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

This prospective study defines the clinical and biochemical features of acromegaly in a large cohort of patients. There was no difference in sex distribution, and for men and women the mean ages at diagnosis (40 +/- 12 and 40 +/- 14 yr, respectively) were similar. Nearly three-quarters of patients were overweight and some 12% severely overweight; the frequency and severity of obesity also was not different between the sexes. Half of patients were hypertensive or were taking anti-hypertensive drugs. Neither GH nor insulin levels were significantly different between normotensive and hypertensive patients. Acral growth and facial coarsening, soft tissue swelling, and excessive perspiration were present in the majority (98%) of patients. Mean serum GH, Sm-C, and PRL levels did not differ between the sexes. Sm-C levels correlated with mean GH concentration (r = 0.31, p < 0.001), both variables inversely related to age. With each decade of life, mean GH and Sm-C levels declined by 7.6 +/- 0.2 ng/mL and 0.5 +/- 0.2 U/mL, respectively. Impaired glucose tolerance was diagnosed in 36% and frank diabetes mellitus in 30% of patients. Hyperprolactinemia was noted in 18% of patients. Galactorrhea was noted in 43 (9%) patients, most of whom were female; the mean GH levels of patients with galactorrhea (60.1 +/- 13 ng/mL) were higher than those of patients without (35.4 +/- 2.6 ng/mL, p = 0.02). Acromegaly appears to afflict men and women equally with a preponderance of presentation in the fourth decade of life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acromegaly. Clinical and biochemical features in 500 patients. 793 7

The detection of clinical hyperandrogenism in women presenting with infertility requires detailed hormonal investigations using the decisional plan suggested here. Initial studies including measurement of plasma androgen, gonadotrophic hormones and prolactin levels, may be sufficient to reveal an adrenal origin or pure ovarian origin. Non-tumor androgenic hypercorticism is seen classically in late-presenting enzyme deficits, but also in other situations: excessive adrenarche, hyperprolactinemia, obesity, chronic stress. The immediate Synacthene test can then eliminate diagnostic uncertainties if it leads to the discovery of appearances of 21- or 11-hydroxylase or 3 beta-ol dehydrogenase blocks. Intense virilisation in a woman with a testosterone level above 2 ng/ml (7 nM/l) should lead to suspicion of an androgen-secreting tumor of the ovary or adrenal. CT scan of the abdomen and true pelvis is essential here since it may reveal the presence of an adrenal or ovarian mass. If no morphological abnormality is shown by this investigation, an endocrine lesion of a small ovary should be strongly suspected, the demonstration of which requires isotope techniques and/or catheterisation of the ovarian veins. Two situations also exist which are responsible for severe hyperandrogenism but less alarming in terms of their course and significance: certain homozygous forms of 21-hydroxylase deficit diagnosed late and ovarian hyperthecosis. It may happen that these hormonal investigations do not suffice alone to determine the precise origin of hyperandrogenism and its cause. The dexamethasone adrenal suppression test is useful in the diagnosis of type II micropolycystic dystrophy, in order to define the essentially ovarian, adrenal or mixed origin of hyperandrogenism.
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PMID:[Diagnostic strategy in infertility due to hyperandrogenism. Development of a decision tree]. 803 86

Previous reports have shown that long-term administration of typical and atypical neuroleptics induced obesity in female but not in male rats. It has been suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is necessary to observe the body weight changes. This hypothesis was tested with clozapine, an atypical neuroleptic that produces in rats a shorter increase in serum prolactin levels than do other neuroleptics. The effects of clozapine on body weight and food intake were assessed in female and male rats under treatment with any of the following doses: 0.5, 1, 2.5, 5, 10, and 20 mg/kg IP for 21 days. Vaginal cycle under clozapine treatment, as an indirect indicator of ovarian steroidogenesis, was also assessed. Obesity was not observed in any group. By contrast, clozapine at the doses of 10 and 20 mg/kg significantly decreased body weight and feeding in male rats. Clozapine at the doses of 5 and 10 mg/kg IP induced permanent diestrus. The failure of clozapine to induce obesity in female rats, despite impaired vaginal cycle, can be considered indirect evidence that drug-induced hyperprolactinemia is not sufficient to observe neuroleptic-induced obesity in rats.
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PMID:Effects of long-term administration of clozapine on body weight and food intake in rats. 851 72

