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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prader-Willi syndrome (PWS) is a well-defined syndrome of childhood-obesity which can serve as a model for investigating early onset childhood obesity. Many of the clinical features of PWS (e.g., hyperphagia, hypogonadotropic hypogonadism, growth hormone deficiency) are hypothesized to be due to abnormalities of the hypothalamus and/or pituitary gland. Children who become severely obese very early in life (i.e., before age 4 years) may also have a genetic etiology of their obesity, perhaps with associated neuroendocrine and hypothalamo-pituitary defects, as infants and very young children have limited access to environmental factors that contribute to obesity. We hypothesized that morphologic abnormalities of the pituitary gland would be seen in both individuals with PWS and other subjects with early onset morbid obesity (EMO). This case-control study included individuals with PWS (n = 27, age 3 months to 39 years), patients with EMO of unknown etiology (n = 16, age 4-22 years; defined as body mass index greater than the 97th centile for age before age 4 years), and normal weight siblings (n = 25, age 7 months to 43 years) from both groups. Participants had 3-dimensional magnetic resonance imaging to evaluate the pituitary gland, a complete history and physical examination, and measurement of basal pituitary hormones. Subjects with PWS and EMO had a higher prevalence of pituitary morphological abnormalities than did control subjects (74% PWS, 69% EMO, 8% controls; P < 0.001). Anterior pituitary hormone deficiencies were universal in individuals with PWS (low IGF-1 in 100%, P < 0.001 PWS vs. controls; central hypothyroidism in 19%, P = 0.052, and hypoplastic genitalia or hypogonadotropic hypogonadism in 100%, P < 0.001), and was often seen in individuals with EMO (6%, P = 0.89 vs. control, 31%, P = 0.002, and 25%, P = 0.018, respectively). The presence of a hypoplastic pituitary gland appeared to correlate with the presence of anterior pituitary hormone deficiencies in individuals with EMO, but no correlation was apparent in individuals with PWS. In conclusion, the high frequency of both morphological and hormonal abnormalities of the pituitary gland in both individuals with PWS and EMO suggests that abnormalities in the hypothalamo-pituitary axis are features not only of PWS, but also frequently of EMO of unknown etiology.
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PMID:Pituitary abnormalities in Prader-Willi syndrome and early onset morbid obesity. 1743 97

Prader-Willi Syndrome (PWS) is a genetic disorder that is difficult to detect, particularly at an early age. PWS is caused by disruption of normal, epigenetically controlled gene function in the chromosome 15q11-q13 region. Clinical symptoms are difficult to diagnose in infants and only become clearer at later ages as the patients develop hyperphagia and morbid obesity. Molecular genetic tests are able to definitively diagnose PWS and allow early diagnosis of the syndrome. High resolution cytogenetic testing, methylation-specific PCR (MS-PCR), and linkage analysis are routinely used to diagnose PWS. To establish a linkage analysis method for Chinese patients, this study identified a useful set of STR markers in the typical PWS deletion and adjacent area, for linkage analysis in two Chinese families with PWS offspring. Using this method, the authors confirmed that one patient had a paternal deletion in chromosome 15q11-q13 and the other patient had maternal uniparental heterodisomy of chromosome 15. MS-PCR and high resolution chromosome G-banding also confirmed this diagnosis. This linkage analysis method can detect both deletion and uniparental disomy, thus providing valuable information for genetic counseling and the opportunity to analyze the relationship between the genotype and phenotype of PWS.
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PMID:Molecular genetic diagnostics of Prader-Willi Syndrome: a validation of linkage analysis for the Chinese population. 1794 67

A 16-year-old male adolescent diagnosed to have the Williams-Beuren syndrome was referred to our obesity outpatient clinic, due to his morbid obesity (body mass index 39.2 kilograms per square metre) and gluttony. After several unsuccessful dietary treatments, we started therapy with sibutramine. As growth hormone (GH) deficiency was diagnosed by an additional GH-stimulation test, we commenced with a GH-treatment. This well-tolerated combination therapy led to a remarkable weight loss of 10 kg and a growth-rate acceleration of 3.7 cm/year. Nine months after stopping the treatment with sibutramine, a partial weight gain was noticed. This case report justifies further research work on a combination therapy with sibutramine and GH for similar cases.
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PMID:Successful treatment of a morbidly obese and growth-retarded adolescent with Williams-Beuren Syndrome by combining the medication of growth hormone and sibutramine. 1820 53

