 1994, Zhang et al. of Rockefeller University in New York reported the first successful complementary DNA (cDNA) cloning of leptin by the positional cloning method. Leptin was identified as the gene of ob/ob mouse in genetic obesity syndromes. It has very strong food intake control, and body weight and energy expenditure. The name "leptin" derived from the Greek word leptos, meaning "thin." We hereby review major advances leading to our current finding of leptin, leptin receptor and its structure, the outline of homozygote, and also influence of leptin in the pituitary. (The structure of leptin) The mouse obese gene has been localized to chromosome 6. With human leptin gene on chromosome 7q31.3, its DNA has more than 15000 base pairs and consists of three exons and two introns. For bioactivation of leptin the importance of disulfide-binding site is suggested. Human leptin which replaced the 128-th arginine with glutamine has the function of an aldosteron antagonist, which is reported to have the function of athrocytosis inhibition. The resemblance of leptin precursor of human, mouse and rat is very high, i.e., mouse and rat homology is 96% and mouse and human homology is 83%. (The structure of leptin receptor) The mutant gene, which is the cause of obesity, was shown on map on diabetic mouse (db/db) chromosome 4, and it was proven to be the same as the leptin receptor gene cloned by Tartaglia et all. Further studies have found the Zucker fatty rat (fa/fa) to be incorporated into a linkage map of rat chromosome 5, whose region of rat is the equivalent to the region of conserved synteny of the db/db mouse gene. The leptin receptor is glycoprotein consisting of a single transmembrane-spanning component. The primary structure of leptin receptor belongs to the cytokine-class1 family, the single membrane-spanning receptor, and is highly related to the gp130 signal-transducing component of the interleukin-6 (IL-6) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the leukemia inhibitory factor (LIF) receptor. The leptin receptor is known to have at least six existing isoforms (Ob-Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and hyperphagia. These obesity models show a reproduction disorder with both the male and the female, and they develop with homozygote. The cause is thought to be the gonadotropin secretory abnormality in pituitary. Three family lines report the cases of this deficiency, and it is considered that the secretory abnormality in pituitary develops into hypogonadotropic. These patients show low value in plasma FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta which are produced from pituitary, and the plasma GnRH (gonadotropin releasing hormone) level is also low. Furthermore, the leptin receptor deficient family line was reported in 1998, in which case only the homozygote developed. The plasma leptin concentration of normal human is about 8.0 ng/ml, and this case with leptin receptor deficiency has high value of 500-700 ng/ml, which is the equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary-Periphery Function) The role of leptin which regulates pituitary hormones suggests the promotion the GHRH (growth hormone releasing hormone) secretion in hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular) infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion in the normal rats. On the other hand, topical treatment of GH3 (derived from a rat pituitary GH-secreting cell line) with leptin directly inhibits cell proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump body compared to the normal models, which shows signs of sufficient growth. (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents Pituitary) Aside from being the food intake inhibitor and the energy control factor, leptin takes part in controlling the pituitary hormones. Promoting the secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta, FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic hormone) are the major changes of pituitary hormones which are brought on by leptin. The expressive localization is specific, and immunohistochemistry (IHC) method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta positive cells. In our biochemical examination, the bulk of the expression of leptin is recognized in fraction of the secretory granule. In particular, FSHbeta cells had the highest percentage rate of colocalized leptin in rat pituitary. On the other hand, leptin receptor has been reported to be found only in normal rat pituitary, human pituitary adenoma, and respective cell lines in pituitaries by the RT-PCR method until now, but we disclosed for the first time the localization of leptin receptor on the plasma membrane of GH-secreting cells with the IHC method that has not been cleared so far. These findings show that leptin and leptin receptor have been expressed in different cells, and that the rat pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta cells) and leptin receptor (GH cells). The function of paracrine in this pituitary suggests a new point of view in hypothalamus-pituitary axis, and it shall be concerned with many aspects such as hormone secretions and proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin and leptin-receptor relationship with pituitary adenoma that has secretion abnormality has been filed, and its manifestation is being observed by the RT-PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought to function by autocrine and paracrine pathway in the adenomas. Leptin has been located in ACTH-secreting adenoma most frequently, especially in ACTH carcinoma. The leptin receptor is detected in all adenomas with high percentage rate, with both long and short forms, and then many cases of nonfunctioning pituitary adenomas, compared with other adenomas, have been reported to be positive with both long and short forms of leptin receptor as detected by RT-PCR. The HP75 cell line is derived from the nonfunctioning pituitary adenoma, which produces FSHbeta and LHbeta. The expression of leptin receptor in nonfunctioning pituitary adenoma, and the suppression of HP75 multiplication may lead to the possible hypothesis of leptin becoming one factor for the treatment of pituitary adenoma, especially in gonadotropin adenomas.
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PMID:Leptin and the pituitary. 1182 4


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