The authors report the hormonologic characteristics of 20 obese and hirsute women meeting the criteria for adrenaltype hyperandrogenism, suppressible by dexamethasone, without hyperprolactinemia and without any late developing partial enzyme block appearance. The laboratory profile of these women differed from that of a group of women with type 1 polycystic ovaries syndrome. In this same group obese women in whom LH/FSH ratio was below 1, there was evidence under baseline conditions of a moderate increase in testosterone and delta 4-androstenedione in relation to increased plasma levels of DHA and SDHA, plasma delta 4 and delta 5-androgen levels falling precipitalely during the dexamethasone suppression test. The ACTH stimulation test revealed greater reactivity for 17 hydroxy-pregnenolone (p < 0.001) and less for 21-deoxycortisol than in the control group of normal women (p < 0.01). The essentially adrenal origin of plasma hyperandrogenism in certain cases of obesity is discussed. Insulin could increase adrenal sensitivity to ACTH and its possible action in vivo on the activity of adrenal enzymes requires clarification. The accumulation of certain androgens in the adrenal cortex could also be responsible for dysregulation of 3 beta ol-dehydrogenase and 11-hydroxylase.
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PMID:[Critical study of the characterization of hyperandrogenism in a group of obese women]. 853 5

In hyperprolactinemic patients an exaggerated glucose-induced insulin secretion has been reported, but these results have not been confirmed by other researchers. On the other hand, there are few data concerning somatotrope secretion in this condition. In order to clarify these points, in seven normal weight hyperprolactinemic female patients (HP: age 18-46 years, body mass index = 21.8 +/- 0.6 kg/m(2), basal prolactin = 91.7 +/- 16.5 micrograms/l) we studied the effects of glucose load (100 g orally) and/or arginine (0.5 g/kg infused over 30 min) on insulin glucose and growth hormone (GH) levels. These results were compared with those obtained in seven patients with simple obesity (OB: age 23-48 years, body mass index = 38.3 +/- 2.6 kg/m(2)) in whom exaggerated insulin and low GH secretion are well known. Seven normal women (NS: age 26-32 years, body mass index = 20.6 +/- 1/9 kg/m(2)) were studied as controls. The insulin response to glucose in HP (area under curve = 11,460.8 +/- 1407.5 mU x min x l(-1)) was not significantly different from NS (7743.7 +/- 882.9 mU x min x l(-1)) and OB (14,504.8 +/- 1659.9 mU x min x l(-1)). The arginine-induced insulin release in HP and OB was similar (4219.4 +/- 631.7 and 4107.3 +/- 643.2 mU x min x l(-1), respectively), both being higher (p < 0.02) than in NS (2178.1 +/- 290.9 mU x min x l(-1). Glucose and arginine had an additive effect on insulin release in HP and NS (19,769.1 +/- 3249.6 and 10,996.6 +/- 1201.0 mU x min 1(-1), respectively) and a synergistic effect in OB (28 117.3 +/- 5224.7 mU x min x l(-1)). In HP the insulin response to the combined administration of glucose and arginine was not significantly different from the one in OB, and both were higher (p < 0.05) than in NS. The increase in glucose levels after glucose administered on its own or combined with arginine was higher (p < 0.02) and longer lasting in OB than in NS and HP. After arginine in OB, the glucose levels did not show the late decrease under baseline values observed in HP and NS. Glucose inhibited GH secretion both in HP and NS (p < 0.05), while arginine stimulated it in all groups, although the GH response in HP and NS was higher (p < 0.03) than in OB. The arginine-induced GH secretion was inhibited by glucose in HP and NS but not in OB. These results demonstrate that both in hyperprolactinemic patients and in obesity there is a clear increase in insulin secretion. The insulin hyperresponsiveness in hyperprolactinemia is more clearly demonstrated by combined stimulation with glucose and arginine. In spite of similar insulin hypersecretion in hyperprolactinemic and obese patients, GH secretion is reduced only in the latter; with these data the hypothesis that somatotrope insufficiency in obesity is due to hyperinsulinism is unlikely.
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PMID:Effects of glucose load and/or arginine on insulin and growth hormone secretion in hyperprolactinemia and obesity. 881 Jul 34

