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)

Serum GH concentrations assessed by conventional RIA and immunoradiometric assay (IRMA) are often undetectable in healthy fed and awake humans. Serum GH concentrations are also low in obese, hypothyroid, middle-aged, and older individuals. Accordingly, to better investigate the pathophysiology of GH release in relatively hyposomatotropic states, we compared a new and putatively ultrasensitive GH chemiluminescence (CL) assay with a conventional IRMA. We report that the sensitivity of the CL assay is approximately 0.005 microgram/L, with a median intraassay coefficient of variation over more than 3 logarithms of serum GH concentrations of 5.2% (range, 3.6-8.3%). In each of 2 normal young men and 4 categories of hyposomatotropic adults studied (2 obese, 2 hypothyroid, 2 middle-aged, and 3 older men), we observed detectable serum GH concentrations by CL assay of all samples collected at 10-min intervals for 24 h. In the same sera analyzed by IRMA, 22-98% of the daytime sample values fell below IRMA sensitivity (0.10 microgram/L). Within the IRMA-detectable range, the correlation between the 2 assays ranged between r = 0.893 to 0.989 (P < 0.001 in each subject). In the CL assay, serum GH concentrations declined to 0.018-0.030 microgram/L, but were never undetectable during the awake fed state. Deconvolution analysis of 11 GH series assayed by CL disclosed basal GH release and superimposed GH secretory bursts. In the low GH series, there was a mean frequency of 12 +/- 1.4 secretory events/24 h, a mass of GH secreted per burst of 1.0 +/- 0.35 microgram/L, a secretory burst half-duration of 21 +/- 3.3 min, and an apparent endogenous GH half-life of 14 +/- 0.85 min. Compared to the GH IRMA, the CL assay detected approximately 50% more GH secretory events, and GH secretory burst frequency was increased significantly at night vs. the daytime. Cosinor analysis revealed significant 24-h serum GH concentration rhythms in both assays, but an earlier mean acrophase (time of maximum) and lower mesor (mean values) were estimated in the CL assay than the IRMA. We conclude that within the IRMA-detectable range, the correlation between serum GH concentrations measured by CL and IRMA techniques is high. However, unlike the IRMA, the GH CL assay can detect serum GH concentrations consistently in the awake and fed state not only in young individuals but also in subjects with obesity, hypothyroidism, and middle and older age.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Low basal and persistent pulsatile growth hormone secretion are revealed in normal and hyposomatotropic men studied with a new ultrasensitive chemiluminescence assay. 812 22

Sixty-six dogs with hypothyroidism were identified from dogs examined over a 5-year period. Hypothyroidism was diagnosed only if the dog had a low, resting serum thyroxine concentration and serum thyroxine concentration was not higher than the lower limits of the reference range 6 hours after IV administration of bovine thyrotropin. The prevalence of hypothyroidism was 0.2%. Neutering was determined to be the most significant gender-associated risk factor for development of hypothyroidism. Neutered male and spayed female dogs had a higher relative risk of developing hypothyroidism than did sexually intact females. Sexually intact females had a lower relative risk. Breeds with a significantly increased risk, compared with other breeds, were the Doberman Pinscher and Golden Retriever. The most common clinical findings were obesity (41%), seborrhea (39%), alopecia (26%), weakness (21%), lethargy (20%), bradycardia (14%), and pyoderma (11%). Low voltage R-waves were found on 58% of ECG. Clinicopathologic abnormalities included hypercholesterolemia (73%), nonregenerative anemia (32%), high serum alkaline phosphatase activity (30%), and high serum creatine kinase activity (18%). Serum total triiodothyronine concentrations were within reference ranges in 15% of the hypothyroid dogs. Response to treatment was good in most dogs, but those with severe concurrent disease or neurologic abnormalities were less likely to respond with complete resolution of clinical signs.
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PMID:Hypothyroidism in dogs: 66 cases (1987-1992). 817 72

Hypothyroidism is a possible predisposing factor in a number of disorders of companion psittacine birds. We developed and validated a thyroid-stimulating hormone (TSH) response testing protocol for cockatiels (Nymphicus hollandicus), using 0.1 IU of TSH/bird given IM, with blood sample collection at 0 and 6 hours after TSH, and a commercial radioimmunoassay for thyroxine (T4). This protocol was used to document a seasonal sex difference in stimulated T4 values--females responded with higher T4 values than those in males in summer--and a stress-induced depression of baseline T4 values was detected in a group of cockatiels with normal TSH response. An experimental model for mature-onset hypothyroidism in cockatiels was created by radiothyroidectomizing cockatiels with 3.7 MBq (100 microCi) of 131I/bird given IV. Induction of the hypothyroid state was confirmed by baseline T4 concentration, TSH response test results, thyroid pertechnetate scintigraphy, and gross and microscopic examinations. Classical signs of hypothyroidism (eg, hypercholesterolemia, obesity, poor feathering) were lacking or mild at 48 days after thyroid ablation.
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PMID:Development of an experimental model of hypothyroidism in cockatiels (Nymphicus hollandicus). 819 66

