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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid-stimulating hormone (TSH) belongs to a family of glycoprotein hormones secreted by the anterior lobe of the pituitary gland in a pulsatile fashion. Although this pulsatile pattern of release has been characterized by several groups, its exact physiological relevance remains to be elucidated. We established a model of a chronically cannulated rat allowing us to apply quantified pulses of thyrotropin-releasing hormone intravenously and to monitor the biological response on the anterior pituitary as well as on the thyroid level. Serum rTSH, T3 and T4 levels were measured as functional parameters. During the five day infusion period, TSH increased under both continuous and pulsatile TRH stimulation, but this increase was only maintained following pulsatile TRH but not after continuous application. No differences between the continuous and the pulsatile infusion regimen could be observed in terms of TT3 release, whereas TT4 decreased following an initial stimulation under continuous application, but remained stimulated during pulsatile application. Our data indicate that the model of the chronically cannulated rat appears to be a valuable tool to study the impact of the temporal pattern of TRH/TSH on thyroid physiology.
Exp Clin Endocrinol Diabetes 1996
PMID:Continuous vs. pulsatile administration of thyrotropin-releasing hormone (TRH) in the model of the chronically cannulated rat: long-term effects on thyroid function. 898 25

Since Shimosato et al., in the mid 70s transplanted for the first time thyroid carcinoma tissue onto nude mice, other research groups have made use of the nude mouse model for the investigation of xenotransplanted thyroid tissue. The use of this model for the investigation of benign goiters is briefly discussed in this article. Normal human thyroid tissue has been transplanted either as a control in experiments with benign and malignant goiter tissue, or for the study of thyroid tissue response to stimulators such as TSH or thyroid stimulating antibodies (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and successfully transplanted into nude mice. Moreover, all the variants of human benign goiter tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of animal thyroid tissue xenotransplantation onto nude mice are briefly discussed: Nude mice bearing normal thyroid tissue transplants from 4 different species (man, rat, pig, guinea-pig) have been used for the study of the species specific effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been transplanted. In methodological terms, these experiments have shown that surgically removed goiter tissue can be shipped by air in cell culture medium at 4 degrees C over long distances and then successfully transplanted.-Finally, cell lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either as cell suspension or embedded in collagen, for example for the study of proliferation and folliculogenesis. Using the xenotransplantation model, function and proliferation, morphogenesis and differentiation, as well as thyroid autonomy and response to stimulators have all been studied in xenotransplanted human and animal thyroid thyroid tissue and cell lines under various experimental conditions. Although new research tools, for example transgenic animals, are now increasingly and successfully used, xenotransplantation still offers the possibility of addressing some specific questions which cannot be answered so easily with other experimental models. For example, studies with human tissue, involving drugs or radioactive tracers which cannot be applied to the intact human being, can relatively easily be performed with xenotransplanted human tissue and application of the drug or tracer to the host mouse. Or embryological development can be followed and studied using fetal thyroid (and other) tissue transplanted onto nude mice; here, of course, difficult ethical issues have to be considered. Finally, it should be mentioned that, although many scientific questions can be studied nowadays by cell culture or other in vitro systems, animal models are still needed. Extrapolation to the human being, however, should always be done with caution and we should always keep in mind that for the understanding of a human disease indeed human experimental models remain the goldstandard.
Exp Clin Endocrinol Diabetes 1996
PMID:Model of the athymic nude mouse for the study of benign goiter disease. 898 27