The efficacy of the antiviral agent Amantadine (AM, 5-100 mg/kg/sc, ip or intrahypothalamically, 12.5-100 micrograms bilaterally) in influencing body weight and food intake in drug-free rats, and in preventing neuroleptic-induced weight gain, was assessed in adult female rats. In drug-free rats, acute administration of systemic AM or directly injected in the lateral hypothalamus (LH) displayed a significant dose-dependent anorectic effect (p < 0.001). This effect could be mediated by the brain monoaminergic system, because systemic or local injections of AM increased dopamine and serotonin overflow in the nucleus accumbens and in the LH. Chronic administration of AM significantly decreased body weight gain in drug-free rats only at the dose of 100 mg/kg/sc. Similarly, obesity induced by the neuroleptic drug sulpiride (SUL, 20 mg/kg/ip for 21 days) was prevented by AM only at the dose of 100 mg/kg. AM did not prevent SUL-induced hyperprolactinemia, disruption of the vaginal cycle and a decrement in the weight of the uterus and ovaries at any dosage. This lack of efficacy of AM contrasts with that of bromocriptine, which completely prevented SUL-induced weight gain and hyperprolactinemia. The results show that despite a potent acute anorectic effect, AM displays a weak antagonistic action on SUL-induced obesity in rats, in contrast to the preliminary results obtained in humans. As AM metabolism differs in humans and rats, additional research is needed before its systematic testing in counteracting neuroleptic-induced obesity in patients with mental disorders.
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PMID:Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates. 913 24

To evaluate its potential utility in counteracting neuroleptic-induced obesity, the effects of long-term administration of tamoxifen (TAM) on body weight (BW) and food intake (FI) of gonadally intact and sulpiride-treated (SUL) female rats were assessed. In addition, estradiol and prolactin serum levels were measured in rats treated with SUL. SUL plus TAM and SUL plus bromocriptine (BR). TAM, at doses of 10, 50 and 100 micrograms, significantly decreased BW gain: FI was significantly reduced at the doses of 50 and 100 micrograms. In addition, doses of TAM ranging from 5-100 micrograms completely prevented SUL-induced BW gain and hyperphagia. BR also prevented SUL effects on BW and FI. In contrast to BR, concomitant administration of TAM did not prevent SUL-induced hyperprolactinemia. Estradiol levels were not modified by SUL alone or SUL plus BR, but they were significantly increased in the animals treated with TAM plus SUL. Neuroleptic-induced obesity in female rats might be related to an alteration in gonadal steroid balance secondary to hyperprolactinemia. While BR might counteract neuroleptic-induced weight gain by preventing hyperprolactinemia, TAM might directly interact with estrogen receptors, or indirectly increase estradiol levels. The use of TAM in preventing neuroleptic-induced obesity in humans warrants further investigation.
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PMID:Tamoxifen prevents sulpiride-induced weight gain in female rats. 916 75