Several mutations in the melanocortin receptor 4 gene have been identified in humans and account for 3-6% of morbid obesity. In contrast, strong evidence of a causative role for melanocortin receptor 3 (MC3R) mutations are still lacking. In MC3R knockout mice, high feed efficiency rather than hyperphagia seems to contribute to increased fat mass. On the basis of this evidence, the objective of the present study was to investigate the presence of MC3R mutations in a group of 290 obese subjects (mean BMI 44.2+/-5.9 kg/m2). As a control, a group of 215 normal-weight subjects (mean BMI 22.4+/-2.7 kg/m2) was also screened. Three novel mutations in the MC3R gene (A293T, I335S and X361S) were identified among the obese patients. The mutations segregated with obesity in the members of the families studied. In vitro expression studies of each mutation demonstrated a loss of function of the I335S-mutated receptor. These findings suggest that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity. However, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.
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PMID:Sporadic mutations in melanocortin receptor 3 in morbid obese individuals. 1823 Nov 26

Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity.
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PMID:Appetite enhancement and weight gain by peripheral administration of TrkB agonists in non-human primates. 1838 75

Craniopharyngioma management is challenging. Although histology is benign, the tumour can be clinically aggressive with local invasion and frequent recurrences. Extensive morbidity may be present at diagnosis and furthermore, occurs as a consequence of neurosurgery and radiotherapy. Hypothalamic symptoms can have a devastating effect on quality of life and may reduce life expectancy. This case highlights both the challenge of managing hyperphagia and morbid obesity and the importance of initial treatment preserving existing hypothalamic function and the need to avoid tumour recurrence and further surgery. A 11-year old boy presented with hydrocephalus secondary to a craniopharyngioma (he had visual failure and hypopituitarism but few hypothalamic symptoms). He underwent radical resection followed by radiotherapy. Following this treatment, he developed psychological and behavioural problems and hyperphagia. Weight gain in the first year (an increase from +1.4 to +3.7 s.d.) resulted in poor mobility and a fall which caused a slipped femoral epiphysis. In the next year, there was a 6-month period of unexpected weight loss (+4.2 to +3.8 s.d.) that culminated in emergency treatment for diabetic ketoacidosis secondary to severe insulin resistance. He developed a left hemiplegia, and a subsequent cerebral angiogram identified multiple stenoses of the Circle of Willis with a Moyamoya appearance secondary to radiotherapy. Weight gain has continued (+3.8 to +5.5 s.d.) so that bariatric surgery is a management option.
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PMID:'Do no harm': management of craniopharyngioma. 1877 78

A unique challenge posed by advancing scientific knowledge about the biology of human behavior is how to integrate that understanding with the desire to hold ourselves--and one another--morally accountable. As human beings, we are something more than just passive agents whose behavior is the sum product of biologic determinism. Because of the existence of the mind, we are also active agents with the capacity to influence, at least to some extent, our own destinies. Behavior may be determined, but it is not predetermined. We are one of its determinants. Misconduct by a person of sound mind should not be attributed improperly to brain pathology. On the other hand, suffering, legitimate mental disorder, and associated impairments should not be trivialized. Historically, persons who once were labeled "lazy" are often more appropriately understood by modern standards as clinically depressed. Frequently they are more in need of pharmacologic treatments that alter brain chemistry than "a kick in the behind." Gluttony, one of the original cardinal sins, is often more properly understood as morbid obesity, a condition that deserves appropriate medical care. Persons who have alcoholism, once judged morally as "bums in the gutter," are more frequently referred to treatment facilities, such as The Betty Ford Clinic. One should not approach the issue of human sexual behavior without at least some appreciation of moral values and scientific research. Although clearly some persons choose to act in a sexually selfish and self-indulgent fashion with wanton disregard, others seem to be more genuinely burdened and struggle to integrate their sexual desires into an otherwise healthy and fully responsible lifestyle. When a person, whether male or female, seems to be so driven that it becomes difficult to master erotic desires and he or she experiences difficulty serving his or her own best longterm interests, the concept of sexual compulsivity seems to be relevant. Ultimately, a better understanding of any associated neuropathologies may help to facilitate future treatments and public acceptance. The possibility exists, at least in some instances, that a sexually compulsive individual is less an example of a bad person deserving of punishment than a "broken mind" in need of repair. In time, increased knowledge about the precise workings of the brain in reciprocally initiating and sustaining the sexual interests of the mind may facilitate a much clearer appreciation of the issues at hand.
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PMID:Basic science and neurobiological research: potential relevance to sexual compulsivity. 1899 3