Infection with hepatitis C virus (HCV) may affect not only the liver but also various nonhepatic tissues and organs and may combine with many etiologically unrelated diseases and morbid conditions. Numerous nonhepatic manifestations in HCV infection have been previously reported. For some (eg, cryoglobulinemia), the association is well established. For others, such as sialadenitis and lichen planus, the association is probable (but not completely documented) and, for the remainder, the associations are weak. Extrahepatic manifestations may result from immunological mechanisms as well as virus invasion and replication in the affected extrahepatic tissues and organs. Thyroid abnormalities, primarily Hashimoto's disease, and isolated increases of anti-thyroid antibodies (ATPO) appear to be more frequent in chronic hepatitis C than B or D, with high ATPO titers clustering mainly among females. Interferon-alpha (IFN-alpha) therapy is associated with development of thyroid dysfunction in 5.5-12.9% of patients, usually exposing preexisting subclinical thyroid abnormalities. Mixed cryoglobulinemia (MC) is commonly found (36-45%) in patients with chronic HCV infection; however, only in a minority of cases does it become clinically manifested as systemic vasculitis with purpura, neuropathy, or Raynaud's phenomenon. In a number of patients, MC may terminate in non-Hodgkin's B-cell lymphoma. Treatment of these lymphoproliferative disorders with IFN-alpha is advocated. Idiopathic thrombocytopenia is now recognized more frequently in association with chronic HCV infection and is usually aggravated by IFN-alpha therapy. Patients with porphyria cutanea tarda (PCT) have demonstrated serological markers of HCV infection in 62-82% of cases. The usefulness of IFN-alpha in PCT remains to be demonstrated. Lichen planus has also been found in association with chronic HCV infection, particularly when severe or affecting the oral cavity. Other nonhepatic manifestations have also been reported in HCV infection such as diabetes, corneal ulceration, uveitis, and sialadenitis. These manifestations deserve further study and documentation. Finally, markers of autoimmunity occur with high frequency in chronic HCV infection; however, combination with the classical syndrome of autoimmune hepatitis is rare. In the presence of various autoantibodies, the clinical features of chronic hepatitis C do not appear to be modified and, contrary to general perception, IFN-alpha therapy within randomized controlled trials should not be withheld since the response rate to IFN-alpha does not appear to differ in the presence or absence of low titers of these markers.
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PMID:Nonhepatic manifestations and combined diseases in HCV infection. 901 79

The aim of this study was to evaluate the relationship between subclinical hypothyroidism and/or autoimmune thyroid disease and coronary heart disease (CHD). Ninety seven patients diagnosed as having CHD by a coronary angiography (CHD group) and 103 healthy subjects matched for age, sex and body mass index (control group) were included in the study. Thyroid function, thyroid autoantibodies and serum lipid concentrations were measured in the CHD and control groups. The CHD group exhibited significantly decreased serum free T3 (FT3) and free T4 (FT4) levels, and significantly increased serum TSH levels as compared with the control group, indicating a significant decrease in thyroid function in the CHD patients. Serum high density lipoprotein cholesterol (HDL-C) levels were significantly decreased in the CHD group. The incidence of subclinical hypothyroidism and thyroid autoantibodies was similar in both two groups. These observations were also true of women even after those who had diabetes mellitus (DM), hypertension (HT) and a smoking habit were excluded. This was not the case, however, in men without DM, HT, or a smoking habit. Patients with CHD had significantly lower serum levels of HDL-C than the control subjects, regardless of gender (P < 0.01). In the group with CHD, there was no difference between the serum lipid levels in patients with subclinical hypothyroidism and those with normal thyroid function. Female patients with CHD had significantly lower serum levels of thyroid hormone and HDL-C, but their subclinical hypothyroidism or thyroid autoimmunity did not seem to be related to the development of CHD.
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PMID:Decrease in serum levels of thyroid hormone in patients with coronary heart disease. 907 5