Secondary causes of hyperlipidemia are important to recognize. In fact, hyperlipidemia may be a clue to the presence of an underlying systemic disorder. It may greatly heighten the risk of atherosclerosis with a raised LDL-c, triglyceride-rich lipoprotein excess, and increased lipoprotein(a) as well as lowered HDL-c. The search for secondary causes may provide a clue as to why patients with primary lipid disorders suddenly develop worsening lipid profiles. The point is a crucial one because some acquired causes of hyperlipidemia, such as alcohol, estrogens, steroids, or pregnancy, when superimposed on a primary familial form of hypertriglyceridemia can result in a saturated removal system and a buildup of chylomicrons, which can lead to life-threatening pancreatitis. A convenient way to remember secondary causes is to think of the four D's of diet, drugs, disorders of metabolism, and diseases. Although diets rich in saturated fats and cholesterol are a common cause of the mild hypercholesterolemia seen in our society, alcohol excess and weight gain can explain much of the tendency toward hypertriglyceridemia. Interestingly anorexia nervosa has long been associated with severe but reversible hypercholesterolemia. Several classes of drugs need to be considered as common causes of altered lipid profiles. Glucocorticoids and estrogens elevate triglycerides and raise levels of HDL-c. Anabolic steroids taken orally markedly reduce levels of HDL-c in contrast to injectable testosterone, which does not adversely affect the LDL-to-HDL ratio. Oral contraceptives affect atherosclerotic risk depending on the kind and doses of progestin/estrogen. In those with an underlying primary hypertriglyceridemia and associated obesity, estrogenic medications can depress triglyceride removal mechanisms, leading to the chylomicronemia syndrome and pancreatitis. Antihypertensives have variable effects on lipids and lipoproteins. Although short-term thiazide usage raises cholesterol, triglycerides, and LDL-c, long-term usage is not necessarily associated with significant alterations in lipid levels. Alpha blockers may cause an increase in HDL-c, whereas beta blockers raise triglycerides and lower HDL-c. Sympatholytics, angiotensin converting enzyme inhibitors, and calcium channel blockers are essentially lipid neutral. Retinoids can be associated with increased LDL-to-HDL ratios and occasionally striking elevations in triglycerides. Cyclosporine raises LDL-c and lipoprotein(a). Classes of drugs that may raise HDL-c include cimetidine, antiepileptic drugs, and tamoxifen, but the effect may be seen primarily in women. Hypothyroidism is the most common secondary cause of hyperlipidemia after dietary causes are considered. A thyroxine and TSH level should be obtained on all new cases of clinically important hyperlipidemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Secondary causes of hyperlipidemia. 828 27

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

The aim of the present work was to investigate the impact of disease states and environmental and host factors on the glucuronidation of oxazepam. Glucuronidation represents quantitatively one of the most important metabolic conjugation pathways (phase II) in man for the inactivation and detoxication of xenobiotics and endogenous compounds and the liver is the major site for it to take place. Far less attention has been paid to the conjugation reactions in previous clinical research in this field compared to the immense interest in the oxidative biotransformation pathways (phase I). This fact is mainly due to the latter giving rise to active or reactive metabolites with a toxicological potential. The metabolism of oxazepam expresses exclusively the capacity for glucuronide formation. It was a prerequisite to establish the bioavailability of oxazepam prior to succeeding studies on the oral disposition of the drug. A preparation for intravenous administration was created. Clearance was chosen as measurement of the capacity to glucuronidate oxazepam. Severe decompensated liver disease was associated with a significant decrease in oxazepam clearance, that became even more obvious when corrected for by a diminished binding to plasma proteins. This increase in free fraction of oxazepam was substantial and could mainly be accounted for by low plasma albumin values. The results are in part a settlement with earlier studies on glucuronidation in liver disease and they may undoubtedly be ascribed to the severe degree of liver disease. For the first time it was shown that hypothyroidism led to a decline in the clearance and metabolism of oxazepam and paracetamol that is mainly biotransformed by glucuronidation. It was concluded that the enzymes responsible for glucuronidation in hypothyroidism are under the influence of thyroid hormones as is the case with oxidative enzymes. Further studies focused on the effect of host and environmental factors on glucuronidation. A commercially available very low calorie product for the treatment of obesity resulted in a decrease in oxazepam clearance and a lack of co-factors as a consequence of the low calorie intake was explanatorily proposed. Beta-adrenoceptor antagonists are often prescribed together with other drugs and close knowledge on interactions is mandatory but insufficient in regard of drugs being glucuronidated. Despite the mutual metabolic pathway labetalol exerted no dispositional alterations concerning oxazepam. It was moreover suggested that very elderly subjects between the age of 80 to 94 years had a reduced clearance of oxazepam.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Factors and conditions affecting the glucuronidation of oxazepam. 841 17

