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)

Synthetic human GRF (hGRF (1-44) NH2; SM-8144) was administered as an iv bolus to 141 normal children of short stature (NSC), 73 patients with severe idiopathic GH deficiency (IGD; group A), 30 patients with mild idiopathic GH deficiency (IGD; group B), 29 patients with secondary GH deficiency, 3 patients with primary hypothyroidism, 21 patients with Turner's syndrome and 25 patients with various other disease. Their height was below normal for their age and sex, and they were all below 25 years old without obesity. The maximal GH responses (M+SEM) were 39.5 +/- 2.2, 7.2 +/- 0.9, 27.2 +/- 3.7, 5.2 +/- 0.8, 9.7 +/- 4.4, 25.1 +/- 2.8 and 32.3 +/- 4.8 ng/ml, respectively (significance from the NSC, ; p less than 0.05, ; p less than 0.001). The GH responses to hGRF were greater than those elicited by standard pharmacological tests. There was a negative correlation between bone age and peak plasma GH response to hGRF in patients with idiopathic GH deficiency (IGD) but not in normal children (NSC). In twenty-two percent of the patients with IGD in group A the response was above 10 ng/ml and in 57% of the patients with IGD in group B the response was above 20 ng/ml, suggesting that a large percentage of patients with idiopathic GH deficiency lack hypothalamic GRF. The side effect of flushing was observed in 15.2% of all subjects. These results indicate the potential usefulness of hGRF (1-44) NH2 (SM-8144) in inducing GH release from the pituitary.
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PMID:Plasma growth hormone (GH) response to GH-releasing factor (SM-8144) in children of short stature and patients with GH deficiency. 311 40

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.
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PMID:[Effect of oral administration of L-dopa on the plasma levels of growth hormone-releasing hormone (GHRH) in normal subjects and patients with various endocrine and metabolic diseases]. 312 83

We examined 929 surgically obtained thyroid glands derived from 791 female and 138 male patients and found intrathyroidal adipose tissue in 18 cases (1.94%). Only the thyroid glands of middle aged and older women (mean age 51 years) were affected, as well as in the case of follicular adenomas and nodular and diffuse hyperplasia. With respect to localization in the interstitial connective tissue, as well as between thyroid follicles, interstitial, parenchymatous and mixed types are proposed. In addition to sex and age there is a high correlation with obesity, which is suggestive of hormonal influences. Knowledge of the presence of intrathyroidal fat tissue is of interest to the pathologist since it may lead to erroneous interpretations of histological and cytological specimens of the thyroid gland. In conclusion, not one case of hypothyroidism was detected amongst the 18 cases investigated in this study.
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PMID:[Presence of islands of fatty tissue in struma]. 337 79

Various degrees of persistent or paroxysmal paresis involving only the hindlimbs or all four limbs were observed in 3 dogs with hypothyroidism and lymphocytic thyroiditis. Clinical features included lethargy, obesity, alopecia, insidious and progressive paresis, hypotonia, and slow segmental reflexes in 2 dogs. Obesity, alopecia, paroxysmal paresis, and behavior change were observed in the third dog. Laboratory tests indicated that thyroid function was less than normal in all 3 dogs. Abnormal electromyographic potentials and slow motor nerve conduction velocities were found in each dog. Muscle biopsy specimen abnormalities included selective type-II myofiber atrophy in all dogs, whereas one dog had angular atrophy of type-I and type-II myofibers indicative of denervation. A substance that stained with para-aminosalicylic acid was observed within vacuoles of type-I myofibers in one dog. Lymphocytic thyroiditis characterized by lymphocytic infiltration of excised thyroid glands was observed in all dogs.
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PMID:Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs. 355 92

The present documentation of 23 female patients with pseudotumour cerebri seen in Benghazi, North-Eastern Libya, over a period of 2 years constituted 21 cases with idiopathic pseudotumour and 2 patients with associated endocrine diseases. The clinical, laboratory and CT scan findings indicated idiopathic hypoparathyroidism in 1 case. The association of pseudotumour and hypothyroidism in a 40-year-old woman is suggested to be more than coincidental. The patient group was significantly more obese. Moderate to severe visual loss occurred in 9 patients. The incidence and extent of visual impairment did not correlate with the duration of symptoms, degree of obesity, use of contraceptive pills, steroid treatment, the presence of systemic hypertension, menstrual irregularity or empty sella. The incidence of 1.7 per 100,000 for the total and 3.6 per 100,000 for the female population in Benghazi observed in the present study is believed to be more than the frequency (as assessed by the hospital incidence) reported from other regions. A high prevalence of obesity may partly explain the increased occurrence of pseudotumour cerebri in North-Eastern Libya.
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PMID:Pseudotumour cerebri: incidence and pattern in North-Eastern Libya. 394 85