Maintenance of normal maternal thyroxinemia prevents severe triiodothyronine (T3) deficiency of the fetus with primary thyroid failure (1). We have studied whether thyroxine (T4) would also protect the fetal brain when maternal hypothyroxinemia is caused by nonthyroidal illnesses. We have used the streptozotocin-induced diabetes mellitus pregnant rat as a model of maternal nonthyroidal illness. We measured the effects of diabetes mellitus, and of correction of the ensuing maternal hypothyroxinemia with T4 as compared to insulin, on maternal body weight, the outcome of pregnancy, glucose, insulin, T4, T3, reverse T3, and thyrotropin levels in the maternal and fetal circulation, as well as T4 and T3 concentrations in tissues, and iodothyronine deiodinases in liver, lung, and brain. The diabetic mothers showed changes in thyroid hormone status typical of nonthyroidal illnesses. Thyroid hormone status of the fetuses was severely affected: the total T4 and T3 pools decreased to one-third of normal values. T4 and T3 concentrations in the fetal brain were lower than normal and the expected increase in 5'-deiodinase activity was not observed. Although insulin treatment avoided or mitigated these changes, the low cerebral T3 did not improve with T4 treatment of the maternal hypothyroxinemia. Several findings indicated that treatment of the severely ill dams with T4 was actually harmful for the outcome of pregnancy. These negative effects were observed without the expected increase in the maternal or fetal T3 pools.
Thyroid 1997 Feb
PMID:Maternal diabetes mellitus, a rat model for nonthyroidal illness: correction of hypothyroxinemia with thyroxine treatment does not improve fetal thyroid hormone status. 908 76

Acute suppurative thyroiditis (AST) is a rare disorder. The rarity of AST is a result of the resistance of the thyroid gland to local infection. Thyroid function tests are usually normal in AST. In a review of the literature from 1966 to 1995, only three cases of AST associated with thyrotoxicosis have been convincingly demonstrated. The thyrotoxicosis in these cases was caused by diffuse inflammation of the thyroid gland and to the disruption of follicles with the release of pre-formed thyroid hormone into the circulation. Thus, the thyrotoxicosis in these cases was transient. With successful therapy, nearly all patients showed complete recovery of thyroid function within two to three months. The patient in the case here was a diabetic woman with Graves' disease in whom thyrotoxicosis occurred after Klebsiella pneumoniae thyroiditis, with relapse nine months after discharge. Thus, the patient's thyrotoxicosis might not have been caused simply from thyroid tissue destruction by AST, but also as a result of enhancing autoimmune activity. No previous case has ever been reported in the English literature. In diabetics, the impairment of chemotaxis and phagocytosis has been noted. Therefore, diabetes mellitus (DM) might have been the precipitating factor for this patient's acquiring this unusual infection. Thyrotoxicosis and AST will increase insulin requirements and thus aggravate diabetes. In addition, poor control of blood sugar will enhance the severity of AST.
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PMID:Graves' disease and diabetes mellitus associated with acute suppurative thyroiditis: a case report. 913 26

Since experimental diabetes in rats and mice is associated with impairment of several aspects of thyroid function, we determined glucose and amino acid uptake in vitro by isolated thyroid glands from normal and streptozotocin-diabetic rats. Adult male Wistar rats weighing 150-200 g were used. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) and after five days only rats with blood glucose levels higher than 250 mg/dl were used. The thyroid glands were preincubated in Krebs-Ringer bicarbonate buffer in the presence or absence of insulin (0.7 nM to 7 muM) for 90 min and then incubated with the same concentration of the hormone or its vehicle plus 0.2 microCi of [1-14C]-2-deoxy-D-glucose ([14C]DG) or [1-14C] methylaminoisobutyric acid ([14C]MeAIB) for 15 to 180 min. The uptake of [14C]DG or [14C]MeAIB by the thyroid glands of normal rats increased as a function of incubation time, and the presence of insulin (7 microM) induced a significant increase of labelled DG from 3.30 +/- 0.11 to 4.16 +/- 0.12 and of labelled meAIB from 1.79 +/- 0.06 to 3.10 +/- 0.17 tissue/medium ratio (T/M) and after 45 min of incubation. The lowest concentration of insulin that increased both [14C]DG and [14C]MeAIB transport was 7 nM. Thyroid glands from STZ rats exhibited lower basal values of [14C]DG (4.03 +/- 0.11 T/M) or [14C]MeAIB uptake (1.05 +/- 0.05 T/M) than glands from normal rats (4.62 +/- 0.13 and 1.70 +/- 0.08 T/M, respectively). Insulin produced a stimulatory effect on the transport of both substrates in STZ rats. However, the maximal stimulating concentration of the hormone did not restore [14C]DG and [14C]MeAIB uptake to control values (4.89 +/- 0.17 in STZ rats versus 5.44 +/- 0.17 T/M in controls for [14C]DG, and 1.51 +/- 0.11 in STZ rats versus 2.19 +/- 0.10 T/M in controls for [14C]MeAIB). These results indicate that insulin exerts a direct action on the thyroid gland, and its absence or reduction affects thyroid metabolism, contributing, at least in part, to the abnormality in thyroid function associated with diabetes mellitus.
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PMID:Decreased basal and acute insulin-stimulated effect on the uptake of glucose and amino acid in vitro by thyroid glands from streptozotocin-diabetic rats. 919 60

