Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new euthyrox research articles will be listed here shortly after becoming available to us.
Medical research on euthyrox
Lab Invest. 2010 Mar 15;
Zvibel I, Atias D, Phillips A, Halpern Z, Oren R
We have previously shown that hyperthyroidism is detrimental for liver fibrosis and in this study we have investigated the mechanisms regulating triiodothyronine (T3) and L-thyroxine (T4) activation of hepatic stellate cells (HSC). Expression of alpha-smooth muscle actin (alphaSMA) and p75 neurotrophin receptor (p75NTR) was determined by western blot analyses and transient transfection of the promoters. Rho activation was assayed using a pull-down assay and by ELISA. Expression of thyroid hormone receptor alpha1 decreases, whereas T4 receptor integrin alphaVbeta3 increases, with transdifferentiation of HSC to myofibroblasts. T3 and T4 enhance HSC activation, without affecting proliferation or phosphorylation of mitogen-activated protein kinase, signal transducer and activator of transcription 3 or Akt. Addition of 10(-7) M T3 or T4 to thyroid hormone-depleted serum induces a twofold increase in activation marker alphaSMA, as well as upregulation of p75NTR protein levels. Both hormones enhance transcription of alphaSMA and p75NTR. We report a novel signaling pathway for thyroid hormones, activation of Rho. T4 induces activation of Rho acting through alphavbeta3 integrin, and the activation is abolished by the T4 antagonist, tetraiodothyroacetic acid, by peptide RGD and by a function-blocking antibody to integrin beta3. T3 and T4 increase phosphorylation of non-muscle myosin light chain II, a downstream signal to Rho/Rho-kinase activation. T3 also induces expression of tumor necrosis factor-alpha. In vivo, administration of T3 or T4 together with thioacetamide (TAA) enhances fibrosis after 3 weeks, compared with the TAA-treated group, accompanied by increased alphaSMA in T3- and T4-treated groups, and of p75NTR in T4-treated rats. Thyroid hormones enhance activation of HSC through increased p75NTR and alphaSMA expression and activation of Rho, therefore accelerating development of liver fibrosis.Laboratory Investigation advance online publication, 15 March 2010; doi:10.1038/labinvest.2010.48.
Concomitant Graves Hyperthyroidism with Thyrotrophin-Secreting Pituitary Adenoma.
South Med J. 2010 Mar 10;
Lee MT, Wang CY
The relationship of autoimmune thyroid disease and TSH-producing pituitary tumor is rarely found. We report two patients with hyperthyroidism, a 27-year-old man and a 28-year-old woman, who were diagnosed with Graves hyperthyroidism with elevated free thyroxine (FT4), suppressed TSH and positive thyrotropin receptor autoantibodies. After treatment with antithyroid drugs, FT4 did not return to normal, and serum TSH levels were found to be above-normal range. Pituitary tumors were subsequently found via pituitary magnetic resonance imaging (MRI). We suggest that Graves hyperthyroidism concomitant with TSH-producing pituitary tumor be kept in mind, as it may confuse the therapeutic course of hyperthyroidism and make it more complicated.
Pituitary-Adrenal Functions in a Hereditary Hypothyroid (rdw) Rat.
Exp Anim. 2010; 59(1): 95-8
Tohei A, Umezu M, Kanai T, Yamaguchi K, Kosaku A, Kon H, Shinoda M
The rdw rat is a hereditary hypothyroid strain isolated from Wistar-Imamichi rats. In the present study, adrenocorticotropic hormone (ACTH) and corticosterone responses to restraint stress (120 min) were examined in rdw adult male rats. ACTH response to restraint stress was higher in rdw rats than in hetero control rats. The plasma concentrations of corticosterone were lower in rdw rats than in control rats during the first 30 min after the onset of stress. Both ACTH and corticosterone responses to restraint stress in rdw rats recovered to control levels after thyroxine (T4) replacement therapy. These results suggest that hereditary hypothyroidism causes adrenal dysfunction directly and that hypersecretion of ACTH is a result of reduced corticosterone in rdw rats.
J Feline Med Surg. 2010 Mar 9;
Quante S, Fracassi F, Gorgas D, Kircher PR, Boretti FS, Ohlerth S, Reusch CE
A 7-month-old male kitten was presented with chronic constipation and retarded growth. Clinical examination revealed disproportional dwarfism with mild skeletal abnormalities and a palpable thyroid gland. The presumptive diagnosis of congenital hypothyroidism was confirmed by low serum total thyroxine (tT(4)) concentration prior to and after the administration of thyroid stimulation hormone (TSH), increased endogenous TSH concentration and abnormal thyroid scintigraphic scan. The kitten had abnormal liver function tests and decreased insulin-like growth factor 1 (IGF-1) concentration, both of which returned to normal in correspondence with an improvement of the clinical signs after 6 weeks of thyroxine therapy. Congenital hypothyroidism is a rare disease that may present with considerable variation in clinical manifestation. In cases in which clinical signs are ambiguous, disorders such as portosystemic shunt and hyposomatotropism have to be taken into account as differential diagnosis. As hypothyroidism may be associated with abnormal liver function tests and low IGF-1 concentrations, test results have to be interpreted carefully.
Newborn Screening Results in Children with Central Hypothyroidism.
J Pediatr. 2010 Mar 9;
Nebesio TD, McKenna MP, Nabhan ZM, Eugster EA
OBJECTIVE: To investigate newborn screening results in children with congenital hypopituitarism, including central hypothyroidism, and to determine whether there were differences between children who had abnormal results and children with normal newborn screening results. STUDY DESIGN: Medical records of children with central hypothyroidism observed in our pediatric endocrinology clinics from 1990 to 2006 were reviewed. RESULTS: Forty-two subjects (22 boys) were identified. Eight children (19%) had a low total thyroxine level (
Subclinical hypothyroidism presenting with gait abnormality.
