Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se.
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PMID:Acanthosis nigricans with severe obesity, insulin resistance and hypothyroidism: improvement by diet control. 1032 66

Central or visceral obesity is recognized as a main risk factor for cardiovascular disease and type 2 diabetes mellitus. The co-existence of visceral obesity, increased blood lipid levels, hypertension and impaired glucose tolerance defines the metabolic syndrome that today is widely recognized as one of the prime factors behind cardiovascular morbidity and mortality. Endocrine disorders such as insulinoma, hypothyroidism and hypercortisolism are known to cause obesity. However, it is only hypercortisolism that is associated with increased abdominal fat accumulation. Recently, new findings have shed light on subtle endocrinopathies that are prevalent in individuals presenting with the metabolic syndrome. Such derangements are of borderline character and often fall within the normal reference range. Intervention studies demonstrate that correction of relative hypogonadism in men with visceral obesity and other manifestations of the metabolic syndrome seem to decrease the abdominal fat mass and reverse the glucose intolerance, as well as lipoprotein abnormalities in the serum. Further analysis of the underlying mechanism has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrates that relatively low testosterone levels are a risk factor for development of visceral obesity. The primary event that triggers the initial development of visceral obesity is not known, but it seems plausible that increased activity in the hypothalamus-pituitary-adrenal axis can be of major importance.
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PMID:Androgens and abdominal obesity. 1033 65

Hypothyroidism was diagnosed in 50 dogs and excluded in 86 dogs suspected of hypothyroidism, on the basis of the results of bovine thyrotropin response tests. Breed, pedigree, sex or neutering status did not significantly influence the likelihood of the dogs being hypothyroid. The hypothyroid dogs were significantly older than the non-hypothyroid dogs referred to the University of Glasgow during the same period. However, when dogs under two years of age were excluded from the statistical analyses there was no significant difference in age between the two groups. The most common clinical characteristics associated with hypothyroidism were metabolic signs (84 per cent of cases), particularly lethargy (76 per cent), obesity or weight gain (44 per cent), and exercise intolerance (24 per cent); and dermatological abnormalities (80 per cent), including alopecia (56 per cent), poor coat quality (30 per cent) and hyperpigmentation (20 per cent). When compared with the laboratory reference limits the most common biochemical and haematological abnormalities were increased concentrations of triglycerides (88 per cent), cholesterol (78 per cent), glucose (49 per cent), and fructosamine (43 per cent), and increased activities of creatine kinase (35 per cent), and decreased concentrations of inorganic phosphate (63 per cent), and a low red blood cell count (40 per cent). When compared with reference limits derived from the euthyroid dogs the most common abnormalities were increased concentrations of gamma-glutamyltransferase (21 per cent), cholesterol (18 per cent), and aspartate aminotransferase (15 per cent) and a decreased red blood cell count (29 per cent), and decreased neutrophils (18 per cent) and decreased activity of creatine kinase (15 per cent). Assessment of cholesterol, creatine kinase, aspartate aminotransferase, gamma-glutamyltransferase, and red blood cell and neutrophil counts may be particularly useful in distinguishing hypothyroid dogs from euthyroid animals with similar clinical signs.
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PMID:Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism. 1059 70