The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non-insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of androgens, particularly T. A fundamental mechanism of ovarian hyperandrogenism in PCOS is LH hypersecretion. Whether the central nervous system is a possible locus for initiating LH hypersecretion remains unclear, because exaggerated LH secretion is temporarily reversed by induced ovulatory cycles or physiologic luteal concentrations of progesterone. On the other hand, desynchronization of pulsatile LH secretion from sleep in girls with PCOS and an exaggerated (e.g., masculinized) early LH response to GnRHa testing in women with hyperandrogenic anovulation and congenital adrenal virilizing disorders suggest that events occurring before puberty, perhaps during fetal life, may irreversibly alter neuroendocrine function. Hyperinsulinemia from insulin resistance is an important regulatory mechanism governing ovarian hyperandrogenism. Hyperinsulinemia in hyperandrogenic anovulatory women potentiates ovarian hyperandrogenism by enhancing LH secretion; potentiating 17-hydroxylase and, to a lesser extent, 17,20-lyase activity; and suppressing SHBG capacity. It is a key component of hyperandrogenic anovulation caused by a type of insulin resistance that in independent and additive to that of obesity alone. Although the mechanisms governing insulin action on ovarian steroidogenesis are unknown, abnormalities of intracellular insulin signaling or cytochrome P450c 17[alpha] activity may render the 17-hydroxylase/17,20-lyase enzyme complex more sensitive to insulin. Hyperinsulinemia in hyperandrogenic anovulatory women is accompanied by upper-body obesity characterized by an increased amount of abdominal fat. Upper-body obesity is an important independent risk factor for CVD and diabetes. Although genetic and environmental factors affect fat distribution, sex steroids, particularly androgens, regulate lipid metabolism, suggesting yet another link between the hormonal and metabolic abnormalities of hyperandrogenic anovulation. A careful history and physical examination guide the extent of diagnostic testing. Slowly progressive hirsutism with anovulation of peripubertal onset usually reflects hyperandrogenic anovulation. This type of clinical presentation requires an evaluation to rule out other endocrinopathies (e.g., virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome). Virilization or severe rapidly progressive hirsutism requires immediate investigation to rule out a possible virilizing tumor. The ultimate goals of therapy for hyperandrogenic anovulatory women are to normalize the endometrium, antagonize androgen action at target tissues, reduce insulin resistance, and correct anovulation, if necessary.
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PMID:Polycystic ovary syndrome. 942 64

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, particularly hypogonadism, may be involved in the excessive body weight gain observed during treatment with antipsychotic drugs. The present study was conducted in healthy men in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. Sulpiride (200 mg daily for 30 days) or placebo was nonblindly administered, and body weight gain was correlated with the serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, free testosterone, thyrotropic hormone, free tetraiodothyroxine, cortisol, dehydroepiandrosterone sulphate (DHEA-S), and the ratios estradiol/testosterone and testosterone/DHEA-S; the blood lipids were also assessed. Body weight gain and the serum levels of prolactin were significantly increased by sulpiride; in addition, a significant positive correlation was observed between prolactin levels and body weight gain. Other endocrine parameters were not significantly affected by the drug. These short-term results show that in healthy men, body weight can be increased by antipsychotic drug administration; this effect may be related to hyperprolactinemia alone, since other endocrine parameters were normal at the time of treatment. A more prolonged treatment with antipsychotic agents might be required to observe the alterations in gonadal and adrenal steroids often detected in subjects with primary obesity.
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PMID:Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy men: relationship with body weight regulation. 944 47

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, such as hypogonadism and hyperandrogenicity, may be involved in the excessive body weight gain induced by antipsychotic drugs in women. The present study was conducted in healthy premenopausal women, in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. After a control menstrual cycle, sulpiride (200 mg/day) or placebo was nonblindly administered for 28 days; blood lipids and the serum levels of the following hormones which are involved in body weight regulation were assessed at days 3, 10, 20 and 26 of the cycle: prolactin (PRL), 17-beta estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), cortisol, tyrotropic hormone (TSH), tetraiodothyroxine (T4), and the areas under the insulin and glucose tolerance curve. During sulpiride administration, the following changes were observed when compared to placebo administration: PRL levels were significantly increased; E2 levels were significantly reduced at days 10 and 20; P4 levels were significantly reduced at day 20, and the area under the glucose tolerance curve was significantly increased. The other variables were not significantly affected. The body weight gain was higher during sulpiride than during placebo administration, but it did not reach statistical significance, perhaps because the period of treatment was too short. The decrease in the serum levels of E2 during sulpiride administration is probably secondary to hyperprolactinemia. It affects the E2/T5 ratio in the direction of increasing the androgenic activity, as observed in women with well-established obesity. This effect, along with a genetic predisposition, increased appetite, hypoactivity and ignorance of proper dietary habits, may explain the excessive weight gain and obesity observed in women during chronic treatment with sulpiride and other antipsychotic agents.
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PMID:Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy premenopausal women: relationship with body weight regulation. 944 48


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