Showing papers by "Massimo Tonacchera published in 2011"
TL;DR: Thirty unrelated children with CH or subclinical hypothyroidism (SH) identified during infancy with a eutopic thyroid gland, coming from the Screening Centre for CH or referred from other regions of Italy, were studied with the perchlorate discharge test to identify organification defects.
Abstract: Context: Congenital hypothyroidism (CH) associated with goiter or a gland of normal size has been linked to dual oxidase 2 (DUOX2) mutations in the presence of iodide organification defect. Objective: Thirty unrelated children with CH or subclinical hypothyroidism (SH) identified during infancy with a eutopic thyroid gland, coming from our Screening Centre for CH or referred from other regions of Italy, were studied with the perchlorate discharge test to identify organification defects. Eleven children with iodide organification defect were considered for the genetic analysis of TPO, DUOX2, and dual oxidase maturation factor 2 (DUOXA2) genes. Patients: Eight children with CH and three with SH and eutopic thyroid gland were included in the study. After discontinuation of therapy, a partial or complete organification defect was shown after 123I scintigraphy and perchlorate test. Methods: TPO, DUOX2, and DUOXA2 genes were analyzed, and functional activity of DUOX2 variants was studied in HeLa cells. Results:...
56 citations
TL;DR: No persistent and dose-dependent response to T(1)AM was observed after treatment with increasing doses of this substance for different times in terms of cAMP production and iodide uptake, and a slight inhibition of glucose uptake in FRTL5 cells, but it was taken up and catabolized by these cells.
Abstract: 3-Iodothyronamine (T(1)AM), produced from thyroid hormones (TH) through decarboxylation and deiodination, is a potent agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor belonging to the family of TAARs. In vivo T(1)AM induces functional effects opposite to those produced on a longer time scale by TH and might represent a novel branch of TH signaling. In this study, we investigated the action of T(1)AM on thyroid and determined its uptake and catabolism using FRTL5 cells. The expression of TAAR1 was determined by PCR and western blot in FRTL5 cells, and cAMP, iodide uptake, and glucose uptake were measured after incubation with increasing concentrations of T(1)AM for different times. T(1)AM and its catabolites thyronamine (T(0)AM), 3-iodothyroacetic acid (TA(1)), and thyroacetic acid (TA(0)) were analyzed in FRTL5 cells by HPLC coupled to tandem mass spectrometry. The product of amplification of TAAR1 gene and TAAR1 protein was demonstrated in FRTL5 cells. No persistent and dose-dependent response to T(1)AM was observed after treatment with increasing doses of this substance for different times in terms of cAMP production and iodide uptake. A slight inhibition of glucose uptake was observed in the presence of 100 μM T(1)AM after 60 and 120 min (28 and 32% respectively), but the effect disappeared after 18 h. T(1)AM was taken up by FRTL5 cells and catabolized to T(0)AM, TA(1), and TA(0) confirming the presence of deiodinase and amine oxidase activity in thyroid. In conclusion, T(1)AM determined a slight inhibition of glucose uptake in FRTL5 cells, but it was taken up and catabolized by these cells.
23 citations
TL;DR: In patients with low RAIU, rhTSH pre-treatment may optimize (131)I therapy, and one single dose of 0.03 mg of rhTSh increased the thyroid RAIU by 40% in patients with nodular goiter and low basal uptake.
Abstract: Background: 131I therapy is effective in reducing the volume of large nodular goiters (thyroid volume [TV]), mainly after stimulation with recombinant human thyrotropin (rhTSH). The amount of 131I to be administered inversely depends on thyroid radioactive iodine uptake (RAIU). In patients with low RAIU, we evaluated the efficacy of 131I treatment at lower doses with respect to those calculated on the basal RAIU, after rhTSH stimulation. Methods: Eighteen consecutive patients (17 women and 1 man, 49–83 years) with large nodular goiter were included in the study. At enrolment, 24th h RAIU, TSH, free thyroxine, free triiodothyronine, thyroglobulin antibodies, thyroid peroxidase antibodies, TSH receptors antibodies, urinary iodine, and TV were measured. RAIU was 40% in 7 (higher uptake group [HUG]). RAIU difference in the two groups was significant (p < 0.0001). LUG patients were treated with rhTSH (0.03 mg i.m.) and RAIU was measured again after 24 hours. ...
21 citations
TL;DR: Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.
Abstract: Aim: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/periventricular leukomalacia), with gestational age ≤30 (group I) and of 31–32 weeks (group II). Patients and methods: A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26–32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3–4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. Results: Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31–32 weeks: Apgar at 5 min 4, 3 mU/I and sub-optimal neuromotor outcome in both groups. Conclusions: Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.
13 citations
13 citations
TL;DR: This study carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NIS-mediated iodide uptake by using CHO-hNIS cells and found that perchlorate and thyocianate ions were able to inhibit iodine uptake in a dose-dependent manner.
Abstract: Background: Thyroid gland is highly dependent on dietary intake of iodine for normal function, so it is particularly subjected to “endocrine disruptor” action. The human sodium/iodide symporter (hNIS) is an integral plasma membrane glycoprotein mediating the active transport of iodide into thyroid follicular cells, a crucial step for thyroid hormone biosynthesis. Beyond to perchlorate and thyocianate ions a few other inhibitors of iodide uptake have been described. Aim: The aim of this study was to investigate if 10 substances usually used as drugs in clinical practice were able to inhibit NIS-mediated iodide uptake in vitro. Materials and methods: A CHO cell line stably expressing hNIS was used to test any inhibition of NIS-mediated iodide uptake exerted by drugs. Perchlorate and thyocianate ions were used as positive controls. Results: None of the analyzed substances was able to significantly inhibit iodide uptake in our system. As we expected, perchlorate and thyocianate ions were able to inhibit iodide uptake in a dose-dependent manner. Conclusions: In conclusion, we carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NIS-mediated iodide uptake by using CHO-hNIS cells. None of the analyzed substances was able to inhibit iodide uptake; only perchlorate and thyocianate were able to inhibit iodide uptake in a dose-dependent manner.
6 citations
TL;DR: EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro, and the effects caused by a GSM signal (900 MHz) on cultured thyroid cells (FR TL-5) are analyzed.
Abstract: Background: Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described. Aim: The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL-5). Material and methods: The experimental setup was designed in order to expose samples to a radio frequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800–900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured. Results: The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL-5 cells with respect to basal conditions. Conclusions: In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro.
2 citations