The pathogenesis of slipped upper femoral epiphysis is unknown but the condition has been linked with various endocrine disorders. Nine patients with slipped epiphyses in association with primary juvenile hypothyroidism are presented. In all patients, slipping occurred or symptoms developed in the affected hip before the hypothyroidism was diagnosed. A generalised pathology was suggested by the absence of trauma (8 patients), by bilateral slipping (6 patients), and by obesity and short stature in all patients. All cases had delayed skeletal maturation and characteristic metaphysial changes were seen on their radiographs. The clinical diagnosis of juvenile hypothyroidism can be difficult but it merits consideration in patients who have a slipped upper femoral epiphysis in association with short stature, obesity, delay in skeletal maturity, or any one of these.
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PMID:Slipped upper femoral epiphysis and primary juvenile hypothyroidism. 396 33

An obese 15-year-old boy with a one-year history of acanthosis nigricans was found to have primary hypothyroidism, with a thyrotropin level in excess of 50 microU/mL. At the same time, he was found to have subclinical insulin resistance. Therapy with thyroxine resulted in weight loss, reversal of hyperinsulinemia, and resolution of the acanthosis nigricans. Hypothyroidism can be added to the list of endocrine diseases associated with acanthosis nigricans. This is unlikely to be a direct effect of the hypothyroid state, but may instead be an indirect action mediated through obesity and subsequent insulin resistance. Insulin resistance and hyperinsulinemia seem to be commonly associated with (and perhaps causative of) the acanthosis nigricans that is seen in many endocrine diseases.
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PMID:Acanthosis nigricans and insulin resistance associated with hypothyroidism. 397 37

The limited value of plasma measurements in the management of treatment with lithium is discussed in the light of the mechanisms of its therapeutic actions and toxic effects.The plasma level of lithium usually rises twofold or threefold in the three to five hours after ingestion of each dose of delayed-release tablets and then gradually falls. The precise shape and height of the lithium curve depend on gastric emptying, which can be slowed with propantheline or speeded with metoclopramide. Depressed or demented patients may be irregular in taking their tablets and variable in food intake. Both the time of the blood test and this behaviour must be considered before changing the prescribed dose of lithium salt because of a laboratory result. A lithium tolerance curve may be a safer guide to treatment than single measures.Mild intermittent thirst is a common early side effect, and severe persistent thirst with polyuria is an uncommon later effect of daily intakes of at least 1,500 mg lithium carbonate. This diabetes insipidus is reversible, non-progressive, unrelated to plasma level, and distinct in attack from lithium-induced hypothyroidism, which may occur at low dosage but is also usually of late onset and reversible or treatable with thyroxine while lithium is continued. Obesity is another occasional effect of large doses. These side effects and the antimanic and prophylactic effects may have different mechanisms.
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PMID:Blood levels and management of lithium treatment. 442 91