In the majority of patients admitted to an Intensive Care Unit with acute respiratory failure (ARF), the aetiology for ARF is quite evident. In a minority of patients no obvious aetiology is apparent at presentation. In this group a previously unrecognized sleep-related breathing disorder (SRBD) may be the cause of the ARF. In spite of clinical suspicion SRBD remains infrequently diagnosed in ARF also because the technology necessary for this type of diagnosis (polysomnography) is usually unavailable in Intensive Care Units. The aim of this study was to evaluate the utility of portable polysomnography system (PSGp) in a group of patients with ARF of unclear aetiology and with a clinical suspicion of SRBD. We studied a selected group of 14 patients (eight males, six females) admitted to an Intermediate Intensive care unit with varying degree of acute respiratory failure. Mean (SD) age was 57 (13) years, pH 7.28 (0.04), PaO2 5.6 (0.7) kPa), PaO2 (8.8 (1.6) kPa), Body mass index 42.7 (9.6) kg m(-2). The patients had no history of skeletal, neuromuscular or cardiovascular disease. None of them had a history of overt chronic lung diseases or had obvious respiratory tract infections. They were submitted to cardiac and respiratory functional evaluation and to nightly PSGp (VITALOG HMS 5000, Respironics Inc., Redwood City, CA, U.S.A.) which was performed in an intermediate intensive care unit. Ten subjects had obstructive sleep apnoea-hypopnoea syndrome (OSAS), with mean respiratory disorder index h(-1) (RDI) 60.1 (25.9) [in five associated with obesity-hypoventilation syndrome (OHS)]; two had central sleep apnoea with mean RDI 45 (28.3) (one with hypothyroidism and one with cerebral multiple infarctions and right hemidiaphragmatic paralysis) and two had OHS with mean RDI 12.5 (3.5). Nocturnal hypoventilation was present in almost all patients. Continuous positive airway pressure (CPAP) was effective in three patients. Eight patients needed to be treated with BILEVEL (BiPAP, Respironics Inc.) airway positive pressure in timed or spontaneous/timed modes. Two patients required intubation and mechanical ventilatory treatment. In one patient with hypothyroidism was sufficient to institute hormonal therapy. Our study shows that acute respiratory failure due to SRBD is not exceptional in an Intermediate Intensive Care Unit and that if clinical suspicion is strong, portable polysomnography may yield diagnostic confirmation and help in establishing appropriate treatment and in avoiding the invasive ventilatory treatment.
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PMID:Sleep-related breathing disorders in acute respiratory failure assisted by non-invasive ventilatory treatment: utility of portable polysomnographic system. 1071 17

Previous observations raised the possibility that circulating GH-binding protein (GHBP) may serve as a useful index for tissue GH receptor (GHR) responsiveness in humans. Indeed, there are many examples to indicate that across a wide scope of comparative studies, ontogenic data, experimental systems, physiological conditions, nutritional states, and diseases there is a close relationship between the concentration of GHR and the level of serum GHBP. In the present review, we discuss various aspects that might affect differentially cellular GHR and circulating GHBP, based on species and tissue divergence, regulation of cell-surface GHR turnover, GHR cleavage mechanism, GHR mRNA splicing, and GH insensitivity (GHI) syndrome patients with normal or high serum GHBP levels. Most previous experimental data were collected through comparative analysis of human GHBP against GHR and GHBP determinations in animal models. Yet, GHBPs possess species-specific properties, and the mechanism for their generation and regulation display evolutionary divergence. Another important aspect is tissue divergence, in terms of GHR regulation and its cleavage to GHBP. Although GHBP is generated mainly from the liver GHR, many other tissues express GHRs and probably also contribute to the total GHBP level. Human GHBP is generated by proteolytic cleavage of GHR at the cell-surface and, thus, occupancy or modulation of GHR turnover/internalization would impact the level of cell-surface GHR that are available for proteolysis. An additional degree of complexity arises from recent reports, implicating a protein kinase C-regulated metalloprotease activity in GHBP generation. This suggests that the proteolytic system, which controls the specific cleavage mechanism and switch between GHR proteolysis and GHBP shedding, is a regulated process. Finally, differential splicing regulation to the full-length, active human GHR (hGHR) and the inactive truncated hGHRtr isoform messenger RNA transcripts might regulate both the production of GHBP and GHR bioactivity, as hGHRtr generates large amounts of GHBP but has a dominant negative effect on GH signaling. Several clinical GH-resistant conditions, such as liver cirrhosis, renal insufficiency, insulin-dependent diabetes mellitus, hypothyroidism, malnutrition, or critical illness are associated with reduced GHBP levels. However, this is not universally true, as in other conditions (e.g. early childhood, acromegaly) decreased GHBP levels are not associated with GHI. Divergence between serum GHBP and insulin-like growth factor I, such as which occur during puberty or obesity, also questions whether GHBP levels reflect GHR function. Even in patients with GHI syndrome, serum GHBP cannot be relied on to detect all GHR mutations. The correct assessment of GHR expression and GH functionality in an individual patient will require, in parallel to measurements of serum GHBP, additional detailed diagnostic screening of the entire GH-insulin-like growth factor I axis.
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PMID:Clinical review 112: Does serum growth hormone (GH) binding protein reflect human GH receptor function? 1072 17