Neurologist. 2010 Mar; 16(2): 115-6
Edvardsson B, Persson S
ABSTRACT:: Subclinical thyroid disease is a common disorder, particularly in middle-aged and elderly individuals. Some patients with manifest hypothyroidism complain of unsteadiness of gait. The management of subclinical hypothyroidism is controversial. A 61-year-old man presented with a mild gait abnormality. He walked unsteadily on a broad base. Examination revealed a slight cerebellar ataxic gait. Laboratory evaluation showed elevated levels of thyroid-stimulating hormone. Serum free thyroxine was normal and thyroglobulin antibodies were present. Computer tomography of the patient's head was normal, as were other investigations. The patient responded rapidly to thyroxin treatment with resolution of the gait disturbance. A laboratory evaluation of thyroid function should be performed in similar cases, and treatment should be initiated when called for. Subclinical hypothyroidism can present as a cerebellar ataxic gait.
Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia.
N Engl J Med. 2010 Mar 11; 362(10): 906-16
Ladenson PW, Kristensen JD, Ridgway EC, Olsson AG, Carlsson B, Klein I, Baxter JD, Angelin B
BACKGROUND: Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided. METHODS: We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 microg per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary. RESULTS: The addition of placebo or eprotirome at a dose of 25, 50, or 100 microg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome. CONCLUSIONS: In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)
Ital J Pediatr. 2010 Mar 10; 36(1): 24
Rovelli R, Vigone MC, Giovanettoni C, Passoni A, Maina L, Corrias A, Corbetta C, Mosca F, Chiumello G, Weber G
ABSTRACT: BACKGROUND: Evaluation of thyroid function in neonates born from mother affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb) and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated. METHODS: 129 neonates were tested for thyroid function by measurement of free thyroxine (FT4) and thyroid stimulating hormone (TSH) in 3th day, 15th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected. RESULTS: 28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population. CONCLUSIONS: Transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mother affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to careful monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2 nd and 4 th week of life.
Endokrynol Pol. 2010 Jan-Feb; 61(1): 112-6
Siemińska L, Wojciechowska C, Kos-Kudła B, Marek B, Kajdaniuk D, Nowak M, Głogowska-Szelag J, Foltyn W, Strzelczyk J
Introduction: Leptin and adiponectin are involved in the pathogenesis of several autoimmune diseases. Very little is known about adipocytokine production in autoimmune thyroid diseases. Interleukin-6 (IL-6) plays an important role in the inflammatory and autoimmune processes. Material and methods: The aim of this study was to assess the serum levels of leptin, adiponectin, and IL-6 in postmenopausal euthyroid women with Hashimoto's thyroiditis and compared them with concentrations in control women. Ninety-eight euthyroid women with Hashimoto's thyroiditis were enrolled in the study. The diagnosis was confirmed with elevated thyroid peroxidise autoantibody (TPOAb) levels in serum and typical hypoechogenic pattern on thyroid ultrasound. The control group, matched for body mass index (BMI), consisted of 105 healthy postmenopausal euthyroid women. Serum levels of leptin, adiponectin, IL-6, thyroid-stimulating hormone (TSH), free thyroxine (fT(4)), and TPOAbs were determined. Results: When compared with controls, the women with Hashimoto's thyroiditis were characterized by significantly elevated serum concentrations of IL-6, whereas concentrations of leptin and adiponectin were not different. Hashimoto's thyroiditis patients had significantly higher serum levels of TSH than the controls. The simple linear regression analyses of the Hashimoto's thyroiditis group and all of the studied women indicated that serum leptin levels correlated positively with BMI, waist to hip ratio (WHR), TSH, and IL-6 and negatively with adiponectin. No correlation was observed between serum adiponectin and TSH, fT(4), or TPOAbs. There were no associations between serum IL-6 levels, TPOAbs, and TSH levels; however, positive correlations between IL-6 and BMI, WHR, and leptin were observed. TSH correlated positively with leptin, age, and TPOAbs. Conclusions: Hashimoto's thyroiditis is characterized by an increased production of IL-6 but does not have a direct influence on leptin or adiponectin serum levels. The correlations between TSH and leptin demonstrated in this study highlight the need for future investigations. (Pol J Endocrinol 2010; 61 (1): 112-116).
Effects of Growth Hormone and Thyroxine Replacement Therapy on Insulin Signaling in Ames Dwarf Mice.
J Gerontol A Biol Sci Med Sci. 2010 Mar 3;
Louis A, Bartke A, Masternak MM
Ames dwarf (Prop1(df), df/df) mice lack growth hormone (GH), prolactin, and thyrotropin and live remarkably longer than their normal siblings. Significance of reduced activity of the somatotropic and thyroid axes during development and adulthood on longevity are unknown. Because enhanced insulin sensitivity and reduced insulin levels are among likely mechanisms responsible for increased longevity in these mutants, we compared the effects of GH and thyroxine (T4) replacement on various parameters related to insulin signaling in young and old male df/df mice. The results suggest that altered plasma adiponectin and insulin-like growth factor-1 (IGF-1) and hepatic IGF-1, insulin receptor (IR), IR substrate-1, peroxisome proliferator-activated receptor (PPAR) gamma, and PPARgamma coactivator-1 alpha may contribute to increased insulin sensitivity in Ames dwarfs. The stimulatory effect of GH and T4 treatment on plasma insulin and inhibitory effect on expression of hepatic glucose transporter-2 were greater in old than in young dwarfs. These results indicate that GH and T4 treatment has differential impact on insulin signaling during development and adulthood.