Hypothyroidism is the condition most commonly treated with exogenous thyroid hormone. The goal of therapy is to normalize levels of serum thyrotropin (thyroid-stimulating hormone), which should be monitored by a high-sensitivity test. Adjustments in optimal dose may be necessary for a number of physiologic reasons (eg, decreased gastrointestinal absorption, pregnancy). Thyroid hormone therapy is also appropriate after surgery for thyroid cancer and for patients with goiter or benign thyroid nodules. In the absence of hypothyroidism, such treatment should not be used for obesity, fatigue, irregular menses, or infertility.
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PMID:Thyroid hormone therapy. What, when, and how much. 841 59

The elderly are more liable to problems from drugs used systemically. An accurate diagnosis may reveal conditions in which drug treatment is not required, especially those due to faulty habits and environmental problems, and local conditions susceptible to injections or surgery. Obesity, sepsis, hypothyroidism, osteomalacia, unsuspected fractures and drug side-effects may give correctable rheumatological problems. Use of analgesic anti-inflammatory drugs needs great care in the elderly; use analgesics instead when possible. Rheumatoid arthritis in the elderly demands maximum use of nonpharmacological treatment and local treatment. Analgesic anti-inflammatory drugs should be used carefully and sparingly. Use slow-acting drugs as in younger patients.
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PMID:Anti-rheumatic treatment in the elderly. 846 80

Secondary hyperlipoproteinemias are found in connection with other primary organic diseases. Typical examples are those seen with diabetes mellitus, liver and kidney diseases. In addition there are changes induced by hormonal dysfunctions such as hypothyroidism, by the use of oral contraceptives or in postmenopausal women. During pregnancy there is a physiological transient increase in lipoproteins. In addition to primary organic diseases there are a number of exogenous factors such as obesity, malnutrition and alcohol abuse causing hyperlipidemia. The relation between hypertension and hyperlipidemia described as familial dyslipidemic hypertension is less well known. Obesity, hypertension, dyslipidemia, hyperuricemia and impaired glucose tolerance are the basic conditions of the metabolic syndrome. Familial combined hyperlipidemia is a genetically determined, dyslipidemic syndrome with a high prevalence among patients with coronary artery disease and stroke. As there are some links between familial combined hyperlipidemia and secondary hyperlipoproteinemias, this disease entity is discussed together in this paper. Familial combined hyperlipidemia is metabolically, genetically and by this on a molecular level closely linked to familial dyslipidemic hypertension as well as the metabolic syndrome. The exact mechanism of this disease is currently unknown.
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PMID:[Secondary disorders of lipid metabolism, metabolic syndrome and familial combined hyperlipidemia]. 865 Sep 33

The aims of this study were to review what is currently known about comorbidity in people with Down's syndrome and to determine if their relative risk for certain disorders was increased. Analysis was carried out on the published literature from 1982 through 1994. In order to be included in this study, articles had to meet predetermined criteria. The strengths and weaknesses of the selected articles were considered in this review. The estimation of relative risks was done by calculating the odds ratio (OR). Odds ratios of > 2 or < 0.5 were found in more than one article for congenital heart defects, hypothyroidism, hearing impairment and hepatitis B. Only one article indicated an OR within this range for all of the following disorders: obesity, epilepsy, degenerative spine disorders and a wide atlanto-axial distance. The results were unclear in the areas of hyperthyroidism, visual disorders, dementia and psychiatric disorders. The concept of comorbidity, i.e. establishing the relationships between the various conditions in one person and understanding the implications for medical care, seems promising, especially for people with intellectual disability. Further work in this area may well improve the quality of care offered to these people.
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PMID:Comorbidity in people with Down's syndrome: a criteria-based analysis. 890 27


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