The authors report on a young girl with generalized developmental deficits originally thought to be caused by an unusual reaction to DPT vaccination. At the age of 4(1/2) years, chromosome analysis showed that the terminus of the short arm of chromosome 9 had extra material believed to originate from 7p terminus, thus she was considered to be trisomic for a segment of 7p and monosomic for a small portion of 9p [46,XX,der (9), t(7;9)(p15;p24)]. Ten years later, molecular cytogenetic testing using fluorescence in situ hybridization (FISH) confirmed that the extra chromosomal material represented partial trisomy 7p. The proposita had a high and large forehead, hypertelorism, and broad nasal bridge, findings seen in most individuals with trisomy 7p. Long-term follow-up showed the presence of hypothyroidism, obesity, and cerebral palsy. A review of all published cases of trisomy 7p with focus on associated complications suggests a well-defined pattern of abnormalities characterized by musculoskeletal, cardiovascular, neurological, genital, and ocular abnormalities in decreasing frequency. At least one-third of affected individuals died in infancy and close to half had severe mental retardation. FISH was essential in the confirmation of the cytogenetic abnormality and further delineation of the chromosomal disorder.
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PMID:Trisomy 7p resulting from 7p15;9p24 translocation: report of a new case and review of associated medical complications. 1076 85

Multiple symmetric lipomatosis (MSL), also known as Launois-Bensaude syndrome or Madelung's disease, is a rare disorder predominantly seen in middle-aged male patients. The disorder is characterized by large subcutaneous fat masses distributed around the neck, shoulders, and other parts of the trunk, often associated with nervous system abnormalities. A close relationship to alcoholism, metabolic disturbances and malignant tumours has been observed. Until now, MSL has only been described in adults. We report on the first two children, a 9-year-old girl and a 13-year-old boy, with the characteristic clinical findings of MSL. The girl presented with severe obesity, developmental delay, mild mental retardation, peripheral neuropathy, and latent hypothyroidism. In addition, she had elevated lactate concentrations in blood and cerebral spinal fluid suggesting mitochondrial dysfunction. Biochemical analyses of muscle showed a respiratory chain complex II deficiency. The boy suffered from severe obesity, mild mental retardation and insulin resistant diabetes mellitus. In both children, analyses of the mitochondrial genome did not reveal major deletions nor the MERRF 8344 point mutation. MSL seems to be a new neurometabolic disorder with heterogeneous clinical expression whose pathogenesis is still unknown.
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PMID:Multiple symmetric lipomatosis: an unusual cause of childhood obesity and mental retardation. 1081 86

Obstructive sleep apnea (OSA) syndrome is now recognized as a relatively common cause of excessive daytime sleepiness, with resultant psychosocial impairment and motor vehicle accidents, and it likely contributes to premature cardiovascular disease. Treatment is naturally directed at the upper airway; however, it is also important to identify and correct significant risk factors, such as obesity and hypothyroidism, whenever possible. Oral appliances or nasal continuous positive airway pressure may immediately reverse symptoms caused by OSA and can be used either indefinitely or as a bridge to potentially definitive surgery.
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PMID:What are the nonsurgical treatment options for obstructive sleep apnea syndrome? 1128 28