Prader-Willi syndrome is an uncommon multisystem genetic disorder caused by defects of chromosome 15 (15qll-ql3), often due to deletions or uniparental disomy The syndrome is characterized by neonatal hypotonia, dysmorphic facial features, short stature, motor and mental disabilities, behavioral changes, hyperphagia, precocious obesity and hypogonadotropic hypogonadism. We present a 17 year-old woman, with a previous genetic diagnosis of Prader-Willi syndrome and BMI of 74 Kg/m(2), that was admitted in anasarca, with marked cyanosis, dyspnea and oliguria. She presented high levels of blood urea, creatinine and aminotransferases, in addition to hyperkalemia and hyperuricemia. She had been in regular use of fluoxetine during the last six months, and evolved with severe high blood pressure and respiratory failure, which needed intensive care support. Moreover, sequels and clear signs of recent self-injuries were observed in her trunk, forearms and hands. The findings of morbid obesity, anasarca, self-injury, hyperuricemia and hypoxemia in Prader-Willi syndrome are emphasized.
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PMID:Morbid obesity in an adolescent with Prader-Willi syndrome. 1954 50

Following extensive suprasellar operations for excision of hypothalamic tumors, some patients develop morbid obesity, the so-called hypothalamic obesity (HyOb). HyOb complicates disorders related to the hypothalamus, including those that cause structural damage to the hypothalamus, pituitary macroadenoma with suprasellar extension, glioma, meningioma, teratoma, germ cell tumors, radiotherapy, Prader-Willi syndrome, and mutations in leptin, leptin receptor, POMC, MC4R and CART genes. It is conceivable that a subgroup of patients with 'simple obesity' also have HyOb. The hypothalamus regulates body weight by precisely balancing the intake of food, energy expenditure and body fat tissue. Orexigenic and anorexigenic hypothalamic centers (hyperphagia when impaired) play a central role, connecting to adipose tissue by means of an intricate efferent and afferent signals circuit. Other mechanisms by which the brain regulates adipose tissue and beta cells of the pancreas include the sympathetic nervous system, vagally mediated hyperinsulinemia and the endocrine system, namely growth hormone, thyroid-stimulating hormone and the hypothalamo-pituitary-adrenal axis. Corticotropin-releasing hormone, adrenocorticotropic hormone glucocorticoids and the 11beta-HSD-1 shuttle regulate lipolysis both directly and indirectly. All the above mechanisms may be impaired in HyOb. Management of HyOb targets the major manifestations: hyperphagia, autonomic dysfunction, hyperinsulinemia and impaired energy expenditure. Individual variation is considerable. Satisfactory therapy is currently unavailable.
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PMID:Hypothalamic obesity. 1995 67

Leptin acts as an anorexigenic hormone in the brain, where the long form of the leptin receptor (LRb) is widely expressed in hypothalamic and extra-hypothalamic sites that are known to participate in diverse feeding circuits. The important role of leptin in energy homeostasis is demonstrated by the profound hyperphagia and morbid obesity in humans and rodents null for leptin or LRb. However, common forms of obesity are associated with high leptin levels and a failure to respond effectively to exogenous leptin; indicating a state of leptin resistance. Leptin resistance is thought to be an important component in the development of obesity. Several defects may contribute to the leptin resistant state, including a defective leptin transport across the blood-brain barrier, which reduces the availability of leptin at its receptor. Furthermore, defects in LRb signal transduction involving reduced LRb expression or the induction of feedback inhibitors have been found in leptin resistance; these defects are commonly termed cellular leptin resistance,. Finally, reduced leptin action can result in the disruption of proper neuronal interactions, by altering neuronal wiring. Interestingly, some leptin functions remain intact in the leptin-resistant state, such as cardiovascular leptin effects. The appearance of selective leptin resistance is mirrored by the observation that cellular leptin resistance has been found only in some subpopulations of hypothalamic LRb neurons. Current efforts to dissect leptin function in specific populations of LRb neurons will increase our understanding of these complexities of leptin physiology.
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PMID:Leptin-signaling pathways and leptin resistance. 1995 80


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