Short-term experimental diabetes mellitus (DM) produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days), short-term (15 days) and chronic (6 months) streptozotocin-induced diabetes mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 microM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 micrograms/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 micrograms/dl after 15 days of DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary.
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PMID:Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus. 923 15

Autoimmune thyroid diseases (AITD) and insulin-dependent diabetes mellitus (IDDM) are two autoimmune syndromes of unknown etiology with common immune features. One is that the target cells, thyrocytes and pancreatic islet beta cells respectively, hyperexpress several proteins encoded in the HLA region: HLA class I, HLA class II and transporter associated with antigen processing (TAP-1): the clinical course and many aspects of the immunopathology are, however, quite different. Low-molecular-mass polypeptides 2 and 7 (LMP2 and LMP7) are proteasome subunits that increase the efficiency of endogenous antigen processing and are encoded in close vicinity to the TAP genes. We investigated whether LMP2 and LMP7 are hyperexpressed in thyrocytes and islet cells in AITD and IDDM. Thyroid tissue from Graves' disease patients (GD, n = 8) and Hashimoto thyroiditis (HT, n = 1) and pancreatic tissue from IDDM patients (n = 4) as well as control tissues were examined by the two-color indirect immunofluorescence technique. The results demonstrate that, in normal glands, thyrocytes and pancreatic islet cells express comparable moderate to low levels of LMP2 and LMP7. In AITD and IDDM, expression of LMP2/7 in the endocrine cells was disparate: while in AITD glands there was hyperexpression of LMP2 and 7 parallel to that of HLA class I and TAP-1, in the islet cells of recent onset diabetic pancreases (n = 2) the level of LMP2 and 7 expression was totally normal, including islets that were infiltrated by lymphocytes and hyperexpressed HLA class I and TAP-1. These observations suggest different mechanisms of endogenous peptides generation at the target cells in AITD from IDDM. Since this is a key step for the maintenance of peripheral tolerance, it may help to understand some of the different clinical features of the two autoimmune diseases.
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PMID:Proteasome subunits, low-molecular-mass polypeptides 2 and 7 are hyperexpressed by target cells in autoimmune thyroid disease but not in insulin-dependent diabetes mellitus: implications for autoimmunity. 927 25

We experienced a case of MEN type 2a with bilateral and large pheochromocytomas. A 39-year-old man was admitted to the previous hospital with complaints of paroxysmal headache. hypertension and diabetes mellitus. Radiographic imagings showed thyroid tumors in both lobes and bilateral adrenal tumors. Thyroid tumors were histologically proved to be medullary thyroid carcinoma by needle biopsy and systemic investigations revealed an excessive secretion of plasma and urinary cathecholamines which suggested the presence of pheochromocytoma. The patient was diagnosed as MEN type 2a. He was admitted to our hospital for the treatment of bilateral adrenal tumors for which we performed one-stage bilateral adrenalectomy by thoracoabdmonal approach. Both adrenal tumors were histologically confirmed as pheochromocytoma. The patient's postoperative course was uneventful. He underwent uneventful total thyroidectomy approximately 2 months after bilateral adrenalectomy. Even in bilateral and large pheochromocytomas, one-stage bilateral adrenarectomyenables safe postoperative managements. We concluded that the thoracoabdominal approach is feasible in the patients with huge and cranially spreading adrenal tumor, which gives us a wide operative field for easy vascular control.
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PMID:[One-stage-bilateral adrenalectomy by thoracoabdominal approach for bilateral large pheochromocytomas in men type IIa. A case report]. 938 71


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