The present state of knowledge about growth hormone binding proteins (GHBP) is reviewed, with particular emphasis on the high affinity GHBP, which represents the circulating ectodomain of the growth hormone receptor (GHR). GHBP is conserved through vertebrate evolution, is produced in many tissues (especially liver) by either alternative GHR mRNA splicing (rodents) or by proteolytic cleavage from the GHR (humans, rabbits and several other species). The metalloprotease TACE (tumor necrosis factor-alpha converting enzyme) is the likely enzyme responsible for cleavage, but the structural requirements for TACE recognition or catalysis, and hence the precise cleavage point in the GHR, are unknown. GHBP is widely distributed in biological fluids, with marked concentration differences amongst them. GHBP binds about half of the circulating GH under basal conditions but is easily saturated at high GH levels; it subserves complex functions, including a circulating buffer/reservoir function for GH, prolongation of plasma GH half-life, competition with GHRs for GH, and probably unproductive heterodimer formation with the GHR. The net effect of these partly enhancing and partly inhibitory functions on GH action in vivo is complex and difficult to ascertain. Serum GHBP levels roughly parallel GHR expression (particularly in liver) through the life span, with very low levels in fetal life, upregulation to adult levels during childhood, and decline in senescence. Rodent pregnancy is associated with a massive increase in GHBP expression. Although the regulation of GHBP expression/production is not necessarily tightly linked to GHR expression, in general, low GHBP levels occur in conditions associated with GH resistance (e.g., malnutrition, uncontrolled diabetes, catabolic states, renal failure, hypothyroidism). Conversely, obesity, a condition with enhanced GH responsivity, is associated with elevated GHBP levels. This suggests that in many (but not all) instances of abnormal GH action, the GHBP level reflects GHR status. Laron syndrome (genetic GHR deficiency/dysfunction due to mutations in the GHR gene) is associated with low or undetectable GHBP in 75-80% of patients; GHBP measurement can therefore be used diagnostically. Depending on the design of assays for serum GH, endogenous GHBP may interfere to varying degrees, and GH assays should be individually validated and optimized in this regard. The ultimate biological role and physiological significance of the GHBP remain to be established.
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PMID:Growth hormone binding protein 2001. 1132 70

Thyroid function tests might be affected by diabetes and obesity. To evaluate the influence of these parameters in routine conditions, 72 diabetic and 53 non-diabetic outpatients without known thyroid diseases or severe chronic illness were recruited over a 7-month period. For each patient, dosages of thyrotropin (TSH), total and free thyroxine (TT4 and FT4, respectively), total and free triiodothyronine (TT3 and FT3) and T3 resin uptake (T3RU) were performed by radioimmunoassays. The simultaneous influence of various parameters known to affect thyroid-function tests was evaluated by multivariate linear regression. The studied variables included gender, age, glucosteroids, estrogens, tobacco habits, iodine contacts, body mass index (BMI) and diabetes mellitus. Tobacco habits and iodine contacts did not influence any tests. As expected, estrogens induced an increase in TT4 and TT3 values (p < 0.001 and 0.020, respectively) associated with a decrease in T3RU (p < 0.001). Consequently, females had lower T3RU than males (p < 0.0001). Corticotherapy was associated with decreased TSH values (p = 0.022). TT3 and FT3 decreased with age (p < 0.001), whereas T3RU and FT4 increased (p = 0.020 and 0.004, respectively). In contrast to an increase in TSH (p = 0.006), TT4 and FT4 decreased at higher BMI levels (p = 0.018 and 0.004, respectively), which is consistent with subclinical hypothyroidism. In diabetic patients, TSH was lower than in nondiabetic subjects (p = 0.039). Thus, the present study indicates that besides known parameters such as age and drugs, thyroid-function tests can also be altered by diabetes mellitus and obesity.
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PMID:Minor alterations in thyroid-function tests associated with diabetes mellitus and obesity in outpatients without known thyroid illness. 1138 17


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