We have assessed the presence of VIP/PHI/secretin receptors in heart by: (1) testing the ability of the corresponding peptides to activate adenylate cyclase in cardiac membranes from rat, dog, Cynomolgus monkey and man, and (2) examining the ability of the same peptides to exert inotropic and chronotropic effects on heart preparations from rat and Cynomolgus monkey in vitro. Based on their affinity for natural peptides and synthetic analogs, two types of VIP/PHI/secretin receptors were characterized: the relatively nonspecific "secretin/VIP receptor" of rat heart (that is "secretin-preferring" only in that secretin was more efficient than VIP in stimulating adenylate cyclase), and the "VIP/PHI-preferring" receptor of man, monkey and dog heart. Four physiopathological situations affecting secretin/VIP receptors in rat heart were explored: In male rats from the Okamoto strain and the Lyon strain, two strains presenting spontaneous hypertension, heart membranes exhibited a markedly decreased response of adenylate cyclase to secretin/VIP, with lesser alterations in the responses to isoproterenol and glucagon. This impairment developed in parallel with the occurrence of hypertension and was reproduced in normotensive rats submitted to chronic isoproterenol treatment (but not in Goldblatt hypertensive rats). These findings are consistent with a hyperactivity of norepinephrine pathways in spontaneously hypertensive rats, leading to a reduced number of cardiac post-junctional secretin/VIP receptors bound to adenylate cyclase. Heart membranes from genetically obese (fa/fa) Zucker rats also exhibited severely decreased responses to secretin/VIP with lesser alterations in the responses to glucagon and isoproterenol. These anomalies were specific for the heart, and developed in concomitance with obesity. The first anomaly could not be corrected by severe food restriction. Secretin stimulation of heart adenylate cyclase was also selectively altered in streptozotocin-diabetic rats. Thus, two types of diabetic cardiomyopathy were characterized by a severe local alteration of secretin/VIP receptors coupled to adenylate cyclase. Hypothyroidism, provoked in rat by thyroidectomy or propylthiouracil treatment, again induced a marked decrease in secretin-stimulated cardiac adenylate cyclase activity. In rat papillary muscle electrically stimulated in vitro, secretin exerted a positive inotropic effect. This effect was reduced in obese (fa/fa) Zucker rats. In rat right atrium, secretin also exerted a positive chronotropic effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Heart receptors for VIP, PHI and secretin are able to activate adenylate cyclase and to mediate inotropic and chronotropic effects. Species variations and physiopathology. 608 34

In order to assess iodothyronine receptor interactions in man, we have developed a receptor assay for T3 and T4 in solubilized nuclear extracts from circulating mononuclear cells. This assay utilizes the technique of salt solubilization to isolate nuclear receptors and employs standard saturation analysis for T3 and T4 to determine maximal binding capacity (MBC) and equilibrium dissociation constants (Kd). We have determined that 11 normal subjects had a MBC for T3 of 1.20 +/- 0.20 pmol/mg DNA (+/- SE) and a Kd of 3.4 +/- 0.2 X 10(-10) M; the T4 MBC was 8.44 +/- 1.22 pmol/mg DNA and the Kd was 2.7 +/- 0.3 X 10(-10) M. Hypothyroid patients had a mean T3 MBC of 7.32 +/- 2.28 pmol/mg DNA and a mean T4 MBC of 40.04 +/- 21.36 pmol/mg DNA (P less than 0.05 compared to normal). Obese subjects (n = 12) had a basal fed MBC that was 0.66 +/- 0.13 pmol/mg DNA for T3 (P less than 0.05 compared to normal) and was 3.58 +/- 0.56 pmol/mg DNA for T4 (P less than 0.01 compared to normal). During fasting, the average T3 MBC increased to 1.43 +/- 0.31 pmol/mg DNA and the average T4 MBC increased to 9.63 +/- 2.46 pmol/mg DNA, values that are both significantly higher than those in the fed period; the dissociation constants were unaltered in obese subjects (compared to normals) in fed and fasting states. Gel filtration with 0.5 M agarose was employed to ascertain if the physicochemical properties of the solubilized mononuclear human cell receptor were similar to those previously observed in rat and human liver and kidney receptors. The elution profile obtained was similar to that reported earlier. The major binding activity has an estimated Stokes radius of 35 A and a molecular weight ratio of approximately 50,000 daltons. These studies indicate that: 1) high affinity T3 and T4 receptors exist in human mononuclear cells and have properties similar to those for T3 and T4 described previously in rat liver; 2) T3 and T4 receptor number tends to increase in hypothyroid subjects and tend to be lower in obese patients than in normal weight control subjects; 3) fasting is associated with an increase in both T3 and T4 MBC; and 4) despite their apparent physicochemical similarity, T3 receptors in rat liver and human mononuclear cells may be regulated differently, at least during fasting since hepatic T3 receptors decrease in the fasted rat. Collectively, these observations support the concept that human white cell T3 nuclear receptor binding is capable of rapid fluctuations, suggesting a mechanism for homeostatic regulation of T3 action.
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PMID:Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells. 624 59


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